Soluble highly reactive form of calcium and reagents thereof

A soluble highly reactive form of calcium, prepared from Ca(II) salts and a reducing agent in ethereal, polyethereal, or hydrocarbon solvents, is presented. This form of calcium can be used in the preparation of organocalcium reagents. The organocalcium reagents resulting from the reaction of the soluble highly reactive calcium with organic compounds containing either halide, cyanide, a 1,3-diene, or a polyunsaturated functionality, are stable, useful reagents for organic synthesis. The organocalcium halide reagents undergo Grignard-type reactions. They also undergo reactions with Cu(I) salts to form organocalcium cuprate reagents. The organocalcium cuprate reagents undergo a variety of cross-coupling reactions. The soluble highly reactive calcium reacts with 1,3-dienes to yield the corresponding 2-butene-1,4-diylcalcium complexes. These bis-organocalcium reagents can undergo dialkylation reactions with .alpha.,.omega.-alkylene dihalides and dichlorosilanes to form the corresponding 3-, 5-, and 6-membered ring derivatives. The soluble highly reactive calcium also reacts with organic dihalides to form mono- or diorganocalcium compounds which can be converted into a wide variety of polymers.

BACKGROUND OF THE INVENTION 
Organocalcium reagents are highly desirable reagents for organic synthesis. 
They possess many attributes that are distinct from organomagnesium and 
other organometallic reagents. For example, they often react 
stereoselectively and regioselectively. Furthermore, they do not possess 
the extreme nucleophilicity of such reagents as Grignard reagents. 
Consequently, organocalcium reagents can generate distinctly different 
chemistry from that of other organometallic reagents. 
The development of organocalcium chemistry has been slow with respect to 
extensive studies of organometallic reagents of other light metals, such 
as magnesium. The neglect of organocalcium chemistry has been due, at 
least in part, to the lack of a facile method of preparing the 
organocalcium compounds. Furthermore, the few dialkyls and alkyl halides 
of calcium studied in the early to mid-1900's proved to be thermally 
unstable, generally insoluble, and difficult to manipulate. 
Another impediment to the development of organocalcium chemistry has been 
the expectation that calcium and organocalcium compounds should parallel 
that of their magnesium analogs. In fact, calcium is known to more closely 
resemble sodium rather than magnesium in its chemical reactivity, although 
calcium is somewhat less reactive than sodium. For example, unlike 
magnesium but much like sodium, calcium is known to be an excellent 
reducing agent. Furthermore, unlike magnesium, calcium is soluble in 
liquid ammonia giving a blue solution similar to the solutions of the 
Group I metals, which are believed to be solvated metal ions and 
electrons. 
Although there is little known about organocalcium compounds, direct 
oxidative addition of organic substrates to bulk calcium metal, suspended 
in a suitable solvent, has traditionally been the method of forming 
organocalcium compounds. This has been limited, however, by the reduced 
reactivity of the bulk calcium metal. Although it is not entirely clear, 
this is presumably due to surface poisoning factors. 
Thus, developments in the production of organocalcium compounds have 
centered around activating the bulk calcium metal. Typically, this has 
involved alloying of the bulk metal, the addition of activating agents to 
a reaction mixture, or the use of highly purified bulk metal. For example, 
Ca amalgam or Ca-Mg alloys have been used to activate the Ca metal to 
oxidative addition reactions. Iodine has also been used as an activating 
agent in a reaction mixture. 
Although there are several procedures known for the reduction of metal 
salts to metal powders reactive towards oxidative addition, each metal 
typically requires unique permutations of the procedures to obtain a 
reactive species. That is, there is no standardized approach that can 
produce metal powders of identical, or even similar, reactivity. For 
example, magnesium metal in the form of a black powder can be obtained by 
reducing magnesium salts in an ethereal solvent with molten sodium or 
potassium; however, the use of an alkali metal in conjunction with an 
electron carrier such as naphthalene can produce magnesium powder of even 
greater reactivity. These procedures can produce finely divided highly 
reactive metal powders; however, these procedures are not standardized or 
generalized. 
The organocalcium derivatives RCaX are typically most readily formed when 
X=I; however, the preparation of RCaX (X=Br, Cl) usually requires 
activated calcium. Even with activated, or highly pure calcium, few 
examples of organocalcium halides, or other organocalcium reagents, have 
actually been prepared. Typically, of the reagents prepared, the overall 
yields are generally low. Although simple primary and secondary alkyl 
iodides have been shown to react with highly pure calcium, i.e., Ca 
containing less than 0.5% Mg and 0.002% Na, in reasonable yields, the 
tertiary alkyliodocalcium compounds have proven to be very difficult to 
prepare. In fact, most tertiary alkyls are generally formed in only trace 
amounts. 
Therefore, an object of the invention is to produce a calcium species that 
is more reactive than those obtained from traditional methods. Another 
object of the invention is to produce a calcium species that is soluble 
and highly reactive towards oxidative addition. Yet another object of the 
invention is the direct production of a wide variety of organocalcium 
compounds, e.g., aryl and alkyl calcium compounds, particularly tertiary 
alkyl calcium compounds. Furthermore, an object of the invention is the 
synthesis of new organic compounds or the synthesis of known organic 
compounds using more effective and/or more direct synthetic methods. 
SUMMARY OF THE INVENTION 
These and other objects are achieved by the present invention which is 
directed to the use of a soluble highly reactive calcium species to form 
new organocalcium reagents and to synthetic reactions performed with these 
organocalcium reagents. As used herein, the phrase "highly reactive" 
refers to the reactivity of the calcium species in organic reactions, 
particularly oxidative addition reactions. A calcium species is highly 
reactive if it reacts with a wide variety of primary, secondary, and 
particularly tertiary alkyl halides in relatively high yields, for example 
in greater than about 50% yields, preferably in greater than about 70% 
yields. 
The soluble highly reactive calcium species is composed of formally 
zerovalent calcium metal atoms in combination or complexation with a 
solubilizing agent in an ethereal, polyethereal, or hydrocarbon solvent. 
The solubilizing agent can be any of a variety of macrocyclic polyethers, 
cryptates, or polyenes capable of interacting with the formally zerovalent 
calcium metal atoms in such a manner that a less reactive finely divided 
powder does not substantially precipitate out of solution. Preferably, the 
solubilizing agent is a polyene. More preferably, the solubilizing agent 
is an aromatic polyene, i.e., an arene or polyarylene, such as an aromatic 
electron-transfer compound. Examples of aromatic electron-transfer 
compounds include biphenyl, naphthalene, and anthracene. The soluble 
highly reactive calcium species can also be in combination with an alkali 
metal salt. 
The soluble highly reactive calcium species is formed from the reduction of 
a calcium(II) salt, preferably a soluble calcium(II) salt, the counterion 
of which can be any of a variety of anions without an acidic proton. For 
example, the anion can be a sulfate, nitrate, nitrite, cyanide, or halide. 
Preferably, the anion is a cyanide or a halide, and most preferably a 
halide. Of the halides, the most effective counterion is a bromide or 
iodide. 
The solubilizing agent is from a solubilized reducing agent that is capable 
of reducing calcium(II) salts in an ethereal, polyethereal, or hydrocarbon 
solvent. A reducing agent with a reduction potential of about -1.5 volts 
or more negative is acceptable. Preferably, the reducing agent has a 
reduction potential of about -1.8 volts or more negative, and most 
preferably about -2.0 volts or more negative. Examples of such reducing 
agents include alkali metal salts of aromatic anions. Examples of 
preferred reducing agents include sodium, potassium, cesium, or lithium 
naphthalenide, biphenylide, or anthracenide. Other examples of preferred 
reducing agents include alkali metal-polyether solvates, alkali 
metal-crown ether solvates, alkali metal-cryptate solvates, etc. 
Typically, the reduction of the calcium(II) salt is carried out in an 
ethereal, polyethereal, or hydrocarbon solvent. These include, but are not 
limited to, ethyl ether, tetrahydrofuran, glyme, diglyme, triglyme, 
benzene, and the like. If a hydrocarbon solvent is used, it preferably 
contains a secondary solubilizing agent such as 
N,N,N',N'-tetramethylethylenediamine (TMEDA) to assist in solubilizing the 
starting materials and product, but particularly the starting materials. 
Preferably, the reaction is carried out in an ethereal or polyethereal 
solvent. More preferably, it is carried out in tetrahydrofuran (THF). 
The organocalcium reagents of the present invention are prepared from the 
soluble highly reactive calcium species produced as described above and an 
organic compound. The organic radical of the organocalcium reagent can be 
an aliphatic, aryl, arylalkyl, heterocyclic or polymeric group. The 
aliphatic, aryl, arylalkyl or polymeric group of this reagent may 
optionally be functionalized with such groups as allyls or ethers. 
The organocalcium reagent can also contain one or more halide groups 
(herein referred to as organocalcium halides). However, this is not 
necessarily a requirement for the use of organocalcium reagents in organic 
synthesis. For example, if the organic compound reactant contains a 
1,3-diene functionality or other conjugated polyunsaturated functionality, 
no halide is generally present. Thus, the organocalcium reagent does not 
necessarily contain a halide group. 
In the context of this invention, the term "aliphatic" means a saturated or 
unsaturated linear, branched, or cyclic hydrocarbon radical. The term 
"alkyl" means a saturated linear, branched, or cyclic hydrocarbon radical. 
The term "heterocyclic" means a mono- or polynuclear cyclic radical 
containing carbons and one or more heteroatoms such as nitrogen, oxygen, 
or sulfur or a combination thereof in the ring or rings, including but not 
limited to pyridine, pyrrole, indole, thiazole, pyrazine, guanine, 
cytosine, thymine, adenine, uredine, uracil, oxazole, pyrazole, hydantoin, 
piperazine, quinoline, xanthene, 1,10-phenanthroline, and acridine. The 
term "aryl" means a mono- or polynuclear aromatic hydrocarbon radical. The 
term "arylalkyl" means a linear, branched, or cyclic alkyl hydrocarbon 
radical having a mono- or polynuclear aromatic hydrocarbon or heterocyclic 
substituent. 
The term "polymeric" or "polymer" is used herein in its most general sense 
to mean a compound consisting essentially of repeating structural units. 
It refers to inorganic polymers such as silica and alumina. It also refers 
to organic polymers such as polyolefins, polystyrenes, polyesters, 
polyurethanes, polyamides, polycarbonates, polyethers, etc. 
The organocalcium reagents of the present invention can be used in a 
variety of organic synthetic reactions. For example, the organocalcium 
halide reagents react in a Grignard-type fashion to form alcohols from 
aldehydes and ketones. They also react with copper(I) salts to form 
organocalcium cuprates, which can further react with enones and acid 
chlorides. Organocalcium dihalides can be used in the preparation of novel 
polymeric materials, such as two-dimensional linear polymers. 
The present invention is also directed to a method for the preparation of 
spirocycles, .gamma.-lactones, particularly spiro .gamma.-lactones, 
.delta.-lactones, including spiro .delta.-lactones, .gamma.-lactams, and 
chiral vicinal diols. These compounds can be prepared from calcium 
complexes of 1,3-dienes that are prepared from the highly reactive calcium 
of the present invention. For example, the preparation of a 
.gamma.-lactone includes the steps of: contacting a calcium(II) salt in an 
ethereal, polyethereal, or hydrocarbon solvent with a reducing agent 
having a reduction potential of about -1.5 volts, or more negative, 
relative to SCE, to form a highly reactive calcium species; contacting the 
highly reactive calcium species with a conjugated diene to form a 
2-butene-1,4-diylcalcium complex; contacting the 2-butene-1,4-diylcalcium 
complex with a ketone or aldehyde in an ethereal, polyethereal, or 
hydrocarbon solvent to form a 1,2-addition adduct resulting from the 
incorporation of one molecule of the ketone or aldehyde into the 
2-butene-1,4-diylcalcium complex; contacting the 1,2-addition adduct with 
carbon dioxide to form a nucleophilic addition product; and contacting the 
nucleophilic addition product with an aqueous acid to form a 
.gamma.-lactone, preferably a spiro .gamma.-lactone. The conjugated diene 
can be a cyclic hydrocarbon containing at least two conjugated exocyclic 
double bonds or an open-chain conjugated diene, such as 
2,3-dimethyl-1,3-butadiene. The ketone and aldehyde can be any aryl or 
alkyl ketone or aldehyde including those containing heteroatoms, such as 
nitrogen. For example, the ketone can be any cyclic ketone such as 
cyclohexanone to yield a spiro .gamma.-lactone, or it can be an acyclic 
ketone to yield a .gamma.-lactone. Any alkyl or aryl aldehyde would yield 
a .gamma.-lactone.

DETAILED DESCRIPTION OF THE PRESENT INVENTION 
The present invention is based upon the discovery that a highly reactive 
soluble calcium metal species displays surprising and unexpected 
reactivity and usefulness in organic synthetic procedures. For example, 
the highly reactive soluble calcium species displays surprising and 
unexpected reactivity toward a wide variety of aliphatic, aryl, 
heterocyclic, arylalkyl and polymeric compounds, particularly compounds 
containing one or more halide atoms (hereinafter organic halides), or 
compounds containing a 1,3-diene functionality or conjugated 
polyunsaturation. 
The Calcium Species 
The soluble highly reactive calcium species is composed of formally 
zerovalent calcium metal atoms in combination or complexation with a 
solubilizing agent. By "formally zerovalent" it is meant that the formal 
oxidation state, or charge, is equal to the group number (i.e., 2) minus 
the number of unshared electrons (i.e., 2) minus the number of bonds 
(i.e., 0). 
The solubilizing agent that is in combination or complexation with the 
formally zerovalent calcium species of the present invention preferably 
comes from a corresponding solubilized reducing agent that is capable of 
reducing Ca(II) salts in an ethereal, polyethereal, or hydrocarbon 
solvent. The solubilizing agent can be any of a variety of macrocyclic 
polyethers, cryptates, or polyenes, and the like, capable of interacting 
with the formally zerovalent calcium metal atoms in such a manner that a 
less reactive finely divided powder does not precipitate out of solution 
to any significant extent. By this it is meant that the formally 
zerovalent calcium species of the present invention is substantially 
completely soluble in a ethereal, polyethereal, or hydrocarbon solvent 
with only about 20% or less of the calcium species in a solid state, i.e., 
a state without any significant interaction with the solubilizing agent. 
Preferably, the solubilizing agent is a polyene. More preferably, the 
solubilizing agent is an aromatic polyene, i.e., an arene or polyarylene, 
such as an aromatic electron-transfer compound. Examples of aromatic 
electron-transfer compounds include but are not limited to, biphenyl, 
naphthalene, and anthracene. Compounds such as these are typically capable 
of transferring electrons in an oxidation reduction reaction through the 
formation of radical anions. 
Thus, in a preferred embodiment, the highly reactive calcium species of the 
present invention is composed of zerovalent calcium metal atoms in 
combination or complexation with one or more of the arenes naphthalene, 
anthracene, or biphenyl. More preferably, the highly reactive calcium 
species of the present invention is composed of zerovalent calcium metal 
atoms in combination or complexation with the arene biphenyl. 
The highly reactive calcium species of the present invention, whether in a 
mixture or complex, is soluble in ethereal, polyethereal, or hydrocarbon 
solvents. These include, but are not limited to, ethyl ether, 
tetrahydrofuran, glyme, diglyme, triglyme, benzene, and the like. If a 
hydrocarbon solvent is used, it preferably contains a secondary 
solubilizing agent such as N,N,N',N'-tetramethylethylenediamine, or other 
diamine or bidentate ligand capable of solubilizing the starting materials 
and product, particularly the starting materials. 
The soluble highly reactive calcium species can also be in combination with 
an alkali metal salt wherein the anion does not contain an acidic proton. 
The alkali metal of the salt can be Li, Na, K, Rb, or Cs. Preferably, it 
is Li, Na, or K, and most preferably it is Li. The anion can be, but is 
not limited to, a nitrate, nitrite, sulfate, cyanide, and/or halide. 
Preferably, the anion is a halide or cyanide. More preferably, the anion 
is a halide. Most preferably, the anion is bromide or iodide. 
