Preparation of cis--olefins

A cis-olefin of the formula: R.sub.1 --CH.dbd.CH--R.sub.2 is prepared by reducing an alkyne of the formula: R.sub.1 --C.ident.C--R.sub.2 with formic acid in the presence of a palladium catalyst. R.sub.1 and R.sub.2 are independently selected from the group consisting of a hydrogen atom, ester group, substituted silyl group, carboxyl group, cyano group, aliphatic C1-C20 hydrocarbon group, and phenyl group. The cis-olefin which is a useful intermediate for the synthesis of fine chemicals is selectively produced in high yields.

FIELD OF THE INVENTION
 This invention relates to the preparation of cis-olefins, and more
 particularly, a method for preparing cis-olefins through formic acid
 reduction of alkynes in the presence of palladium catalysts.
 BACKGROUND OF THE INVENTION
 Cis-olefins are useful intermediates for the synthesis of many fine
 chemicals, especially for the synthesis of bioactive materials having a
 double bond cis-conformed in their structural formula.
 In the prior art, cis-olefins were prepared by the hydrogen reduction of
 alkynes using Lindlar catalysts. Also known in the art are silicon hydride
 reduction using palladium catalysts (Barley M. Trost, Tetrahedron Letters,
 Vol. 30, No. 35 pp. 4657, 1989).
 These method have several drawbacks. The hydrogen reduction method using
 Lindlar catalysts is difficult to obtain cis-olefins of high purity since
 trans-olefins and saturated compounds are by-produced in addition to the
 desired cis-olefins. The hydrogen reduction method has the danger of a
 fire. The silicon hydride reduction method must use expensive silicon
 hydrides and is generally low in cis-olefin selectivity so that
 trans-olefins can be a major product.
 In Tetrahedron, Vol. 44, pp. 481, 1988, A. Arcadi et al discloses formic
 acid reduction in which aryl iodides are reacted with alkyl
 4-hydroxy-2-alkynoates and in the presence of formic acid,
 tri-n-butylamine and a palladium (II) catalyst.
 However, the above formic acid reduction method only provides cyclic
 product as shown below. No cis-olefins which are pure hydrogenated
 products are available.
 ##STR1##
 There is a need to have a simple method capable of selectively producing
 cis-olefins in high yields.
 SUMMARY OF THE INVENTION
 Therefore, an object of the present invention is to provide a method for
 selectively preparing cis-olefins without substantial formation of
 trans-olefins and saturated compounds.
 The present invention is addressed to a method for preparing a cis-olefin
 of the following general formula (2):
 ##STR2##
 wherein R.sub.1 and R.sub.2 are independently selected from the group
 consisting of a hydrogen atom, ester group, substituted silyl group,
 carboxyl group, cyano group, substituted or unsubstituted aliphatic
 hydrocarbon group having 1 to 20 carbon atoms, and substituted or
 unsubstituted phenyl group. The method is characterized by reducing an
 alkyne of the following general formula (1):
EQU R.sub.1 --C.ident.C--R.sub.2 (1)
 wherein R.sub.1 and R.sub.2 are as defined above with formic acid in the
 presence of a palladium catalyst.
 DETAILED DESCRIPTION OF THE INVENTION
 The method of the invention starts with an alkyne of formula (1).
EQU R.sub.1 --C.ident.C--R.sub.2 (1)
 In formula (1), R.sub.1 and R.sub.2, which may be identical or different,
 are independently selected from the group consisting of (a) a hydrogen
 atom, (b) an ester group, (c) a substituted silyl group, (d) a carboxyl
 group, (e) a cyano group, (f) a substituted or unsubstituted aliphatic
 hydrocarbon group having 1 to 20 carbon atoms, and (g) a substituted or
 unsubstituted phenyl group. Examples of the group represented by R.sub.1
 and R.sub.2 are given below.
