Cycloalkene Carbonitriles in Rhodium-Catalyzed 1,4-Addition and Formal Synthesis of Vabicaserin

Cycloalkenes
with exocyclic acceptor substituents still remain
challenging substrates for enantioselective rhodium-catalyzed 1,4-addition.
Cycloalkene carbonitriles and carboxylates have been investigated,
and a highly diastereo- and enantioselective protocol for 1,4-addition
to cyclopentene and cycloheptene carbonitrile has been developed.
This new asymmetric transformation was subsequently applied in the
asymmetric formal synthesis of the drug candidate Vabicaserin.