Azolylmethyloxabicyclohexane derivatives and fungicidal compositions thereof

Disclosed herein is a process for preparing a cis-azole derivative represented by the general formula (I) ##STR1## wherein R.sup.1 and R.sup.2 denote each a hydrogen atom or an alkyl group, R denotes a halogen atom, a nitro group, a cyano group, an alkyl group, a haloalkyl group or a phenyl group, A denotes a nitrogen atom or a methine group, and n stands for an integer of 1-5, which comprises reducing an azolylmethyloxabicyclohexane derivative represented by the general formula (VI) ##STR2## wherein R.sup.1, R.sup.2, R, A and n have the same meanings as defined above. A fungicidal composition comprising the azolylmethyloxabicyclohexane derivative represented by the above-mentioned general formula (VI) is also desclosed.

BACKGROUND OF THE INVENTION 
1.) Field of the Invention 
The present invention relates to a process for selectively preparing 
racemic or optically active cis-azole derivatives which are active 
ingredients of agricultural and horticultural compositions, and to 
intermediates for preparing the azole derivatives, a process for 
preparation thereof, and fungicidal compositions. 
2) Description of the Related Art 
Azole derivatives represented by the following general formula (I) have 
heretofore been known to have excellent agricultural and horticultural 
fungicidal effects and plant growth controlling effects, and a process for 
preparation thereof has been known too. 
##STR3## 
wherein R.sup.1 and R.sup.2 mean a hydrogen atom or an alkyl group, 
independently, R denotes a halogen atom, a nitro group, independently, R 
denotes a halogen atom, a nitro group, a cyano group, an alkyl group, a 
haloalkyl group or a phenyl group, A denotes a nitrogen atom or a methine 
group, and n stands for 0 or an integer of 1-5. 
Namely, EP-A-329397 discloses a process for preparation of a racemic 
mixture of cis-azole derivatives and trans-azole derivatives represented 
by the above general formula (I), and EP-A-267778 discloses a process for 
preparation of cis- or trans-azole derivatives represented by the general 
formula (I') 
##STR4## 
wherein R.sup.1' and R.sup.2' denote each a C.sub.1 -C.sub.5 alkyl group 
or a hydrogen atom, but R.sup.1' and R.sup.2' are not hydrogen atom at the 
same time, X' denotes a halogen atom, a C.sub.1 -C.sub.5 alkyl group or a 
phenyl group, n' stands for 0 or an integer of 1 or 2, and A' denotes a 
nitrogen atom or a methine group, 
which comprises using cis- or trans-oxaspiroheptane derivatives represented 
by the general formula (II') 
##STR5## 
wherein R.sup.1' and R.sup.2', X' and n have the same meanings as defined 
above. 
It has been known that the azole derivatives represented by the general 
formula (I) has a higher activity in the cis form than in the trans form. 
It is therefore desired to provide a process by which cis-form azole 
derivatives represented by the general formula (I) having a higher 
fungicidal activity are selectively prepared. In the process described in 
EP-A-329397, however, since a mixture of cis form and tans form is 
prepared, the yield of the cis form is reduced under the influence of the 
by-produced trans form and it is necessary to separate the cis-azole 
derivatives from the mixture of the cis form and trans form. Further, in 
the process described in Japanese Patent Application Laid-Open No. 
93574/1989, a process for separating the cis form is required in a stage 
of preparing oxaspiroheptane derivatives represented by the general 
formula (II') in order to obtain the cis azole derivatives. 
As be described above, the prior processes require a separation step for 
obtaining purified cis form. In the separation step, large amounts of 
column packings or solvents are used and a loss is caused when separation 
is carried out. Accordingly, it is not advantageous to combine the 
separation step in the indusutrial process for preparation of the cis 
form. 
The present invention has been achieved in the light of the above described 
circumstances in the prior arts. 
SUMMARY OF THE INVENTION 
An object of the present invention is therefore to provide a process for 
selectively preparing cis-azole derivatives represented by the general 
formula (I) which show reliable effects in a smaller amount because of 
having a high fungicidal activity, by which the amount existent in the 
environment becomes small. 
Another object of the present invention is to provide intermediates useful 
for producing the cis-azole derivatives 
A further object of the present invention is to provide processes for 
preparation of the intermediates. 
A still further object of the present invention is to provide a fungicidal 
composition. 
The present inventors have noticed the fact that the cis-azole derivatives 
represented by the general formula (I) has a higher effectiveness as 
compared with trans-azole derivatives which are geometrical isomers. As a 
result of earnest studies concerning the process for selective preparation 
in order to solve the above mentioned problems, it has found a process by 
which only cis form can be prepared, leading to completion of this 
invention. 
With respect to configuration of the azole derivatives represented by the 
general formula (I) in the present specification, cis form means those 
wherein a substituted or non-substituted phenylmethyl group is bonded to 
the cis position of the hydroxyl group attached on the cyclopentane ring, 
and trans form means those wherein said group is bonded to the trans 
position of the hydroxyl group attached on the cyclopentane ring. 
The characteristic of the present invention is as follows. 
In one aspect of this invention, there is thus provided a process for 
preparing a cis-azole derivatives represented by the general formula (I) 
##STR6## 
wherein R.sup.1 and R.sup.2 denotes each a hydrogen atom or an alkyl 
group, R denotes a halogen atom, a nitro group, a cyano group, an alkyl 
group, a haloalkyl group or a phenyl group, A denotes a nitrogen atom or a 
methine group, and n stands for 0 or an integer of 1-5, 
which comprises subjecting an oxaspiroheptane derivative represented by the 
general formula (II) to a rearrangement reaction 
##STR7## 
wherein R.sup.1, R.sup.2, R, and n have the same meanings as defined 
above, 
epoxidating the resultant cyclopentenemethanol derivative represented by 
the general formula (III) 
##STR8## 
wherein R.sup.1, R.sup.2, R, and n have the same meanings as defined 
above, 
conducting sulfonic esterification of the resultant oxabicyclohexanemetanol 
derivative represented by the general formula (IV) 
##STR9## 
wherein R.sup.1, R.sup.2, R, and n have the same meanings as defined 
above, 
sujecting to a substitution reaction the resultant oxabicyclohexanemethanol 
sulfonic acid ester derivative represented by the general formula (V) with 
a 1,2,4-triazole or imidazole 
##STR10## 
wherein R.sup.1, R.sup.2, R, and n have the same meanings as defined 
above, and Y denotes an alkyl group or a nonsubstituted or substituted 
phenyl group, 
and reducing the resultant azolylmethyloxabicyclohexane derivative 
represented by the general formula (VI) 
##STR11## 
wherein R.sup.1, R.sup.2, R, A and n have the same meanings as defined 
above. 
In another aspect of this invention, there is also provided a process for 
preparing a cis-azole derivatives represented by the above-mentioned 
general formula (I) which comprises reducing an 
azolylmethyloxabicyclohexane derivative represented by the general formula 
(VI) 
##STR12## 
wherein R.sup.1, R.sup.2, R, A and n have the same meanings as defined 
above. 
In a further aspect of this invention, there is also provided an 
azolylmethyloxabicyclohexane derivative represented by the general formula 
(VI) 
##STR13## 
wherein R.sup.1, R.sup.2, R, A and n have the same meanings as defined 
above. 
In a further aspect of this invention, there is also provided a process for 
preparing an azolylmethyloxabicyclohexane derivative represented by the 
above described general formula (VI) which comprises sujecting to a 
substitution reaction an oxabicyclohexanemethanol sulfonic acid ester 
derivative represented by the general formula (V) with a 1,2,4-triazole or 
an imidazole. 
##STR14## 
wherein R.sup.1, R.sup.2, R, and n have the same meanings as defined 
above, and Y denotes an alkyl group or a nonsubstituted or substituted 
phenyl group. 
In a further aspect of this invention, there is also provided an 
oxabicyclohexanemetanol sulfonic acid ester derivative represented by the 
general formula (V) 
##STR15## 
wherein R.sup.1, R.sup.2, R, n and Y have the same meanings as defined 
above. 
In a further aspect of this invention, there is also provided a process for 
preparing an oxabicyclohexanemetanol sulfonic acid ester derivatives 
represented by the above described formula (V) which comprises conducting 
sulfonic esterification of an oxabicyclohexanemethanol derivative 
represented by the general formula (IV) 
##STR16## 
wherein R.sup.1, R.sup.2, R, and n have the same meanings as defined 
above. 
In a further aspect of this invention, there is also provided an optically 
active oxabicyclohexanemethanol deirvative represented by the general 
formula (IV) 
##STR17## 
wherein R.sup.1, R.sup.2, R, and n have the same meanings as defined 
above. 
In a further aspect of this invention, there is also provided a process for 
preparing an oxabicyclohexanemethanol derivative represented by the above 
described general formula (IV) which comprises epoxidating a 
cyclopentenemethanol derivative represented by the general formula (III) 
##STR18## 
wherein R.sup.1, R.sup.2, R, and n have the same meanings as defined 
above. 
In a further aspect of this invention, there is also provided a 
cyclopentenemethanol deirvative represented by the general formula (III) 
##STR19## 
wherein R.sup.1, R.sup.2, R, and n have the same meanings as defined 
above. 
In a further aspect of this invention, there is also provided a process for 
preparing a cyclopentenemethanol derivative represented by the above 
described general formula (III) which comprises subjecting an 
oxaspiroheptane derivative represented by the general formula (II) to a 
rearrangement reaction 
##STR20## 
wherein R.sup.1, R.sup.2, R, and n have the same meanings as defined 
above. 
