Preparation of (4S)-4-hydroxy-3-methyl-2-(2′-propynyl)-2-cyclopentenone by combination of enzymatic hydrolysis and chemical transformation

Article abstract of DOI:10.1016/S0040-4039(00)93443-9

(4S)-4-Hydroxy-3-methyl-2-(2′-propynyl)-2-cyclopentenone ((S)-2), which is an important alcohol moiety of optically active pyrethroid insecticides, was prepared from the corresponding racemic acetate ((±)-1) by the combination of enzymatic hydrolysis and chemical transformation in high chemical and optical yields.

Full text of DOI:10.1016/S0040-4039(00)93443-9

Te~rahedron Letters, Vol.32, No.38, lop 5119-5122, 1991
Printed in Great Britain
0040-4039/91 $3.00+ .00
Pergamon Pressplc
PREPARATION OF
(4S)-4-HYDROXY-3-METHYL-2-(2'-PROPYNYL)-2-CYCLOPENTENONE
BY
COMBINATION OF ENZYMATIC HYDROLYSIS AND CHEMICAL TRANSFORMATION
Hidencgi DANDA,* AkiraMAEHARA, and Takeaki UMEMURA
Takarazuka Resem~h Center, Sumitomo Chemical Co., Ltd., 2-I, 4-Chome, Takatsukasa, Takarazuka, Hyogo 665
Abstract
:
(4S)-4-Hydroxy-3-mcthyl-2-(2'-propynyl)-2-cyclopcntenone((S)-2), which is an important
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and optical yields.
(4S)-4-Hydroxy-3-methyl-2-(2'-propynyl)-2-cyclopcntenone ((S)-2) is an important alcohol moiety of optically active pyrethroid
insecticides.l,2 V~ recently reported the preliminary strategy to prepare the optically active (S)-2 from the corresponding racemic
acetate ((±)-1) (Scheme 1), in which enzymatic hydrolysis of (±)-1 was discussed in detail. 3,4 As a part of our ongoing program, we
have investigated the sequential chemical transformation of (R)-alcohol ((R)-2) and (S)-acetate ((S)-1) obtained by the enzymatic
hydrolysis, and accomplished the mute to prepare (S)-alcohol ((S)-2) in high chemical and optical yields, starting from the mcemic
acetate ((±)-1). The result is described herein.
A c O - ~ ~ Lipase [ H ~ . , , f ~
H
(+)-1
(R)-2
(S)-1
H
H20~ H ( ~ ~
(S)-1
~
R
+
3
(S)-2
3 a
3 b
~ :
:
:
:
R~-~-NO2
R==Ms
R~--B(OH)2
Scheme 1
The raccmic acetate ((±)-1) was hydrolyzed by using Arthrd~cter lipase.3.4 The crude product was purified by column
chromatography on silica gel (30% EtOAc in hexane) to give optically pure (R)-alcohol ((R)-2) as pale yellow crystals (46%),5 and
optically pure (S)-acemte ((S)-I) was recovered as white crystals (46%).6
5119

