Asymmetric Coupling of Carbon‐Centered Radicals Adjacent to Nitrogen: Copper‐Catalyzed Cyanation and Etherification of Enamides

Abstract

The first copper-catalyzed asymmetric cyanation and etherification reactions of enamides have been established, where a carbon-centered radical adjacent to a nitrogen atom (CRAN) is enantioselectively trapped by a chiral copper(II) species. Moreover, the asymmetric cyanation of vinyl esters was disclosed as well. These reactions feature very mild reaction conditions and high functional group tolerance, and give a series of chiral a-cyano amides, a-cyano esters and ahemiaminals in good yields with excellent enantioselectivity. The chiral a-cyano amides can be easily converted into enantioenriched 1,2-diamines and amino acids. Scheme 1. Asymmetric radical difunctionalization of enamides.

Enantioselective Radical‐Type 1,2‐Alkoxy‐Phosphinoylation to Styrenes Catalyzed by Chiral Vanadyl Complexes

“…To our knowledge, no similar enantioselective events in 1,2‐alkoxy‐phosphinoylation/phosphonylation or asymmetric benzylic etherification have been reported by chiral Cu(I/II) or other metal complex catalysts. As noted in Prof. G. Liu's recent report that only racemic etherification products were observed by Cu(II)‐Box systems [17a] . Alternatively, nucleophilic or radical‐type addition to an N ‐acyl‐imine intermediates by nucleophiles or alcohols becomes feasible if electron‐accepting N ‐acyl‐enamines are the acceptors towards phosphinoyl or CF 3 radicals [17b,c] .…”

“…Alternatively, nucleophilic or radical‐type addition to an N ‐acyl‐imine intermediates by nucleophiles or alcohols becomes feasible if electron‐accepting N ‐acyl‐enamines are the acceptors towards phosphinoyl or CF 3 radicals [17b,c] . Its corresponding asymmetric variant in 1,2‐alkoxy‐trifluoromethylation has recently been realized by Prof. Liu with chiral Cu(I/II) with associated alkoxides [17a] …”

Enantioselective Amino- and Oxycyanation of Alkenes via Organic Photoredox and Copper Catalysis

“…Since then, several groups have reported cyanofunctionalizations of alkenes via this radical relay strategy. − More specifically, several examples of enantioselective aminocyanations have been disclosed using a similar copper system − (Figure C). N -centered radicals that are derived from NFSI, trimethylsilyl azide, and N -hydroxypthalamide (NHP) esters add to alkenes, resulting in an alkyl radical primed for a copper-mediated cyanation event, delivering the β-amino nitrile products.…”