In a still further aspect of this invention, there is also provided a 
fungicidal composition comprising as an effective ingredient an 
azolylmethyloxabicyclo-hexane derivative represented by the following 
formula (VI) together with an inert carrier or adjuvants; 
##STR21## 
wherein R.sup.1, R.sup.2, R, A and n have the same meanings as defined 
above.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS 
The process for preparing the cis-azole derivative represented by the above 
described general formula (I) is shown as the following reaction formulas. 
##STR22## 
In the following, the present invention will be illustrated in greater 
detail. 
The cis-azole derivative represented by the general formula (I) and 
intermediates thereof of the present invention will be first explained. In 
the azole derivatives represented by the above-mentioned general formula 
(I), R.sup.1 and R.sup.2 mean a hydrogen atom or an alkyl group, and 
preferably a hydrogen atom or an C.sub.1 -C.sub.3 alkyl group. R means a 
halogen atom, a nitro group, a cyano group, an alkyl group, a haloalkyl 
group or a phenyl group, and preferably a chlorine atom bonded to the 
4-position. 
n is 0 or an integer or from 1 to 5 and preferably 0-1. A means a nitrogen 
atom or a methine group. 
In the intermediates represented by the above-mentioned general formulas 
(II), (III), (IV), (V) and (VI), the substituents R.sup.1, R.sup.2 and R, 
n and A have the same meanings as those in the azole derivative 
represented by the general formula (I), and preferred embodiments are also 
the same. In the oxabicyclohexanemethanol sulfonic acid ester derivative 
represented by the general formula (V), Y means an alkyl group or a 
non-substituted or substituted phenyl group, and preferably a C.sub.1 
-C.sub.4 alkyl group, a phenyl group or a p-methylphenyl group. The 
process of the present invention will be explained in the following in 
accordance with the above-mentioned reaction formulas 
Rearrangement Reaction 
The oxaspiroheptane derivative represented by the general formula (II) can 
be changed into the cyclopentene methanol derivatives represented by the 
general formula (III) by a rearrangement reaction in a presence of an acid 
catalyst in an organic solvent at a reaction temperature in a range of 
from 0.degree. C. to 40.degree. C. for a reaction time in a range of from 
1 hour to 5 hours. As the organic solvent, ethers can be used. 
Particularly preferred examples include dioxane, tetrahydrofuran (THF) and 
diethyl ether. As the acid catalyst, it is possible to use, for example, 
sulfuric acid, hydrochloric acid, AlCl.sub.3, BF.sub.3 and the like. 
Epoxidation Reaction 
The oxabicyclohexanemethanol derivative represented by the general formula 
(IV) is obtained by epoxidation of the cyclopentenemethanol derivative 
represented by the general formula (III) using an inorganic or organic 
peroxide in an organic solvent at a reaction temperature in a range of 
from -78.degree. C. to 25.degree. C. for a reaction time in a range of 
from 1 hour to 5 hours. 
Examples of the organic solvents include alkyl halides such as 
dichloromethane or dichloroethane etc., aromatic hydrocarbons such as 
toluene etc., aliphatic hydrocarbons such as hexane, heptane or isooctane 
etc. As the peroxide, it is possible to use metachloroperbenzoic acid, 
cumene hydroperoxide and tertiary butyl hydroperoxide and the like. 
Furthermore, when the epoxidation is carried out using an asymmetric 
reagent, it is possible to obtain an optically active 
oxabicyclohexanemethanol derivative represented by the general formula 
(IV). For example, an optically active (+)-oxabicyclohexanemethanol 
derivative represented by the general formula (IV) can be obtained by 
carrying out the epoxidation reaction using as an asymmetric reagent a 
combination of (2R,3R)-(+)-diethyl tartarate and titanium 
tetraisopropoxide. Likewise, an optically active 
(-)-oxabicyclohexanemethanol derivative represented by the general formula 
(IV) can be obtained by carrying out the epoxidation reaction using as an 
asymmetric reagent a combination of (2S,3S)-(-)-diethyl tartarate and 
titanium tetraisopropoxide. 
In such cases, the above-mentioned combination of the reagents can be used 
together with Molecular seives. 
Using the thus resulted optically active oxabicyclohexanemethanol 
derivative represented by the general fromula (IV), the optically active 
cis-azole derivative represented by the general formula (I) can be 
prepared by the sulfonic esterification, the azolation reaction and the 
reduction reaction in accordance with the above-mentioned chemical 
formulas as follows. 
Sulfonic Esterification Reaction 
The oxabicyclohexanemethanol sulfonic acid ester derivatives can be 
obtained by subjecting the oxabicyclohexanemethanol derivative represented 
by the general formula (V) to sulfonic esterification in an organic 
solvent using benzenesulfonyl chloride, substituted benzenesulfonyl 
chloride or alkanesulfonyl chloride and a hydrochloric acid binding agent 
at a reaction temperature in a range of from 0.degree. C. to 40.degree. C. 
for a reaction time in a range of from 0.5 hours to 5 hours. 
A preferred example of the substituted benzenesulfonyl chloride is 
p-methylbenzenesulfonyl chloride, and a preferred example of the 
alkanesulfonyl chloride is methanesulfonyl chloride. 
Examples of the hydrochloric acid binding agent include trimethylamine, 
triethylamine, N,N-dimethylaniline and N,N-diethylaniline, etc., but the 
present invention is not limited to using them. 
Examples of the organic solvent include aromatic hydrocarbons such as 
benzene, toluene and xylene, etc., aliphatic hydrocarbons such as hexane, 
heptane and isooctane etc., alkyl halides such as dichlorometane, 
chloroform, carbon tetrachloride and dichloroethane, etc., and ethers such 
as dioxane, THF and diethyl ether etc. 
Azolation Reaction 
The azolylmethyloxabicyclohexane derivative represented by the general 
formula (VI) can be obtained by reacting the oxabicyclohexanemethanol 
sulfonic acid ester represented by the general formula (V) with a 
1,2,4-triazole or an imidazole, and a base compound in an organic solvent 
at a reaction temperature in a range of from 0.degree. C. to 100 .degree. 
C. for a reaction period in a 
range of from 1 hour to 5 hours to substitute a YSO.sub.2 O group with an 
azole ring. 
As the base compound, sodium hydride may be preferably used. 
Preferred example Of the Organic solvent used in this reaction step include 
aromatic hydrocarbons such as benzene, toluene and xylene etc., aliphatic 
hydrocarbons such as hexane, heptane and isooctane, etc., alkyl halides 
such as dichloromethane, chloroform, carbon tetrachloride and 
dichloroethane etc., ethers such as dioxane, THF and diethyl ether, etc., 
alcohols such as methyl alcohol, ethyl alcohol, etc., and polar aprotic 
solvents such as acetonitrile, acetone, DMF, DMSO and N-methylpyrrolidone 
etc. 
Reduction Reaction 
The cis-azole derivative represented by the general formula (I) can be 
obtained by reducing the azolylmethyloxabicyclohexane derivatives in an 
ether using a metal hydride or a combination of metal hydride and Lewis 
acid at a reaction temperature in a range of from 0.degree. C. to 
100.degree. C. for a reaction period in a range of from 0.5 hours to 5 
hours. 
Examples of the ethers used in this reaction step include diethyl ether, 
THF and diglym. As the metal hydride, lithium aluminium hydride may be 
preferably used. An example of the Lewis acid used together with the metal 
hydride is AlCl.sub.3. 
According to the process of the present invention, cis-azole derivatives 
represented by the above mentioned general formula (I) which show reliable 
effects in a smaller amount because of having a higher activity, by which 
the amount existent in the environment becomes small, can be selectively 
prepared. 
As a result of studies by the present inventors about the use, it has been 
found that the above-mentioned azolylmethyloxabicyclohexane represented by 
the general formula (VI) can be used as fungicides in addition to as the 
intermediate. 
In the following, use of the azolylmethyloxabicyclohexane derivative 
represented by the formula 
##STR23## 
wherein R.sup.1, R.sup.2, R, A and n have the same meanings as defined 
above. 
When the azolylmethyloxabicyclohexane derivative represented by the formula 
(VI) (referred to as "compound of this invention", hereinafter) is used as 
a fungicidal composition, it is generally used in the form of dust, 
wettable powder, granules, emulsion and the like together with carriers or 
other adjuvants. In such a case, the preparations are prepared so as to 
contain one or more of the compound of this invention in an amount of 
0.1%-95% by weight , preferably, 0.5%-90% by weight, and more preferably 
2%-70% by weight. 
Examples of carriers, diluents and surfactants used as the adjuvants for 
preparations include the following. 
Examples of solid carriers include talc, kaolin, bentonite, diatomaceous 
earth, white carbon and clay, etc. 
Examples of liquid carriers (diluents) include water, xylene, toluene, 
chlorobenzene, cyclohexane, cyclohexanone, dimethylsulfoxide, 
dimethylformamide and alcohol, etc. 
Examples of the surfactants include polyoxyethylene alkylaryl ether and 
polyoxyethylene sorbitan monolaurylate etc., as emulsifiers; lignin 
sulfonates, dibutylnaphthalenesulfonates, etc., as dispersing agents; and 
alkylsulfonates and alkylphenylsulfonates, etc., as wetting agents. 
The above preparations are classified into those which can be used 
directly, and those which are used after diluting so as to have a suitable 
concentration with a diluent such as water, etc. 
