Rh-Catalyzed Desymmetric Hydroformylation of 1,3-Bis(methylene)cyclopentanes

A highly enantio- and diastereoselective rhodium-catalyzed desymmetric hydroformylation of 1,3-bis(methylene)cyclopentanes has been developed using (R,R)-DTBM-YanPhos (up to 99% yield, 99% ee, and 50:1 dr), enabling access to chiral aldehydes bearing two contiguous stereocenters, including a quaternary center. The reaction proceeds under mild conditions and exhibits a broad substrate scope and functional group tolerance. Gram-scale synthesis and diverse downstream derivatizations demonstrate efficient access to densely substituted chiral cyclopentane derivatives and further expand the synthetic utility of desymmetric hydroformylation.