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Highly enantio- and diastereoselective reduction of sulfur-functionalized cyclic ketones with baker's yeast
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T&&&on Letters, Vo1.32. No.3. pi 399400.1991 Primed in Great Britain
HIGHLY ENANTIO- AND DIASTEREOSELECTIVE
REDUCTION
OF SIJLFUR-FUNCTIONALIZED
CYCLIC KETONES WlTH BAKER’S YEAST Tamotsu FUJISAWA,* Department
Kengo YAMANAKA,
Bingidimi I. MOBELB, and Makoto SHIMIZU
of Chemistry for Materials, Mie University,
Tsu, Mie 5 14, Japan
Summary : Bakers’ yeast reduction of 2-phenylthiocyclopentanone, 2-phenylthiocyclohexanone, and 2phenylthio-2-cyclopentenone affords the corresponding (lS,2R)-2-phenylthiocycloalkanols in optically pure form and excellent diastereomeric excess. Cyclic P-phenylthiocycloalkanols
possess
potentially
versatile
properties
as building
blocks due to the
characteristic features of sulfur atom1 and will constitute a valuable class of synthons for the specific construction of natural products involving forskolin.2 2-arylthiocycloalkanols cyclopentene
oxide
heterogeneous
However, hitherto no method has been available for the preparation
in optically pure form. The only reported examples involve asymmetric and cyclohexene
oxide with thiols catalyzed
chiral Lewis acid catalysts,
of
ring opening of
by zinc and manganese
d-tartrates
in which the optical purity dose not exceed 85%.3
as
Bakers’ yeast
(Saccharomyces cerevisiae) has been used as a convenient
reducing reagent to produce chiral secondary alcohols
of high enantiomeric
ketones. 4 We wish to report herein the bakers’ yeast
excess from various functionalized
(la, lb)and alkenones (4, !$’ to (lS,2R)-2-phenylthio-cycloalkanols
reduction of 2-phenylthiocycloalkanones in optically pure form.6
OH
0
n= 1, la n = 2, lb
n= 1,2a n = 2,2b
In a representative I. L. Lesaffre) vigorously ethanol
solution
femjenting
c)
?
n = 1, 3a n = 2,3b
reduction, to 50 ml of distilled water were added at rt (23 “C) 5 g of dry bakers’ yeast (S,
and 6 g of saccharose suspension
and the incubation
experiments,
OH
(Wake Ltd) and the resultant
slurry was stirred for 30 min.
was then added 1 mmol of the appropriate
was carried
out at t-t until complete
consumption
pressed bakers’ yeast (Oriental Yeast Co., Ltd) was substituted
(KH2POq.Na2HP04,
substrate
dissolved
of the ketone.
in 5 ml of
In alternative
for dry yeast and phosphate
ph 7.0) was used instead of water. After the usual work-up,
To this
buffer
the alcohols were
isolated by preparative TLC. The optical purity of the alcohols was determined either by capillary GC analysis or by examination
of 1% NMR spectra of the corresponding
3a, 2b, and 3b was determined determined
by derivatization
by examination
to (S)-(-)-2-cyclopentenyl
(-)-2-cyclohexenyl3,5-dinitrobenzoate
(R)-MTPA esters.
The relative stereochemistry
of their tH NMR spectra7 benzoate
and the absolute
([a] ;?,3-176.6’ (c 0.06, CHC13)),a and/or (S)-
([a] 5 -15 l-lo (c 0.32, CHC13))9 followed by comparison
signs with those of authentic samples and/or the literature values. 399
of 2a,
configuration of the rotation
400
Table 1. Bakers’ Yeast Reduction of 2-Phenylthiocycloalkanones Entry
1
la
2
la
3
4
w
4
4
dry
Time
Yielda)
(days)
%
buffer
5
47
buffer
6
64
MlZdiUm
Ketone Yeast
drl
m
m
cis : frum
2:3 1w:
and 2-Phenylthio-Z-cycloalkenones %eeb) cis
0
>YY
86: 14
>YY
%eeC)
W$“d)
[aJgad)
cis
tram
bans
+76.2(c 0.76) >95
-
+70.2(c 2.0)
+1.2(c 0.34)
H20
6
47
100:
0
>99
+89.O(c 1.4)
-
buffa
5
60
loo:
0
>99
+75.5(c 0.94)
-
5
4
buffex
9
64
69: 31
>95
+82.O(c 0.95)
+1.9(c 0.86)
6
lb
W
H20
4
81
88: 12
>99
92@
>95
+25.4(c 1.12)
+50.6(c 0.34)
7
lb
dry
buffer
2
59
90: 10
>99
>95
+27.8(c 0.9)
+64.5(c 0.2)
8
5
dry
H20
20
0
-
a) Isolated yield. b) Determinedby capillary GC analysis of the corresponding (R)-MTPA esters. c) Determined by analysis of lgF NhER specma of the corresponding (R)-h4TPA esters. d) All values determined in CHCl3
From the examination different selectivides.