The concentration of the present compounds in case of using after diluting 
is preferred to be in a range of 0.001%-1.0%. 
Further, the application dosage of the compound of this invention is in a 
range of 20 g-5000 g and preferably 50 g -1000 g per 1 ha of agricultural 
and horticultural land such as farm, paddy field, fruit garden, hothouse, 
etc. 
It is of course possible to increase and decrease the concentration and the 
application dosage beyond the above-mentioned ranges, because they depend 
upon the form of preparations, method of application, place to be used, 
target crops, etc. 
Furthermore, the compound of this invention can be used in combination with 
other effective ingredients, such as other fungicides, insectcides, 
miticides, herbicides, etc. 
EXAMPLES 
Preparation examples, formulation examples and test examples are described 
in the following, by which the present invention is illustrated in detail. 
Preparation examples 6 and 10 and Preparation examples 14, 15, 16, 17 and 
18 in the exmples relates to preparation of optically active epoxyalcohol 
derivatives. 
Preparation examples 14-18 disclose the process in which a reagent for 
asymmetric epoxidation is used together with Molecular Sieves. 
Further, the following abbreviations and chemical formulas are used in 
Preparation examples 6, 10, 14, 15, 16, 17 and 18. 
______________________________________ 
(2R,3R)-(+)-diethyl tartarate 
(+)-DET 
(2S,3S)-(-)-diethyl tartarate 
(-)-DET 
Titanium tetraisopropoxide 
Ti(O i-Pr).sub.4 
tert-Butylhydroperoxide 
TBHP 
______________________________________ 
Enantiomer excess ratio (% ee) described in Preparation examples 6, 9, 10, 
13, 14, 15, 16, 17 and 18 was determined by high performance liquid 
chromatography equipped with an optically active column (CHIRALCEL OK, 
produced by Daicel Co.) 
PREATION EXAMPLE 1 
Cyclopentene methanol derivative [Formula (III): R.sup.1 .dbd.R.sup.2 
.dbd.CH.sub.3 , (R).sub.n .dbd.4-Cl] 
Preparation of 
2-[(4-chlorophenyl)methyl]-5,5-dimethyl-1-cyclopentene-1-methanol: 
To 20 g (0.08 mol) of 
7-[(4-chlorophenyl)methyl]-4,4-dimethyl-1-oxaspiro[2.4]heptane 
[Formula(II): R.sup.1 .dbd.R.sup.2 .dbd.CH.sub.3 ,(R).sub.n .dbd.4-Cl] was 
added 150 ml of dioxane, and 5 ml of 10% sulfuric acid was added thereto 
with stirring under room temperature. The mixture was then stirred at room 
temperature for 2 hours. 
The reaction solution was poured into a saturated aqueous solution of 
sodium hydrogen carbonate, followed by extracting with ethyl acetate. The 
resultant organic layer was washed with saturated aqueous saline solution. 
After dried with anhydrous sodium sulfate, the organic layer was 
concentrated under reduced pressure to yield 17.22 g of a yellowish oily 
product. 
The resultant product was purified by chromatography on a column of silica 
gel to obtain 13.16 g (0.052 mmol) of 
2-[(4-chlorophenyl)methyl]-5,5-dimethyl-1-cyclopentene-1-methanol [Formula 
(III): R.sup.1 .dbd.R.sup.2 .dbd.CH.sub.3 ,(R).sub.n .dbd.4-Cl] as a 
colorless transparent oily product. 
Yield: 65.8%. 
Colorless transparent oil 
.sup.1 H NMR(CDCl.sub.3); .delta. 
1.10(s,6H),1.40-1.83(m,2H),1.97-2.33(m,2H),3.43(s,2H), 
4.22(s,2H),7.03(d,2H,J=8 Hz),7.23(d,2H,J=8 Hz) IR(neat, .nu.max); 3350, 
2950, 2850, 1490, 1408, 1360, 1090, 1012, 990, 840 cm.sup.-1 
PREATION EXAMPLE 2 
Oxabicyclohexanemethanol derivative [Formula (IV): R.sup.1 .dbd.R.sup.2 
.dbd.CH.sub.3 ,(R).sub.n .dbd.4-Cl] 
Preparation of 
5-[(4-chlorophenyl)methyl]-2,2-dimethyl-6-oxabicyclo[3.1.0]hexane-1-methan 
ol: 
10.06 g (0.04 mol) of 
2-[(4-chlorophenyl)methyl]5,5-dimethyl-1-cyclopentene-1-methanol [Formula 
(III): R.sup.1 .dbd.R.sup.2 .dbd.CH.sub.3 ,(R).sub.n .dbd.4-Cl] were 
dissolved in 100 ml of chloroform, followed by adding 8.08 g (0.048 mol) 
of metachloroperbenzoic acid with stirring under cooling with ice. 
The mixture was then stirred at room temperature for 1 hour. To the 
reaction solution was added 7.4 g (0.1 mol) of calcium hydroxide, and the 
formed precipitate was removed by filtration. The chloroform layer was 
washed with a saturated aqueous saline solution. 
After the chloroform layer was dried with anhydrous sodium sulfate, it was 
concentrated under reduced pressure to yield 11.86 g of light-yellowish 
oily product. 
The resultant product was purified by chromatography on a column of silica 
gel to obtain 10.21 g (0.038 mmol) of 
5-[(4-chlorophenyl)methyl]-2,2-dimethyl-6-oxabicyclo[3.1.0]hexane-1-methan 
ol [Formula (IV): R.sup.1 .dbd.R.sup.2 .dbd.CH.sub.3 ,(R).sub.n .dbd.4-Cl] 
Yield: 95% 
White crystal, m.p.: 37.degree.-39.degree. C. 
.sup.1 H NMR(CDCl.sub.3); .delta. 
0.9(s,3H),1.10(s,3H),1.0-1.83(m,4H),2.43(brs,1H,OH), 3.0(s,2H), 
3.8(d,1H,J=12 Hz),4.1(d,1H,J=12 Hz),7.13(m,4H) 
IR(KBr, .nu.max); 3400, 2950, 2850, 1482, 1360, 1082, 1010, 836, 780 
cm.sup.-1 
PREATION EXAMPLE 3 
Oxabicyclohexanemethanol sulfonic acid ester derivative [Formula (V): 
R.sup.1 .dbd.R.sup.2 .dbd.CH.sub.3 ,(R).sub.n .dbd.4-Cl,Y.dbd.CH.sub.3 ] 
Preparation of 
5-[(4-chlorophenyl)methyl]-2,2-dimethyl-6-oxabicyclo[3.1.0]hexane-1-methan 
ol methanesulfonic acid ester: 
1.33 g (5 mmol) of 
5-[(4-chlorophenyl)methyl]-2,2-dimethyl-6-oxabicyclo[3.1.0]hexane-1-methan 
ol were dissolved in 10 ml of dichloromethane, followed by adding thereto 
0.63 g (5.5 mmol) of methanesulfonyl chloride and 0.55 g (5.65 mmol) of 
triethylamine with stirring under cooling with ice. 
The mixture was then stirred under cooling with ice for 1 hour. After 
conclusion of the reaction was confirmed by TLC, the reaction solution was 
poured into water and extracted with dichlorometane. The resultant organic 
layer was washed with aqueous solution of saturated sodium hydrogen 
carbonate and aqueous saline solution. 
After dried with anhydrous sodium sulfate, the organic layer was 
concentrated under reduced pressure to yield 1.86 g of a light-yellowish 
oily product. 
The resultant product was purified by chromatography on a column of silica 
gel to obtain 1.57 g (4.55 mmol) of 
5-[(4-chlorophenyl)methyl-2,2-dimethyl-6-oxabicyclo[3.1.0]hexane-1-methano 
l methanesulfonic acid ester [Formula (V): R.sup.1 .dbd.R.sup.2 
.dbd.CH.sub.3 ,(R).sub.n .dbd.4-Cl, Y.dbd.CH.sub.3 ] 
Yield: 91% 
White crystal, m.p. 78.5.degree.-79.0.degree. C. 
.sup.1 H NMR (CDCl.sub.3); .delta. 
0.98(s,3H),1.10(s,3H),0.83-2.0(m,4H),2.93(s,2H),3.07 (s,3H),4.37(d,1H,J=12 
Hz),4.70(d,1H,J=12 Hz),7.07(d,2H,J=8 Hz), 7.25(d,2H,J=8 Hz) 
IR(KBr, .nu.max); 3000, 2940, 2850, 1480, 1350, 1162, 1080, 944, 810 
cm.sup.-1 
PREATION EXAMPLE 4 
Azolylmethyloxabicyclohexane derivative [Formula(VI): R.sup.1 .dbd.R.sup.2 
.dbd.CH.sub.3 , (R).sub.n .dbd.4-Cl, A.dbd.N] 
Preparation of 
5-[(4-chlorophenyl)methyl]-2,2-dimethyl-1-(1H-1,2,4-triazol-1-ylmethyl)-6- 
oxabicyclo[3.1.0]hexane (Compound No. VI-1): 
To 0.42 g (10.5 mmol) of oily 60% sodium hydride washed with hexane was 
added 15 ml of dimethylformamide (DMF) and stirred at room temperature. 