The most specific and preferred embodiment of the soluble highly reactive 
calcium species of the present invention is composed of zerovalent calcium 
metal atoms in combination with, or complexed with, biphenyl and a lithium 
halide. The solvent used to solubilize the most preferred embodiment of 
the calcium species is tetrahydrofuran (THF). 
The soluble highly reactive calcium species of the present invention is 
prepared from the reduction of a calcium(II) salt, the counterion of which 
can be any of a variety of anions that does not contain an acidic proton. 
For example, the anion can be a sulfate, nitrate, nitrite, cyanide, or 
halide. Preferably, the anion is a cyanide or a halide. More preferably, 
the anion is F, Cl, Br, or I. Most preferably the anion of the Ca(II) salt 
is Br or I. 
Generally, the reducing agent can be any solubilized reducing agent that is 
capable of reducing Ca(II) salts in an ethereal, polyethereal, or 
hydrocarbon solvent. Any reducing agent having a reduction potential of 
about -1.5 volts or more negative, relative to the standard calomel 
electrode (SCE), will satisfy this relation. It is preferred, however, if 
the reducing agent has a reduction potential of about -1.8 volts or more 
negative, and most preferred if the reducing agent has a reduction 
potential of about -2.0 volts or more negative. Preferably, the reduction 
takes place in an ethereal or polyethereal solvent, and more preferably in 
tetrahydrofuran. 
Examples of suitable solubilized reducing agents include alkali metal salts 
of aromatic anions, such salts being, for instance, sodium or lithium 
naphthalenide, anthracenide, or biphenylide; alkali metal-polyether 
solvates; alkali metal-crown ether solvates; alkali metal-cryptate 
solvates, etc. Preferably, the reducing agent is an alkali metal arene 
salt. More preferably, the reducing agent is a combination of an alkali 
metal cation and an anion of an aromatic electron transfer compound, such 
as biphenyl, anthracene, or naphthalene. Most preferably, the reducing 
agent is preformed. Of the preformed alkali metal arene salts, the most 
preferred is lithium biphenylide. 
By "preformed" it is meant that the alkali metal and about 1-1.2 
equivalents of the arene are allowed to react substantially completely, 
i.e., until substantially all the alkali metal is consumed, before 
contacting any calcium salts. The formation of the preformed reducing 
agent typically takes place in an ethereal, polyetheral, or hydrocarbon 
solvent, and generally is substantially complete in about 2 hours. 
Because the soluble highly reactive calcium species is preferably utilized 
within a short period of time after its preparation, it can also contain 
the alkali metal salt produced from the cation of the aromatic reducing 
agent and the anion of the calcium salt starting material. Generally, the 
alkali metal salt is not believed to effect the reactivity of the soluble 
highly reactive calcium; however, it may facilitate the reactivity of the 
organic compounds, particularly the oxidative addition reaction with the 
organic halides. 
The process for reduction to produce the soluble highly reactive calcium 
species of the present invention is conducted under conditions designed to 
prevent its reoxidation and substantial precipitation as calcium powder. 
Generally, these conditions include use of ethereal, polyethereal, or 
hydrocarbon solvents and the exclusion of oxygen. Also, the conditions are 
controlled so as to promote the existence of the calcium atoms as small 
soluble clusters and to avoid their agglomeration into larger 
configurations that could precipitate out of solution. Larger clusters of 
metal atoms generally means lower solubility and lower reactivity. 
Preferably, these conditions include temperatures of about 100.degree. C. 
or less, an inert atmosphere, e.g., an argon or nitrogen atmosphere, a 
reaction time of about 1 hour, and an ether or polyether solvent such as 
diethyl ether, dimethyl ether, tetrahydrofuran and the like, or a 
hydrocarbon solvent. The Ca(II) salt can be soluble in the solvent of the 
reaction, or it can be a suspension therein. The Ca(II) salt is preferably 
soluble in the solvent at room temperature, as is the resultant soluble 
highly reactive calcium species. The reduction can as well be conducted in 
a hydrocarbon solvent with N,N,N',N'-tetramethylethylenediamine (TMEDA) to 
solubilize or disperse the starting material complex and reducing agent. 
Typically, the molar ratio of the reducing agent to the Ca(II) salt is 
about 2:1 for an equivalent amount; however, the Ca(II) salt can be in 
excess. Preferably, the Ca(II) salt is present in an amount of about 
1.1-2.0 equivalents, and more preferably in an amount of about 1.5-2.0 
equivalents, per equivalent of reducing agent. Excess Ca(II) salt is used 
to ensure there is little or no reducing agent present to interfere with 
subsequent reactions, particularly if the highly reactive calcium species 
is used without isolation. 
Although the soluble calcium species can be maintained for a time under 
these conditions, it is also quite reactive. Consequently, it is 
preferably synthesized and used immediately or within a very short period 
of time. However, it can be stored for several days and much longer at 
lower temperatures under an inert atmosphere. 
The formal oxidation state of the calcium metal in the preferred highly 
reactive calcium species is considered to be zero; however, it is believed 
that the calcium arene, e.g., calcium biphenyl complex, has considerable 
charge transfer between the calcium and the arene. Thus, the calcium 
species can exist as a tight ion pair, or as a complex with significant 
charge transfer, between the calcium atoms and the anion. In contrast, it 
is believed that in solvents such as liquid ammonia, the Ca(II) ions are 
uninvolved ions in any reaction. With the soluble highly reactive calcium 
complex of the present invention, however, it is believed that the calcium 
ions are tightly bound and play an intimate role in the electron transfer 
process. 
Notwithstanding these theoretical considerations, the soluble calcium 
species of this invention will react with organic halides and 1,3-diene 
compounds, for example, to produce selectively reactive organocalcium 
compounds. The organocalcium species undergo a variety of reactions to 
produce both novel organic compounds and novel synthetic methods for known 
organic compounds. 
The Organocalcium Reagents 
The soluble highly reactive calcium species of the present invention reacts 
readily with a wide variety of substrates to generate excellent yields of 
organocalcium reagents, which can be used to produce unique organic 
compounds or known organic compounds from unique synthetic routes. 
Generally, the organocalcium reagents of this invention are composed of an 
aliphatic, aryl, heterocyclic, arylalkyl or polymeric organic radical in 
combination with calcium atoms derived from the foregoing soluble highly 
reactive calcium species. These organocalcium compounds can be monomeric 
or polymeric. 
Preferably, the organocalcium reagents of this invention are mixtures or 
combinations of the organocalcium compounds and alkali metal salts. With 
respect to these mixtures or combinations it is believed the calcium 
moiety or moieties of the organocalcium compounds associate in some manner 
with alkali metal salts present to form the organocalcium reagent. It is 
further believed that this association is in part responsible for the 
novel and selective reactivity of certain of the organocalcium reagents of 
this invention, although this is not intended to be limiting. 
The organocalcium reagents are produced by reaction of the highly reactive 
calcium species, prepared as described above, with an aliphatic, aryl, 
heterocyclic, arylalkyl, or polymeric compound. Preferably, these organic 
starting materials have one or more halide groups. If the aliphatic, aryl, 
arylalkyl, heterocyclic, or polymeric compound contains a 1,3-diene or 
polyunsaturation functionality, no halide is generally required for 
reactivity. 
The reactions are generally conducted under conditions designed to preserve 
the integrity of the organocalcium reagents, those conditions include, for 
example, the exclusion of water and oxygen. Preferably the reactions are 
carried out in an ethereal, polyethereal, or hydrocarbon solvent. More 
preferably, the are carried out in an ethereal or polyethereal solvent. 
Most preferably they are carried out in tetrahydrofuran (THF). 
Preferably, the conditions also include temperatures of less than about 
100.degree. C. Alkyl halides typically react with the soluble highly 
reactive calcium at temperatures between about -140.degree. C. and about 
100.degree. C., preferably between about -80.degree. C. and about 
35.degree. C. Aryl halides react with the soluble highly reactive calcium 
at temperatures between about -80.degree. C. and about 100.degree. C., 
preferably between about -30.degree. C. and about 30.degree. C. Organic 
compounds containing a 1,3-diene functionality react with the soluble 
highly reactive calcium at temperatures between about -140.degree. C. and 
about 100.degree. C., preferably between about -30.degree. C. and about 
30.degree. C. Typical yields of the organocalcium reagents are greater 
than about 50%, and preferably greater than about 70%. In some instances 
the organocalcium reagents can be produced in nearly quantitative yields. 
The organocalcium reagents are typically prepared in the same medium used 
to produce the highly reactive calcium species. The highly reactive 
calcium species is preferably present in an equimolar ratio with the 
organic compound, i.e., about 1 mole calcium to 1 mole reactive organic 
compound. More preferably, the calcium is present in an excess amount, 
e.g., about 1.1-2.0 moles calcium to 1 mole reactive organic compound. 
Generally, the organic group of the organocalcium reagent can be any 
saturated, olefinically unsaturated or aromatic hydrocarbon or a 
heterocycle containing carbon, nitrogen, oxygen, sulfur, phosphorous or 
combinations thereof in the heteronucleus. Examples of organic compounds 
that react with the highly reactive calcium species of the present 
invention include, but are not limited to, 1-bromooctane, 1-chlorooctane, 
1-bromo-3-phenoxypropane, 1-bromo-5phenoxypentane, bromocyclohexane, 
1-bromoadamantane, m-bromotoluene, m-bromoanisole, p-chlorotoluene, 
fluorobenzene, 1,4-diphenyl-1,3-butadiene, 2,3-dimethyl-1,3-butadiene, 
1,4-dibromobenzene, and 2,5-dibromothiophene. 
The molecular size of the organocalcium reagents can range from organic 
compounds and monomers, typically having from 1 to about 300 carbons, to 
polymeric compounds having molecular weights up to and including the 
million range. Preferred aliphatic, aryl, heterocyclic, and arylalkyl 
groups include linear or branched alkyl, cycloalkyl, allyl, vinyl, phenyl, 
benzyl, pyridyl, quinolinyl, piperadinyl, cytosinyl, uracinyl, guaninyl, 
adenosinyl, pyrrolyl, thiazolyl, the methylenyl derivatives of such 
heterocycles and phenyl alkyl groups as well as the hydrocarbon 
substituted and/or functionalized forms thereof. The hydrocarbon 
substituents can be one or more of such groups as alkyl, cycloalkyl, 
heterocyclic, olefinic and aromatic groups as well as combinations 
thereof, each substituent having from 1 to about 30 carbons. The 
hydrocarbons can be optionally functionalized with such groups as allyls, 
ethers, esters, nitriles, amides, and ketones. 
Although the organocalcium reagents can be functionalized as outlined above 
with groups such as allyls, ethers, esters, nitriles, amides, and ketones, 
they will maintain a stable state and will typically not self-react to a 
significant extent as long as they are maintained within the appropriate 
low temperature range. At higher temperatures, however, the organocalcium 
species can self-react, but if they are modified by reaction with Cu(I) 
salts to yield derivatives of organocalcium reagents, i.e., organocalcium 
cuprates as discussed below, synthetic chemistry can be carried out with 
the more highly functionalized organocalcium species. 
Reactivity of the Organocalcium Reagents 
In general, the organocalcium reagents undergo coupling reactions with 
organic electrophiles, i.e., compounds that are deficient in electrons, 
such as acid chlorides, ketones, aldehydes, nitriles, esters, amides, 
.alpha.,.beta.-unsaturated carbonyl compounds, epoxides, and the like. 
Specific illustrations of the novel utility of the soluble highly reactive 
calcium species of the present invention and the organocalcium reagents 
produced from the soluble highly reactive calcium are described below. In 
certain situations the organocalcium reagents can also react with 
copper(I) salts to produce organocalcium reagents containing copper atoms, 
herein referred to as organocalcium cuprate reagents, which possess unique 
reactivity patterns. 
Generally, the coupling reactions between the organocalcium reagent and the 
organic electrophile are typically conducted in the same medium used to 
produce the organocalcium reagent. The reaction is conducted under 
conditions designed to favor the production of the desired coupled 
product. Those conditions generally include low temperature, use of 
appropriate electrophiles, addition of the electrophile to the 
organocalcium reagent and stirring with appropriate reaction times. One or 
more of these conditions will be appropriate for use in particular 
instances. Choice of some or all of them is within the ordinary artisan's 
skill. 
Preferably, the reactions are carried out in an ethereal, polyethereal, or 
hydrocarbon solvent such as ethyl ether, tetrahydrofuran, glyme, diglyme, 
triglyme, benzene, and the like. If a hydrocarbon solvent is used, it 
preferably contains a secondary solubilizing agent such as 
N,N,N',N'-tetramethylethylenediamine, or the like. More preferably, the 
reactions are carried out in an ethereal or polyethereal solvent. Highly 
solvating solvents, such as THF, glyme, diglyme, and triglyme, facilitate 
the oxidative addition reactions with the organic halides and facilitate 
complex formation with 1,3-dienes. 
Residual alkali metal halide, e.g., lithium halide, is preferably present 
in the reaction mixture of the electrophiles and the organocalcium 
reagents. Although not intended to be limited by any theory, it is 
believed that the excess alkali metal halide facilitates electron transfer 
to the organic halide and 1,3-dienes in some manner. 
The reagents and reactions of this invention are useful in the organic 
synthesis of organic compounds that are difficult or impossible to prepare 
by other techniques. In particular, the facility to react aryl chlorides 
and fluorides at low temperatures, the ability to prepare tertiary 
organocalcium reagents, and the ability to modify the chemical reactivity 
by formation of a calcium cuprate, are all useful for designing organic 
synthetic procedures. As a result, these unique capabilities promote the 
use of the reagents and reactions of this invention in the organic 
synthesis of pharmaceutical compounds, insecticides, herbicides, polymeric 
compounds, organic additives for polymer compositions, organic conductors, 
and organic information storage devices. Specific examples include the 
syntheses of two-dimensional polymers, prostaglandins, penicillins, 
tranquilizers, and carbocyclic anticancer agents. These syntheses are made 
more efficient, are economically feasible, and, in several cases, 
represent the only route possible. They open the synthetic and 
investigatory arenas to the development and use of rare or previously 
unavailable organic compounds. 
Grignard-Type Reactions with Highly Reactive Calcium 
As stated above, the highly reactive calcium species of the present 
invention reacts readily with a wide variety of substrates to generate 
excellent yields of organocalcium reagents, which can be used in a wide 
variety of synthetic preparations. For example, the organocalcium 
reagents, prepared directly from the soluble highly reactive calcium 
species and organic halides, efficiently undergo Grignard-type reactions. 
Example 2 and Table I summarize some specific examples of 1,2-addition 
reactions with cyclohexanone utilizing the soluble highly reactive calcium 
species of the present invention. 
Traditional Grignard reactions involve the 1,2-addition of RCaX to 
aldehydes to form alcohols. Prior to the present developments with the 
soluble highly reactive calcium species, the preparation of RCaX reagents, 
i.e., organocalcium halides, has been limited. Thus, the development of 
synthetic procedures, such as Grignard-type reactions, has been limited. 
The present RCaX reagents undergo 1,2-addition reactions to the carbonyl 
groups of aldehydes and ketones, for example, under typical Grignard 
reaction conditions, to form alcohols in yields greater than about 50%, 
preferably greater than about 70%. 
Any of the organocalcium halide reagents, containing one or more halide 
atoms, discussed above can be used in Grignard-type 1,2-addition 
reactions. Furthermore, any of a variety of aldehyde, ketones, esters, 
amides, and nitriles can be used effectively in the 1,2-addition 
reactions. 
Significantly, the organocalcium halide reagents of the present invention 
can be used to prepare tertiary organocalcium reagents. For example, the 
Grignard-type reaction for 1-bromoadamantane utilizing the soluble highly 
reactive calcium affords 1-(1-adamantyl)cyclohexanol in 80% yield. The 
direct reaction of 1-bromoadamantane with metals is well known to yield 
mainly reductive cleavage or dimerization. Accordingly, this method 
represents a significant new approach to the preparation of 
1-metalloadamantane. More importantly, use of the active calcium 
represents a general route to tertiary organocalcium reagents. 
The Grignard-type reactions are carried out under conditions designed to 
produce high yields, i.e., yields greater than about 50%, and preferably 
greater than about 70%, of the resultant alcohols. These conditions 
include the exclusion of oxygen and temperatures of less than about 
100.degree. C., preferably between about -140.degree. C. and about 
100.degree. C., and more preferably between about -80.degree. C. and about 
100.degree. C. 