of the above table, it is apparent that dry yeast and pressed yeast show appreciably
An important feature to be pointed out is that, using the same strain of dry yeast (S. I. L.
Lesaffre),
cr-phenylthiocyclohexanone
solution
is used instead of distilled
phenylthiocycloalkanones phenylthiocycloalkanones ketones
suggests
lb is reduced faster but in lower yield (entry 7) when a phosphate buffer water. Preferential
production
that the latter are preferentially
prior to yeast reduction.
of cis (lS,2R) isomerized
alcohols
In the case of the yeast reduction
In conclusion,
ring
of an unsaturation
In this case, specific reduction of olefin followed by carbonyl reduction,
to cis (lS,2R) alcohol would account for the increase in yield. In contrast to the cyclopentenone the cyclohexenone
2-
to (5)-Z-
of five membered
la and 4 where dry yeast and buffer are used (entries 1 and 4), the introduction
increased the yield of alcohol.
from racemic
via enolization
leading
4, incubation of
derivative 5 for 20 days lead to the recovery of this substrate. this work provides
from readily available
ketosulfides,
the first example
of synthesis
and contrary to previous
found to be actually a good substrate for bakers’ yeast reduction.
of optically pure 2-arythiolcycloalkanols
observation, 6 a-phenylthiocyclohexanone
was
These chiral synthons can be used as building
blocks in natural products synthesis. References 1. For a review, B. M. Trost, Chem. Rev., 78, 363 (1978). 2. E. J. Corey, P. D. S. Jardine, and T. Mohri, Tetrahedron Left., 29, 6409 (1988). 3. H. Yamashita and T. Mukaiyama, Chem. Lett., 1643 (1985); H. Yamashita, Bull. Chem. Sot. Jpn., 61, 1213 119881. 4. See for example, S. Servi, Synrhesis, 1 (1990); T. Sato and T. Fujisawa, Biocatulysis, 3, 1 (1990). 5. The starting materials are readily available via the standard procedures. See, B. M. Trost, T. N. Salzmann, and K. Hiroi, J. Am. Chem. Sot., 98, 4887 (1976); H. J. Monteiro, J. Org. Chem., 42, 2324 (1977); H. J. Monteiro and A. L. Gemal, Synthesis, 437 (1975). 6. In the reduction of 2-phenylthiocyclohexanone with a mutant of bakers’ yeast, Crumbie et al., reported that the reduced alcohol was formed in only 2% yield. See, R. L. Crumbie, B. S. Deol, J. E. Nemorin, and D. D. Ridley, Aust. .I. Chem., 31, 1965 (1978). 7. For the stereochemistry of 2a and 3a, see, T. Cohen, R. T. Ritfer, D. Quellette, J. Am. Chem. Sot., 104, 7142 (1982). NMR spectra of 2b and 3b follow; 2b: (CDCl3) 6 1.20-2.13 (m. 8H), 2.53 (bs, lH), 3.173.50 (m, lH), 3.60-3.97 (m, lH), 7.07-7.63 (m, SH); 3b: (CC14) S 0.93-1.90 (m, 6H), 1.90-2.30 (m, 2H), 2.40-2.93 (m, ZH), 2.98-3.47 (m, lH), 7.10-7.67 (m, 5H). For the stereochemistry of 3b, see ref. 3. 8. For the preparation of (S)-(-)-2-cyclopenten-l-01, see, T. Sato, Y. Gotoh, Y. Wakabayashi, and T. Fujisawa, Tetrahedron Lett., 24, 4123 (1983). 9. B. D. Denney, R. Napier, and A. Cammarata, J. Org. Chem., 30, 3151 (1965). (Received in Japan 22 October 1990)
T&&&on Letters, Vo1.32. No.3. pi 399400.1991 Primed in Great Britain
HIGHLY ENANTIO- AND DIASTEREOSELECTIVE
REDUCTION
OF SIJLFUR-FUNCTIONALIZED
CYCLIC KETONES WlTH BAKER’S YEAST Tamotsu FUJISAWA,* Department
Kengo YAMANAKA,
Bingidimi I. MOBELB, and Makoto SHIMIZU
of Chemistry for Materials, Mie University,
Tsu, Mie 5 14, Japan