0.73 g (10.56 mmol) of 1,2,4-triazole were then added thereto. After the 
mixture was stirred for 30 minutes, 5 ml of a DMF solution containing 3.05 
g (8.8 mmol) of 
5-[(4-chlorophenyl)methyl]-2,2-dimethyl-6-oxabicyclo[3.1.0]hexane-1-methan 
ol methanesulfonic acid ester [Formula (V): R.sup.1 .dbd.R.sup.2 
.dbd.CH.sub.3 ,(R).sub.n .dbd.4-Cl, Y.dbd.CH.sub.3 ]was added dropwise 
thereto. 
Thereafter, the mixture was stirred at room temperature for 4 hours and at 
40.degree. C. for 4 hours, and the reaction solution was poured into ice 
water, followed by extracting with ethyl acetate. The resultant organic 
layer was washed with 1N-hydrochloric acid, saturated aqueous solution of 
sodium hydrogen carbonate and saturated aqueous saline solution. After 
dried with anhydrous sodium sulfate, the organic layer was concentrated 
under reduced pressure to yield 2.88 g of a light-yellowish oily product. 
The resultant oily product was purified by chromatography on a column of 
silica gel, followed by crystallizing with hexane to obtain 2.71 g (8.5 
mmol) of 
5-[(4-chlorophenyl)methyl]-2,2-dimethyl-1-(1H-1,2,4-triazol-1-ylmethyl)-6- 
oxabicyclo[3.1.0]hexane as white crystal [Formula (VI): R.sup.1 
.dbd.R.sup.2 .dbd.CH.sub.3 ,(R).sub.n .dbd.4-Cl, A.dbd.N]. 
Yield: 96.6% 
White crystal, m.p. 101.5.degree.-102.5.degree. C. 
.sup.1 H NMR(CDCl.sub.3); .delta.0.73(s,3H),1.0(s,3H), 
0.83-2.17(m,4H),2.93(s,2H), 3.07(s,3H),4.33(d,1H,J=16 Hz),4.87(d,1H,J=16 
Hz), 7.17(d,2H, J=8 Hz),7.33(d,2H,J=8 Hz),7.93(s,1H),8.33(s,1H) 
IR(KBr, .nu.max); 3100, 2940, 2850, 1480, 1420, 1260, 1200, 1130, 1084, 
1020, 950, 840, 720, 660 cm.sup.-1 
With the same procedure as preparation example 4, except using an imidazole 
in stead of a 1,2,4-triazole, 
5-[(4-chlorophenyl)methyl]-2,2-dimethyl-1-(1H-imidazol-1-ylmethyl)-6-oxabi 
cyclo[3.1.0]hexane (Compound No. VI-2) can be prepared. 
PREATION EXAMPLE 5 
Cis-azole derivative [Formula (I): R.sup.1 .dbd.R.sup.2 .dbd.CH.sub.3 
,(R).sub.n .dbd.4-Cl, A.dbd.N] 
Preparation of 
cis-5-[(4-chlorophenyl)methyl]-2,2-dimethyl-1-(1H-1,2,4-triazol-1-ylmethyl 
)cyclopentanol: 
To 210 mg (1.57 mmol) of aluminium chloride was added 5 ml of 
dimethoxyethane (DME) and stirred at room temperature. To the mixture was 
added 178.7 mg (4.71 mmol) of lithium aluminium hydride and stirred for 30 
minutes with elevating the temperature to 50.degree.C. 500 mg (1.57 mmol) 
of 
5-[(4-chlorophenyl)methyl-2,2-dimethyl-1-(1H-1,2,4-triazol-1-ylmethyl)-6-o 
xabicyclo[3.1.0]hexane [Formula (VI): R.sup.1 .dbd.R.sup.2 .dbd.CH.sub.3 
,(R).sub.n .dbd.4-Cl, A.dbd.N] was added to the mixture and stirred at 
50.degree. C. for 1 hour. 
The reaction solution was poured into 50 ml of ice water and extracted with 
ethyl acetate. The separated organic layer was washed with saturated 
aqueous saline solution. After dried with anhydrous sodium sulfate, the 
organic layer was concentrated under reduced pressure to yield 580 mg of a 
yellowish oily product. 
The resultant oily product was isolated and purified by chromatography on a 
column of silica gel to obtain 280.3 mg (0.88 mmol) of 
cis-5-[(4-chlorophenyl)methyl]-2,2-dimethyl-1-(1H-1,2,4-triazol-1-ylmethyl 
)cyclopentanol [Formula (I): R.sup.1 .dbd.R.sup.2 .dbd.CH.sub.3 ,(R).sub.n 
.dbd.4-Cl, A.dbd.N]. 
Yield: 55.4% 
White crystal, m.p. 113.degree.-114.degree. C. 
.sup.1 H NMR(CDCl.sub.3); .delta. 
0.60(s,3H),1.00(s,3H),1.07-1.90(m,5H),2.33(bs,2H), 
3.53(s,1H),4.13(s,2H),7.06(d,2H,J=8 Hz),7.25(d,2H,J=8 Hz), 
8.02(s,1H),8.25(s,1H) 
IR(KBr, .nu.max); 3250, 2940, 2850, 1480, 1380, 1262, 1200, 1124, 1080, 
1002, 840, 800, 720, 670 cm.sup.-1 
With the same procedure as preparation example 5, except using the compound 
(VI-2) instead of the compound (VI-1), 
cis-5-[(4-chlorophenyl)methyl-2,2-dimethyl-1-(1H-imidazol-1-ylmethyl)cyclo 
pentanol can be prepared. 
PREATION EXAMPLE 6 
Optically active (+)-oxabicyclohexamethanol derivative [Formula (IV): 
R.sup.1 .dbd.R.sup.2 .dbd.CH.sub.3 ,(R).sub.n .dbd.4-Cl] 
Preparation of 
(+)-5-[(4-chlorophenyl)methyl]-2,2-dimethyl-6-oxabicyclo[3.1.0]hexane-1-me 
thanol: 
1.42 g (5 mmol) of Ti(O i-Pr)were dissolved in 15 ml of dichloromethane and 
stirred at -20.degree. C. (dry ice/carbon tetrachloride) under a nitrogen 
stream. To the mixture was added 1.03 g (5 mmol) of (+)-DET and 1.25 g (5 
mmol) of 2-[(4-chlorophenyl)methyl]-5,5-dimethyl-1-cyclopentene-1-methanol 
[Formula (III): R.sup.1 .dbd.R.sup.2 .dbd.CH.sub.3 ,(R).sub.n .dbd.4-Cl]. 
After stirred at -20.degree. C. for 5 minutes, 6 ml (10 mmol) of a toluene 
solution of anhydrous TBHP (1.67 mol/1) was added dropwise thereto. The 
reaction concluded at -20.degree. C. for 1 hour. After stirred at room 
temperature for 60 minutes, 6 ml of 30% sodium hydroxide-saturated aqueous 
solution of sodium chloride were added to the resulted mixture and stirred 
for further 30 minutes After allowed to stand for a while by adding 1 ml 
of methanol, the formed organic layer was separated. The aqueous layer was 
extracted with dichloromethane. The separated organic layers were 
combined, dried with anhydrous sodium sulfate, and concentrated under 
reduced pressure to yield 1.35 g of a light-yellowish oily product. 
The resultant oily product was purified by chromatography on a column of 
silica gel to obtain 1.16 g (4.35 mmol) of 
(+)-5-[(4-chlorophenyl)methyl]-2,2-dimethyl-6-oxabicyclo[3.1.0]hexane-1-me 
thanol [(Formula (I): R.sup.1 .dbd.R.sup.2 .dbd.CH.sub.3 ,(R).sub.n 
.dbd.4-Cl]. 
Yield: 87% 
Colorless transparent oil 
[.alpha.].sub.D.sup.20 +25.4.degree. (c=1.26, EtOH):91% ee (by HPLC) 
.sup.1 H NMR(CDCl.sub.3); .delta. 0.9(s,3H),1.10(s,3H),1.0-1.83(m,4H), 
2.43(s,1H), 3.0(s,2H), 3.8(d,1H,J=12 Hz), 4.1(d,1H,J=12 Hz), 7.13(m,4H) 
IR(neat, .nu. max); 3400, 2950, 2850, 1482, 1360, 1082, 1010, 836, 780 
cm.sup.-1 
PREATION EXAMPLE 7 
Optically active (+)-oxabicyclohexanemethanol sulfonic acid ester 
[Formula(V): R.sup.1 .dbd.R.sup.2 .dbd.CH.sub.3 , (R).sub.n .dbd.4-Cl, 
Y.dbd.CH.sub.3 ] 
Preparation of 
(+)-5-[(4-chlorophenyl)methyl]-2,2-dimethyl-6-oxabicyclo[3.1.0]hexane-1-me 
thanol methanesulfonic acid ester: 
0.84 g (3.15 mmol) of (+)-5-[(4-chlorophenyl) 
methyl-2,2-dimethyl-6-oxabicyclo [3.1.0]hexane-1-methanol [Formula (IV): 
R.sup.1 .dbd.R.sup.2 .dbd.CH.sub.3 , (R).sub.n .dbd.4-Cl] were dissolved 
in 10 ml of dichloromethane, followed by adding 0.41 g (3.5 mmol) of 
methanesulfonyl chloride and 0.3 g (3.5 mmol) of triethylamine were added 
thereto with stirring under cooling with ice. 
The mixture was then stirred under cooling with ice for 1 hour. After 
conclusion of the reaction was confirmed by TLC, the reaction solution was 
poured into water and extracted with dichlorometane. The resultant organic 
layer was washed with aqueous solution of saturated sodium hydrogen 
carbonate and aqueous common salt liquor. After dried with anhydrous 
sodium sulfate, the organic layer was concentrated under reduced pressure 
to yield 1.22 g of a light-yellowish oily product. 
