Stereoselective Suzuki Reactions by Overcoming Rh-Catalyst Memory Effects

Chiral non-racemic allylic species are key building blocks in the synthesis of a wide range of important carbon-containing molecules, including pharmaceuticals and polymers. Metal-catalyzed asymmetric additions of nucleophiles to allylic species undergo different reaction pathways depending on the combination of metal and nucleophile used, which has hindered the development of broadly useful addition reactions with aromatic nucleophiles. Here, we report an asymmetric cross-coupling method between aryl boronic acids and linear allylic phosphates to give branched allylic products. This Suzukitype reaction overcomes the ‘memory effect’ in Rh-catalysis to allow an overall SN2’ transformation by rate-determining reductive elimination and forms a new stereogenic centre adjacent to a terminal vinyl moiety. The method tolerates pre-existing stereogenic centres allowing the development of 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 synthetic strategy to give arrays of aryl substituted contiguous stereogenic centres, and we anticipate this approach will be a useful compliment to existing catalyst controlled stereoselective methods for forming C-C bonds.