| Amine and phosphine-containing Lewis bases have been established as nucleophilic catalysts for reactions of allenoates with various coupling partners. Although examples of catalytic processes involving allenoates are numerous, enantioselective methods employing chiral amines or phosphines remain limited. The Miller laboratory has established a biomimetic approach to the discovery and design of new chiral catalysts for such transformations. In this vein, a protected, phosphine-containing single amino acid catalyst has been identified that promotes [3+2]-cycloaddition reactions between alpha-allenic esters and enone substrates providing spirocyclic products in up to 95% yield with up to 84% enantiomeric excess (ee). This single amino acid also catalyzes cycloadditions of racemic gamma-substituted allenoates with chalcones. Such dynamic kinetic asymmetric transformations (DYKATs) give cyclopentene products containing three contiguous stereogenic centers in high yields (up to 96%) and enantioselectivities (up to 91% ee). Following these studies, a novel amine-catalyzed reaction has been discovered that couples allenoates with imines. This method has been rendered asymmetric through the design of a pyridylalanine (Pal)-containing tetrameric peptide catalyst. This peptide catalyzes the coupling of allenoates with N-acyl imines to provide amide products in high yields (up to 88%) and enantioselectivities (up to 89% ee). The development of these methodologies, a review of Lewis base-catalyzed reactions involving allenoates, and mechanistic considerations for such processes are presented herein. |