The resultant oily product was purified by chromatography on a column of 
silica gel to obtain 1.02 g (2.96 mmol) of 
(+)-5-[(4-chlorophenyl)methyl]-2,2-dimethyl-6-oxabicyclo[3.1.0]hexane-1-me 
thanol methanesulfonic acid ester [Formula (V): R.sup.1 .dbd.R.sup.2 
.dbd.CH.sub.3 , (R).sub.n .dbd.4-Cl, Y.dbd.CH.sub.3 ] 
Yield: 94% 
Colorless transparent oil 
[.alpha.].sub.D.sup.20 +24.degree. (c=1.08, EtOH) 
.sup.1 H NMR(CDCl.sub.3); .delta. 0.98(s,3H),1.10(s,3H),0.83-2.0 
(m,4H),2.93(s,2H),3.07(s,3H),4.37(d,1H,J=12 Hz),4.70(d,1H,J=12 Hz), 
7.07(d,2H,J=8 Hz),7.25(d,2H,J=8 Hz) 
IR(neat, .nu. max); 3000, 2940, 2850, 1480, 1350, 1162, 1080, 944, 810 
cm.sup.-1 
PREATION EXAMPLE 8 
Optically active (-)-azolylmethyloxabicyclohexane derivative [Formula (VI): 
R.sup.1 .dbd.R.sup.2 .dbd.CH.sub.3 ,(R).sub.n .dbd.4-Cl, A.dbd.N] 
Preparation of 
(-)-5-[(4-chlorophenyl)methyl]-2,2-dimethyl-(1H-1,2,4-triazol-1-ylmethyl)- 
6-oxabicyclo[3.1.0]hexane (Compound No. VI - 3): 
To 0.12 g (3.0 mmol) of oily 60% sodium hydride washed with hexane was 
added 5 ml of DMF and stirred at room temperature. 0.21 g (3.0 mmol) of 
1,2,4-triazole were then added thereto. After the mixture was stirred for 
10 minutes, 2 ml of a DMF solution containing 0.86 g (2.5 mmol) of 
(-)-5-[(4-chlorophenyl)methyl]-2,2-dimethyl-6-oxabicyclo[3.1.0]hexane-1-me 
thanol methanesulfonic acid ester [Formula (V): R.sup.1 .dbd.R.sup.2 
.dbd.CH.sub.3 ,(R).sub.n .dbd.4-Cl, Y.dbd.CH.sub.3 ] was added dropwise 
thereto. 
Thereafter, the mixture was stirred at room temperature for 1 hour and at 
40.degree. C. for 4 hours, and the reaction solution was poured into ice 
water, followed by extracting with ethyl acetate. The resultant organic 
layer was washed with 1N-hydrochloric acid, saturated aqueous solution of 
sodium hydrogen carbonate and saturated aqueous salinel solution. After 
dried with anhydrous sodium sulfate, the organic layer was concentrated 
under reduced pressure to yield 0.82 g of a light-yellowish oily product. 
The resultant oily product was purified by chromatography on a column of 
silica gel, followed by crystallizing with hexane to obtain 0.77 g (2.42 
mmol) of 
(-)-5-[(4-chlorophenyl)methyl]-2,2-dimethyl-1-(1H-1,2,4-triazol-1-ylmethyl 
)-6-oxabicyclo[3.1.0]hexane as white crystal [Formula (VI): R.sup.1 
.dbd.R.sup.2 .dbd.CH.sub.3 ,(R).sub.n .dbd.4-Cl, A.dbd.N]. 
Yield: 96.8% 
[.alpha.].sub.D.sup.20 -11.degree. (c=1.0, EtOH) 
White crystal, m.p. 97.degree.-99.degree. C. 
.sup.1 H NMR(CDCl.sub.3), .delta. 0.73(s,3H),1.0(s,3H),0.83-2.17 
(m,4H),2.93(s,2H),3.07(s,3H),4.33(d,1H,J=16 Hz),4.87(d,1H,J=16 Hz), 
7.17(d,2H,J=8 Hz),7.33(d,2H,J=8 Hz),7.93(s,1H), 8.33(s,1H) 
IR(KBr, .nu. max); 3100, 2940, 2850, 1480, 1420, 1260, 1200, 1130, 1084, 
1020, 950, 840, 720, 660 cm.sup.-1 
With the same procedure as preparation example 8, except using an imidazole 
in stead of a 1,2,4-triazole, 
(-)-5-[(4-chlorophenyl)methyl]-2,2-dimethyl-(1H-imidazol-1-ylmethyl)-6-oxa 
bicyclo[3.1.0]hexane (Compound No. VI - 4) can be prepared. 
PREATION EXAMPLE 9 
Optically active cis-azole derivative [Formula (I): R.sup.1 .dbd.R.sup.2 
.dbd.CH.sub.3 , (R).sub.n .dbd.4-Cl, A.dbd.N] 
Preparation of 
(-)-cis-5-[(4-chlorophenyl)methyl]-2,2-dimethyl-1-(1H,-1,2,4-triazol-1-ylm 
ethyl)cyclopentanol: 
To 212.4 mg (1.59 mmol) of aluminium chloride was added 5 ml of 
dimethoxyethane (DME) and stirred at room temperature. To the mixtutre was 
added 181.6 mg (4.78 mmol) of lithium aluminium hydride and stirred for 30 
minutes with elevating the temperature to 50.degree. C. 503.7 mg(1.58 
mmol) of (-)-5-[(4-chlorophenyl)methyl]-2,2- 
dimethyl-1-(1H,1,2,4-triazol-1-ylmethyl)-6-oxabicyclo[3.1.0]hexane, 
[Formula (VI): R.sup.1 .dbd.R.sup.2 .dbd.CH.sub.3 ,(R).sub.n .dbd.4-Cl, 
A.dbd.N] were added to the mixture and stirred at 50.degree. C. for 1 
hour. 
The reaction solution was poured into 50 ml of ice water and extracted with 
ethyl acetate. The separated organic layer was washed with saturated 
aqueous saline solution. After dried with anhydrous sodium sulfate, the 
organic layer was concentrated under reduced pressure to yield 550 mg of a 
yellowish oily product. 
The resultant oily product was isolated and purified by chromatography on a 
column of silica gel to obtain 267.4 mg (0.836 mmol) of 
(-)-cis-5-[(4-chlorophenyl)methyl]-2,2-dimethyl-1-(1H-1,2,4-triazol-1-ylme 
thyl)cyclopentanol [Formula (I): R.sup.1 .dbd.R.sup.2 .dbd.CH.sub.3 
,(R).sub.n .dbd.4-Cl, A.dbd.N]. 
Yield: 52.9% 
White crystal, m.p. 137.degree.-138.degree. C. (recrystallization from 
n-hexane/ethyl acetate=10/1) 
[.alpha.].sub.D.sup.20 -23.7.degree. (c=10.0, EtOH), 99% ee (by HPLC) 
.sup.1 H NMR(CDCl.sub.3); .delta. 
0.60(s,3H),1.00(s,3H),1.07-1.90(m,5H),2.33(bs,2H),3.53 
(s,1H),4.13(s,2H),7.06(d,2H,J=8 Hz),7.25(d,2H,J=8 Hz),8.02 
(s,1H),8.25(s,1H) 
IR(KBr, .nu. max); 3250, 2940, 2850, 1480, 1380, 1262, 1200, 1124, 1080, 
1002, 840, 800, 720, 670 cm.sup.-1 
With the same procedure as preparation example 9, except using the compound 
(VI - 4) instead of the compound (VI - 3), 
(-)-cis-5-[(4-chlorophenyl)methyl]-2,2-dimethyl-1-(1H-imidazol-1-ylmethyl) 
cyclopentanol can be prepared. 
PREATION EXAMPLE 10 
Optically active (-)-oxabicyclohexamethanol derivative [Formula 
(IV):R.sup.1 .dbd.R.sup.2 .dbd.CH.sub.3 ,(R).sub.n .dbd.4-Cl] 
Preparation of 
(-)-5-[(4-chlorophenyl)methyl]-2,2-dimethyl-6-oxabicyclo[3.1.0]hexane-1-me 
thanol: 
1.42 g (5 mmol) of Ti(O i-Pr)were dissolved in 15 ml of dichloromethane and 
stirred at -20.degree. (dry ice/carbon tetrachloride) under a nitrogen 
stream. To the mixture was added 1.03 g (5 mmol) of (-)-DET and 1.25 g (5 
mmol) of 2-[(4-chlorophenyl)methyl]-5,5-dimethyl-1-cyclopentene-1-methanol 
[Formula (III): R.sup.1 .dbd.R.sup.2 .dbd.CH.sub.3 ,(R).sub.n .dbd.4-CL]. 
After stirred at -20.degree. C. for 5 minutes, 6 ml (10 mmol) of a toluene 
solution of anhydrous TBHP (1.67 mol/1) was added dropwise thereto. The 
reaction concluded at -20.degree. C. for 1 hour. After stirred at room 
temperature for 60 minutes, 6 ml of 30% sodium hydroxide-saturated aqueous 
solution of common salt were added to the resulted mixture and stirred for 
further 30 minutes. After allowed to stand for a while by adding 1 ml of 
methanol, the formed organic layer was separated. The aqueous layer was 
extracted with dichloromethane. The separated organic layers were 
combined, dried with anhydrous sodium sulfate, and concentrated under 
reduced pressure to yield 1.40 g of a light-yellowish oily product. 
