Catalytic, enantioselective oxyallylation of activated carbonyl compounds

Abstract

Stereoselective alkylations are a very useful tool in synthetic chemistry and, specifically, natural product synthesis. One such reaction, named the Tsuji-Trost allylation, is a palladium-catalyzed substitution with the overall transformation being the replacement of an allylic leaving group with a nucleophile. First observed in 1965 with the allylation of diethyl malonate [1], and in 1973 made asymmetric with the use of chiral phosphine ligands by B. M. Trost [2], the reaction has been studied and utilized extensively over the years. While there have been many examples of this reaction in the literature, few explore functionalizing the allylic electrophile. Functionalizing the "2" position of an allylic acetate or carbonate could prove to be a useful synthetic tool. Allylic acetates, chlorides and carbonates bearing a methoxymethyl group at this middle position were synthesized. beta-carbonyl ketones which work well under the Tsuji-Trost conditions were also synthesized. Phosphine ligands that provided enantiomeric excess with a variety of nucleophiles in allylic alkylations were used. Upon reaction with a palladium (0) source, the pro-nucleophiles were successfully alkylated in a stereospecific manner. The work described herein investigates modification of the Tsuji-Trost allylation in which oxy-allylation is carried out with a high yield and high degree of enantioselectivity.