Preparation and Reactions of Organocalcium Cuprate Reagents 
While a wide spectrum of different metal cuprates are known, calcium 
cuprates are not generally known. Addition of copper(I) salts to the 
organocalcium reagents described above result in new organocalcium cuprate 
complexes of unique and different chemical reactivity. The organocalcium 
cuprate complexes are composed of a mixture or combination of an 
aliphatic, aryl, heterocyclic, arylalkyl or polymeric calcium cuprate and 
alkali metal salts. The alkali metal salts are from the copper(I) salt, 
which is preferably a thienyl cyanide, cyanide, or halide. More 
preferably, it is a thienyl cyanide or a cyanide. 
The copper(I) salts that are reactive with the organocalcium reagents of 
the present invention are preferably soluble copper(I) salts in an 
ethereal, polyethereal, or hydrocarbon solvent. They include, but are not 
limited to, CuCN.2LiBr, CuI, CuBr, CuCl, CuF, lithium thienylcyanocuprate, 
or other Cu(I) salts with nonprotic anions. Preferably, the Cu(I) salt is 
CuCN.2LiBr or lithium thienylcyanocuprate. 
The reaction conditions used for the formation of the organocalcium cuprate 
reagents are those typically designed to preserve the integrity of the 
organocalcium cuprate reagents. These conditions include the exclusion of 
water and oxygen, temperatures of less than about 100.degree. C., 
preferably between about -140.degree. C. and about 100.degree. C., and 
more preferably between about -80.degree. C. and about 30.degree. C. The 
copper is usually added in an equimolar amount relative to the 
organocalcium reagent, but can be added in an excess amount. The formation 
of the calcium cuprate reagents is typically carried out in the same 
medium used to produce the organocalcium reagent. 
Reaction of the organocalcium reagent prepared from an organic halide and 
the highly reactive calcium, with acid chlorides in the absence of a Cu(I) 
salt, typically afford complex mixtures of products. However, in the 
presence of a Cu(I) salt, high yields, i.e., greater than about 50% and 
often greater than about 70%, of ketone formation are observed. Example 3 
and Table II presents some specific examples of the ketone formation 
reactions of the calcium cuprates with benzoyl chloride. 
The reaction conditions for the ketone formation reactions include 
temperatures of less than about 100.degree. C., preferably between about 
-140.degree. C. and about 100.degree. C., more preferably between about 
-80.degree. C. and about 30.degree. C., and the absence of oxygen or 
protic solvents. 
These calcium cuprate compounds also undergo the conjugate 1,4-addition 
reactions with .alpha.,.beta.-unsaturated species. Example 4 and Table III 
presents some specific examples of conjugate 1,4-addition reactions with 
.alpha.,.beta.-unsaturated ketones, utilizing these calcium cuprates. 
The .alpha.,.beta.-unsaturated species that undergo the 1,4-addition 
reactions can be any of a variety .alpha.,.beta.-unsaturated species. For 
example, they can be .alpha.,.beta.-unsaturated ketones, aldehydes, 
esters, and amides. They can be acyclic, aryl, and even sterically 
hindered. If they are sterically hindered, i.e., if any group in the 
molecule hinders attack of the .beta.-position, it is preferred that the 
reaction mixture contains BF.sub.3 etherate and chlorotrimethylsilane, 
(TMSCl). These reagents perform the function of activation of the 
.alpha.,.beta.-unsaturated system. Other useful reagents such as this 
include alkyl and phosphines. 
Typically, the product yields of the 1,4-addition reactions using the 
organocalcium cuprate reagents are greater than about 40%, and preferably 
greater than about 70%. The reaction conditions for the 1,4-addition 
reactions include temperatures of less than about 100.degree. C., 
preferably between about -140.degree. C. and about 100.degree. C., more 
preferably between about -80.degree. C. and about 30.degree. C., and the 
absence of oxygen. 
Preparation and Reactions of Calcium Metallocycle 
Calcium complexes of 1,3-dienes can be prepared by reaction of the highly 
reactive calcium with a wide variety of conjugated dienes, e.g., 
1,3-dienes, such as 1,4-diphenyl-1,3-butadiene, 1,3-butadiene, 
2,3-dimethyl-1,3-butadiene, 2-methyl-1,3-butadiene, or any mono-, di-, 
tri-, or tetra-substituted 1,3-diene to form 2-butene-1,4-diylcalcium 
reagents. The dienes can be symmetrical or unsymmetrical. They can be 
open-chain hydrocarbons containing at least two conjugated double bonds or 
cyclic hydrocarbons containing at least two conjugated exocyclic double 
bonds, such as occur in 1,2-dimethylenecyclohexane, 
1,2-dimethylenecyclopentane, and 1,2-dimethylenecycloheptane, for example. 
Preferably, the 1,3-dienes do not contain any functional groups that react 
with the active calcium preferentially to the 1,3-diene functionality. The 
resulting bis-organocalcium reagents readily undergo alkylation reactions 
with a variety of electrophiles, i.e., compounds that are deficient in 
electrons, in a highly regio- and stereospecific manner (Table IV). 
The electrophiles include, but are not limited to, organodihalides, such as 
1,3-dibromopropane, 1,4-dibromobutane, .alpha.,.omega.-alkylene dihalides, 
mono- and dihalosilanes, mono- and dihalostannanes, acid chlorides, 
esters, amides, nitriles, gemdihalides, .alpha.,.omega.-alkyl 
halonitriles, and the like. The reactions with the electrophiles, such as 
the organodihalides, typically yield 4-, 5-, and 6-membered rings in 
yields greater than about 50%, and often greater than about 70% isolated 
yield. Preferably, and advantageously, the stereochemistry of these 
reactions is stereospecific. 
This chemistry can also be extended to 2,3-dimethyl-1,3-butadiene, which is 
a molecule which is much more difficult to reduce. Reaction of the 
resulting calcium complex with 1,3-dichloropropane and 1,4-dibromobutane 
produces the 5-membered ring product and 6-membered ring products in 
greater than about 50% yield. Further reactions of 2-butene-1,4-diyl 
calcium species to produce spirocycles, lactones, lactams, and vicinal 
diols are described below. 
The reaction conditions for production of calcium reagents with 1,3-dienes 
include temperatures of less than about 100.degree. C., preferably between 
about -140.degree. C. and about 100.degree. C., and more preferably 
between about -80.degree. C. and about 100.degree. C. and the absence of 
oxygen. The subsequent reactions of these 2-butene-1,4-diylcalcium 
complexes include temperatures of less than about 100.degree. C., 
preferably between about -140.degree. C. and about 100.degree. C., and 
more preferably between about -80.degree. C. and about 100.degree. C., and 
the absence of oxygen. 
Preparation of Polymers From Soluble Highly Reactive Calcium 
Significantly, the soluble highly reactive calcium species of the present 
invention reacts with organic halides substituted with more than one 
halide atom, such as dihalothiophenes and dihalobenzenes. Upon reaction 
with organodihalides, mono- or diorganocalcium compounds typically form 
which are capable of being converted into a wide variety of polymeric 
compounds. 
It is also envisioned that the soluble highly reactive calcium species of 
the present invention will react with other dihaloarenes, such as 
2,5-dichlorothiophene, 2,7-dibromo-9-fluorenone, 2,7-dibromofluorene, 
2,5-dibromopyridine, 3,4-dibromothiophene, 4,4'-dibromobiphenyl, and 
9,10-dibromoanthracene, Br--C.sub.6 H.sub.4 --CH.sub.2 Br, Br--C.sub.6 
H.sub.4 --CH.sub.2 --C.sub.6 H.sub.4 --Br, and the like. Each of these 
organodihalides can optionally be functionalized with groups such as --CN, 
--CO.sub.2 CH.sub.2 CH.sub.3, --OH. The dihaloarenes can also include 
heterocyclic arenes. 
Preferably, the soluble highly reactive calcium species of the present 
invention reacts with dihalothiophene and dihalobenzene. As a specific 
example, it can react with 2,5-dibromothiophene and 1,4-dibromobenzene. 
Furthermore, it is envisioned that the highly reactive calcium species of 
the present invention will react with trihaloarenes, such as 
1,3,5-tribromobenzene, and the like. 
The mono- and/or disubstituted organocalcium species formed can further 
react with electrophiles, such as those disclosed above, as well as 
numerous others, as for example terephthaloyl chloride, to form unique 
polymeric materials. Preferably, the resultant polymers formed are 
two-dimensional linear polymers. However, both the monosubstituted and 
disubstituted organocalcium species formed should be capable of generating 
novel block polymers. 
Typically, the formation of the polymers includes the use of a catalyst, 
such as NiCl.sub.2 and low temperatures. These polymeric materials, 
especially two-dimensional linear polymers, have significant applicability 
in nonlinear optical materials, highly conductive materials, magnetic 
storage devices, etc. 
The soluble highly reactive calcium of the present invention will also 
likely react with derivatives of C.sub.60 and C.sub.70 fullerenes. Both 
mono- and disubstituted calcium fullerenes are envisioned. These calcium 
derivatives will then cross couple with most, if not all, of the 
electrophiles discussed above. Furthermore, these calcium derivatives 
could be used to incorporate fullerenes into polymers and generate novel 
block copolymers. Examples would include copolymers of 
2,5-thienylene/fullerene, phenylene/fullerene, and acetylene/fullerene. 
Thus, the use of the highly reactive calcium species of the present 
invention should allow for the preparation of a wide variety of 
substituted fullerenes. These substituted fullerenes are envisioned to be 
of significant importance in biological applications, as nonlinear optical 
materials, highly conductive materials, magnetic storage devices, etc. 
Spiroannelation 
Highly reactive calcium reacts smoothly with cyclic hydrocarbons containing 
at least two conjugated exocyclic double bonds to produce the 
corresponding 2-butene-1,4-diylcalcium complexes in high yield. The cyclic 
hydrocarbons can be any of a variety of cyclic alkanes or cyclic alkenes 
containing at least two conjugated exocyclic double bonds providing, 
however, that any double bonds in the ring are not in conjugation with the 
exocyclic double bonds. Preferably, these cyclic hydrocarbons do not 
contain any additional functional groups that react with the highly 
reactive calcium preferentially to the conjugated exocyclic double bond 
functionalities. More preferably, the cyclic hydrocarbons are cycloalkanes 
containing at least two exocyclic double bonds. Most preferably, the 
cycloalkanes are 1,2-dimethylenecycloalkanes, such as 
1,2-dimethylenecyclohexane, 1,2-dimethylenecyclopentane, and 
1,2-dimethylenecycloheptane. These resulting 2-butene-1,4-diylcalcium 
complexes prepared from cyclic hydrocarbons with conjugated exocyclic 
double bonds react with a variety of electrophiles, i.e., compounds that 
are deficient in electrons, to form carbocycles, including spirocycles, 
i.e., structures with two rings having one carbon atom in common. 
Spirocycles, particularly the spiro[4.5]decane and spiro[5.5]undecane ring 
systems, constitute the basic carbon framework found in a wide variety of 
naturally occurring sesquiterpenes. 
The electrophiles include, but are not limited to, organodihalides, such as 
1,2-dibromoethane, 1,3-dibromopropane, 1,4-dibromobutane, and 
1,5-dibromopentane, organoditosylates, such as ethylene glycol 
di-p-tosylate, haloalkylnitriles, such as Br(CH.sub.2).sub.n CN compounds 
wherein n=1-3, organoditriflates, esters, amides, and the like. The 
reactions with the electrophiles typically yield carbocycles in isolated 
yields greater than about 40%, and often greater than about 50%. 
Significantly, a wide variety of ring sizes can be generated using this 
approach, making this an advantageous method for the easy preparation of a 
wide variety of carbocycles, particularly spirocycles. Furthermore, the 
spirocycles typically formed by this method contain functional groups, 
such as an exocyclic double bond or a keto group, in one of the rings that 
can be used for further elaboration of these molecules. 
The reaction conditions for production of 2-butene-1,4-diylcalcium 
complexes resulting from the reaction of highly reactive calcium with 
cyclic hydrocarbons having conjugated exocyclic double bonds include 
ambient or room temperatures, i.e., about 20.degree. C. to 30.degree. C., 
the absence of oxygen, and an excess of highly reactive calcium. 
Generally, these conditions include use of ethereal, polyethereal, or 
hydrocarbon solvents. Preferably, the reactions are carried out under an 
inert atmosphere of argon or nitrogen with a ratio of calcium to cyclic 
hydrocarbon present in a range of about 1:1 to 2:1 molar equivalents. The 
reaction time is preferably 3-4 hours, and the solvent is preferably an 
ether or polyether solvent such as diethyl ether, dimethyl ether, 
tetrahydrofuran, and the like. More preferably, the solvent is 
tetrahydrofuran. 
The subsequent reactions of these 2-butene-1,4-diylcalcium complexes with 
electrophiles to produce carbocycles, particularly spirocycles, include 
temperatures of less than about 100.degree. C., preferably at a 
temperature of about -80.degree. C. to about 80.degree. C., and the 
absence of oxygen. Generally, these reactions are carried out in ethereal, 
polyethereal, or hydrocarbon solvents. Preferably, the reactions are 
carried out in tetrahydrofuran under an inert atmosphere of argon or 
nitrogen at a temperature of about -78.degree. C. with subsequent warming. 
The method for the preparation of keto-functionalized products also 
include a step whereby H.sub.3 O.sup.+ is added subsequent to warming. 
Preparation of .gamma.-Lactones Including Spiro .gamma.-Lactones 
A useful application of substituted 2-butene-1,4-diylcalcium complexes 
formed from a conjugated diene, e.g., either cyclic hydrocarbons 
containing at least two conjugated exocyclic double bonds or open-chain 
hydrocarbons containing at least two conjugated double bonds, is the novel 
one-pot synthesis of .gamma.-lactones, preferably spiro .gamma.-lactones. 
The cyclic hydrocarbons useful in this synthetic method are the same as 
those discussed above with respect to spiroannelation. The open-chain 
conjugated dienes can be a variety of dienes containing at least two 
double bonds in conjugation, i.e., separated by a carbon-carbon single 
bond. Preferably, these open-chain conjugated dienes do not contain any 
additional functional groups that react with the highly reactive calcium 
preferentially to the conjugated double bond functionalities. More 
preferably, the open chain conjugated dienes are 1,3-dienes. Most 
preferably the open chain conjugated dienes are 1,3-butadienes, such as 
2,3-dimethyl-1,3-butadiene. 
Spiro .gamma.-lactones and other .gamma.-lactones can be obtained in yields 
in excess of 50%, preferably in excess of 60%, by initially treating 
2-butene-1,4-diylcalcium complexes, with a ketone or aldehyde to give the 
corresponding 1,2-addition adduct. Preferably, this reaction is carried 
out at a temperature of about -90.degree. C. to about -70.degree. C. The 
ketone or aldehyde is preferably present in an amount of approximately one 
mole of ketone or aldehyde per mole of 2-butene-1,4-diylcalcium complex. 
The ketones can be any alkyl, aryl, or mixed alkyl-aryl ketone. 
Preferably, the ketone is selected from the group consisting of acetone, 
cyclohexanone, and cyclopentanone. The aldehydes can be any alkyl or aryl 
aldehyde. Preferably, the aldehyde is selected from the group consisting 
of benzaldehyde and acetaldehyde. It is noted that the aryl ketones and 
aryl aldehydes include within their scope groups containing heteroatoms 
such as nitrogen, for example. 
Subsequent to this initial step, carbon dioxide is combined with the 
1,2-addition adduct to form a nucleophilic addition product. This reaction 
is preferably carried out by bubbling gaseous carbon dioxide through the 
reaction mixture containing the 1,2-addition adduct. This nucleophilic 
addition product is a calcium salt of an organic molecule containing both 
an alkoxy (--CR.sub.2 O--) and a carboxylate group (--COO.sup.-). The 
nucleophilic addition reaction with CO.sub.2 preferably occurs at a 
temperature of about 0.degree. C. to about 20.degree.-30.degree. C., 
preferably about 25.degree. C. Acidic hydrolysis using an aqueous acid, 
followed by a slight warming of the reaction mixture to a temperature of 
about 30.degree. C. to about 50.degree. C. forms the .gamma.-lactone. The 
aqueous acid is preferably a relatively strong mineral, i.e., inorganic, 
acid. More preferably, the acid is selected from the group consisting of 
HCl, H.sub.2 SO.sub.4, and H.sub.3 PO.sub.4. Most preferably, the acid is 
HCl. Significantly, this approach can also be used to prepare spiro 
.gamma.-lactones containing two spiro centers. 
