Organic & Biomolecular Chemistry 2012-10-07

Diastereoselective construction of syn-α-oxyamines via three-component α-oxyaldehyde-dibenzylamine-alkyne coupling reaction: application in the synthesis of (+)-β-conhydrine and its analogues.

Sharad Chandrakant Deshmukh, Arundhati Roy, Pinaki Talukdar

Index: Org. Biomol. Chem. 10(37) , 7536-44, (2012)

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Abstract

A Cu(I)-catalyzed α-oxyaldehyde-dibenzylamine-alkyne coupling reaction was delineated for the construction of α-oxyamines with excellent yields and diastereoselectivity. Crystal structure analysis and theoretical calculations were also supportive of the formation of syn-α-oxyamines as the major products. Application of the methodology addresses the synthesis of (+)-β-conhydrine along with analogs having two different diversity features. A ring size variation allows construction of piperidine and pyrrolidine rings while a variation of side arm functionality is achieved by complete regioselective opening of epoxide by different organocopper ylides (Gilman reagents). A lactam-Cu(I) complexation motif is proposed which allows an intramolecular attack of ylides at the terminal epoxy carbon via the six-membered cyclic transition state. The present work features the synthesis of (+)-β-conhydrine over eight steps in 26% yield and its seven analogs in 21-28% yields.