Enantioselective synthesis of inherently chiral 9-benzylidene-9H-tribenzo[a,c,e][7]annulene and its application as a ligand platform

Summary

Saddle-shaped tribenzoannulene derivatives are conformationally stable and inherently chiral. The first catalytic enantioselective synthesis of this uncommon class of chiral molecules was achieved through palladium-catalyzed coupling of hydrazone derivatives of 9H-tribenzo[a,c,e][7]annulen-9-ones and benzyl bromides. The stereo-determining step in this process is the formation of the exocyclic double bond, which occurs through carbene migration insertion and β-hydride elimination. A wide range of inherently chiral 9-benzylidene-9H-tribenzo[a,c,e][7]annulenes were accessed under mild conditions in good yields with excellent enantioselectivity. A chiral phosphine ligand derived from this rigid and inherent chiral scaffold exhibited excellent asymmetric performance in Pd-catalyzed Tsuji-Trost and Rh-catalyzed 1,4-addition reactions. The reaction mechanism was confirmed by density functional theory calculations, which also shed light on the origin of the observed enantioselectivity.