The following scheme illustrates this route for spiro .gamma.-lactone 
synthesis. 
##STR1## 
Referring to the above scheme, treatment of 
1,2-dimethylenecyclohexanecalcium (2) with one molar equivalent of acetone 
at -78.degree. C. results in the formation of a 1,2-addition adduct (3) 
derived from the incorporation of one molecule of acetone with the diene 
complex. (The actual structure of this complex is unknown.) Protonation of 
the 1,2-addition adduct (3) at -78.degree. C. yields a tertiary alcohol 
containing a quaternary center (4). Carbon dioxide is bubbled as a second 
electrophile through the reaction mixture at 0.degree. C. to room 
temperature (about 20.degree.-30.degree. C., preferably about 25.degree. 
C.). Intermediate (3) reacts with carbon dioxide, yielding presumably a 
calcium salt of an organic molecule containing both an alkoxy and a 
carboxylate group (5). After acidic hydrolysis followed by slight warming, 
a spiro .gamma.-lactone, 
4,4-dimethyl-6-methylene-3-oxaspir[4.5]decan-2-one (7) is obtained. 
Treatment of (2) with two molar equivalents of acetone at -78.degree. C. 
followed by acidic hydrolysis at -78.degree. C. also yields (4), 
indicating that the initially formed adduct (3) does not undergo further 
addition with unreacted acetone under the reaction conditions. Thus, both 
acetone and subsequently added CO.sub.2 are delivered to the original 
diene at desired positions. 
Significantly, this approach can also be used to prepare spiro 
.gamma.-lactones containing two spiro centers. For example, (2) can be 
treated with cyclopentanone at -78.degree. C. and the reaction mixture 
then bubbled with CO.sub.2. Workup gives 11- 
methylene-14-oxadispiro[4.0.5.3]tetradecan-13-one. Similar chemistry can 
be observed when cyclohexanone is used as the first electrophile. 
A notable advantage of this new .gamma.-lactone synthesis is that the 
construction of a quaternary center and the introduction of both a 
hydroxyl and a carboxyl used for lactonization are accomplished in one 
synthetic operation. Remarkably, this chemistry can be easily extended to 
the calcium complex of acyclic 1,3-diene. The following scheme gives an 
outline for the synthesis of spiro .gamma.-lactones from 
(2,3-dimethyl-2-butene-1,4-diyl)calcium (11). Generally, reaction of a 
cyclic ketone with (11) at -78.degree. C. results in initial attack at the 
2-position of the diene complex, giving an internal alkoxy Grignard (12). 
After warming up, the intermediate is allowed to react with carbon dioxide 
at 0.degree. C. to room temperature. Upon hydrolysis and gentle heating, a 
spiro .gamma.-lactone containing a quaternary center is obtained (14). The 
method is equally useful for the preparation of .gamma.-lactones. Use of 
an acyclic ketone or aldehyde instead of a cyclic ketone will result in 
the synthesis of the corresponding .gamma.-lactone. 
##STR2## 
Preparation of .delta.-Lactones Including Spiro .delta.-Lactones 
A direct, one-pot process for the synthesis of spiro .delta.-lactones, 
.delta.-lactones, and alcohols utilizing active calcium is also provided. 
This technique involves the treatment of a conjugated diene-calcium 
reagent, i.e., a 2-butene-1,4-diylcalcium complex, with an epoxide 
affording an intermediary organocalcium addition complex, i.e., a 
1,2-addition adduct, derived from the incorporation of one molecule of 
epoxide with the diene-calcium complex. Upon warming, the intermediate 
undergoes further nucleophilic addition to carbon dioxide. After acidic 
hydrolysis and subsequent warming, a .delta.-lactone is afforded by the 
lactonization of the resulting .delta.-hydroxy acid. 
Spiro .delta.-lactones and other .delta.-lactones can be obtained in yields 
in excess of 50%, preferably in excess of 60%, by initially treating 
2-butene-1,4-diylcalcium complexes, with an epoxide to give the 
corresponding addition adduct. Preferably, this reaction is carried out at 
a temperature of about -90.degree. C. to about -70.degree. C. The epoxide 
is preferably present in an amount of approximately one mole of epoxide 
per mole of 2-butene-1,4-diylcalcium complex. The epoxide can have alkyl, 
aryl, or heterocyclic substituents about the epoxide group. Suitable 
epoxides include, but are not limited to, ethylene oxide, propylene oxide, 
t-butylene oxide, cyclohexene oxide and styrene oxide. Preferably, the 
epoxide is selected from the group consisting of ethylene oxide, propylene 
oxide, 1-butylene oxide, and cyclohexene oxide. 
Subsequent to this initial step, carbon dioxide is combined with the 
addition adduct to form a nucleophilic addition product. This reaction is 
preferably carried out by bubbling gaseous carbon dioxide through the 
reaction mixture containing the addition adduct. This nucleophilic 
addition product is a calcium salt of an organic molecule containing both 
an alkoxy and a carboxylate group (--COO.sup.-). The nucleophilic addition 
reaction with CO.sub.2 preferably occurs at a temperature of about 
0.degree. C. to about 20.degree.-30.degree. C., preferably about 
25.degree. C. Acidic hydrolysis using an aqueous acid, followed by a 
slight warming of the reaction mixture to a temperature of about 
30.degree. C. to about 50.degree. C. forms the .delta.-lactone. The 
aqueous acid is preferably a strong mineral, i.e., inorganic, acid. More 
preferably, the acid is selected from the group consisting of HCl, H.sub.2 
SO.sub.4, and H.sub.3 PO.sub.4. Most preferably, the acid is HCl. 
Significantly, this approach can also be used to prepare spiro 
.delta.-lactones containing two spiro centers. 
The following scheme illustrates the general reaction scheme. 
##STR3## 
The above Scheme illustrates a route for spiro .delta.-lactone synthesis 
from the calcium complex of 1,2-bis(methylene)cyclohexane (1). Initially, 
treatment of 1,2-bis(methylene)cyclohexane calcium reagent (2), i.e., a 
2-butene-1,4-diylcalcium complex, with an excess of ethylene oxide at 
-78.degree. C., results in the formation of the 1,2-addition adduct (3) 
derived from the incorporation of one molecule of epoxide with the diene 
complex. Significantly, the bis-organocalcium reagent (2) reacts with only 
one mole of epoxide, and preferably reacts with 100% regioselectivity in 
the 2-position, to give the addition adduct (3). Protonation of this 
adduct (3) at -78.degree. C. affords a primary alcohol containing a 
quaternary center (4). Upon warming, 3 reacts with CO.sub.2 to yield the 
calcium salt of a .delta.-hydroxy acid (5). Upon acidic hydrolysis, the 
.delta.-hydroxy acid (6) is formed which upon slight warming undergoes 
lactonization to yield the spiro .delta.-lactone (7). It is significant to 
note that even though (2) is treated with an excess of the epoxide, only 
one equivalent of the epoxide reacts with (2). Importantly, this approach 
can be used to prepare bicyclic spiro .delta.-lactones. For example, 
1,2-bis(methylene)cyclohexane-calcium reagent (2) can be treated with 
cyclohexene oxide at -78.degree. C. and the reaction mixture bubbled with 
CO.sub.2 at 0.degree. C. with warming to room temperature. 
This approach is also equally applicable to acyclic 1,3-dienes and provides 
a facile route to .delta.-lactones. The following scheme displays an 
outline for the synthesis of .delta.-lactones from 
(2,3-dimethyl-2-butene-1,4-diyl)calcium (9). Reaction of cyclohexene oxide 
with (9) at -78.degree. C. results in an initial attack at the 2-position 
of the calcium-diene complex, affording an internal alkoxy calcium complex 
(10). After gradual warming to 0.degree. C., intermediate (10) is reacted 
with carbon dioxide to presumably yield the calcium salt (11), which 
contains both an alkoxy and a carboxylate functional group. Upon 
hydrolysis, the .delta.-hydroxy carboxylic acid is presumably formed and 
gently heated to afford a bicyclic .delta.-lactone (12), as a mixture of 
diastereomers, accommodating a quaternary center. 
##STR4## 
This methodology exhibits relatively good regioselectivity when unsymmetric 
epoxides are utilized as the primary electrophile. The attack of the 
unsymmetric epoxide occurs at the less sterically hindered carbon. 
Hydrolysis after treatment with 2-epoxybutane and 1,2-epoxyhexane, 
respectively, affords the secondary alcohols with a quaternary carbon 
center. 
The overall procedure of the spiro .delta.-lactone and .delta.-lactone 
syntheses can be thought of as a molecular assembling process in which 
three simple independent species, i.e., a conjugated diene, an epoxide, 
and carbon dioxide, mediated by active calcium are used to build a complex 
organic molecule in a well-controlled fashion. In the process, the 
construction of a quaternary carbon center and the introduction of both a 
hydroxyl group and a carboxyl group required for lactonization are 
achieved in one synthetic operation. 
Preparation of .gamma.-Lactams from Conjugated Diene-Calcium Reagents 
The present invention also provides a molecular assembling process in which 
three simple independent species, i.e., a conjugated diene, an imine, and 
carbon dioxide, mediated by active calcium are utilized to construct a 
.gamma.-lactam in an orderly fashion. See the following reaction scheme. 
Also, the construction of a quaternary carbon center is generated in the 
process. 
##STR5## 
.gamma.-Lactams can be obtained in yields in excess of 40%, preferably in 
excess of 60%, by initially treating 2-butene-1,4-diylcalcium complexes, 
with an imine to give the corresponding 1,2-addition adduct. Preferably, 
this reaction is carried out at a temperature of about -90.degree. C. to 
about -70.degree. C. and subsequently allowed to warm to about 0.degree. 
C. The imine is preferably present in an amount of approximately one mole 
of imine per mole of 2-butene-1,4-diylcalcium complex. This reaction is 
very general and will work with any imine according to the following 
formula: 
##STR6## 
Examples of suitable imines include, but are not limited to, 
N-benzylideneaniline, benzophenone imine, acetone imine, 
N-benzylidenemethylamine, and acetophenone imine. 
Subsequent to this initial step, carbon dioxide is combined with the 
1,2-addition adduct to form a nucleophilic addition product. This reaction 
is preferably carried out by bubbling gaseous carbon dioxide through the 
reaction mixture containing the 1,2-addition adduct. This nucleophilic 
addition product is a calcium salt of an organic molecule containing both 
an amine anion and a carboxylate group (--COO.sup.-). The nucleophilic 
addition reaction with CO.sub.2 preferably occurs at a temperature of 
about 0.degree. C. to about 20.degree.-30.degree. C., preferably about 
25.degree. C. Acidic hydrolysis using an aqueous acid, followed by a 
slight warming of the reaction mixture to a temperature of about 
30.degree. C. to about 50.degree. C. forms the .gamma.-lactam. The aqueous 
acid is preferably a strong mineral, i.e., inorganic, acid. More 
preferably, the acid is selected from the group consisting of HCl, H.sub.2 
SO.sub.4, and H.sub.3 PO.sub.4. Most preferably, the acid is HCl. 
Preparation of Chiral Vicinal Diols 
The incorporation of an unsymmetric, chiral epoxide containing a hydroxyl 
functional group as a primary electrophile, followed by treatment with a 
proton source, affords a vicinal diol containing a chiral quaternary 
carbon center. See the following reaction scheme. It is significant to 
note that the 1,3-diene calcium complex tolerates the presence of an 
unprotected hydroxyl group in this transformation. 
##STR7## 
Vicinal diols can be obtained in yields in excess of 40%, preferably in 
excess of 60%, by initially treating 2-butene-1,4-diylcalcium complexes, 
with an unsymmetrical chiral epoxide to give the corresponding epoxide 
ring opened addition adduct. Preferably, this reaction is carried out at a 
temperature of about -90.degree. C. to about -70.degree. C. The chiral 
epoxide is preferably present in an amount of approximately one mole of 
epoxide per mole of 2-butene-1,4-diylcalcium complex. This reaction is 
very general and will work with any chiral .alpha.-hydroxy epoxide of the 
following formula: 
##STR8## 
wherein R.sub.1 and R.sub.2 and R.sub.3 can be alkyl, aryl, vinyl, or 
heterocyclic groups. Examples of suitable chiral epoxides include, but are 
not limited to, R- or S- 3-hydroxy-2-methyl-1-propene oxide, R- or S- 
3-hydroxy-1-methyl-1-propene oxide, R- or S- 3-hydroxy-2-ethyl-1-propene 
oxide, and R- or S- 3-hydroxy-2-phenyl-1-propene oxide. 
Subsequent to this initial step, acidic hydrolysis using an aqueous acid, 
followed by a slight warming of the reaction mixture to a temperature of 
about 30.degree. C. to about 0.degree. C. forms the vicinal diol. The 
aqueous acid is preferably a relatively strong mineral, i.e., inorganic, 
acid. More preferably, the acid is selected from the group consisting of 
NH.sub.4 Cl, HCl, H.sub.2 SO.sub.4, and H.sub.3 PO.sub.4. Most preferably, 
the acid is NH.sub.4 Cl. 
The invention will be further exemplified with respect to the various 
specific and preferred embodiments and techniques. It should be 
understood, however, that many variations and modifications may be made 
while remaining within the scope of the invention. 
Experimental Examples 
Melting points were determined on a Thomas-Hoover melting point apparatus 
or on an Electrothermal.TM. melting point apparatus and are corrected. IR 
spectra were taken on an Analect.TM. RFX-30 Fourier Transform Infrared 
(FTIR) spectrometer. The spectra were taken of neat samples between NaCl 
or KBr plates or as KBr pressed pellets. .sup.1 H NMR spectra were 
recorded on a Nicolet.TM. NT-360 (360 MHz) or on a Varian.TM. VXR-200 (200 
MHz) spectrometer. All chemical shifts are reported in parts per million 
(.delta.) downfield from internal tetramethylsilane. Fully decoupled 
.sup.13 C NMR spectra and Distortionless Enhanced Polarization Transfer 
(DEPT) experiments were recorded on a Varian.TM. VXR-200 (50 MHz) 
spectrometer. The center peak of CDCl.sub.3 (77.0 ppm) was used as the 
internal reference. Two-dimensional Correlation Spectroscopy (COSY) 
spectra were recorded on a Nicolet.TM. NT-360 (360 MHz) spectrometer. High 
resolution mass spectra were performed by the Midwest Center for Mass 
Spectrometry at the University of Nebraska-Lincoln using a Kratos.TM. 
MS-80 mass spectrometer. Elemental analyses were performed by Oneida 
Research Services, Inc., Whitesboro, N.Y. Gas chromatography analysis was 
done on a Hewlett-Packard.TM. 5890A chromatograph using stainless steel 
columns (12 ft.times.1/8 in) packed with OV-17 (3%) on 100/120 
Chromosorb.TM. G-AW or SE-30 (5%) on 100/120 Chromosorb.TM. G-NAW (both of 
which are available from Supelco, Inc., Bellefonte, Pa.). Analytical 
thin-layer chromatography was performed using Merck.TM. 5735 (0.2 mm 
thickness) indicating plates (available from Whatman Ltd., Maidstone, 
Kent, England). Preparative thin-layer separations were performed using 
Anatech.TM. silica gel GF (1 or 2 mm thickness) preparative plates 
(available from Newark, Del.), or using Whatman.TM. PLKC 18F linear-K 
reversed phase (1 mm thickness) preparative plates (available from Whatman 
Ltd., Maidstone, Kent, England). Low-temperature reactions were performed 
utilizing a Neslab Endocal.TM. ULT-80 refrigerated circulating bath or 
utilizing dry ice/acetone baths. All manipulations were carried out on a 
dual manifold vacuum/argon system. The Linde.TM. prepurified grade argon 
was further purified by passing it through a 150.degree. C. catalyst 
column (BASF.TM. R3-11 ), a phosphorous pentoxide column, and a column of 
granular potassium hydroxide. Lithium and naphthalene, byphenyl, or 
anthracene were weighed out and charged into reaction flasks under argon 
in a Vacuum Atmospheres Company dry box. Tetrahydrofuran was freshly 
distilled under argon from sodium/potassium alloy. Anhydrous calcium(II) 
iodide and calcium(II) bromide were purchased from Cerac, Inc., Milwaukee, 
Wis. Anhydrous calcium(II) chloride was purchased from Alfa Chemicals, 
Denver, Colo. 2,3-Dimethyl-1,3-butadiene was distilled prior to use. Other 
commercially available reagents were used as received unless specially 
noted. 