5120
FIX
H20
( R ) - 2
=
3
-~ ( R ) - 2 + ( S ) - 2
I::D(=HNO3
RX=MsCI
3a" R=NO2
3b : R--Ms
H20
(S)-1
~- (R)-2 + (S)-2
RX=B(OH)3
3C : R=B(OH)2
S c h e m e
2
S c h e m e 3
In order to convert (R)-2 to (S)-2, several kinds of esters (3 a : nitrate, 3 b : mesylate, 3c : borate) of (R)-2 w ~ prepaw~,7"9
and their hydrolysis under acidic or neutral conditions was examined (Scheme 2). The results are summarized in Table 1. The esters
(3a-c) were prepared by using 10 mmol of (R)-2. The hydrolysis of 3a-v was carried out in 30 mL of water in the presence of
CaCO3 at 85°C for 4h. After neutralization with aq. NaHCO3 and extraction with EtOAc, the organic phase was concentrated in
vacuo. The yields of the resulting alcohols ((R)-2
+ (S)-2) and the ratios ((R)-2 : (S)-2) were determined by HPLC, using
LiChrosorb RP-8 and an optically active stationary phase, Sumipax OA-4100. Borate (3V) preferentially gave (R)-alcohoi ((R)-2)
with retention, which may be due to preferential C-O bond fission rather than B-O bond in this case (entry 7). On the other hand, the
hydrolysis of niwate (3 a) and mesylate (3 b) under neutral or acidic conditions was followed by inversion to give (S)-alcohol ((S)-2)
preferen~dly. For example, the rate of inversion was 86% for 3 a and 94% for 3 b under the presence of I eq of CaCO3 (entries 1 and
4). As the amount of CaCO3 was decreased, the rate of inversion was decreased. In the absence of CaCO3, the rate of inversion was
72% for 3 a and 91% for 3 b (entries 3 and 6). This tendency may be due that the contribution of SNI reaction is getting larger as the
reaction mixture becomes acidic. Thus, it was found that the esters of (R)-2, nitrate (3 a) and mesylate (3 b), are hydrolyzed under
neutral or acidic conditions to give (S)-alcohol ((S)-2) preferentially as a result of inversion of (R)-alcohol ((R)-2).
Next, the hydrolysis of (S)-acetate ((S)-1) underacidic conditions was investigated (Scheme 3). The hydrolysis of (S)-1 was carded
out on a 10 mmol scale in 30 mL of aqueous acid at 80°C. The resaldng Ixoducts were treated in the same manner as described above.
The results are summarized in Table 2. BoW aqueous H2SO4 a~l HNO3 gave (S)-alcohol ((S)-2) quantitatively with retention. The
rate of retention was over 99% in both cases. Thus, it was also found that (S)-acetate ((S)-1) are hydrolyzed under acidic conditions to
afford (S)-alcobel ((S)-2) with retention.
Finally, our strategy to prepare (S)-alcohol ((S)-2) from the corresponding racemic acetate ((±)-1) was proved to be realized as
follows. The racemic acetate ((+)-1) was hydrolyzed by Arthrobacter lipasc, and the crude mixture of (R)-alcohol ((R)-2) and (S)-
acetate ((S)- 1 ) was esterified with fuming HNO3 (Method A) or MsCI (Method B) to afford the mixture of the corresponding nitrate
(3 a) or mesylate (3 b) and (S)-acetate ((S)- 1 ). The (S)-acetate ((S)-1) was unaffeczed by the esterification conditions. The resultant
mixture of 3 a and (S)-1 or 3 b and (S)-1 was hydrolyzed in the presence of 0.2 eq of CaCO3. Method A afforded (S)-alcohol ((S)-2)
of 82 %ce in 74 % yield. 10 Similarly, Method B gave (S)-2 of 90 %ec in 82 % yield. 10 Thus, the racemic acetate ((±)-1) was
converted with maximum efficiency to the desired (S)-alcohol ((S)-2) in high chemical and optical yields without separation or
purification of any intermediates.
A further study on generalization of this methodology is in progress.

•
5121
Table 1. Hydrolysis of Esters ( 3 a - ~ ) a
CaCO 3 for
Yield of
Neuwalization
((R)-2 + (S)-2)b Isomer Ratio c
Entry
Substrate
(cq.)
(%)
85
(R)-2 : (S)-2
14 : 86
1
3 a
1
2
3
0.2
- -
84
90
19 : 81
28 : 72
4
3 b
1
92
6 : 94
5
0.2
95
7 : 93
6
7
- -
90
99
9 : 9 1
3¢
0.2
98 : 2
a) The reaction conditions are described in the text. b) Determined by HPLC
(LiChrosorb RP-8). c) Determined by HPLC (Sumipax OA-4100).
Table 2. Hydrolysis of (S)-Acetate ((S)-1) a
Yield of
((R)-2 + (S)-2) b Isomer Ratio c
Temp.
Time
Entry
1
Aq. Acid
(°C)
80
(h)
3
(%)
96
(R)-2 : (S)-2
0.7 : 99.3
2.5%H2SO4
2
2. 5%HNO3
80
1.5
100
0.8 : 99.2
a) The hydrolysis was carried out on a 10 mmol scale in 30 mL of aqueous acid. b) Determined by HPLC (LiChrosorb
PR-8). c) Determined by HPLC (Sumipax OA-4100).
References and notes
(1)
(2)
0)
T. Matsuo, T. Nishioka, M. Hirano, Y. Suzuki, K. Tsushima, N. Itaya, and H. Yoshioka, Pestic. Sci., 11,202 (1980).
K. Aketa, N. Ohno, and H. Yoshioka, Agric. Biol. Chem., 4 2, 895 (1978).
S.Mitsuda, T. Umemum, and H. Hiroham, Appl. Microbiol. Biotech., 2 9, 310 (1988).
T.Umemura, and H. Hirohara, ACS Symposium Series, No. 389, 371 (1989).
(4)

