Latent nucleophiles in organic synthesis: advancing the concept towards synthetic applications

Abstract

The most common problem in enantioselective Lewis base catalyzed reactions is the typically narrow scope for the nucleophilic reaction partner. It was hypothesized that this problem can be addressed using latent nucleophiles, derivatives of otherwise nucleophilic molecules which are not nucleophilic themselves but can be activated to participate in the reaction as a nucleophile. If activation of a latent nucleophile is dependent on the activation of electrophilic reaction partner, activated nucleophile is produced only when activated electrophile is already present in the reaction mixture and the fast reaction between the two activated species outcompetes other reaction pathways. This improves reaction efficiency, selectivity and, most importantly, expands the scope of Lewis base catalyzed reactions. This concept was applied to Lewis base catalyzed allylic substitutions with focus on otherwise problematic N- and C-nucleophiles such as pyrroles, indoles, carbazoles, amides, carbamates, ketones, alcohols, difluoromethylphosphonates and quinaldines