C O M M U N I C A T I O N S
Scheme 2 a
a Reaction conditions: (a) 3 mol % of 4, trimethyl orthoformate (3 equiv),
2,6-lutidine (3 equiv), BF3‚OEt2 (3 equiv), CH2Cl2, -78 to 0 °C, 84%; (b)
LiBH4 (3 equiv), Et2O, 0 °C, 58%; (c) Me(OMe)NH‚HCl (5 equiv),
imidazole (5 equiv), Et3N (5 equiv), CH2Cl2, rt, 92%; (d) ethyl malonate,
K-salt (2 equiv), MgCl2 (1 equiv), imidazole (1 equiv), THF, rt, 73%.
converted into a broad range of functional groups means this
chemistry should find application to the synthesis of a wide variety
of molecules.
Acknowledgment. Support has been provided by the National
Science Foundation and the National Institutes of Health (GM-
33328-18).
Supporting Information Available: Experimental procedures,
spectral data, crystallographic data, and stereochemical proofs (PDF).
This material is available free of charge via the Internet at http://
pubs.acs.org.
Figure 1. Model for the observed sense of stereoinduction and double-
stereodifferentiating experiments.
Scheme 1
References
(1) For reviews, see: (a) Evans, D. A. In Asymmetric Synthesis; Morrison, J.
D., Ed.; Academic Press: New York, 1983; Vol. 3, Chapter 1, pp 83-
110. (b) Meyers, A. I. In Asymmetric Synthesis; Morrison, J. D., Ed.;
Academic Press: New York, 1983; Vol. 3, Chapter 3, pp 213-274. Also
see: (c) Job, A.; Janeck, C. F.; Bettray, W.; Peters, R.; Enders, D.
Tetrahedron 2002, 58, 2253-2329. (d) Oppolzer, W.; Moretti, R.; Thomi,
S. Tetrahedron Lett. 1989, 30, 5603-5606. (e) Myers, A. G.; Yang, B.
H.; Chen, H.; McKinstry, L.; Kopecky, D. J.; Gleason, J. L. J. Am. Chem.
Soc. 1997, 119, 6496-6511.
(2) Evans, D. A.; Downey, C. W.; Hubbs, J. L. J. Am. Chem. Soc. 2003,
125, 8706-8707.
(3) For reviews, see: Hughes, D. L. In ComprehensiVe Asymmetric Catalysis,
Supplement; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer-
Verlag: Berlin, 2004: Vol. 1, pp 161-169. (b) Hughes, D. L. In
ComprehensiVe Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A.,
Yamamoto, H., Eds.; Springer-Verlag: Berlin, 1999; Vol. 3, Chapter 3,
pp 1273-1294. For a recent example, see: (c) Doyle, A. G.; Jacobsen,
E. N. J. Am. Chem. Soc. 2005, 127, 62-63.
(4) Evans, D. A.; Urpi, F.; Somers, T. C.; Clark, J. S.; Bilodeau, M. T. J.
Am. Chem. Soc. 1990, 112, 8215-8216.
(5) For a different approach, see: Hosokawa, T.; Yamanaka, T.; Itotani, M.;
Murahashi, S. J. Org. Chem. 1995, 60, 6159-6167.
(6) N-Propionyloxazolidinone gave no reaction under similar conditions.
(7) Treatment of acetals with TMSOTf and base affords the corresponding
enol ethers. See: Gassman, P. G.; Burns, S. J. J. Org. Chem. 1988, 53,
5574-5578.
situ from trimethyl orthoformate and BF3‚OEt2. Product dissociation
then regenerates catalyst I.14
(8) See Supporting Information for details.
(9) The lower selectivity observed for 5 versus that for 1a is presumably the
result of a change about the metal due to the benzyl substituent.
(10) [Ni((S)-BINAP)]Br2 is distorted square planar. See: Spielvogel, D. J.;
Davis, W. M.; Buchwald, S. L. Organometallics 2002, 21, 3833-3836.
(11) [Ni((S)-BINAP)]OTf2 is an effective catalyst for the alkylation of 1a, but
gives slightly lower enantiomeric excess (94%).
(12) Model generated from the X-ray structure of [Ni((S)-BINAP)]Cl2 by
docking the enolate to the Ni center, followed by PM3 minimization. See
Supporting Information for crystal structure of [Ni((S)-BINAP)]Cl2.
(13) Ren, J.; Cramer, C. C.; Squires, R. R. J. Am. Chem. Soc. 1999, 121, 2633-
2634.
(14) The counterion may be OTf or another anion derived from the reagents.
(15) (a) Crimmins, M. T.; King, B. W.; Tabet, E. A.; Chaudhary, K. J. Org.
Chem. 2001, 66, 894-902. (b) Crimmins, M. T.; Chaudary, K. Org. Lett.
2000, 2, 775-777. For other manipulations, see: (c) Mukaiyama, T.;
Iwasawa, N. Chem. Lett. 1982, 1903-1906.
(16) The moderate yield is due to volatility and water solubility of the product.
(17) Smith, T. E.; Djang, M.; Velander, A. J.; Downey, C. W.; Carrol, K. A.;
van Alphen, S. Org. Lett. 2004, 6, 2317-2320.
On a larger scale (2.0 g, 11.4 mmol 1a), the catalyst loading
could be lowered to 3 mol % with no detrimental effect on yield
or enantioselectivity (Scheme 2). As shown in Scheme 2, 3a is
readily converted into a variety of potentially useful substrates.
Reduction of 3a with LiBH415 provides the corresponding alcohol
7 in moderate yield (58%).16 Conversion to Weinreb amide 8 is
achieved in a straightforward manner upon exposure of 3a to Me-
(OMe)NH‚HCl, Et3N, and imidazole. Under the conditions de-
scribed by Smith and co-workers, â-ketoester 9 can be prepared in
good yield (73%).17
In conclusion, we have developed a Ni(II) (S)-Tol-BINAP-
catalyzed orthoester alkylation of N-acylthiazolidinethiones that
displays wide substrate scope for the nucleophile and excellent
enantioselectivity. The ease with which the products may be
JA053386S
9
J. AM. CHEM. SOC. VOL. 127, NO. 30, 2005 10507