ORGANIC
LETTERS
2
005
Vol. 7, No. 8
465-1468
New General Sulfinylating Process for
Asymmetric Synthesis of Enantiopure
Sulfinates and Sulfoxides
1
Bruce Z. Lu,*,† Fuqiang Jin, Yongda Zhang, Xinhe Wu, Stephen A. Wald, and
†
Chris H. Senanayake*,
‡
Chemical Process R&D, Sepracor, Inc., 84 Waterford DriVe,
Marlborough, Massachusetts 01752
Received January 18, 2005
ABSTRACT
A general process for the efficient synthesis of sulfinyl transfer agents has been developed using cinchona alkaloids quinine and quinidine
as chiral auxiliaries. The importance of these new and unique sulfinyl transfer agents is exemplified by the expedient synthesis of several
sulfoxides in excellent enantiopurities and high yields.
Enantiopure sulfinamides and sulfoxides have stimulated
great interest in recent years due to their broad scope as
versatile chiral synthons for C-C and C-N bond forma-
tions.1 Although the preparation of sulfoxides by catalytic
such as the Andersen’s (S)-menthyl p-toluenesulfinate 1a,4
5
Alcudia’s sulfinate 1b derived from diacetone D-glucose,
6
Evans’ N-sulfinyloxazolidinone 2, Oppolzer’s N-sulfinyl
,2
7
sultam 3, asymmetric oxidation of disulfides such as
3
8
asymmetric oxidation of prochiral sulfides has been reported,
Ellman’s tert-butyl-t-butanethiosulfinate 4, and formation
of cyclic sulfites or oxathiazolidines such as Wudl’s 1,2,3-
the most frequently used precursors to access both sulfoxides
and sulfinamides are chiral sulfinates.1,2 A variety of methods
have been developed for the synthesis of these important
precursors, including kinetic resolution of sulfinates from
reaction of racemic sulfinyl chlorides with a chiral auxiliary
9
oxathiazolidine-2-oxide 5 derived from (-)-ephedrine,
1
0
Kagan’s cyclic sulfite 6, etc. (Figure 1).
(4) (a) Andersen, K. K. Tetrahedron Lett 1962, 3, 93. (b) Andersen, K.
K.; Gaffield, W.; Papanikolaou, N. F.; Foley, J. W.; Perkin, R. I. J. Am.
Chem. Soc. 1964, 88, 5637.
(
5) (a) Fern a´ ndez, I.; Khiar, N.; Llera, J. M.; Alcudia, F. J. Org. Chem.
†
Current address: Chemical Development, Boehringer-Ingelheim Phar-
1992, 57, 6789. (b) El Ouazzani, H.; Khiar, N.; Fern a´ ndez, I.; Alcudia, F.
J. Org. Chem. 1997, 62, 287. (c) Khiar, N.; Araujo, C. S.; Alcudia, F.;
Fern a´ ndez, I. J. Org. Chem. 2002, 67, 345.
(6) Evans, D. A.; Faul, M. M.; Colombo, L.; Bisaha, J. J.; Clardy, J.;
Cherry, D. J. Am. Chem. Soc. 1992, 114, 5977.
(7) Oppolzer, W.; Froelich, O.; Wiaux-Zamar, C.; Bernardinelli, G.
Tetrahedron Lett. 1997, 38, 2825.
(8) (a) Cogan, D. A.; Liu, G.; Kim, K.; Backes, B. J.; Ellman, J. A. J.
Am. Chem. Soc. 1998, 120, 8011. (b) For racemic synthesis of 6, see: Khiar,
N.; Fern a´ ndez, I.; Alcudia, F. Tetrahedron Lett. 1994, 35, 5719.
(9) (a) Wudl, F.; Lee, T. B. K. J. Chem. Soc., Chem. Commun. 1972,
61. (b) Wudl, F.; Lee, T. B. K. J. Am. Chem. Soc. 1973, 95, 6349.
(10) (a) Rebiere, F.; Samuel, O.; Ricard, L.; Kagan, H. B. J. Org. Chem.
1991, 56, 5991. (b) Kagan, H. B.; Rebiere, F. Synlett 1990, 643.
maceuticals, Inc., 800 East Leigh Street, Suite 205, Richmond, VA
2
3219.
‡
Current address: Chemical Development, Boehringer-Ingelheim Phar-
maceuticals, Inc., 900 Ridgebury Road, Ridgefield, CT 06877.
1) For recent reviews on sulfinylamines, see: (a) Ellman, J. A.; Owens,
T. D.; Tang, T. P. Acc. Chem. Res. 2002, 35, 984 and references therein.
b) Ellman, J. A. Pure Appl. Chem. 2003, 75, 39. (c) Zhou, P.; Chen, B.
(
(
C.; Davis, F. A. Tetrahedron 2004, 60, 8003. (d) Senanayake, C. H.;
Krishnamurthy, D.; Lu, Z.-H.; Gallou, I. Aldrichimica Acta, in press.
(
2) For a comprehensive review on chiral sulfoxides, see: Fern a´ ndez,
I.; Khiar, N. Chem. ReV. 2003, 103, 3651.
3) Kagan, H. B. In Catalytic Asymmetric Synthesis, 2nd ed.; Ojima, I.,
Ed.; Wiley-VCR: New York, 2000; Chapter 6c.
(
1
0.1021/ol0501020 CCC: $30.25
© 2005 American Chemical Society
Published on Web 03/18/2005