Iterative Catalyst-Controlled\nDiastereoselective Matteson\nHomologations Enable the Selective Synthesis of Benzestrol Isomers

We report the development of an iterative Matteson homologation\nreaction with catalyst-controlled diastereoselectivity through the\ndesign of a new catalyst. This reaction was applied to the selective\nsynthesis of each stereoisomer of benzestrol, a bioactive compound\nwith estrogenic activity featuring three contiguous stereocenters.\nThe different stereoisomers were assayed to determine their binding\naffinity for the estrogen receptor α (ERα), and the absolute\nconfiguration of the compound having uniquely high activity was determined.\nThis research lays a framework for the catalytic synthesis and study\nof complete stereoisomeric sets of other bioactive molecules and chemical\nprobes containing contiguous stereocenters.