 Examples of (b) ester group include substituted or unsubstituted
 alkoxycarbonyl groups having 1 to 10 carbon atoms and substituted or
 unsubstituted phenoxycarbonyl groups. The substituted or unsubstituted
 alkoxycarbonyl groups having 1 to 10 carbon atoms include methoxycarbonyl,
 ethoxycarbonyl, n-propoxycarbonyl, i-propoxycarbonyl, n-butoxycarbonyl,
 sec-butoxycarbonyl, t-butoxycarbonyl, pentoxycarbonyl, hexoxycarbonyl,
 heptoxycarbonyl, octoxycarbonyl, nonanoxycarbonyl, decisoxycarbonyl,
 methoxymethoxycarbonyl, methylthiomethoxycarbonyl,
 tetrahydropyranoxycarbonyl, tetrahydrofuranotoxycarbonyl,
 benzyloxymethoxycarbonyl, phenasiloxycarbonyl,
 o-methylphenoxymethoxycarbonyl, m-methylphenoxymethoxycarbonyl,
 p-methylphenoxymethoxycarbonyl, o-bromophenasiloxycarbonyl,
 m-bromophenasiloxycarbonyl, p-bromophenasiloxycarbonyl, bezyloxycarbonyl,
 o-methylphenasiloxycarbonyl, m-methylphenasiloxycarbonyl,
 p-methylphenasiloxycarbonyl, 2,2,2-trichloroethoxycarbonyl,
 2-chloroethoxycarbonyl, 2-methylthioethoxycarbonyl,
 cyclopentyloxycarbonyl, cyclohexyloxycarbonyl, allyloxycarbonyl groups,
 etc. The substituted or unsubstituted phenoxycarbonyl groups include
 biphenoxycarbonyl, 4-(4-fluorophenyl)phenoxycarbonyl,
 4-(4-chlorophenyl)phenoxycarbonyl, 4-(4-bromophenyl)phenoxycarbonyl,
 4-(4-iodophenyl)phenoxycarbonyl groups, etc.
 Examples of (c) substituted silyl group include trimethylsilyl,
 i-propyldimethylsilyl, t-butyldimethylsilyl groups, etc.
 Examples of (f) unsubstituted aliphatic hydrocarbon group having 1 to 20
 carbon atoms include methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl,
 sec-butyl, t-butyl, n-amyl, i-amyl, hexyl, heptyl, octyl, nonyl, decyl,
 undecyl, dodecyl, tridecyl, hexadecyl, octadecyl, eicosyl groups, etc.
 The substituents on (f) aliphatic hydrocarbon groups and (g) phenyl group
 include hydroxyl, protected hydroxyl, halogen, formyl, ester, carbonyl,
 amide, carboxyl, cyano, p-methylthio, phenyl, fluorophenyl, chlorophenyl,
 bromophenyl, and iodophenyl groups.
 By the protected hydroxyl groups are meant those hydroxyl groups protected
 with substituted silyl groups such as trimethylsilyl and
 t-butyldimethylsilyl groups, alkoxyalkyl groups such as methoxymethyl and
 ethoxymethyl groups, acyl groups such as acetyl and benzoyl groups,
 trityl, tetrahydropyranyl, benzyl and p-chlorobenzyl groups.
 The ester substituents include substituted or unsubstituted alkoxycarbonyl
 groups having 1 to 10 carbon atoms and substituted or unsubstituted
 phenoxycarbonyl groups as mentioned for (b).
 The halogen substituents include fluorine, chlorine, bromine and iodine
 atoms.
 The amide substituents include substituted or unsubstituted
 alkoxycarbonylamide groups having 1 to 10 carbon atoms and substituted or
 unsubstituted phenoxycaronylamide groups. The substituted or unsubstituted
 alkoxycarbonylamide groups having 1 to 10 carbon atoms include
 methoxycarbonylamino, ethoxycarbonylamino, n-propoxycarbonylamino,
 i-propoxycarbonylamino, n-butoxycarbonylamino, sec-butoxycarbonylamino,
 t-butoxycarbonylamino, pentoxycarbonylamino, hexoxycarbonylamino,
 heptoxycarbonylamino, octoxycarbonylamino, nonanoxycarbonylamino,
 decisoxycarbonylamino, methoxymethoxycarbonylamino,
 methylthiomethoxycarbonylamino, tetrahydropyranoxycarbonylamino,
 tetrahydrofuranotoxycarbonylamino, benzyloxymethoxycarbonylamino,
 phenasiloxycarbonylamino, o-methylphenoxymethoxycarbonylamino,
 m-methylphenoxymethoxycarbonylamino, p-methylphenoxymethoxycarbonylamino,
 o-bromophenasiloxycarbonylamino, m-bromophenasiloxycarbonylamino,
 p-bromophenasiloxycarbonylamino, benzyloxycarbonylamino,
 o-methylphenasiloxycarbonylamino, m-methylphenasiloxycarbonylamino,
 p-methylphenasiloxycarbonylamino, 2,2,2-trichloroethoxycarbonylamino,
 2-chloroethoxycarbonylamino, 2-methylthioethoxycarbonylamino,
 cyclopentyloxycarbonylamino, cyclohexyloxycarbonylamino,
 allyloxycarbonylamino groups, etc. The amide moiety of the
 alkoxycarbonylamide and phenoxycarbonylamide groups may have a substituent
 which is selected from the above-mentioned substituents on the C1-C10
 aliphatic hydrocarbon and phenyl groups and which may further have a
 substituent such as a hydroxyl, protected hydroxyl, halogen, formyl,
 ester, amide, carboxyl, cyano, p-methylthio, phenyl, fluorophenyl,
 chlorophenyl, bromophenyl, and iodophenyl group.