5122
(5)
The absolute configuration has already been determined, l' 2 (11)-2 :mp 43~5°C ; [or] 2 5 -21.6° (c 1.47, CHCI3) ; IR
(nujol) 3350, 3270, 2900, 1690, 1640, 1460, 1375 em-1 ; 1H NMR (60 MI-lz, CDCI3) 8=1.98 (t, J-.-3I-Iz, IH), 2.20
(S, 3I-I), 2.25 (dd, J--3, 18Hz, 1I-I), 2.85 (dd, J--6, 18I-Iz, 1I-I), 3.07 (d, J=3Hz, 2H), 3.72 (br.s, II-I), 4.72 (br.d, J--5I-Iz, 1H) ;
13C NMR (67.5 MI-lz, CDC13) 8=12.17, 13.85, 43.80, 68.80, 71.15, 79.51,135.97, 172.00, 204.30.
The absolute conf~mration has already been determined.1"3 (5)-1 : mp 45--6°C ; [Or]D23 +39.4° (e 1.25, CHCI3) ;
IR (nujol) 3250, 2900, 1710, 1660, 1460, 1375, 1240 cm-1 ; IH NMR (60 MHz, CDCI3) 8=1.99 (t, J=3Hz, II-1),
2.09 (S, 3H), 2.14 (S, 3I-I), 2.21 (dd, J---3, 18Hz, IH), 2.90 (dd, J=6, 18Hz, 1I-I), 3.14 (d, J--3Hz, 2I-1), 5.65 (bt:s, J~6I-Iz, 1H)
13C NMR (67.5 MHz, CDCI3) 8=12.23, 13.93, 20.66, 41.17, 68.92, 72.65, 79.14, 138.17, 166.51, 170.44, 202.02.
3 I! was obtained as a pale yellow oil (97%) by column chromatography on silica gel (30% EtOAc in hexane) for analysis :
[~t] 2 3 -103.1° (c 1.41, CHCI3) ; IR (neat) 3290, 2120, 1715, 1650, 1630, 1280 cm 1 ; 1H NMR (60 MHz, CDC13)
8=2.04 (t, J=3Hz, 1H), 2.26 (s, 3H), 2.48 (dd, J=2, 18Hz, 1I-1), 3.06 (dd, J=6, 18Hz, liT), 3.19 (d, J=3Hz, 2I-I),
5.90 (br.d, J--6Hz, IH).
(6)
(7)
(8)
II1~ was obtained as yellow crystals (97%) by column chromatography on silica gel (50% EtOAe in bexane) for analysis :
mp 75~6°C ; [a] 2 3 -18.6° (c 1.25, CHCI3) ; IR (nujol) 3280, 2120, 1700, 1650, 1350, 1170 cm"1 ; 1H NMR
(60 MI-Iz, CDCI3) 8=2.03 (t, J=3Hz, It0, 2.26 (s, 3H), 2.54 (dd, J=6, 18I-Iz, 114), 2.99 (dd, J=6, 18Hz, IH), 3.11 (s, 3I-0,
3.17 (d, J--31-Iz, 2H), 5.60 (br.d, J=6I-Iz, 1H).
(9)
3 ¢ was obtained in a quantitative yield by azeolropic distillation in benzene.
(10)
A small part of the crude products was purified by column chromatography on silica gel 00% EtOAc in bexane) for analysis.
The IR, 1H NMR and 13C NMR speetra of the products were identical with those of (S)-alcohoi ((S)-2).
Method A : laid23 +17.7° (c 1.25, CHCI3), Method B : [a] 2 3 +19.2° (c 1.14, CHCI3).
(Received in J a p a n 27 M a r c h 1991; accepted 11 July 1991)