EXAMPLE 1 
Typical Procedure for Preparation of Highly Reactive Calcium 
Lithium (9.0 mmol) and biphenyl (9.8 mmol) were stirred in freshly 
distilled THF (20 mL) under argon until the lithium was substantially 
completely consumed (approximately 2 hours). To a well-suspended solution 
of CaI.sub.2 or CaBr.sub.2 in freshly distilled THF (20 mL), the preformed 
lithium biphenylide was transferred via a cannula at room temperature. 
Typically, an approximate equivalent ratio of the calcium salt to the 
lithium biphenylide was used; i.e., 1 mole of the Ca(II) salt to 2 moles 
of the lithium biphenylide; however, when the resultant soluble highly 
reactive calcium was used in further reactions, an excess (1.5-2.0 
equivalents) of the calcium salt was used in the preparation of the 
soluble highly reactive calcium. The reaction mixture was stirred for 1 
hour at room temperature prior to use. 
EXAMPLE 2 
Formation of Organocalcium Reagents and Use in a Grignard-Type Reactions 
The following experimental procedure is representative of the reactions set 
forth below in Table I. Highly reactive calcium (3.07 mmol), prepared from 
lithium biphenylide (6.15 mmol) and excess CaI.sub.2 (4.91 mmol) in THF 
(30 mL), was cooled to -78.degree. C. The color turned green upon cooling. 
An organocalcium reagent was prepared by adding p-chlorotoluene (324 mg, 
2.56 mmol) to this mixture via a disposable syringe at -78.degree. C. The 
reaction mixture was allowed to warm to -20.degree. C. It was stirred at 
-20.degree. C. for 30 minutes. The reaction mixture was then cooled to 
-35.degree. C. A Grignard-type reaction was carried out by adding excess 
cyclohexanone (510 mg, 5.20 mmol) to the solution of the organocalcium 
reagent via a disposable syringe at -35.degree. C. The resulting mixture 
was gradually warmed to room temperature and was stirred at room 
temperature for 30 minutes. The reaction mixture was again cooled to 
-35.degree. C. Neutral H.sub.2 O (distilled water, 20 mL) was added at 
-35.degree. C. After being warmed to room temperature, the reaction 
mixture was filtered through a small pad of Celite.TM. filter agent 
(available from Aldrich Chemical Co., Milwaukee, Wis.) and was washed with 
Et.sub.2 O (50 mL). The aqueous layer was extracted with Et.sub.2 O 
(3.times.30 mL). The combined organic phases were washed with H.sub.2 O 
(15 mL), and dried over anhydrous MgSO.sub.4. Removal of solvent and 
flash-column chromatography on silica gel (100 g, 230-400 mesh, available 
from EM Science; Gibbstown, N.J.) afforded 1-(p-methylphenyl)cyclohexanol 
(417 mg, 86% yield) as white crystals: mp 53.degree.-55.degree. C.; IR 
(KBr) 3419, 3030, 2935, 2843, 1514, 1446, 1392, 1134, 1036, 964, 810 
cm.sup.-1 ; .sup.1 H NMR (200 MHz, CDCl.sub.3) .delta. 7.35-7.45 (m, 2 H), 
7.10-7.20 (m, 2 H), 2.33 (s, 3 H), 1.55-1.85 (m, 11 H); .sup.13 C NMR (50 
MHz, CDCl.sub.3) .delta. 146.5, 136.2, 128.9, 124.5, 72.9, 38.9, 25.5, 
22.2, 20.9. Known compound: IR, see Sadtler 36367; .sup.1 H-NMR, see 
Sadtler 21529; .sup.13 C-NMR, see Sadtler 5269. 
TABLE I 
__________________________________________________________________________ 
Grignard-Type Reactions of Organocalcium Reagents with Cyclohexanone 
Entry 
Halide CaX.sub.2 
Product.sup.a % Yield.sup.b 
__________________________________________________________________________ 
1 Cl(CH.sub.2).sub.7 CH.sub.3 
CaI.sub.2 
1-(CH.sub.2).sub.7 CH.sub.3 -1-OH-c-C.sub.6 H.sub.10 
1 83 
2 Br(CH.sub.2).sub.7 CH.sub.3 
CaI.sub.2 
1-(CH.sub.2).sub.7 CH.sub.3 -1-OH-c-C.sub.6 H.sub.10 
79 
3 Br(CH.sub.2).sub.3 OPh 
CaBr.sub.2 
1-(CH.sub.2).sub.3 OPh-1-OH-c-C.sub.6 H.sub.10 
75 
4 Br-c-C.sub.6 H.sub.11 
CaBr.sub.2 
1-c-C.sub.6 H.sub.11 -1-OH-c-C.sub.6 H.sub.10 
75 
##STR9## CaBr.sub.2 
##STR10## 80 
6 BrC.sub.6 H.sub.4 (m-CH.sub.3) 
CaI.sub.2 
1-C.sub.6 H.sub.4 (m-CH.sub.3)-1-OH-c-C.sub.6 
H.sub.10 76 
7 ClC.sub.6 H.sub.4 (p-CH.sub.3) 
CaI.sub.2 
1-C.sub.6 H.sub.4 (p-CH.sub.3)-1-OH-c-C.sub.6 
H.sub.10 86 
8 FPh CaI.sub.2 
1-Ph-1-OH-c-C.sub.6 H.sub.10 
85 
9 BrC.sub.6 H.sub.4 (m-OCH.sub.3) 
CaBr.sub.2 
1-C.sub.6 H.sub. 4 (m-OCH.sub.3)-1-OH-c-C.sub.6 
H.sub.10 79 
__________________________________________________________________________ 
.sup.a All new substances have satisfactory spectroscopic data including 
IR, .sup.1 H NMR, .sup.13 C NMR, and highresolution mass spectral data, a 
presented below. 
.sup.b Isolated yields. 
Alkyl halides, particularly alkyl bromides and alkyl chlorides, rapidly 
reacted with the calcium species of the present invention at temperatures 
as low as -78.degree. C. As shown in Table I, 1-bromooctane and 
1-bromo-3-phenoxypropane reacted with the calcium species at -78.degree. 
C. to form the corresponding alkylbromocalcium reagents, which underwent 
Grignard-type reactions with cyclohexanone to produce the tertiary 
alcohols in 79% and 75% yields, respectively. Oxidative addition of alkyl 
chlorides to this soluble calcium species was also very efficient at low 
temperature (-78.degree. C.). 1-Chlorooctane gave 1-octylcyclohexanol in 
83% yield. Similar results were noted for the secondary halides. 
Bromocyclohexane reacted readily with the calcium species at -78.degree. 
C. and the resulting organocalcium reagent underwent carbonyl addition to 
give the alcohol in 75% yield. 
Significantly, the highly reactive calcium species reacted rapidly with 
tertiary bromides at -78.degree. C. For example, the Grignard-type 
reaction for 1-bromoadamantane utilizing the reactive calcium afforded 
1-(1-adamantyl)cyclohexanol in 80% yield. The direct reaction of 
1-bromoadamantane with metals is well known to yield mainly reductive 
cleavage or dimerization. Accordingly, this method represents a 
significant new approach to the 1 -metalloadamantane. 
Reactions of aryl halides with reactive calcium required slightly higher 
temperatures, up to -30.degree. C. for aryl bromides and up to -20.degree. 
C. for aryl chlorides. The aryl calcium compounds are very stable at room 
temperature. Reactions of m-bromotoluene, m-bromoanisole, and 
p-chlorotoluene with the soluble highly reactive calcium complex gave the 
corresponding arylcalcium reagents in quantitative yields based on the GC 
analyses of reaction quenches. The 1,2-addition of these arylcalcium 
compounds with ketones gave the alcohols in excellent yields (76%, 79% and 
86%, respectively). The soluble highly reactive calcium readily reacted 
with fluorobenzene at room temperature to form the corresponding 
organometallic compound which underwent an addition reaction with 
cyclohexanone to give 1-phenylcyclohexanol in 85% yield. 
1-Octylcyclohexanol (83% yield): IR (neat) 3379, 2929, 2856, 1448, 1259, 
968 cm.sup.-1 ; .sup.1 H NMR (200 MHz, CDCl.sub.3) .delta. 1.15-1.65 (m, 
25 H), 0.88 (t, J=7.0 Hz, 3 H); .sup.13 C NMR (50 MHz, CDCl.sub.3) .delta. 
71.4, 42.5, 37.5, 31.9, 30.3, 29.6, 29.3, 25.9, 22.9, 22.7, 22.3, 14.1; MS 
(EI) m/e (relative intensity) 212 (M.sup.+, 1.2), 194 (5.8), 183 (1.5), 
169 (23.5), 141 (11.4), 127 (10.9), 109 (13.6), 99 (100.0), 81 (67.0); 
High Resolution Mass Spec. (HRMS) calcd. for C.sub.14 H.sub.28 O m/e 
212.2140, found m/e 212.2137. 
1-Phenylcyclohexanol (85% yield): mp 62.degree.-63.degree. C.; IR (KBr) 
3336, 3059, 3030, 1444, 1381, 1259, 1134, 1032, 974, 756, 696 cm.sup.-1 ; 
.sup.1 H NMR (360 MHz, CDCl.sub.3) .delta. 7.20-7.55 (m, 5 H), 1.20-1.92 
(m, 11 H); .sup.13 C NMR (50 MHz, CDCl.sub.3) .delta. 149.4, 128.2, 126.7, 
124.6, 73.1, 38.8, 25.5, 22.2. 
1-(m-Methylphenyl)cyclohexanol (76% yield): IR (neat) 3406, 3024, 2931, 
2856, 1606, 1446, 1259, 1167, 1132, 1036, 972, 783, 704 cm.sup.-1 ; .sup.1 
H NMR (200 MHz, CDCl.sub.3) .delta. 7.02-7.35 (m, 4 H), 2.36 (s, 3 H), 
1.57-1.88 (m, 11 H); .sup.13 C NMR (50 MHz, CDCl.sub.3) .delta. 149.4, 
137.7, 128.1, 127.4, 125.3, 121.6, 73.1, 38.8, 25.5, 22.2, 21.6. Known 
compound: .sup.1 H-NMR, see Sadtler 33855. 
1-Cyclohexylcyclohexanol (75% yield): IR (KBr) 3469, 2929, 2850, 1446, 
1254, 1165, 1132, 960 cm.sup.-1 ; .sup.1 H NMR (200 MHz, CDCl.sub.3) 
.delta. 0.80-1.90 (m, 22 H); .sup.13 C NMR (50 MHz, CDCl.sub.3) .delta. 
73.0, 48.2, 34.3, 26.9, 26.6, 26.5, 26.0, 21.9. 
1-(3-Phenoxypropyl)cyclohexanol (75% yield): IR (neat) 3433, 2931, 2858, 
1601, 1587, 1496, 1246, 754, 690 cm.sup.-1 ; .sup.1 H NMR (200 MHz, 
CDCl.sub.3) .delta. 7.20-7.32 (m, 2 H), 6.84-6.97 (m, 3 H), 3.96 (t, 2 H, 
J=6.3 Hz), 1.15-1.95 (m, 15 H); .sup.13 C NMR (50 MHz, CDCl.sub.3) .delta. 
158.9, 129.3, 120.5, 114.5, 71.0, 68.3, 38.6, 37.4, 25.8, 23.0, 22.2; MS 
(EI) m/e (relative intensity) 234 (M.sup.+, 1.4), 216 (0.7), 191 (1.2), 
141 (52.5), 123 (32.1), 120 (34.7), 99 (42.0), 94 (90.9), 81 (100.0); HRMS 
calcd. for C.sub.15 H.sub.22 O.sub.2 m/e 234.1620, found m/e 234.1625. 
Anal. Calcd.: C, 76.88; H, 9.46. Found: C, 76.57; H, 9.55. 
1-(m-Methoxyphenyl)cyclohexanol (79% yield): IR (neat) 3437, 2933, 2854, 
1601, 1583, 1483, 1448, 1431, 1288, 1265, 1248, 1049, 781, 698 cm.sup.-1 ; 
.sup.1 H NMR (200 MHz, CDCl.sub.3) .delta. 6.75-7.31 (m, 4 H), 3.81 (s, 3 
H), 1.40-1.90 (m, 11 H); .sup.13 C NMR (50 MHz, CDCl.sub.3) .delta. 159.6, 
151.3, 129.2, 117.0, 111.8, 110.7, 73.1, 55.2, 38.8, 25.5, 22.2. 
1-(1-Adamantyl)cyclohexanol (80% yield): mp 166.degree.-168.degree. C.; IR 
(KBr) 3465, 2931, 2902, 2844, 1448, 1344, 980, 955, 935 cm.sup.-1 ; .sup.1 
H NMR (200 MHz, CDCl.sub.3) .delta. 0.95-2.05 (m, 26 H); .sup.13 C NMR (50 
MHz, CDCl.sub.3) .delta. 74.6, 39.1, 37.3, 35.8, 29.8, 28.7, 26.0, 21.9; 
MS (El) m/e (relative intensity) 234 (M.sup.+, 0.2), 135 (26.0), 98 
(100.0); HRMS calcd. for C.sub.16 H.sub.26 O m/e 234.1984, found m/e 
234.1982. Anal. Calcd.: C, 81.99; H, 11.18. Found: C, 82.13; H, 11.41. 
EXAMPLE 3 
Typical Ketone Formation Reaction Using Organocalcium Cuprate Reagents 
The following experimental procedure is representative of the reactions set 
forth below in Table II. The organocalcium reagent (2.72 mmol) was 
prepared from p-chlorotoluene (344 mg, 2.72 mmol) and highly reactive 
calcium (3.15 mmol) as described above. CuCN 2LiBr in THF (10 mL) was 
added to the organocalcium reagent via a cannula at -35.degree. C. The 
CuCN.2LiBr can be prepared from CuCN and approximately two equivalents of 
LiBr in THF, as outlined in P. Knochel et at., J. Org. Chem., 53, 2390 
(1989), which is incorporated herein by reference. The reaction mixture 
was stirred at -35.degree. C. for 30 minutes. Benzoyl chloride (950 mg, 
6.76 mmol) was added to the mixture via a disposable syringe at 
-35.degree. C. and the resulting mixture was gradually warmed to room 
temperature. Saturated aqueous NH.sub.4 Cl solution (20 mL) was then added 
to the reaction mixture at room temperature for the purpose of 
neutralizing the reaction mixture. The reaction mixture was then filtered 
through a small pad of Celite.TM. filter agent and was washed with 
Et.sub.2 O (50 mL). The aqueous layer was extracted with Et.sub.2 O 
(2.times.30 mL). The combined organic phases were washed with H.sub. 2 O 
(3.times.15 mL) and dried over anhydrous MgSO.sub.4. Removal of solvent 
and flash-column chromatography on silica gel (100 g, 230-400 mesh, eluted 
sequentially with 20:1 hexanes/EtOAc, 15:1 hexanes/EtOAc, and 10:1 
hexanes/EtOAc) yielded (4-methylphenyl)phenylmethanone (458 mg, 86% 
yield): IR (neat) 3058, 3027, 2921, 1658, 1606, 1446, 1317, 1278, 1178, 
937, 924, 835, 787, 730, 700 cm.sup.-1 ; .sup.1 H NMR (200 MHz, 
CDCl.sub.3) .delta. 7.24-7.82 (m, 9 H), 2.43 (s, 3 H); .sup.13 C NMR (50 
MHz, CDCl.sub.3) .delta. 196.4, 143.2, 137.9, 134.8, 132.1, 130.3, 129.9, 
128.9, 128.2, 21.6. 