The resultant oily product was purified by chromatography on a column of 
silica gel to obtain 1.16 g (4.35 mmol) of 
(+)-5-[(4-chlorophenyl)methyl]-2,2-dimethyl-6-oxabicyclo[3.1.0]hexane-1-me 
thanol [Formula (I): R.sup.1 .dbd.R.sup.2 .dbd.CH.sub.3 ,(R).sub.n 
.dbd.4-Cl]. 
Yield: 81% 
Colorless transparent oil 
[.alpha.].sub.D.sup.20 -25.0.degree. (c=1.64, EtOH),:98.8% ee (by HPLC) 
.sup.1 H NMR (CDCl.sub.3); .delta. 0.9(s,3H),1.10(s,3H),1.0-1.83(m,4H), 
2.43(s,1H), 3.0(s,2H), 3.8(d,1H,J=12 Hz), 4.1(d,1H,J=12 Hz), 7.13(m,4H) 
IR(neat, .nu. max); 3400, 2950, 2850, 1482, 1360, 1082, 1010, 836, 780 
cm.sup.-1 
PREATION EXAMPLE 11 
Optically active (-)-oxabicyclohexanemethanol sulfonic acid ester [Formula 
(V): R.sup.1 .dbd.R.sup.2 .dbd.CH.sub.3 ,(R).sub.n .dbd.4-Cl, 
Y.dbd.CH.sub.3 ] 
Preparation of 
(-)-5-[(4-chlorophenyl)methyl]-2,2-dimethyl-6-oxabicyclo[3.1.0]hexane-1-me 
thanol methanesulfonic acid ester: 0.93 g (3.48 mmol) of 
(-)-5-[(4-chlorophenyl)methyl]-2,2-dimethyl-6-oxabicyclo[3.1.0]hexane-1-me 
thanol [Formula (IV): R.sup.1 .dbd.R.sup.2 .dbd.CH.sub.3 ,(R).sub.n 
.dbd.4-Cl] were dissolved in 10 ml of dichloromethane, followed by adding 
0.44 g (3.8 mmol) of methanesulfonyl chloride and 0.38 g (3.8 mmol) of 
triethylamine were added thereto with stirring under cooling with ice. 
The mixture was then stirred under cooling with ice for 1 hour. After 
conclusion of the reaction was confirmed by TLC, the reaction solution was 
poured into water and extracted with dichlorometane. The resultant organic 
layer was washed with aqueous solution of saturated sodium hydrogen 
carbonate and aqueous common salt liquor. After dried with anhydrous 
sodium sulfate, the organic layer was concentrated under reduced pressure 
to yield 1.27 g of a light-yellowish oily product. 
The resultant oily product was purified by chromatography on a column of 
silica gel to obtain 1.14 g (3.3 mmol) of 
(-)-5-[(4-chlorophenyl)methyl]-2,2-dimethyl-6-oxabicyclo[3.1.0]hexane-1-me 
thanol methanesulfonic acid ester [Formula (V): R.sup.1 .dbd.R.sup.2 
.dbd.CH.sub.3 ,(R).sub.n .dbd.4-Cl, Y.dbd.CH.sub.3 ] 
Yield: 95% 
Colorless transparent oil 
[.alpha.].sub.D.sup.20 -24.5.degree. (c=1.2, EtOH) 
.sup.1 H NMR(CDCl.sub.3 ); .delta. 
0.98(s,3H),1.10(s,3H),0.83-2.0(m,4H),2.93(s,2H),3.07 (s,3H),4.37(d,1H,J=12 
Hz),4.70(d,1H,J=12 Hz),7.07(d,2H, J=8 Hz),7.25(d,2H,J=8 Hz) 
IR(neat,.nu. max); 3000, 2940, 2850, 1480, 1350, 1162, 1080, 944, 810 
cm.sup.-1 
PREATION EXAMPLE 12 
Optically active (+)-azolylmethyloxabicyclohexane derivative [Formula (VI): 
R.sup.1 .dbd.R.sup.2 .dbd.CH.sub.3 ,(R).sub.n .dbd.4-Cl, A.dbd.N] 
Preparation of 
(+)-5-[(4-chlorophenyl)methyl]-2,2-dimethyl-(1H-1,2,4-triazol-1-ylmethyl)- 
6-oxabicyclo-[3.1.0]hexane (Compound No. VI - 5): 
To 0.14 g (3.5 mmol) of oily 60% sodium hydride washed with hexane was 
added 5 ml of dimethylformamide (DMF) and stirred at room temperature. 
0.25 g (3.6 mmol) of 1,2,4-triazole were then added thereto. After the 
mixture was stirred for 10 minutes, 2 ml of a DMF solution containing 1.03 
g (3.0 mmol) of 
(-)-5-[(4-chlorophenyl)methyl]-2,2-dimethyl-6-oxabicyclo[3.1.0]-hexane-1-m 
ethanol methanesulfonic acid ester [Formula (V): R.sup.1 .dbd.R.sup.2 
.dbd.CH.sub.3 ,(R).sub.n .dbd.4-Cl, Y.dbd.CH.sub.3 ] was added dropwise 
thereto. 
Thereafter, the mixture was stirred at room temperature for 1 hour and at 
40 .degree. C. for 4 hours, and the reaction solution was poured into ice 
water, followed by extracting with ethyl acetate. The resultant organic 
layer was washed with 1N-hydrochloric acid, saturated aqueous solution of 
sodium hydrogen carbonate and saturated aqueous saline solution. After 
dried with anhydrous sodium sulfate, the organic layer was concentrated 
under reduced pressure to yield 1.05 g of a light-yellowish oily product. 
The resultant oily product was purified by chromatography on a column of 
silica gel, followed by crystallizing with hexane to obtain 0.89 g (2.8 
mmol) of 
(+)-5-[(4-chlorophenyl)methyl]-2,2-dimethyl-1-(1H-1,2,4-triazol-1-ylmethyl 
)-6-oxabicyclo[3.1.0]hexane as white crystal [Formula (VI): R.sup.1 
.dbd.R.sup.2 .dbd.CH.sub.3 ,(R).sub.n =4-Cl, A.dbd.N]. 
Yield: 93.3% 
[.alpha.].sub.D.sup.20 +12.degree. (c=1.0, EtOH) 
White crystal, m.p. 97.degree.-99.degree. C. 
.sup.1 H NMR(CDCl.sub.3); .delta. 
0.73(s,3H),1.0(s,3H),0.83-2.17(m,4H),2.93(s,2H),3.07 (s,3H),4.33(d,1H,J=16 
Hz),4.87(d,1H,J=16 Hz),7.17(d,2H, J=8 Hz),7.33(d,2H,J=8 
Hz),7.93(s,1H),8.33(s,1H) 
IR(KBr, .nu. max); 3100, 2940, 2850, 1480, 1420, 1260, 1200, 1130, 1084, 
1020, 950, 840, 720, 660 cm.sup.-1 
With the same procedure as preparation example 12, except using an 
imidazole in stead of a 1,2,4-triazole, triazole, 
(+)-5-[(4-chlorophenyl)methyl]-2,2-dimethyl- 
(1H-imidazol-1-ylmethyl)-6-oxabicyclo[3.1.0]hexane (Compound No. VI - 6) 
can be prepared. 
PREATION EXAMPLE 13 
Optically active cis-azole derivative [Formula (I):R.sup.1 .dbd.R.sup.2 
.dbd.CH.sub.3 ,(R).sub.n .dbd.4-Cl, A.dbd.N] 
Preparation of 
(+)-cis-5-[(4-chlorophenyl)methyl]-2,2-dimethyl-1-(1H-1,2,4-triazol-1-ylme 
thyl)cyclopentanol 
To 0.27 g (2.0 mmol) of aluminium chloride was added 5 ml of 
dimethoxyethane (DME) and stirred at room temperature. To the mixtutre was 
added 0.23 g (6.1 mmol) of lithium aluminium hydride and stirred for 30 
minutes with elevating the temperature to 50.degree. C. 0.64 g (2.0 mmol) 
of 
(+)-5-[(4-chlorophenyl)methyl]-2,2-dimethyl-1-(1H-1,2,4-triazol-1-ylmethyl 
)-6-oxabicyclo[3.1.0]hexane [Formula (VI): R.sup.1 .dbd.R.sup.2 
.dbd.CH.sub.3 ,(R).sub.n .dbd.4-Cl, A.dbd.N] were added to the mixture and 
stirred at 50.degree. C. for 1 hour. 
The reaction solution was poured into 50 ml of ice water and extracted with 
ethyl acetate. The separated organic layer was washed with saturated 
aqueous saline solution. After dried with anhydrous sodium sulfate, the 
organic layer was concentrated under reduced pressure to yield 0.72 g of a 
yellowish oily product. 
The resultant oily product was isolated and purified by chromatography on a 
column of silica gel to obtain 0.36 g (1.13 mmol) of 
(+)-cis-5-[(4-chlorophenyl)methyl]-2,2-dimethyl-1-(1H-1,2,4-triazol-1ylmet 
hyl)cyclopentanol [Formula (I): R.sup.1 .dbd.R.sup.2 .dbd.CH.sub.3 
,(R).sub.n .dbd.4-Cl, A.dbd.N]. 
