Synthesis of New Chiral Vinyl Halides from L-Serinal

Abstract

The synthesis of new chiral and functionalized vinyl halides from protected L-serinal is described.

Notes

Furber M. “Acetylenes”, and Urch, C. J. “Vinyl and Aryl Halides” in “Comprehensive Organic Functional Group Transformations”, Pergamon, Katritzky, A. R.; Meth-Cohn, O. and Rees, C. W. Editors-in-Chief, vol. 1 and 2 respectively.

For a stereoselective synthesis of (Z)-vinyl bromides see ref. 2c.

In our hands, alkyne 2 is obtained with a maximum 50% yield when 2eq. nBuLi is aded slowly on a THF solution of dibromovinyl derivative 3, at −78°C. 2 is often contaminated with vinyl bromide 4 and with enamine 9.^5a Formation of 9 is probably due to abstraction of the proton with enhanced acidity α to NBoc (see Beak, P.; Lee, W.-K.Tetrahedron Lett. 1989 30 1197) with concomitant acetone elimination. We also observed this reaction with other oxazolidines derived from L-serinal 1 with a double or a triple bond in the 4-position.^3b Unstable enamine 9 is obtained in 65% yield if alkyne 2 is treated with excess nBuLi in THF.

9: ¹H-NMR (200MHz, CDCl₃, δ in ppm): 1.49 (s, 9H); 2.88 (s, 1H); 5.05 (s, 1H); 5.82 (s, 1H); 6.0 (brs, 1H). MS (DCI, NH₃) 185 (M+NH₄)⁺, 168 (M+H)⁺, 129 (M-tBu+NH₄)⁺.

Formation of enamine 9 (see note 11 above) is observed (crude yield ∼40%).