TABLE II 
______________________________________ 
Cross-Coupling Reactions of Organocalcium Cuprate 
Reagents with Benzoyl Chloride.sup.a 
Entry Halide Product.sup.b % Yield.sup.c 
______________________________________ 
1 Cl(CH.sub.2).sub.7 CH.sub.3 
PhC(O)(CH.sub.2).sub.7 CH.sub.3 
84 
2 Br(CH.sub.2).sub.5 OPh 
PhC(O)(CH.sub.2).sub.5 OPh 
76 
3 Br-c-C.sub.6 H.sub.11 
PhC(O)-c-C.sub.6 H.sub.11 
82 
4 1-Cl-4-CH.sub.3 C.sub.6 H.sub.4 
1-PhC(O)-4-CH.sub.3 C.sub.6 H.sub.4 
86 
5 1-Br-4-OCH.sub.3 C.sub.6 H.sub.4 
1-PhC(O)-4-OCH.sub.3 C.sub.6 H.sub.4 
71 
______________________________________ 
.sup.a Active calcium was prepared by the lithium biphenylide reduction o 
CaBr.sub.2 in THF. CuCN 2LiBr was used for reaction with organocalcium 
reagents. 
.sup.b Most products were compared with authentic samples. The new 
substance, 1phenyl-6-phenoxy-1-hexanone, has satisfactory IR, .sup.1 H 
NMR, .sup.13 C NMR, and highresolution mass spectral data. 
.sup.c Isolated yields. 
A soluble copper(I) complex, CuCN 2LiBr was used for the reactions with 
organocalcium reagents to form the copper calcium complexes, i.e., the 
organocalcium cuprate reagents. The CuCN 2LiBr can be prepared from CuCN 
and LiBr in THF, as outlined in P. Knochel et at., J. Org. Chem., 53, 2390 
(1988), which is incorporated herein by reference. Reaction of these 
organocalcium cuprate reagents with benzoyl chloride proceeded smoothly at 
-35.degree. C. to yield ketones in excellent yields. As shown in Table II, 
the primary alkylcalcium cuprates, n-octyl and (5-phenoxypentyl)calcium 
cuprate, reacted rapidly with benzoyl chloride at -35.degree. C. to give 
1-phenyl-1-nonanone and 1-phenyl-6-phenoxy-1-hexanone in 84% and 76% 
yield, respectively. The secondary alkylcalcium cuprate, cyclohexyl 
calcium cuprate, reacted smoothly with benzoyl chloride to form 
cyclohexylphenylmethanone in 82% yield. The tertiary alkylcalcium cuprate 
is also expected to undergo this transformation. In the aryl cases, 
4-methylphenyl and 4-methoxyphenyl cuprate, for example, also reacted with 
benzoyl chloride to afford (4-methylphenyl)phenylmethanone and 
(4-methoxyphenyl)phenylmethanone in 86% and 71% yield, respectively. 
(4-Methoxyphenyl)phenylmethanone (71% yield): mp 60.degree.-61.degree. C.; 
.sup.1 H NMR (200 MHz, CDCl.sub.3) .delta. 7.42-7.87 (m, 7 H), 6.92-7.01 
(m, 2 H), 3.89 (s, 3 H); .sup.13 C NMR (50 MHz, CDCl.sub.3) .delta. 195.4, 
163.2, 138.3, 132.5, 131.9, 130.2, 129.7, 128.2, 113.5, 55.5. 
1-Phenyl-1-nonanone (84% yield): .sup.1 H NMR (200 MHz, CDCl.sub.3) .delta. 
7.90-8.02 (m, 2 H), 7.38-7.62 (m, 3 H), 2.96 (t, J=7.4 Hz, 2 H), 1.14-1.74 
(m, 12 H), 0.88 (t, J=6.5 Hz, 3 H); .sup.13 C NMR (50 MHz, CDCl.sub.3) 
.delta. 200.5, 137.2, 132.7, 128.5, 128.0, 38.6, 31.8, 29.4, 29.4, 29.1, 
24.4, 22.6, 14.0. 
1-Phenyl-6-phenoxy-1-hexanone (76% yield): mp 53.5.degree.-54.5.degree. C.; 
IR (KBr) 3059, 2941, 2900, 2869, 1678, 1599, 1498, 1475, 1244, 752, 729, 
687 cm.sup.-1 ; .sup.1 H NMR (200 MHz, CDCl.sub.3) .delta. 7.92-8.00 (m, 2 
H), 7.19-7.60 (m, 5 H), 6.84-6.98 (m, 3 H), 3.97 (t, J=6.4 Hz, 2 H), 3.00 
(t, J=7.3 Hz, 2 H), 1.48-1.93 (m, 6 H); .sup.13 C NMR (50 MHz, CDCl.sub.3) 
.delta. 200.2, 159.0, 137.0, 132.9, 129.4, 128.5, 128.0, 120.5, 114.4, 
67.5, 38.4, 29.2, 25.8, 24.0; MS (EI) m/e (relative intensity) 268 
(M.sup.+, 3.2), 175 (45.3), 105 (100.0), 94 (20.3), 77 (30.0); HRMS calcd. 
for C.sub.18 H.sub.20 O.sub.2 m/e 268.1463, found m/e 268.1459. Anal. 
Calcd.: C, 80.56; H, 7.51. Found: C, 80.63; H, 7.69. 
Cyclohexylphenylmethanone (82% yield): mp 54.degree.-56.degree. C.; IR 
(KBr) 2927, 2850, 1668, 1595, 1577, 1444, 1252, 1209, 974, 703 cm.sup.-1 ; 
.sup.1 H NMR (200 MHz, CDCl.sub.3) .delta. 7.90-8.00 (m, 2 H), 7.38-7.60 
(m, 3 H), 3.16-3.35 (m, 1 H), 1.14-1.97 (m, 10 H); .sup.13 C NMR (50 MHz, 
CDCl.sub.3) .delta. 203.8, 136.3, 132.7, 128.5, 128.2, 45.6, 29.4, 25.9, 
25.8. The spectral data are identical to the authentic sample. 
Commercially available compound from Aldrich Chemical Co., Milwaukee, 
Wis., has mp=55.degree.-57.degree. C. 
EXAMPLE 4 
Conjugate 1,4-Addition Reactions Using Organocalcium Cuprate Reagents 
The following experimental procedure is representative of the reactions set 
forth below in Table III. The organocalcium reagent (2.66 mmol) was 
prepared from 1-chlorooctane (395 mg, 2.66 mmol) and highly reactive 
calcium (3.10 mmol) as described above. An organocalcium cuprate reagent 
was prepared by adding lithium 2-thienylcyanocuprate (Aldrich Chemical 
Co., Milwaukee, Wis., 0.25M in THF, 14 mL, 3.50 mmol) to the calcium 
reagent via a syringe at -50.degree. C. The reaction mixture was gradually 
warmed to -35.degree. C. over a 30 minute period. The reaction mixture was 
cooled to -50.degree. C. and 2-cyclohexen-1-one (210 mg, 2.18 mmol) was 
added via a disposable syringe. The resulting mixture was gradually warmed 
to room temperature. Saturated aqueous NH.sub.4 Cl solution (20 mL) was 
added at room temperature. The reaction mixture was then filtered through 
a small pad of Celite.TM. filter agent and was washed with Et.sub.2 O (50 
mL). The aqueous layer was extracted with Et.sub.2 O (2.times.30 mL). The 
combined organic phases were washed with H.sub.2 O (3.times.15 mL) and 
dried over anhydrous MgSO.sub.4. Removal of solvent and flash-column 
chromatography on silica gel (70 g, 230-400 mesh, eluted sequentially 
with 50:1 hexanes/EtOAc and 10:1 hexanes/EtOAc) gave 3-octylcyclohexanone 
(401 mg, 87% yield): IR (neat) 2954, 2925, 2854, 1714, 1458, 1225 
cm.sup.-1 ; .sup.1 H NMR (200 MHz, CDCl.sub.3) .delta. 1.10-2.50 (m, 23 
H), 0.88 (t, J=6.4 Hz, 3 H); .sup.13 C NMR (50 MHz, CDCl.sub.3) .delta. 
212.0, 48.2, 41.5, 39.1, 36.6, 31.8, 31.3, 29.7, 29.5, 29.2, 26.6, 25.3, 
22.6, 14.1. 
TABLE III 
__________________________________________________________________________ 
Conjugate 1,4-Addition Reactions of Calcium Organocuprate Reagents with 
Enones 
Entry 
Halide Cu(I) salt Enone Product.sup.a % 
__________________________________________________________________________ 
Yield.sup.b 
1 Cl(CH.sub.2).sub.7 CH.sub.3 
CuCN2LiBr 
##STR11## 
##STR12## 46 
2 Cl(CH.sub.2).sub.7 CH.sub.3 
##STR13## 
##STR14## 
##STR15## 87 
3 Cl(CH.sub.2).sub.7 CH.sub.3 
##STR16## 
##STR17## EtC(O)CH.sub.2 CH(CH.sub.3)(CH.sub 
.2).sub.7 CH.sub.3 
47 
4 Cl(CH.sub.2).sub.7 CH.sub.3 
##STR18## 
##STR19## 
##STR20## &lt;3 
5 Cl(CH.sub.2).sub.7 CH.sub.3 
##STR21## 
##STR22## 
##STR23## 84 
+TMSCl & BF.sub.3.Et.sub.2 
##STR24## 
##STR25## 
##STR26## 
##STR27## 68 
__________________________________________________________________________ 
.sup.a Most products were compared with authentic samples. The new 
substance, 3(p-methylphenyl)cyclohexanone, has satisfactory IR, .sup.1 H 
NMR, .sup.13 C NMR, and highresolution mass spectra data. 
.sup.b Isolated yields. 
The organocalcium cuprate reagents of the present invention undergo 
conjugate 1,4-addition reactions with .alpha.,.beta.-unsaturated ketones. 
n-Octyl calcium cuprate, generated by reaction of the n-octanocalcium 
compound with CuCN 2LiBr, reacted with 2-cyclohexenone to give 
3-octylcyclohexanone in moderate yield (46% yield). However, a more 
reactive calcium cuprate species was produced and the yield was greatly 
improved to 87% when lithium 2-thienylcyanocuprate (available from Aldrich 
Chemical Company, Inc., Milwaukee, Wis.) was used. This organocalcium 
cuprate reagent also underwent the conjugate addition with acyclic enones, 
e.g., 2-hexen-4-one, to give 5-methyl-3-tridecanone in 47% yield; however, 
further optimization of the yield is possible. Reaction of this 
organocalcium cuprate reagent with a sterically hindered enone, for 
example isophorone, produced less than 3% of the desired compound in 24 
hours. The isolated yield, however, increased to 84% when the additives 
BF.sub.3 etherate and chlorotrimethylsilane (TMSCl) were used. In the aryl 
case, p-tolyl calcium cuprate also underwent this transformation with 
2-cyclohexenone to give 3-(p-methylphenyl)cyclohexanone in reasonable 
yield. 
5-Methyl-3-tridecanone (46% yield): IR (neat) 2958, 2927, 2856, 1718, 1460, 
1414, 1376 cm.sup.-1 ; .sup.1 H NMR (200 MHz, CDCl.sub.3) .delta. 
1.90-2.47 (m, 5 H), 1.10-1.40 (m, 14 H), 1.04 (t, J=7.3 Hz, 3 H), 0.88 (t, 
J=6.4 Hz, 3 H), 0.88 (d, J=6.6 Hz, 3 H); .sup.13 C NMR (50 MHz, 
CDCl.sub.3) .delta. 211.6, 49.9, 37.0, 36.4, 31.8, 29.7, 29.6, 29.3, 29.3, 
26.9, 22.6, 19.8, 14.0, 7.7. 
3-(p-methylphenyl)cyclohexanone (68% yield): IR (neat) 3020, 2935, 2864, 
1712, 1516, 1446, 1421, 1313, 1248, 1223, 806 cm.sup.-1 ; .sup.1 H NMR 
(200 MHz, CDCl.sub.3) .delta. 7.01-7.32 (m, 4 H), 2.88-3.06 (m, 1 H), 2.32 
(s, 3 H), 1.66-2.67 (m, 8 H); .sup.13 C NMR (50 MHz, CDCl.sub.3) .delta. 
210.9, 141.4, 136.1, 129.3, 126.4, 49.0, 44.3, 41.1, 32.8, 25.5, 20.9; 
Electron Impact MS (El) m/e (relative intensity) 188 (M.sup.+, 60.8), 173 
(4.4), 145 (19.8), 131 (100.0), 118 (31.1), 105 (14.9), 91 (13.5); HRMS 
calcd. for C.sub.13 H.sub.16 O m/e 188.1201, found m/e 188.1209. Anal. 
Calcd.: C, 82.94; H, 8.57. Found: C, 82.83; H, 8.60. 
3,5,5-Trimethyl-3-octylcyclohexanone (84% yield): IR (neat) 2954, 2927, 
2856, 1714, 1466, 1281, 1226 cm.sup.-1 ; .sup.1 H NMR (200 MHz, 
CDCl.sub.3) .delta. 2.04-2.24 (m, 4 H), 1.63 (d, J=14.2 Hz, 1 H), 1.49 (d, 
J=14.2 Hz, 1 H), 1.16-1.38 (m, 14 H), 1.05 (s, 3 H), 1.04 (s, 3 H), 0.99 
(s, 3 H), 0.88 (t, J=6.5 Hz, 3 H); .sup.13 C NMR (50 MHz, CDCl.sub.3) 
.delta. 212.5, 54.3, 53.2, 49.0, 44.8, 38.7, 36.0, 32.2, 31.8, 30.7, 30.3, 
29.5, 29.3, 27.5, 23.7, 22.6, 14.1. Anal. Calcd. for C.sub.17 H.sub.32 O: 
C, 80.89; H, 12.78. Found: C, 80.50; H, 12.80. 
EXAMPLE 5 
Reaction of the Highly Reactive Calcium Species with 1,3-Dienes 
The following experimental procedure is representative of the reactions set 
forth below in Table IV. Highly reactive calcium (5.02 mmol) was prepared 
from CaI.sub.2 (5.02 mmol) and lithium biphenylide (10.30 mmol) in THF (20 
mL) as described above. To this highly reactive calcium solution, 
trans,trans-1,4-diphenyl-1,3-butadiene (0.863 g, 4.18 mmol) in THF (10 mL) 
was added at room temperature to form an organocalcium reagent. (An 
internal standard n-dodecane was added with starting material for the GC 
analyses in the cases of 2,3-dimethyl-1,3-butadiene.) After being stirred 
at room temperature for 30 minutes, the reaction mixture of the 
organocalcium reagent was cooled to -78.degree. C. and excess 
1,3-dibromopropane (1.020 g, 5.05 mmol) was added via a disposable syringe 
at -78.degree. C. The reaction was monitored by GC (OV-17 column). (In the 
cases of 2,3-dimethyl-1,3-butadiene, GC yields were reported based on the 
analyses of reaction quenches by an OV-17 column.) The reaction mixture 
was gradually warmed to -60.degree. C. and stirred at -60.degree. C. for 1 
hour. Saturated aqueous NH.sub.4 Cl solution (20 mL) was then added at 
-40.degree. C. The reaction mixture was filtered through a small pad of 
Celite.TM. filter agent and was washed with Et.sub.2 O (30 mL). The 
aqueous layer was extracted with Et.sub.2 O (2.times.30 mL). The combined 
organic phases were washed with H.sub.2 O and brine and dried over 
anhydrous MgSO.sub.4. Removal of solvent and flash-column chromatography 
on silica gel (200 g, 230-400 mesh, eluted sequentially with hexanes and 
1% Et.sub.2 O/hexanes) afforded 
trans-(1-phenyl)-2-(trans-.beta.-styrenyl)cyclopentane (940 mg, 91% 
yield): IR (neat) 3080, 3059, 3024, 2952, 2868, 1599, 1495, 1448, 964, 
744, 694 cm.sup.-1 ; .sup.1 H NMR (200 MHz, CDCl.sub.3) .delta. 7.01-7.33 
(m, 10 H), 6.06-6.27 (m, 2 H), 2.57-2.88 (m, 2 H), 1.99-2.66 (m, 2 H), 
1.55-1.95 (m, 4 H); .sup.13 C NMR (50 MHz, CDCl.sub.3) .delta. 144.5, 
137.4, 133.5, 129.2, 128.4, 128.2, 127.5, 126.7, 126.0, 125.9, 52.7, 51.6, 
35.0, 33.2, 24.2. Anal. Calcd. for C.sub.19 H.sub.20 : C, 91.88; H, 8.12. 
