Stereoselective Synthesis of Unsymmetrical β,β-Diarylacrylates by a Heck-Matsuda Reaction: Versatile Building Blocks for Asymmetric Synthesis of β,β-Diphenylpropanoates, 3-Aryl-indole, and 4-Aryl-3,4-dihydro-quinolin-2-one and Formal Synthesis of (-)-Indatraline

beta,beta-Disubstituted alpha,beta-unsaturated esters may serve as valuable derivatives for the preparation of other highly functionalized systems found in many natural products and marketed drugs. The stereoselective synthesis of unsymmetrical beta,beta-diarylacrylate compounds possessing two similar aromatic groups remains a substantial challenge. A simple and convenient stereoselective protocol for the preparation of beta,beta-disubstituted acrylates via a Heck-Matsuda reaction is reported. Good to high yields were accomplished by a ligand-free Pd-catalyzed arylation reaction of cinnamate esters with arenediazonium tetrafluorborates. Both electron-deficient and electron-rich arenediazonium salts could be employed as arylating reagents, and cinnamate esters were generally more reactive when substituted with an electron-donating group. The overall methodology is highly stereoselective, and this attribute was taken advantage of in the asymmetric Cu-catalyzed 1,4 reduction reaction to provide beta,beta-diarylpropanoates in high enantioselectivities. The synthesis of a 3-aryl indole and a chiral 4-aryl-2-quinolone from beta,beta-diarylacrylates was achieved by cyclization in the presence of a diphosphine ligated CuH catalyst. A convenient route for the asymmetric formal synthesis of the psychoactive compound (-)-Indatraline is also presented.