Nickel-catalyzed reductive coupling reactions : application to the total syntheses of pumiliotoxins 209F and 251D

Abstract

Catalytic Asymmetric Reductive Coupling of 1,3-Enynes and Aromatic Aldehydes Nickel-catalyzed reductive coupling reactions of 1,3-enynes and aromatic aldehydes efficiently afford conjugated dienols in excellent regioselectivity and modest enantioselectivity. These reactions were conducted in the presence of a catalytic ligand (R)-ferrocenyl(2-isopropylphenyl)phenylphosphine, whose overall synthesis was improved during the course of this investigation. 1-(Trimethylsilyl)-substituted enynes are shown to be efficient coupling partners in these reactions, and the dienol products formed readily undergo protiodesilylation under mild conditions. ... Catalytic, Asymmetric, Intramolecular Reductive Coupling of 1,1-Disubstituted Epoxides and Alkynes: Total Synthesis of Pumiliotoxin 209F and 251D Pumiliotoxins 209F and 251 D were prepared using a novel nickel-catalyzed intramolecular cyclizations between alkynes and 1,1-disubstituted epoxides. These cyclizations formed exclusively endo products without the use of a directing group on the alkyne. The synthesis of the reductive coupling precursors involved a diastereoselective sulfur ylide epoxidation of a proline-derived methyl ketone, where the choice of sulfonium salt conferred a major effect on the diastereoselectivity.