New enantioselective metal-catalysed conjugate addition-initiated reactions of alkenyl(aza)arenes

Abstract

I. ENANTIOSELECTIVE RHODIUM-CATALYSED ARYLATION OF ELECTRON-DEFICIENT ALKENYLARENES

β-substituted alkenyl-para-nitroarenes, an unexplored substrate class for catalytic asymmetric addition reactions, undergo highly enantioselective rhodium-catalysed arylations with arylboronic acids in the presence of a dibenzylamide-containing chiral diene ligand. One example of the asymmetric arylation of an alkenyl-p-cyano-m-( trifluoromethyl)benzene is also reported. The scope of this process is broad with variation in the β-position of the alkene, additional substituents on the electrondeficient arene, and sterically and electronically unique arylboronic acids all tolerated. The synthetic utility of the developed methodology is demonstrated by smoothly converting one arylated product into its corresponding indole via the Bartoli reaction.

II. ENANTIOSELECTIVE COPPER-CATALYSED REDUCTIVE COUPLING OF ALKENYLAZAARENES WITH KETONES

Catalytic enantioselective methods for the preparation of chiral azarene-containing compounds are of high value. By combining the utility of copper hydride catalysis with the ability of C=N-containing azaarenes to activate adjacent alkenes toward nucleophilic additions, the enantioselective reductive coupling of alkenylazaarenes with ketones has been developed. The process is tolerant of a wide variety of azaarenes and ketones, and provides aromatic heterocycles bearing tertiary-alcoholcontaining sidechains with high levels of diastereo- and enantioselection.