Found: C, 91.87; H, 8.22. 
TABLE IV 
__________________________________________________________________________ 
Reactions of 1,3-Diene/Calcium Complex with Organic Dihalides.sup.a 
Entry 
Diene Li/Ar CaX.sub.2 
Electrophile 
Product.sup.b 
% Yield.sup.c 
__________________________________________________________________________ 
##STR28## Li/Biph 
CaI.sub.2 
Br(CH.sub.2).sub.3 Br 
##STR29## 91.sup. 
2 
##STR30## Li/Np -- Br(CH.sub.2).sub.3 Br 
##STR31## 51.sup.d 
3 
##STR32## Li/-- CaI.sub.2 
Br(CH.sub.2).sub.3 Br 
##STR33## 74.sup.e 
4 
##STR34## Li/Biph 
CaI.sub.2 
Br(CH.sub.2).sub.3 Br 
##STR35## 53.sup. 
5 
##STR36## Li/Biph 
CaI.sub.2 
Br(CH.sub.2).sub.3 Br 
##STR37## 7.sup.f 
6 
##STR38## Li/Biph 
CaI.sub.2 
Cl(CH.sub.2).sub.2 Cl 
##STR39## 80.sup.g 
7 
##STR40## Li/Biph 
CaI.sub.2 
ClCH.sub.2 Cl 
##STR41## 47.sup.h 
8 
##STR42## Li/Biph 
CaI.sub.2 
(CH.sub.3).sub.2 SiCl.sub.2 
##STR43## --.sup.i 
9 
##STR44## Li/Biph 
CaI.sub.2 
Cl(CH.sub.2).sub.3 Cl 
##STR45## (98).sup.j 
10 
##STR46## Li/Biph 
-- Cl(CH.sub.2).sub.3 Cl 
##STR47## (25) 
11 
##STR48## Li/Biph 
CaI.sub.2 
Cl(Ch.sub.2).sub.4 Cl 
##STR49## (36).sup.j 
12 
##STR50## Li/Biph 
CaI.sub.2 
Br(CH.sub.2).sub.4 Br 
##STR51## (54).sup.j 
13 
##STR52## Li/Biph 
CaI.sub.2 
Ph.sub.2 SiCl.sub.2 
##STR53## (89).sup.k 
__________________________________________________________________________ 
.sup.a The active calcium was prepared from 2.05 equivalents of preformed 
lithium biphenylide and 1.0 equivalent of CaI.sub.2. 
.sup.b The known products were compared with the authentic sample. All ne 
substances have satisfactory spectroscopic data including IR, .sup.1 H 
NMR, .sup.13 C NMR, and highresolution mass spectral data. 
.sup.c Isolated yields. GC yields are given in parentheses. 
.sup.d 31% starting material was recovered. 
.sup.e No starting material was recovered. 
.sup.f 72% starting material was recovered. 
.sup.g 8% starting material was recovered. 
.sup.h 43% starting material was recovered. 
.sup.i Isolation was difficult because of overlapping with biphenyl. 
.sup.j Product was isolated by distillation. 
.sup.k Product was isolated by reversephase thinlayer chromatography. 
The reactivity of the calcium metallocycles was significant with excellent 
chemical yields. For example, 1,4-diphenyl-1,3-butadiene/calcium complex 
reacted rapidly with 1,3-dibromopropane and 1,4-dibromobutane to form 
trans-1-phenyl-2-trans-.beta.-styrenylcyclopentane and 
trans-1-phenyl-2-trans-.beta.-styrenylcyclohexane in 91% and 53% isolated 
yield, respectively. The stereochemistry of these reactions was always 
stereospecific. 
Reaction of (1,4-diphenyl-2-butene-1,4-diyl)calcium complexes with 
.alpha.,.omega.-alkylene dihalides usually gave 1,2-addition products 
while 1,4-addition was always observed in reactions with dichlorosilane. 
Treatment of (1,4-diphenyl-2-butene-1,4-diyl)calcium complex with 
1,2-dibromoethane yielded 7% of the 1,4-addition product, 
cis-3,6-diphenylcyclohexene, along with 72% of the starting material. The 
stereochemistry of 3,6-diphenylcyclohex-1-ene was identified by converting 
the cyclohexene to 1,2-cyclohexanediol via the epoxide (see Example 6 for 
details). In sum, treatment of 3,6-diphenylcyclohex-1-ene with 
m-chloroperbenzoic acid in the presence of K.sub.2 CO.sub.3 in CH.sub.2 
Cl.sub.2 gave only a single product in 60% yield along with 20% of 
recovered starting material. The fully decoupled .sup.13 C-NMR spectrum 
gave only seven peaks which unambiguously proved that two phenyl groups 
were in cis geometry. Reaction of the epoxide with 6% HClO.sub.4 in 
acetone yielded 1,4-diphenylcyclohexan-2,3-diol in 93% yield. The proton 
spin-spin coupling constants further verified that the two phenyl groups 
were cis (see Example 6). 
The yield of the 6-membered ring product was increased to 80% and the 
amount of recovered starting material dropped to 8% when 
1,2-dichloroethane was used (entry 6, Table IV). The higher reduction 
potential of 1,2-dichloroethane presumably eliminated most of the simple 
electron transfer pathway. Interestingly, reaction of this calcium complex 
with dichloromethane afforded only the 1,2-addition product, 
trans-1-phenyl-2-trans-.beta.-styrenylcyclopropane in 47% yield (entry 7, 
Table IV) along with 43% of 1,4-diphenyl-1,3-butadiene. 
Reduction of 1,4-diphenyl-1,3-butadiene with 2.2 equivalents of preformed 
lithium naphthalenide without the presence of Ca(II) salt, followed by the 
addition of 1,3-dibromopropane, also yielded the same cyclopentane 
derivative, but the yield was substantially lower than that obtained in 
the presence of calcium salts. Also of note is the fact that in the 
absence of calcium salts over 30% of the starting material was recovered. 
A similar result was also noted in the nonactivated diene system. The 
yield dramatically decreased from 98% to 25% in the similar experiments 
using 2,3-dimethyl-1,3-butadiene with 1,3-dichloropropane. Thus, the 
observed chemistry is dramatically different when the calcium salts are 
present. 
Direct reduction of the 1,3-dienes with lithium metal in the absence of 
electron carriers was also carried out. Reduction of 
1,4-diphenyl-1,3-butadiene with 2.5 equivalents of lithium metal in THF, 
followed by the sequential addition of 2.0 equivalents of CaI.sub.2 and 
1,3-dibromopropane, yielded the same 5-membered ring product in 74% yield 
along with a small amount of unidentified high molecular weight material. 
Significantly, no starting material was found in the reaction workup. This 
shows that the involvement of calcium ions is significant. 
This chemistry can also be extended to 2,3-dimethyl-1,3-butadiene, which is 
a molecule which is much more difficult to reduce. The calcium complex was 
readily prepared by reacting freshly distilled 2,3-dimethyl-1,3-butadiene 
with either the biphenylide complex or the calcium naphthalenide complex. 
Reaction of the resulting complex with 1,3-dichloropropane and 
1,4-dichlorobutane gave the 5-membered ring product and 6-membered ring 
product in 94% and 36% yield, respectively. For the latter reaction, the 
yield was improved to 54% when 1,4-dibromobutane was used. Similarly, 
treatment of (2,3-dimethyl-2-butene-1,4-diyl)calcium complex with 
dichlorodiphenylsilane yielded the 1,4-addition adduct in 89% yield. 
trans-(1-Phenyl)-2-(trans-.beta.-styrenyl)cyclohexane (53 % yield ): IR 
(neat) 3082, 3059, 3026, 2924, 2850, 1601, 1495, 1446, 962, 744, 698 
cm.sup.-1 ; .sup.1 H NMR (200 MHz, CDCl.sub.3) .delta. 7.02-7.30 (m, 10 
H), 6.11 (d, J=15.9 Hz, 1 H), 5.82-5.98 (m, 1 H), 2.28-2.47 (m, 2 H), 
1.25-2.02 (m, 8 H); .sup.13 C NMR (50 MHz, CDCl.sub.3) .delta. 146.0, 
138.0, 135.0, 128.8, 128.3, 128.2, 127.6, 126.6, 125.9 (2C), 50.6, 46.4, 
35.4, 33.3, 26.7, 26.1. Anal. Calcd. for C.sub.20 H.sub.22 : C, 91.55; H, 
8.45. Found: C, 91.37; H, 8.10. 
cis-3,6-Diphenyl-1-cyclohexene (80% yield): IR (neat) 3080, 3059, 3024, 
2931, 2856, 1601, 1493, 1450, 754, 698 cm.sup.-1 ; .sup.1 H NMR (200 MHz, 
CDCl.sub.3) .delta. 7.16-7.36 (m, 10 H), 5.98 (d, J=1.3 Hz, 2 H), 
3.45-3.55 (m, 2 H), 1.87-2.07 (m, 2 H), 1.60-1.79 (m, 2 H); .sup.13 C NMR 
(50 MHz, CDCl.sub.3) .delta. 145.9, 131.1, 128.3, 127.9, 126.1, 41.2, 29.3 
cm.sup.-1 ; MS (EI) m/e (relative intensity) 234 (M.sup.+, 15.4), 206 
(2.7), 143 (10.8), 130 (100.0), 115 (25.3), 104 (24.8), 91 (21.1), 77 
(6.3); HRMS calcd. for C.sub.18 H.sub.18 m/e 234.1409, found m/e 234.1409. 
trans-(1-Phenyl)-2-(trans-.beta.-styrenyl)cyclopropane (47% yield): IR 
(neat) 3080, 3059, 3024, 2966, 2929, 1647, 1605, 1496, 1460, 1448, 958, 
750, 739, 694 cm.sup.-1 ; .sup.1 H NMR (200 MHz, CDCl.sub.3) .delta. 
7.04-7.35 (m, 10 H), 6.47 (d, J=15.8 Hz, 1 H), 5.90 (dd, J=15.8, 8.6 Hz, 1 
H), 2.03 (ddd, J=8.8, 5.5, 4.3 Hz, 1 H), 1.82 (ddt, J=8.6, 5.6, 4.3 Hz, 1 
H), 1.31 (dt, J=8.5, 5.4 Hz, 1 H), 1.21 (dt, J=8.8, 5.4 Hz, 1 H); .sup.13 
C NMR (50 MHz, CDCl.sub.3) .delta. 142.1, 137.5, 132.8, 128.5 (2C), 128.4, 
128.2, 126.8, 125.7 (2C), 27.4, 25.7, 17.1 cm.sup.-1 ; MS (EI) m/e 
(relative intensity) 220 (M.sup.+, 30.6), 142 (8.0), 129 (100.0), 115 
(25.1), 103 (3.6), 91 (28.8), 77 (9.5); HRMS calcd. for C.sub.17 H.sub.16 
m/e 220.1252, found m/e 220.1252. 
cis-1,1-Dimethyl-2,5-diphenylsilacyclopent-3-ene: IR (neat) 3078, 3059, 
3020, 2954, 2895, 2850, 1599, 1495, 1250, 1061, 858, 802, 746, 698 
cm.sup.-1 ; .sup.1 H NMR (200 MHz, CDCl.sub.3) .delta. 7.00-7.30 (m, 10 
H), 6.11 (s, 2 H), 3.27 (s, 2 H), 0.39 (s, 3 H), -0.67 (s, 3 H); .sup.13 C 
NMR (50 MHz, CDCl.sub.3) .delta. 143.4, 135.0, 128.3, 126.4, 124.3, 39.9, 
-2.8, -6.8. 
1,1-Diphenyl-3,4-dimethylsilacyclopent-3-ene (89% GC yield): IR (neat) 
3066, 3049, 2976, 2906, 2871, 1427, 1174, 1117, 773, 731, 698 cm.sup.-1 ; 
.sup.1 H NMR (200 MHz, CDCl.sub.3) .delta. 7.27-7.62 (m, 10 H), 1.87 (s, 2 
H), 1.77 (s, 3 H); .sup.13 C NMR (50 MHz, CDCl.sub.3) .delta. 136.4, 
134.7, 130.7, 129.3, 127.8, 24.2, 19.3. 
1-Methyl-1-(2-propenyl)cyclopentane (94% GC yield): IR (neat) 2958, 2871, 
1639, 1452, 1369, 889 cm.sup.-1 ; .sup.1 H NMR (200 MHz, CDCl.sub.3) 
.delta. 4.65-4.73 (m, 2H), 1.76 (dd, J=1.3, 0.7 Hz, 3H), 1.35-1.73 (m, 
8H), 1.05 (s, 3H); .sup.13 C NMR (50 MHz, CDCl.sub.3) .delta. 153.3, 
107.6, 48.0, 37.7, 26.0, 23.7, 20.2. 
1-Methyl-1-(2-propenyl)cyclohexane (54% GC yield): .sup.1 H NMR (200 MHz, 
CDCl.sub.3) .delta. 4.72-4.82 (m, 2H), 1.71 (dd, J=1.4, 0.7 Hz, 3H), 
1.20-1.75 (m, 10H), 0.98 (s, 3H); .sup.13 C NMR (50 MHz, CDCl.sub.3) 
.delta. 152.6, 109.1, 38.8, 36.4, 27.1, 26.4, 22.6, 19.5. 
EXAMPLE 6 
Synthesis of 1,2-Epoxy-3,6-diphenylcyclohexane and 
3,6-Diphenylcyclohexan-1,2-diol 
1,2-Epoxy-3,6-diphenylcyclohexane: 3,6-Diphenylcyclohex-1-ene (50 mg, 0.21 
mmol), m-chloroperbenzoic acid (55%, 200 mg, 0.64 mmol), and K.sub.2 
CO.sub.3 (150 mg, 1.09 mmol) were stirred in CH.sub.2 Cl.sub.2 (10 mL) for 
24 hours. The reaction mixture was filtered and washed with CH.sub.2 
Cl.sub.2 (40 mL). The filtrate and aqueous Na.sub.2 S.sub.2 O.sub.3 
solution (10%, 10 mL) were stirred for 2 hours. The organic phase was 
washed with saturated NaHCO.sub.3 solution and H.sub.2 O and dried over 
anhydrous magnesium sulfate. Preparative thin-layer chromatography (silica 
gel, 2 mm, developed with 10:1 hexane/EtOAc) gave 
1,2-epoxy-3,6-diphenylcyclohexane (32 mg, 60% yield) as a colorless oil 
along with recovery of starting material (10 mg, 20%). 
1,2-Epoxy-3,6-diphenylcyclohexane: .sup.1 H NMR (200 MHz, CDCl.sub.3) 
.delta. 7.20-7.45 (m, 10 H), 3.45 (s, 2 H), 3.37 (t, J=6.4 Hz, 2 H), 
1.67-1.88 (m, 2 H), 1.37-1.58 (m, 2 H); .sup.13 C NMR (50 MHz), 143.2, 
128.6, 128.0, 126.5, 56.2, 39.9, 25.0. 
3,6-Diphenylcyclohexan-1,2-diol: 1,2-Epoxy-3,6-diphenylcyclohexane (32 mg, 
0.13 mmol) was dissolved in acetone (10 mL). HClO.sub.4 (6%, 10 mL) was 
added and the mixture was stirred at room temperature for 24 hours. The 
reaction solution was neutralized with Na.sub.2 CO.sub.3 and the reaction 
mixture was reduced to approximately half volume under reduced pressure. 