Summary : Bakers’ yeast reduction of 2-phenylthiocyclopentanone, 2-phenylthiocyclohexanone, and 2phenylthio-2-cyclopentenone affords the corresponding (lS,2R)-2-phenylthiocycloalkanols in optically pure form and excellent diastereomeric excess. Cyclic P-phenylthiocycloalkanols
possess
potentially
versatile
properties
as building
blocks due to the
characteristic features of sulfur atom1 and will constitute a valuable class of synthons for the specific construction of natural products involving forskolin.2 2-arylthiocycloalkanols cyclopentene
oxide
heterogeneous
However, hitherto no method has been available for the preparation
in optically pure form. The only reported examples involve asymmetric and cyclohexene
oxide with thiols catalyzed
chiral Lewis acid catalysts,
of
ring opening of
by zinc and manganese
d-tartrates
in which the optical purity dose not exceed 85%.3
as
Bakers’ yeast
(Saccharomyces cerevisiae) has been used as a convenient
reducing reagent to produce chiral secondary alcohols
of high enantiomeric
ketones. 4 We wish to report herein the bakers’ yeast
excess from various functionalized
(la, lb)and alkenones (4, !$’ to (lS,2R)-2-phenylthio-cycloalkanols
reduction of 2-phenylthiocycloalkanones in optically pure form.6
OH
0
n= 1, la n = 2, lb
n= 1,2a n = 2,2b
In a representative I. L. Lesaffre) vigorously ethanol
solution
femjenting
c)
?
n = 1, 3a n = 2,3b
reduction, to 50 ml of distilled water were added at rt (23 “C) 5 g of dry bakers’ yeast (S,
and 6 g of saccharose suspension
and the incubation
experiments,
OH
(Wake Ltd) and the resultant
slurry was stirred for 30 min.
was then added 1 mmol of the appropriate
was carried
out at t-t until complete
consumption
pressed bakers’ yeast (Oriental Yeast Co., Ltd) was substituted
(KH2POq.Na2HP04,
substrate
dissolved
of the ketone.
in 5 ml of
In alternative
for dry yeast and phosphate
ph 7.0) was used instead of water. After the usual work-up,
To this
buffer
the alcohols were
isolated by preparative TLC. The optical purity of the alcohols was determined either by capillary GC analysis or by examination
of 1% NMR spectra of the corresponding
3a, 2b, and 3b was determined determined
by derivatization
by examination
to (S)-(-)-2-cyclopentenyl
(-)-2-cyclohexenyl3,5-dinitrobenzoate
(R)-MTPA esters.
The relative stereochemistry
of their tH NMR spectra7 benzoate
and the absolute
([a] ;?,3-176.6’ (c 0.06, CHC13)),a and/or (S)-
([a] 5 -15 l-lo (c 0.32, CHC13))9 followed by comparison
signs with those of authentic samples and/or the literature values. 399
of 2a,
configuration of the rotation
400
Table 1. Bakers’ Yeast Reduction of 2-Phenylthiocycloalkanones Entry
1
la
2
la
3
4
w
4
4
dry
Time
Yielda)
(days)
%
buffer
5
47
buffer
6
64
MlZdiUm
Ketone Yeast
drl
m
m
cis : frum
2:3 1w:
and 2-Phenylthio-Z-cycloalkenones %eeb) cis
0
>YY
86: 14
>YY
%eeC)
W$“d)
[aJgad)
cis
tram
bans
+76.2(c 0.76) >95
-
+70.2(c 2.0)
+1.2(c 0.34)
H20
6
47
100:
0
>99
+89.O(c 1.4)
-
buffa
5
60
loo:
0
>99
+75.5(c 0.94)
-
5
4
buffex
9
64
69: 31
>95
+82.O(c 0.95)
+1.9(c 0.86)
6
lb
W
H20
4
81
88: 12
>99
92@
>95
+25.4(c 1.12)
+50.6(c 0.34)
7
lb
dry
buffer
2
59
90: 10
>99
>95
+27.8(c 0.9)
+64.5(c 0.2)
8
5
dry
H20
20
0
-
a) Isolated yield. b) Determinedby capillary GC analysis of the corresponding (R)-MTPA esters. c) Determined by analysis of lgF NhER specma of the corresponding (R)-h4TPA esters. d) All values determined in CHCl3
From the examination different selectivides.
