Journal of the American Chemical Society 2002-12-11

Enantioselective total synthesis of (-)-strychnine using the catalytic asymmetric Michael reaction and tandem cyclization.

Takashi Ohshima, Youjun Xu, Ryo Takita, Satoshi Shimizu, Dafang Zhong, Masakatsu Shibasaki

Index: J. Am. Chem. Soc. 124(49) , 14546-7, (2002)

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Abstract

The enantioselective total synthesis of (-)-strychnine was accomplished through the use of the highly practical catalytic asymmetric Michael reaction (0.1 mol % of (R)-ALB, more than kilogram scale, without chromatography, 91% yield and >99% ee) as well as a tandem cyclization that simultaneously constructed B- and D-rings (>77% yield). Moreover, newly developed reaction conditions for thionium ion cyclization, NaBH3CN reduction of the imine moiety in the presence of Lewis acid to prevent ring opening reaction, and chemoselective reduction of the thioether (desulfurization) in the presence of exocyclic olefin were pivotal to complete the synthesis. The described chemistry paves the way for the synthesis of more advanced Strychnos alkaloids.