Decarboxylative Benzylations of Alkynes and Ketones

Abstract

Utilization of palladium π-benzyl complexes in cross-coupling reactions is becoming increasingly important in organic synthesis.1 However, methods for benzylic cross-couplings typically rely on the use of basic reagents or preformed organometallics. For example, Buchwald reported the cross-coupling of benzyl halides with alkynes using stoichiometric Cs2CO3; unfortunately, the basic reaction conditions often induce isomerization of the product benzylic alkynes to isomeric allenes.2 Negishi reported the benzylic cross-coupling with acetylides via stoichiometric alkynyl zinc bromides that must be prepared from ZnBr2.3 Not only do these methods require stoichiometric bases or organometallics, but they also utilize benzyl halides that are expensive, hazardous, and more difficult to handle than related benzyl alcohol derivatives.

Legros, Kuwano and others have reported catalytic benzylation of stabilized nucleophiles using activated benzylic alcohol derivatives.4 While benzylations of highly stabilized enolates (pKa ~ 10-13),4a-d phenols (pKa ~ 10),4e and arene sulfinates (pKa ~ 7)4f have been successful, the reaction of less stabilized nucleophiles has proven difficult.5 Since we have previously developed decarboxylative coupling strategies that allow allylation of nonstabilized nucleophiles without the use of an external base or organometallic, we hypothesized that a similar strategy might allow decarboxylative coupling of benzylic esters with nonstabilized nucleophiles (eq. 1).5-7