Ligand-enabled override of the memory effect in Rh-catalyzed asymmetric Suzuki reactions

Abstract

Chiral non-racemic allylic species are key building blocks for many carbon-containing molecules, including pharmaceuticals and polymers. Metal-catalyzed asymmetric additions of nucleophiles to allylic species undergo different pathways depending on the metal and nucleophile combination, hindering the development of useful addition reactions with aromatic nucleophiles. We report an asymmetric cross-coupling method between aryl boronic acids and linear allylic phosphates to give branched allylic products. This Suzuki-type reaction overcomes the “memory effect” in Rh catalysis, enabling an overall SN2′ transformation by rate-determining reductive elimination and forming a new stereogenic center adjacent to a terminal vinyl moiety. The method tolerates preexisting stereogenic centers, allowing for synthetic strategies where drugs and natural products are elaborated via diastereoselective allylic arylations. The method is used, as the catalyst-controlled stereochemistry-setting step, in an iterative strategy to give arrays of aryl-substituted contiguous stereogenic centers. This approach will complement existing catalyst-controlled stereoselective methods for forming C–C bonds.