 Illustrative, non-limiting examples of the alkyne of formula (1) include
 1-decyne, 1-hydroxy-4-heptyne, 1-hydroxy-2-octyne, 3-hydroxy-1-octyne,
 3-hydroxy-4-decyne, 2-hydroxy-2-methyl-3-nonyne,
 1-trimethylsilyl-1-heptyne, 1-t-butyldimethylsiloxy-2-octyne,
 1-trimethylsilyl-3-hydroxy-1-octyne, 1-carboxy-3-hexyne,
 1-carboxy-1-heptyne, 1-methoxycarbonyl-1-heptyne,
 1-ethoxycarbonyl-4-heptyne, 1-allyloxycarbonyl-1-heptyne,
 1-methoxycarbonyl-6-hydroxy-4-hexyne, 1-ethoxycarbonyl-3-hexyne,
 3-oxy-4-decyne, 2-oxo-5-octyne, 1-benzyloxy-2-octyne,
 1-tetrahydropyranoxy-2-octyne, 1-formyl-3-hexyne, 1-bromo-4-heptyne,
 1-cyano-4-heptyne, phenylacetylene, 1-phenyl-1-butyne, and
 1-phenylthio-4-heptyne.
 According to the present invention, these alkynes are reduced with formic
 acid in the presence of palladium catalysts. The palladium catalysts used
 herein may be complexes of palladium having a valence of zero or plus two.
 Examples of the palladium catalyst include Pd(PPh.sub.3).sub.4, Pd(Ph.sup.t
 Bu.sub.2).sub.2, Pd(P.sup.t Bu.sub.3).sub.2, Pd[P(c-C.sub.6
 H.sub.11).sub.3 ].sub.2, Pd[P(OPh).sub.3 ].sub.4, Pd[P(OEt).sub.3 ].sub.4,
 Pd(AsPh.sub.3).sub.4, Pd(CO)(PPh.sub.3).sub.3, Pd(PPh.sub.3).sub.2
 (CH.sub.2.dbd.CH.sub.2), Pd(PPh.sub.3).sub.2 (CF.sub.2.dbd.CF.sub.2), Pd[P
 (c-C.sub.6 H.sub.11).sub.3 ].sub.2 (CH.sub.2.dbd.CH.sub.2), Pd[P(c-C.sub.6
 H.sub.11).sub.3 ].sub.2 (CF.sub.2.dbd.CF.sub.2), Pd(PBu.sub.3).sub.2
 (CH.sub.2.dbd.CH.sub.2), Pd(PPh.sub.3).sub.2 (CF.sub.2.dbd.CF.sub.2),
 Pd[P(OC.sub.6 H.sub.4 CH.sub.3 -o)].sub.2 (CH.sub.2.dbd.CH.sub.2),
 Pd(PPh.sub.3).sub.2 (CH.sub.3 OOCCH.dbd.CHCOOCH.sub.3), Pd[P(OPh).sub.3
 ].sub.2 (CH.sub.3 OOCCH.dbd.CHCOOCH.sub.3), Pd(PPh.sub.3).sub.2
 (NCCH.dbd.CHCN), Pd[P(OPh).sub.3 ].sub.2 (NCCH.dbd.CHCN), Pd(PPh.sub.2
 Me).sub.2 (PhCH.dbd.CH.sub.2), Pd(PPh.sub.2 Me).sub.2
 (CH.sub.2.dbd.CHCOOMe), Pd(PPh.sub.2 Me).sub.2
 [CH.sub.2.dbd.CH(CH.sub.3)CN], Pd(PPh.sub.2 Me).sub.2
 [CH.sub.2.dbd.CH(CH.sub.3)COMe], Pd(1,5-C.sub.8 H.sub.12).sub.2, Pd.sub.2
 (DBA).sub.3, Pd.sub.3 (CO).sub.3 (P.sup.t Bu.sub.3).sub.3, Pd.sub.3
 (2,6-Me.sub.2 C.sub.6 H.sub.3 NC).sub.6, PdCl(CH.sub.3)(COD),
 Pd(CH.sub.3).sub.2 (PEt.sub.3).sub.2, Pd(C.sub.2 H.sub.5).sub.2 (PMe.sub.2
 Ph).sub.2, Pd(CH.sub.3).sub.2 (DPPE), Pd(CH.sub.3)(PPh.sub.3).sub.2,
 PdPh.sub.2 (PEt.sub.3).sub.2, Pd(CH.sub.2 Ph).sub.2 (DMPE), Pd(CH.sub.2
 Ph).sub.2 (PMe.sub.3).sub.2, Pd(CH.sub.3)Cl(PEt.sub.3).sub.2,
 Pd(CH.sub.3)I(PMe.sub.3).sub.2, Pd(CH.sub.3)Br(PEt.sub.3).sub.2,
 PdI(Ph)(PMe.sub.3).sub.2, Pd(COPh)Cl(PMe.sub.3).sub.2, Pd(COMe)I(PMe.sub.3
 Ph.sub.2).sub.2, Pd(COMe)Cl(PPh.sub.3).sub.2,
 Pd(COEt)Cl[P(OMe.sub.3)].sub.2, PdI(Ph)(PMe.sub.2 Ph).sub.2,
 Pd(CH.ident.CH).sub.2 (PEt.sub.3).sub.2,
 Pd(PhC.ident.C)Cl(PBu.sub.3).sub.2, Pd(Me.sub.3 CCH.sub.2).sub.2 (BPY),
 Pd(C.sub.5 H.sub.6)Ph(PEt.sub.3), Pd(.eta.-C.sub.3 H.sub.5)(C.sub.5
 Me.sub.5), [Pd(.eta.-C.sub.3 H.sub.5)(COD)]BF.sub.4, [PdCl(1,1-Me.sub.2
 --C.sub.3 H.sub.5)].sub.2, Pd.sub.2 (DBA).sub.3 CHCl.sub.3, Pd(DBA).sub.2,
 PdCl.sub.2 (MeCN).sub.2, PdCl.sub.2 (PhCN).sub.2, Li.sub.2 PdCl.sub.4,
