LETTER
Transesterification of Methyl 2 Substituted 3-Hydroxy-4-pentenoates
1667
Chirazyme®
Ph
Ph
Ph
CH2=C(OAc)Me
+
AllylO2C
AllylO2C
AllylO2C
PhMe, 70 °C, 90 h
OH
OH
OAc
10
11
12
48% (98.5%ee)
49% (>99%ee)
Scheme 3
O
O
NHBz
BocN
Ph
HN
e, f , g
71%
a, b
80%
c, d
CO2H
Ph
12
O
O
Ph
88%
OH
CO2H
13
14
15
Scheme 4 (a) Pd(OAc)2/PPh3, HCO2H/Et3N/THF, r.t., 10 h; (b) DPPA/Et3N/toluene, r.t., 40 min, then 80 °C, 1.5 h; (c) (Boc)2O/Et3N/DMAP/
THF, r.t., 2 h; (d) RuO2/NaIO4, CCl4/MeCN/H2O = 2:2:3, r.t., 15 h; (e) 2 M NaOH/MeOH, r.t., 1 h; (f) TFA, r.t., 2 h; (g) BzCl/aq NaHCO3, r.t.,
6 h
25
(7) For a review: Carrea, G.; Riva, S. Angew. Chem. Int. Ed.
2000, 39, 2226.
(8) Panunzio, M.; Camerini, R.; Mazzoni, A.; Donati, D.;
Marchioro, C.; Pachera, R. Tetrahedron: Asymmetry 1997,
8, 15.
(9) Vrielynck, S.; Vandewalle, M. Tetrahedron Lett. 1995, 36,
9023.
(10) Wünsche, K.; Schwaneberg, U.; Bornscheuer, U. T.; Meyer,
H. H. Tetrahedron: Asymmetry 1996, 7, 2017.
(11) Kaga, H.; Hirosawa, K.; Takahashi, T.; Goto, K. Chirality
1998, 10, 693.
(12) Lipase-catalyzed enantioselective hydrolysis of 2-methy-3-
acetoxy esters has been reported, see: (a) Akita, H.;
Matsuura, H.; Oishi, T. Tetrahedron Lett. 1986, 27, 5241.
(b) Akita, H.; Chen, C. Y.; Nagumo, S. Tetrahedron:
Asymmetry 1994, 5, 1207.
yield {[ ]D –35.3 (c 1.03, EtOH), mp 173.5–176 °C,
Lit.24 [ ]D20 –35.5 (c 1.07, EtOH), mp 175.5–177 °C} as
outlined in Scheme 4.
In summary, we have established a practical method for
obtaining syn- and anti-methyl 2-substituted 3-hydroxy-
4-pentenoates with high optical purities by means of the
lipase-catalyzed transesterification, which would offer ac-
cess to other synthetically useful intermediates involving
1,2-amino alcohols less available from natural amino ac-
ids.
Acknowledgement
We thank Prof. Kaoru Nakamura (Kyoto University) for his helpful
discussions. We also thank The Promotion and Mutual Aid Corpo-
ration for Private Schools of Japan for financial support (The Sci-
ence Research Promotion Fund).
(13) For instance, compounds 1b and 4b were prepared as
follows. A solution of methyl 4-methylvalerate (7.48 g, 57.5
mmol) in THF (20 mL) was added dropwise to a solution of
LDA (60.3 mmol) in hexane (38.7 mL)/THF (50 mL) at
–78 °C and the mixture was stirred for 1 h. Then, acrolein
(4.61 mL, 68.9 mmol) was added and the mixture was stirred
at –78 °C for 2 min. After usual workup, the oil obtained was
purified by medium-pressure column chromatography
References
(1) Gargano, J. M.; Lees, W. J. Tetrahedron Lett. 2001, 42,
5845.
(Yamazen, Ultra PackTM
,
50 300 mm, hexane/ethyl
(2) (a) Sakaitani, M.; Ohfune, Y. Tetrahedron Lett. 1987, 28,
3987. (b) Sakaitani, M.; Ohfune, Y. J. Am. Chem. Soc. 1990,
112, 1150. (c) Alemany, C.; Bach, J.; Farràs, J.; Garcia, J.
Org. Lett. 1999, 1, 1831; and references therein.
(3) Jost, S.; Gimbert, Y.; Green, A. E.; Fotiadu, F. J. Org. Chem.
1997, 62, 6672; and references therein.
(4) For a review on 1,2-amino alcohols as chiral auxiliaries in
asymmetric synthesis: Ager, D. J.; Prakash, I.; Schaad, D. R.
Chem. Rev. 1996, 96, 835.
(5) (a) Sibi, M. P.; Lu, J.; Edwards, J. J. Org. Chem. 1997, 62,
5864. (b) Ghosh, A. K.; Hussain, K. A.; Fidanze, S. J. Org.
Chem. 1997, 62, 6080. (c) Pais, G. C. G.; Maier, M. E. J.
Org. Chem. 1999, 64, 4551.
acetate = 6:1~4:1 as eluent) to afford the less polar syn-
racemate 1b (5.03 g, 27.0 mmol, 47% yield) and the more
polar anti-racemate 4b (4.70 g, 25.2 mmol, 44% yield). Each
compound can easily be discriminated by the chemical shifts
of methine protons at 2- and 3-positions in 1H NMR spectra
(CDCl3, 500 MHz) : 2.62–2.68 (m, 1 H, CHCOO) and
4.28–4.33 (m, 1 H, CHOH) for 1b, and 2.58–2.63 (m, 1 H,
CHCOO) and 4.14–4.20 (m, 1 H, CHOH) for 4b. The
chemical shifts of the methine protons at 2- and 3-positions
of 1 are generally observed in the down field compared with
those of 4. Additionally, syn-racemates 1 are generally less
polar than anti-racemates 4 on TLC analysis (hexane/ethyl
acetate = 5:1~3:1).
(6) For syn-aldol reactions: (a) Evans, D. A.; Taber, T. R.
Tetrahedron Lett. 1980, 21, 4675. (b) Evans, D. A.;
Bartroli, J.; Shih, T. L. J. Am. Chem. Soc. 1981, 103, 2127.
(c) For anti-aldol reactions: Evans, D. A.; Tedrow, J. S.;
Shaw, J. T.; Downey, C. W. J. Am. Chem. Soc. 2002, 124,
392. (d) Also see: Evans, D. A.; Downey, C. W.; Shaw, J. T.;
Tedrow, J. S. Org. Lett. 2002, 4, 1127.
(14) Lipase-catalyzed enantioselective acylation of 1-alkene-3-
ols has been well examined, see: (a) Ito, T.; Akasaki, E.;
Kudo, K.; Shirakami, S. Chem. Lett. 2001, 262. (b) Ito, T.;
Kudo, K.; Tanaka, N.; Sakabe, K.; Takagi, Y.; Kihara, H.
Tetrahedron Lett. 2000, 41, 4591.
Synlett 2002, No. 10, 1665–1668 ISSN 0936-5214 © Thieme Stuttgart · New York