C–H Bonds as Functional Groups: Simultaneous Generation of Multiple Stereocenters by Enantioselective Hydroxylation at Unactivated Tertiary C–H Bonds
Andrea Palone, Guillem Casadevall, Sergi Ruiz‐Barragán, Arnau Call, Sílvia Osuna, Massimo Bietti, Miguel Costas
Abstract
Enantioselective C–H oxidation is a standing chemical challenge foreseen as a powerful tool to transform readily available organic molecules into precious oxygenated building blocks. Here, we describe a catalytic enantioselective hydroxylation of tertiary C–H bonds in cyclohexane scaffolds with H 2 O 2, an evolved manganese catalyst that provides structural complementary to the substrate similarly to the lock-and-key recognition operating in enzymatic active sites. Theoretical calculations unveil that enantioselectivity is governed by the precise fitting of the substrate scaffold into the catalytic site, through a network of complementary weak non-covalent interactions. Stereoretentive C( sp 3 )–H hydroxylation results in a single-step generation of multiple stereogenic centers (up to 4) that can be orthogonally manipulated by conventional methods providing rapid access, from a single precursor to a variety of chiral scaffolds.