Yield: 56.5% 
White crystal, m.p. 137.degree.-138.degree. C. (recrystallization from 
n-hexane/ethyl acetate=10/1) 
[.alpha.].sub.D.sup.20 +23.7.degree. (c=10.0, EtOH):99% ee (by HPLC) 
.sup.1 H NMR(CDCl.sub.3); .delta. 0.60(s,3H),1.00(s,3H), 
1.07-1.90(m,5H),2.33(bs,2H), 3.53(s,1H),4.13(s,2H),7.06(d,2H,J=8 
Hz),7.25(d,2H,J=8 Hz), 8.02(s,1H),8.25(s,1H) 
IR(KBr, .nu. max); 3250, 2940, 2850, 1480, 1380, 1262, 1200, 1124, 1080, 
1002, 840, 800, 720, 670 cm.sup.-1 
With the same procedure as preparation example 13, except using the 
compound (VI - 6) instead of the compound (VI - 5), 
(+)-cis-5-[(4-chlorophenyl)methyl]-2,2-dimethyl-1-(1H-imidazol-1-ylmethyl) 
cyclopentanol can be prepared. 
PREATION EXAMPLE 14 
Optically active (+)-oxabicyclohexanemethanol derivative [Formula(IV): 
R.sup.1 .dbd.R.sup.2 .dbd.CH.sub.3 ,(R).sub.n .dbd.4-Cl] 
Preparation of 
(+)-5-[(4-chlorophenyl)methyl]-2,2-dimethyl-6-oxabicyclo[3.1.0]hexane 
methanol: 
15 ml of dichloromethane were placed in a 3-neck flask (50 ml) and stirred 
at -40.degree. C. (dry ice/acetone) under a nitrogen stream. After 200 mg 
of Molecular Sieve 4A (powdered, activated molecular sieves; Aldrich Co.) 
with stirring, 28.4 mg (0.1 mmol; 5 mol %) of Ti(O i-Pr).sub.4, 31 mg 
(0.15 mmol; 7.5 mol %) of (+)-DET and 500 mg (2.0 mmol) of 
2-[(4-chlorophenyl)methyl]-5,5-dimethyl-1-cyclopentene-1-methanol [Formula 
(III): R.sup.1 .dbd.R.sup.2 .dbd.CH.sub.3 ,(R).sub.n .dbd.4-Cl] were added 
thereto and the resultant mixture was stirred at -40.degree. C. for 10 
minutes. Thereafter 2.4 ml (4.0 mmol) of a toluene solution of anhydrous 
TBHP (1.67 mol/1) were added dropwise so as not to elevate the temperature 
to -40.degree. C. 
After allowed to react at -40.degree. C. for 5 hours, 20 ml of water were 
added thereto, followed by stirring for 30 minutes. Thereafter, 5 ml of 
30% sodium hydroxide saturated aqueous common salt liquor were added to 
the mixture, followed by stirring further 30 minutes. After allowed to 
stand for a while by adding 1 ml of methanol, the formed organic layer was 
separated. The aqueous layer was extracted with dichloromethane. The 
separated organic layers were combined, dried with anhydrous sodium 
sulfate, and concentrated under reduced pressure to yield 0.63 g of a 
colorless transparent oily product. 
The resultant product was purified by chromatography on a column of silica 
gel to obtain 0.46 g (1.7 mmol) of 
(+)-5-[(4-chlorophenyl)methyl]-2,2-dimethyl-6-oxabicyclo[3.1.0]hexane-1-me 
thanol [Formula (IV): R.sup.1 .dbd.R.sup.2 .dbd.CH.sub.3 ,(R).sub.n 
.dbd.4-Cl]. 
Yield: 81% 
Colorless transparent oil 
[.alpha.].sub.D.sup.20 +18.degree. (c=1.5, EtOH):64% ee (by HPLC) 
.sup.1 H NMR (CDCl.sub.3 ); .delta. 
0.9(s,3H),1.10(s,3H),1.0.about.1.83(m,4H), 2.43(s,1H), 3.0(s,2H), 
3.8(d,1H,J=12 Hz), 4.1(d,1H,J=12 Hz),7.13(m,4H) 
IR(neat, .nu. max); 3400, 2950, 2850, 1482, 1360, 1082, 1010, 836, 780 
cm.sup.-1 
PREATION EXAMPLE 15 
Optically active (+)-oxabicyclohexanemethanol derivative [Formula (IV): 
R.sup.1 .dbd.R.sup.2 .dbd.CH.sub.3 ,(R).sub.n .dbd.4-Cl] 
Preparation of 
(+)-5-[(4-chlorophenyl)methyl]-2,2-dimethyl-6-oxabicyclo[3.1.0]hexane-1-me 
thanol: 
5 ml of dichloromethane were placed in a 3-neck flask (50 ml) and stirred 
at -40.degree. C. (dry ice/acetonitril) under a nitrogen stream. After 200 
mg of Molecular Sieve 4A (powdered, activated molecular sieves; Aldrich 
Co.) with stirring, 28.4 mg (0.1 mmol; 10 mol %) of Ti(O i-Pr ).sub.4, 32 
mg (0.15 mmol; 15 mol %) of (+)-DET and 250 mg (1.0 mmol) of 
2-[(4-chlorophenyl)methyl]-5,5-dimethyl-1-cyclopentene-1-methanol [Formula 
(III): R.sup.1 .dbd.R.sup.2 .dbd.CH.sub.3 ,(R).sub.n .dbd.4-Cl] were added 
thereto and the resultant mixture was stirred at -40.degree. C. for 10 
minutes. Thereafter 1.2 ml (2.0 mmol) of a toluene solution of anhydrous 
TBHP (1.67 mol/1) were added dropwise so as not to elevate the temperature 
to -40.degree. C. 
After allowed to react at -40.degree. C. for 5 hours, 20 ml of water were 
added thereto, followed by stirring for 30 minutes. Thereafter, 5 ml of 
30% sodium hydroxide-saturated aqueous saline solution were added to the 
mixture, followed by stirring further 30 minutes. After allowed to stand 
for a while with adding 1 ml of methanol, the formed organic layer was 
separated. The aqueous layer was extracted with dichloromethane. The 
separated organic layers were combined, dried with anhydrous sodium 
sulfate, and concentrated under reduced pressure to yield 0.28 g of a 
colorless transparent oily product. 
The resultant product was purified by chromatography on a column of silica 
gel to obtain 0.22 g (1.7 mmol) of 
(+)-5-[(4-chlorophenyl)methyl]-2,2-dimethyl-6-oxabicyclo[3.1.0]hexane-1-me 
thanol [Formula (IV): R.sup.1 .dbd.R.sup.2 .dbd.CH.sub.3 ,(R).sub.n 
.dbd.4-Cl]. 
Yield: 82% 
Colorless transparent oil 
[.alpha.].sub.D.sup.20 +23.2.degree. (c=1.5, EtOH):80% ee (by HPLC) 
PREATION EXAMPLE 16 
Optically active (+)-oxabicyclohexanemethanol derivative [Formula (IV): 
R.sup.1 .dbd.R.sup.2 .dbd.CH.sub.3 ,(R).sub.n .dbd.4-Cl] 
Preparation of 
(+)-5-[(4-chlorophenyl)methyl]-2,2-dimethyl-6-oxabicyclo[3.1.0]hexane-1-me 
thanol: 
5 ml of dichloromethane were placed in a 3-neck flask (50 ml) and stirred 
at -20.degree. C. (dry ice/carbon tetrachloride) under a nitrogen stream. 
After 200 mg of Molecular Sieve 4A (powdered, activated molecular sieves; 
Aldrich Co.) with stirring, 28.4 mg (0.1 mmol; 10 mol %) of Ti(O 
i-Pr).sub.4, 33.7 mg (0.16 mmol;16 mol %) of (+)-DET and 250 mg (1.0 mmol) 
of 2-[(4-chlorophenyl)-methyl]-5,5-dimethyl-1-cyclopentene-1-methanol 
[Formula (III): R.sup.1 .dbd.R.sup.2 .dbd.CH.sub.3 ,(R).sub.n .dbd.4-Cl] 
were added thereto and the resultant mixture Was stirred at -20.degree. C. 
for 10 minutes. Thereafter 1.2 ml (2.0 mmol) of a toluene solution of 
anhydrous TBHP (1.67 mol/1) were added dropwise so as not to elevate the 
temperature to -20.degree. C. 
After allowed to react at -20.degree. C. for 2 hours, 20 ml of water were 
added thereto, followed by stirring for 30 minutes. Thereafter, 5 ml of 
30% sodium hydroxide-saturated aqueous saline solution were added to the 
mixture, followed by stirring further 30 minutes. After allowed to stand 
for a while with adding 1 ml of methanol, the formed organic layer was 
separated. The aqueous layer was extracted with dichloromethane. The 
separated organic layers were combined, dried with anhydrous sodium 
sulfate, and concentrated under reduced pressure to yield 0.32 g of a 
colorless transparent oily product. 
The resultant product was purified by chromatography on a column of silica 
gel to obtain 206.4 mg (0.77 mmol) of 
(+)-5-[(4-chlorophenyl)methyl]-2,2-dimethyl-6-oxabicyclo[3.1.0]hexane-1-me 
thanol [Formula (IV): R.sup.1 .dbd.R.sup.2 .dbd.CH.sub.3 ,(R).sub.n 
.dbd.4-Cl]. 
