Atroposelective Synthesis of Axially Chiral Styrenes via an Asymmetric C–H Functionalization Strategy

Abstract

<h2>Summary</h2> Axially chiral styrenes, which exhibit a chiral axis between a substituted alkene and an aromatic ring, have been largely overlooked. The hurdle is the lower barriers to rotation compared with that of their biaryl counterparts, rendering their asymmetric synthesis more difficult. We report herein the highly atroposelective synthesis via a C−H functionalization strategy of axially chiral styrenes with an open-chained alkene. Various axially chiral styrenes were produced by Pd(II)-catalyzed C−H alkenylation and alkynylation in good yields (up to 99%) and enantioselectivities (up to 99% ee) by using L-pyroglutamic acid as an inexpensive chiral ligand. The potent application of the styrene atropisomers is demonstrated by a Co(III)-catalyzed enantioselective C−H amidation of ferrocene with axially chiral styrene-type acid as chiral ligand. Experimental and computational studies were conducted to elucidate the reaction mechanism. The chiral induction model of the enantioselectivity-determining C−H bond activation step was also provided based on DFT calculations.