Extraction with CH.sub.2 Cl.sub.2 and removal of the solvent yielded crude 
product (93% yield) as a white solid. Based upon the analyses of NMR 
spectra of crude and recrystallized product, reaction gave a single 
product. Recrystallization from hexane/CH.sub.2 Cl.sub.2 gave pure product 
as a white crystalline solid: mp 134.degree.-135.degree. C.; IR (KBr) 
3303, 3086, 3059, 3026, 2935, 2858, 1603, 1495, 1454, 1041, 760, 698 
cm.sup.-1 ; .sup.1 H NMR (200 MHz, CDCl.sub.3) .delta. 7.20-7.60 (m, 10 
H), 4.08 (t, J=9.8 Hz, 1 H), 3.95 (dd, J= 9.5, 5.5 Hz, 1 H), 3.56 (m, 1 
H), 2.67 (ddd, J=11.7, 9.9, 4.3 Hz, 1 H), 1.65-2.39 (m, 6 H); .sup.13 C 
NMR (50 MHz, CDCl.sub.3) .delta. 142.3, 140.8, 129.7, 128.8, 128.4, 127.8, 
126.9, 126.5, 76.8, 74.6, 50.6, 44.7, 29.9, 29.2; MS (EI) m/e (relative 
intensity) 268 (M.sup.+, 61.9), 250 (12.9), 237 (11.5), 219 (7.3), 146 
(30.1), 131 (94.9), 117 (55.4), 104 (100.0), 91 (73.6), 77 (15.3); HRMS 
calcd. for C.sub.18 H.sub.20 O.sub.2 m/e 268.1463, found m/e 268.1464. 
EXAMPLE 7 
Preparation of Polymeric Compounds From Organocalcium Dihalides 
Poly(paraphenylene ketone): Highly reactive calcium (4.00 mmol), prepared 
from lithium biphenylide (8.36 mmol) and CaI.sub.2 (4.00 mmol) in THF (30 
mL), was cooled to -78.degree. C. This solution was added dropwise via 
cannula into a solution of 1,4-dibromobenzene (2.01 mmol) at -78.degree. 
C. over a period of 1 hour. The reaction mixture was added to 
terephthaloyl chloride (2.01 mmol) in THF (10 mL) at -78.degree. C. and 
stirred for 30 minutes. It was allowed to warm to room temperature and 
then refluxed for 30 minutes. The reaction mixture was then cooled to room 
temperature and 10% HCl (10 mL) was added with stirring. The mixture was 
stirred for an additional 30 minutes, and then added to methanol (200 mL). 
The solid was filtered and washed several times with 200 mL portions of 
methanol and 10% HCl. The solid was dried under vacuum at 100.degree. C. 
for 24 hours. A brown powder (0.3865 g, 93% yield) of --(--C.sub.6 H.sub.4 
C(O)--).sub.n -- resulted. FTIR (diffuse reflectance): observed an intense 
peak at 1665 cm.sup.-1 for carbonyl (C.dbd.O). 
Poly(paraphenylene): Highly reactive calcium (4.61 mmol), prepared from 
lithium biphenylide (9.36 mmol) and CaI.sub.2 (4.61 mmol) in THF (30 mL), 
was cooled to -78.degree. C. This solution was added dropwise via cannula 
into a solution of 1,4-dibromobenzene (4.62 mmol) at -78.degree. C. over a 
period of 20 minutes. The solution was stirred for an additional 80 
minutes at -78.degree. C., and then it was allowed to warm to room 
temperature over the course of 20 minutes. A solution of NiCl.sub.2 (0.077 
mmol) in THF (5 mL) was added to the reaction mixture, and then refluxed 
for 4 hours. The solution became dark gray in color, 10% HCl (10 mL) was 
added, and then this was added to methanol (300 mL). A solid was filtered 
from the reaction mixture and washed with 500 mL portions of methanol and 
10% HCl. The solid was dried under vacuum at 80.degree. C. for 30 hours. 
A light yellow powder (0.1622 g, 42% yield) of --(--C.sub.6 H.sub.4 
--).sub.n -- resulted. FTIR (diffuse reflectance): observed peaks at 808 
cm.sup.-1 for para-substituted benzene, 1075 cm.sup.-1 for aryl C-Br, and 
at 692 and 764 cm.sup.-1 for aryl C-H. Elemental Analysis: Found: C=87.44, 
H=5.30, Br=3.70. Calcd. for n=13 chain length, C=87.55, H=4.96, Br=7.48. 
Poly(2,5-thienylene): Highly reactive calcium (3.98 mmol), prepared from 
lithium biphenylide (8.17 mmol) and CaI.sub.2 (3.98 mmol) in THF (15 mL), 
was cooled to -78.degree. C. This solution was added dropwise via cannula 
into a solution of 2,5-dibromothiophene (4.04 mmol) at -78.degree. C. over 
a period of 30 minutes. Upon the addition of the 2,5-dibromothiophene, the 
color changed from a dark color to a gray color. The solution was allowed 
to warm to room temperature over the course of 30 minutes. A solution of 
NiCl.sub.2 (0.015 mmol) in THF (10 mL) was added to the reaction mixture, 
and then refluxed for 15 hours. The solution became dark brown in color 10 
minutes after the addition of the NiCl.sub.2. The solution was allowed to 
cool to room temperature and was added to a mixture of 10% HCl (200 mL) 
and methanol (200 mL). This produced a dark brown precipitate. A solid was 
filtered from the reaction mixture and washed with 200 mL portions of 
methanol and 10% HCl. The solid was dried under vacuum at 80.degree. C. 
for 20 hours. A dark brown powder (0.1182 g, 36% yield) resulted. The 
product is soluble in THF and acetone, and insoluble in methanol and 10% 
HCl. FTIR (diffuse reflectance): observed an intense peak at 790 cm.sup.-1 
for C-H out-of-plane vibration for disubstituted thiophene. The peak for 
C-Br at 980 cm.sup.-1 was absent. 
EXAMPLE 8 
Spiroannelation 
In a typical preparation, 1,2-dimethylenecyclohexane (2.0 mmol) is added 
via a disposable syringe to the newly prepared highly reactive Ca (3.0-4.0 
mmol) in THF (15 mL). The mixture is stirred for several hours at room 
temperature under argon. Bis-electrophiles are added to the freshly 
prepared THF solutions of the calcium complexes of 
1,2-dimethylenecycloalkanes at -78.degree. C. The reaction mixture is then 
stirred at -78.degree. C. prior to warm up to room temperature. This same 
method can be extended to other 1,2-dimethylenecycloalkanes, such as 
1,2-dimethylenecyclopentane and 1,2-dimethylenecycloheptane. 
Significantly, treatment of this type of 2-butene-1,4-diylcalcium complex, 
i.e., those resulting from the reaction of highly reactive calcium with 
cycloalkanes having two conjugated exocyclic double bonds, with 
bis-electrophiles, especially 1,n-dibromoalkanes, give spirocycles. 
Representative examples are summarized in Table V. A major advantage of 
using 2-butene-1,4-diylcalcium complexes is that spiroannelation can be 
achieved in one synthetic operation. 
TABLE V 
__________________________________________________________________________ 
Reactions of the Calcium Complexes of 
1,2-Dimethylenecycloalkanes with Bis-electrophiles 
Diene.sup.a 
Electrophile 
Conditions Product 
__________________________________________________________________________ 
1 Br(CH.sub.2).sub.5 Br 
-78.degree. C. to reflux 
##STR54## 
1 Br(CH.sub.2).sub.4 Br 
-78.degree. C. to reflux 
##STR55## 
1 Br(CH.sub.2).sub.3 Br 
-78.degree. C. to room temp. 
##STR56## 
1 Br(CH.sub.2).sub.3 Br 
-78.degree. C. to -30.degree. C. 
##STR57## 
1 Br(CH.sub.2).sub.2 Br 
-78.degree. C. to room temp. 
##STR58## 
1 TsO(CH.sub.2).sub.2 OTs 
-78.degree. C. to room temp. 
##STR59## 
2 Br(CH.sub.2).sub.3 Br 
-78.degree. C. to room temp. 
##STR60## 
3 Br(CH.sub.2).sub.3 Br 
-78.degree. C. to room temp. 
##STR61## 
__________________________________________________________________________ 
.sup.a 1: 1,2Dimethylenecyclohexane; 2: 1,2Dimethylenecyclopentane; 3: 
1,2Dimethylenecycloheptane. 
EXAMPLE 9 
Preparation of .gamma.-Lactones Including Spiro .gamma.-Lactones 
The 2-butene-1,4-diylcalcium complexes prepared from the reaction of highly 
reactive calcium with either cyclic hydrocarbons having at least two 
conjugated exocyclic double bonds or open-chain conjugated dienes, react 
with a ketone or aldehyde and carbon dioxide to form .gamma.-lactones, 
preferably spiro .gamma.-lactones. Calcium complexes of 
1,2-dimethylenecycloalkanes and 1,3-butadienes are prepared as described 
above. A molar equivalent of a ketone is added to the THF solution of 
these complexes at a temperature of about -78.degree. C. The reaction 
mixture is then stirred, warmed to a temperature of 0.degree. C. to 
25.degree. C., and bubbled with carbon dioxide prior to acidic hydrolysis 
and warming to about 40.degree. C. 
In a typical reaction 1,2-dimethylenecyclohexane (0.239 g, 2.21 mmol) is 
added via a disposable syringe to the highly reactive calcium (3.53 mmol) 
in THF (20 mL). After being stirred at room temperature for several hours, 
the reaction mixture is allowed to stand until the solution becomes 
transparent. The THF solution of newly formed calcium complex of 
1,2-dimethylenecyclohexane is cooled to -78.degree. C. using a dry 
ice/acetone bath, and acetone (0.122 g, 2.10 mmol) is added via a 
disposable syringe. The mixture is stirred at -78.degree. C., then 
gradually warmed to 0.degree. C. Carbon dioxide is then bubbled through 
the reaction mixture at 0.degree. C., and then at room temperature. An 
aqueous solution of 1.5N HCl (10 mL) is added at 0.degree. C. The reaction 
mixture is heated slightly to 40.degree. C. After cooling to room 
temperature, the mixture is extracted with diethyl ether (3.times.20 mL). 
The combined organic phases are washed with saturated aqueous NaHCO.sub.3 
(2.times.20 mL) and brine (20 mL) and dried over anhydrous MgSO.sub.4. 
Removal of solvents and flash column chromatography gives 
4,4-dimethyl-6-methylene-3-oxaspiro[4.5]decan-2-one. See Table VI for 
representative examples of compounds that can be made by this method. 
TABLE VI 
______________________________________ 
Synthesis of Spiro .gamma.-Lactones from 
Conjugated Diene, Ketone and CO.sub.2 
Entry Diene.sup.a 
Ketone Product 
______________________________________ 
1 1 Acetone 
##STR62## 
2 1 Cyclopentanone 
##STR63## 
3 1 Cyclohexanone 
##STR64## 
4 4 Cyclopentanone 
##STR65## 
5 4 Cyclohexanone 
##STR66## 
______________________________________ 
.sup.a 1: 1,2Dimethylenecyclohexane; 4: 2,3Dimethyl-1,3-butadiene. 
EXAMPLE 10 
Preparation of .delta.-Lactones 
In a typical procedure, 1,2-bis(methylene)cyclohexane (0.330 g, 3.05 mmol) 
is added via a disposable syringe to the active calcium (4.68 mmol) in 
freshly distilled THF (15 mL). After being stirred at ambient temperature 
for several hours, the reaction mixture is allowed to stand until the 
solution becomes transparent. The THF solution of newly formed calcium 
complex of 1,2-dimethylenecyclohexane is cooled to -78.degree. C. using a 
dry ice/acetone bath. Ethylene oxide (1 mL) is condensed into a small vial 
capped with a rubber septum (at -78.degree. C.) and is subsequently added 
to the reaction mixture via cannula. The mixture is stirred at -78.degree. 
C. and gradually warmed to 0.degree. C. At this point, the reaction 
mixture is bubbled with purified carbon dioxide for 10 minutes at 
0.degree. C., and continued at room temperature. An aqueous solution of 3N 
HCl (10 mL) is added via a syringe at 0.degree. C. The reaction mixture is 
then warmed to 40.degree. C. After subsequent cooling to room 
temperature, the mixture is extracted with diethyl ether (3.times.20 mL). 
The combined organic layers are washed with saturated aqueous NaHCO.sub.3 
(2.times.20 mL), water (1.times.20 mL), and then dried over anhydrous 
MgSO.sub.4. The solvents can be removed under vacuum followed by flash 
chromatography to afford the .delta.-lactone product. See Table VII for 
examples of compounds that can be prepared using this method. If carbon 
dioxide is not used, and the epoxide/diene-calcium addition adducts are 
hydrolyzed with acid, alcohols are produced. See Table VIII for examples 
of compounds that can be prepared using this method. 
TABLE VII 
__________________________________________________________________________ 
Reactions of Conjugated Diene-Calcium Complexes 
with Epoxides Followed by Carbon Dioxide 
Entry 
Diene Epoxide Product 
__________________________________________________________________________ 
##STR67## 
##STR68## 
##STR69## 
2 
##STR70## 
##STR71## 
##STR72## 
3 
##STR73## 
##STR74## 
##STR75## 
4 
##STR76## 
##STR77## 
##STR78## 
5 
##STR79## 
##STR80## 
##STR81## 
__________________________________________________________________________ 
TABLE VIII 
__________________________________________________________________________ 
Reactions of Conjugated Diene-Calcium Complexes 
with Epoxides Followed by Acidic Hydrolysis 
Entry 
Diene Epoxide Product 
__________________________________________________________________________ 
##STR82## 
##STR83## 
##STR84## 
2 
##STR85## 
##STR86## 
##STR87## 
3 
##STR88## 
##STR89## 
##STR90## 
4 
##STR91## 
##STR92## 
##STR93## 
__________________________________________________________________________ 
EXAMPLE 11 
Preparation of .gamma.-Lactams 
In a typical experiment, 2,3-dimethyl-1,3-butadiene (1.5 mL) is added neat 
via a disposable syringe to the active calcium (4.64 mmol) in freshly 
distilled THF (15 mL). After being stirred at ambient temperature for 8 
hours, the reaction mixture is allowed to stand until the solution becomes 
transparent. The THF solution of newly formed calcium-diene complex is 
then cooled to -78.degree. C. using a dry ice/acetone bath. 
N-benzylideneaniline (0.547 g, 3.02 mmol) is weighed into a small vial and 
capped with a rubber septum, evacuated and charged with argon. 5 mL of 
freshly distilled THF is then added to the vial and this is added via 
cannula to the calcium-diene solution at -78.degree. C. The reaction 
mixture is then allowed to warm to 0.degree. C. and is charged with 
purified carbon dioxide at 0.degree. C., and then continued at room 
temperature. An aqueous solution of 3N HCl (10 mL) is added to the 
reaction mixture via a syringe at 0.degree. C. The reaction mixture is 
then warmed to 40.degree. C. After cooling to room temperature, the 
mixture is extracted with diethyl ether (3.times.20 ml). The combined 
organic layers are washed with saturated aqueous NaHCO.sub.3 (2.times.20 
mL), water (1.times.20 mL), and then dried over anhydrous MgSO.sub.4. 
After removal of solvents under vacuo, the residue is flash 
chromatographed on silica gel using gradient mixtures of hexanes and ethyl 
acetate to afford the N-benzyl-.gamma.-lactam. 
EXAMPLE 12 
Preparation of Chiral Vicinal Diols 
In a typical preparation, 1,2-bis(methylene)cyclohexane (0.303 g, 2.80 
mmol) is added via a disposable syringe to the active calcium (4.05 mmol) 
in freshly distilled THF (15 mL). After being stirred at ambient 
temperature, the reaction mixture is allowed to stand until the solution 
becomes transparent. The THF solution of newly formed calcium complex of 
1,2-dimethylenecyclohexane is cooled to -78.degree. C. using a dry 
ice/acetone bath. (R)-2-Methylglycidol (0.109 g, 1.24 mmol) is added to 
the reaction mixture via a disposable syringe at -78.degree. C. and 
stirred. The reaction mixture is then allowed to slowly warm to 0.degree. 
C. followed by subsequent addition of NH.sub.4 Cl (5 mL) via syringe. 
After warming to room temperature, the reaction mixture is extracted with 
diethyl ether (3.times.20 mL) and the combined organic layers are dried 
over anhydrous MgSO.sub.4. After removal of solvents under vacuo, the 
residue is flash chromatographed on silica gel using gradient mixtures of 
hexanes and ethyl acetate to afford the vicinal diol as a 1:1 mixture of 
diastereomers. 
The foregoing detailed description has been given for clarity of 
understanding only and no unnecessary limitations are to be understood 
therefrom. The invention is not limited to the exact details shown and 
described, for obvious modifications will occur to those skilled in the 
art.