 Na.sub.2 PdCl.sub.4, [Pd(MeCN).sub.4 ](BF.sub.4).sub.2, [Pd(.eta.-C.sub.3
 H.sub.5)Cl].sub.2, Pd(.eta.-C.sub.3 H.sub.5).sub.2 and Pd(OAc).sub.2.
 Note that DBA is dibenzylideneacetone, COD is cyclooctadiene, DPPE is
 diphenylphosphinethane, DMPE is dimethylphosphinethane, and BPY is
 dipyridyl.
 The palladium catalyst is generally used in an amount of about 0.1 to 100
 mol %, preferably about 1 to 10 mol % based on the moles of the alkyne of
 formula (1).
 Formic acid is generally used in an amount of about 1 to 1000 mol %,
 preferably about 10 to 500 mol % based on the moles of the alkyne of
 formula (1).
 To the reaction system may be added a compound selected from the group
 consisting of amines, phosphines and phosphites.
 The amines used herein are of the following general formulae (3) to (5),
 the phosphines are of the following general formula (6), and the
 phosphites are of the following general formula (7).
 ##STR3##
 In these formulae, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, and R.sub.8
 are independently hydrocarbon groups having 1 to 10 carbon atoms, for
 example, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, sec-butyl,
 t-butyl, n-amyl, i-amyl, hexyl, heptyl, octyl, nonyl, decyl, benzyl, and
 phenyl groups.
 Preferably, the amines are added in amounts of about 0.1 to 10 equivalents,
 more preferably about 0.5 to 5 equivalents per equivalent of the alkyne of
 formula (1). Also the phosphines or phosphites are preferably added in
 amounts of about 0.1 to 100 mol %, more preferably about 1 to 30 mol %
 based on the moles of the alkyne of formula (1).
 In the practice of the invention, reduction may be carried out in a
 suitable solvent, such as ether, hydrocarbon, ester, amide, and sulfoxide
 solvents. Suitable ether solvents are diethyl ether, di-n-propyl ether,
 di-i-propyl ether, tetrahydrofuran, and 1,4-dioxane. Suitable hydrocarbon
 solvents are n-pentane, i-pentane, n-hexane, benzene, toluene, and xylene.
 Suitable ester solvents are methyl acetate, ethyl acetate, n-propyl
 acetate, and i-propyl acetate. Suitable amide solvents are
 dimethylformamide and dimethylacetamide. A suitable sulfoxide solvent is
 dimethylsulfoxide. These solvents may be used alone or in admixture of two
 or more.
 The reducing temperature generally ranges from about -40.degree. C. to the
 reflux temperature of the solvent, preferably from about -10.degree. C. to
 about 60.degree. C. The reaction time is generally about 1/2 to about 12
 hours.
 By reducing the alkyne of formula (1) with formic acid in the presence of a
 palladium catalyst under the above-mentioned conditions, a cis-olefin of
 formula (2) is selectively obtained in high yields while the formation of
 trans-olefins and saturated compounds is substantially nil.
 ##STR4##
 In formula (2), R.sub.1 and R.sub.2 are as defined above.
 There has been described a method for readily preparing cis-olefins of
 formula (2) from alkynes of formula (1) under moderate conditions, the
 cis-olefins being useful intermediates for the synthesis of fine
 chemicals.