of the above table, it is apparent that dry yeast and pressed yeast show appreciably
An important feature to be pointed out is that, using the same strain of dry yeast (S. I. L.
Lesaffre),
cr-phenylthiocyclohexanone
solution
is used instead of distilled
phenylthiocycloalkanones phenylthiocycloalkanones ketones
suggests
lb is reduced faster but in lower yield (entry 7) when a phosphate buffer water. Preferential
production
that the latter are preferentially
prior to yeast reduction.
of cis (lS,2R) isomerized
alcohols
In the case of the yeast reduction
In conclusion,
ring
of an unsaturation
In this case, specific reduction of olefin followed by carbonyl reduction,
to cis (lS,2R) alcohol would account for the increase in yield. In contrast to the cyclopentenone the cyclohexenone
2-
to (5)-Z-
of five membered
la and 4 where dry yeast and buffer are used (entries 1 and 4), the introduction
increased the yield of alcohol.
from racemic
via enolization
leading
4, incubation of
derivative 5 for 20 days lead to the recovery of this substrate. this work provides
from readily available
ketosulfides,
the first example
of synthesis
and contrary to previous
found to be actually a good substrate for bakers’ yeast reduction.
of optically pure 2-arythiolcycloalkanols
observation, 6 a-phenylthiocyclohexanone
was
These chiral synthons can be used as building
blocks in natural products synthesis. References 1. For a review, B. M. Trost, Chem. Rev., 78, 363 (1978). 2. E. J. Corey, P. D. S. Jardine, and T. Mohri, Tetrahedron Left., 29, 6409 (1988). 3. H. Yamashita and T. Mukaiyama, Chem. Lett., 1643 (1985); H. Yamashita, Bull. Chem. Sot. Jpn., 61, 1213 119881. 4. See for example, S. Servi, Synrhesis, 1 (1990); T. Sato and T. Fujisawa, Biocatulysis, 3, 1 (1990). 5. The starting materials are readily available via the standard procedures. See, B. M. Trost, T. N. Salzmann, and K. Hiroi, J. Am. Chem. Sot., 98, 4887 (1976); H. J. Monteiro, J. Org. Chem., 42, 2324 (1977); H. J. Monteiro and A. L. Gemal, Synthesis, 437 (1975). 6. In the reduction of 2-phenylthiocyclohexanone with a mutant of bakers’ yeast, Crumbie et al., reported that the reduced alcohol was formed in only 2% yield. See, R. L. Crumbie, B. S. Deol, J. E. Nemorin, and D. D. Ridley, Aust. .I. Chem., 31, 1965 (1978). 7. For the stereochemistry of 2a and 3a, see, T. Cohen, R. T. Ritfer, D. Quellette, J. Am. Chem. Sot., 104, 7142 (1982). NMR spectra of 2b and 3b follow; 2b: (CDCl3) 6 1.20-2.13 (m. 8H), 2.53 (bs, lH), 3.173.50 (m, lH), 3.60-3.97 (m, lH), 7.07-7.63 (m, SH); 3b: (CC14) S 0.93-1.90 (m, 6H), 1.90-2.30 (m, 2H), 2.40-2.93 (m, ZH), 2.98-3.47 (m, lH), 7.10-7.67 (m, 5H). For the stereochemistry of 3b, see ref. 3. 8. For the preparation of (S)-(-)-2-cyclopenten-l-01, see, T. Sato, Y. Gotoh, Y. Wakabayashi, and T. Fujisawa, Tetrahedron Lett., 24, 4123 (1983). 9. B. D. Denney, R. Napier, and A. Cammarata, J. Org. Chem., 30, 3151 (1965). (Received in Japan 22 October 1990)