Development of Highly Enantio- and Z-Selective Grubbs Catalysts via Controllable C-H Bond Activation.

Abstract

Asymmetric olefin metathesis is a powerful strategy for stereocontrolled synthesis that allows the formation of chiral elements in conjunction with carbon-carbon double bonds. Here, we report a new series of cyclometalated stereogenic-at-Ru catalysts that enable highly efficient asymmetric ring opening/cross-metathesis (AROCM) and asymmetric ring-closing metathesis (ARCM) reactions. Single enantiomers of these catalysts with either right-handed or left-handed configurations at the Ru center can be easily accessed via highly stereoselective C-H bond activation-based cyclometalation. Right-handed chiral Ru catalysts enabled the Z- and enantioselective AROCM of a wide range of norbornenes and terminal alkenes, generating densely functionalized cyclopentanes with excellent stereo- and enantioselectivities (99:1 Z/E, up to 99% ee). Left-handed chiral Ru catalysts enabled the facile ARCM of sterically unhindered, all-terminal prochiral trienes, which had not been achieved by previous Ru catalysts, providing simple cyclic ethers and amides with tertiary or quaternary carbon stereocenters with excellent enantioselectivities (up to 99% ee).