Yield: 77% 
Colorless transparent oil 
[.alpha.].sub.D.sup.20 +12.6.degree. (c=1.2, EtOH): 48% ee (by HPLC) 
PREATION EXAMPLE 17 
Optically active (+)-oxabicyclohexanemethanol derivative [Formula (IV): 
R.sup.1 .dbd.R.sup.2 .dbd.CH.sub.3 ,(R).sub.n .dbd.4-Cl] 
Preparation of 
(+)-5-[(4-chlorophenyl)methyl]-2,2-dimethyl-6-oxabicyclo[3.1.0]hexane-1-me 
thanol: 
5 ml of dichloromethane were placed in a 3-neck flask (50 ml) and stirred 
at 0.degree. C. under a nitrogen stream. After 200 mg of Molecular Sieve 
4A (powdered, activated molecular sieves; Aldrich Co.) with stirring, 28.4 
mg (0.1 mmol;10 mol %) of Ti(O i-Pr).sub.4, 32 mg (0.15 mmol;15mol %) of 
(+)-DET and 250 mg (1.0 mmol) of 
2-[(4-chlorophenyl)methyl]-5,5-dimethyl-1-cyclopentene-1-methanol [Formula 
(III): R.sup.1 .dbd.R.sup.2 .dbd.CH.sub.3 ,(R).sub.n .dbd.4-Cl] were added 
thereto and the resultant mixture was stirred at 0.degree. C. for 10 
minutes. Thereafter 1.2 ml (2.0 mmol) of a toluene solution of anhydrous 
TBHP (1.67mol/1) were added dropwise so as not to elevate the temperature 
to 0.degree. C. 
The reaction was completed in 30 minutes. After 20 ml of water were added 
and stirred at room temperature for 30 minutes, 5 ml of 30% sodium 
hydroxide-saturated aqueous saline solution were added to the mixture, 
followed by stirring further 30 minutes. After allowed to stand for a 
while with adding 1 ml of methanol, the resulted organic layer was 
separated. The aqueous layer was extracted with dichloromethane. The 
separated organic layers were combined, dried with anhydrous sodium 
sulfate, and concentrated under reduced pressure to yield 0.28 g of a 
colorless transparent oily product. 
The resultant product was purified by chromatography on a column of silica 
gel to obtain 196.4 mg (0.74 mmol) of 
(+)-5-[(4-chlorophenyl)methyl]-2,2-dimethyl-6-oxabicyclo[3.1.0]hexane-1-me 
thanol [Formula (IV): R.sup.1 .dbd.R.sup.2 .dbd.CH.sub.3 ,(R).sub.n 
.dbd.4-Cl]. 
Yield: 74% 
Colorless transparent oil 
[.alpha.].sub.D.sup.20 +7.degree. (c=1.5, EtOH): 20% ee (by HPLC) 
PREATION EXAMPLE 18 
Optically active (+)-oxabicyclohexanemethanol derivative [Formula (IV): 
R.sup.1 .dbd.R.sup.2 .dbd.CH.sub.3 ,(R).sub.n .dbd.4-Cl] 
Preparation of 
(+)-5-[(4-chlorophenyl)methyl]-2,2-dimethyl-6-oxabicyclo[3.1.0]hexane-1-me 
thanol: 
5 ml of dichloromethane were placed in a 3-neck flask (50 ml) and stirred 
at -40.degree. C. (dry ice/acetonitril) under a nitrogen stream. After 200 
mg of Molecular Sieve 4A (powdered, activated molecular sieves; Aldrich 
Co.) with stirring, 29.8 mg (0.105 mmol;7 mol %) of Ti(O i-Pr ).sub.4 , 33 
mg (0.15 mmol; 10 mol %) of (+)-DET and 376 mg (1.5 mmol) of 
2-[(4-chlorophenyl)methyl]-5,5-dimethyl-1-cyclopentene-1-methanol [Formula 
(III): R.sup.1 .dbd.R.sup.2 .dbd.CH.sub.3 ,(R).sub.n .dbd.4-Cl] were added 
thereto and the resultant mixture was stirred at -40.degree. C. for 10 
minutes. Thereafter 1.2 ml (2.0 mmol) of a toluene solution of anhydrous 
TBHP (1.67 mol/1) were added dropwise so as not to elevate the temperature 
to -40.degree. C. 
After allowed to react at -40.degree. for 5 hours, 20 ml of water were 
added thereto, followed by stirring for 30 minutes. Thereafter, 5 ml of 
30% sodium hydroxide-saturated aqueous saline solution were added to the 
mixture, followed by stirring further 30 minutes. After allowed to stand 
for a while with adding 1 ml of methanol, the resulted organic layer was 
separated. The aqueous layer was extracted with dichloromethane. The 
separated organic layers were combined, dried with anhydrous sodium 
sulfate, and concentrated under reduced pressure to yield 0.45 g of a 
colorless transparent oily product. 
The resultant product was purified by chromatography on a column of silica 
gel to obtain 330.6 mg (1.24 mmol) of 
(+)-5-[(4-chlorophenyl)methyl]-2,2-dimethyl-6-oxabicyclo[3.1.0]hexane-1-me 
thanol [Formula (IV): R.sup.1 .dbd.R.sup.2 .dbd.CH.sub.3 ,(R).sub.n 
.dbd.4-Cl]. 
Yield: 82.7% 
Colorless transparent oil 
[.alpha.].sub.D.sup.20 +23.5.degree. (c=1.5, EtOH):72% ee (by HPLC) 
FORMULATION EXAMPLE 1 
Dust 
______________________________________ 
Parts by weight 
______________________________________ 
Compound (VI) 3 
Clay 40 
Talc 57 
______________________________________ 
The above-mentioned ingredients were mixed to prepare a dust. 
FORMULATION EXAMPLE 2 
Wettable Powder 
______________________________________ 
Parts by weight 
______________________________________ 
Compound (VI) 50 
Ligninsulfonate 5 
Alkylsulfonate 3 
Diatomaceous earth 
42 
______________________________________ 
The above-mentioned ingredients were mixed to prepare a wettable powder. 
FORMULATION EXAMPLE 3 
Granule 
______________________________________ 
Part by weight 
______________________________________ 
Compound (VI) 5 
Bentonite 43 
Clay 45 
Ligninsulfonate 
7 
______________________________________ 
The above-mentioned ingredients were mixed and kneaded with adding water 
thereto. The mixture was gnalurated by means of an extrusion granulating 
machine, followed by drying to obtain granules. 
FORMULATION EXAMPLE 4 
Emulsion 
______________________________________ 
Parts by weight 
______________________________________ 
Compound (VI) 20 
Polyoxyethylene alkyl aryl ether 
10 
Polyoxyethylnene sorbitan monolaurate 
3 
Xylene 67 
______________________________________ 
The above mentioned ingredients were mixed and dissolved to obtain an 
emulsion. 
TEST EXAMPLE 
Antimicrobial test against various microorganisms: 
This example shows results of the following antimicrobial test of optically 
active (-)-azolylmethyloxabicyclohexane derivative (formula (VI): R.sup.1 
.dbd.R.sup.2 .dbd.CH.sub.3 , (R).sub.n .dbd.4-Cl, A.dbd.N) prepared in 
Preparation Example 8 against various kinds of plant disease 
microorganisms. 
Method 
The compound of this invention was dissolved in dimethylsulfoxide in a 
suitable concentration. 0.6 ml of the solution was well mixed with 60 ml 
of a PAS culture medium at about 60.degree. C. in a 100 ml conical flask, 
and the resultant mixture was poured into Petri dishes and was caused to 
coagulate, by which plate culture media containing the compound of this 
invention were obtained. 
On the other hand, plate culture media on which test microorganisms were 
previously cultured were punched by a cork borer so as to have a diameter 
of 4 mm, followed by inoculating on the above-mentioned plate culture 
medium. After inoculation was carried out, they were incubated for 1-3 
days at a preferable temperature for each microorganism, and growth of 
microorganisms was obserbed by measuring the diameter of the colony. 
Hyphae elongation inhibitory rates were determined respectively in 
accordance with the below-described equation. 
EQU R=100 (dc-dt)/dc 
wherein 
R=Hyphae elongation inhibitory rate (%) 
dc=Diameter of colony on the non-treated plate culture medium 
dt=Diameter of colony on the plate culture medium containing the tested 
compound 
Test results were ranked in five stages by the following ranking system. 
The results are shown in Table 1. 
5 . . . at least 90%-100% 
4 . . . at least 70% but lower than 90% 
3 . . . at least 40% but lower than 70% 
2 . . . at least 20% but lower than 40% 
1 . . . lower than 20% 
TABLE 1 
______________________________________ 
Biocidal activity 
(concentration: 
Test fungus 100 .mu.g/ml) 
______________________________________ 
Pyricularia oryzae 5 
Cochliobolus miyabeanus 
5 
Gibberella fujikuroi 
5 
Helminthosporium sigmoideum 
5 
Rhizoctonia solani 3 
Botrytis cinerea 5 
Sclerotinia sclerotiorum 
5 
Fusarium oxysporum f.sp. niveum 
5 
Fusarium oxysporum f.sp. 
5 
cucumerinum 
Fusarium oxysporum f.sp. raphani 
5 
Colletotrichum lagenarium 
4 
Cercospola beticola 5 
Cercospore kikuchii 4 
Monilinia fructicola 
5 
Alternaria kikuchiana 
4 
Alternaria mali 5 
Glomerella cingulata 
5 
______________________________________