Asymmetric synthesis of nortropanes via Rh-catalysed allylic arylation

Tropane derivatives are extensively used in medicine, but catalytic asymmetric methods for their synthesis are underexplored. Here we report Rh-catalysed asymmetric Suzuki-Miyaura type crosscoupling reactions between a racemic N-Boc-nortropane-derived allylic chloride and (hetero-)aryl-boronic esters. The reaction proceeds via an unexpected kinetic resolution, and the resolved enantiopure allyl chloride can undergo highly enantiospecific reactions with N, O, and S-containing nucleophiles. The method was applied in a highly stereoselective formal synthesis of YZJ-1139(1), a potential insomnia treatment that recently completed Phase II clinical trials. Our report represents the first synthesis of YZJ-1139(1) and related compounds using asymmetric catalysis.