Aerobic, transition-metal-free, direct, and regiospecific mono-α-arylation of ketones: synthesis and mechanism by DFT calculations

J Am Chem Soc. 2013 Sep 25;135(38):14048-51. doi: 10.1021/ja4074563. Epub 2013 Sep 11.

Abstract

We disclose a facile, aerobic, transition-metal-free, direct, and regiospecific mono-α-arylation of ketones to yield aryl benzyl and (cyclo)alkyl benzyl ketones with substitution patterns that are currently inaccessible or challenging to prepare using conventional methods. The transformation is operationally simple, scalable, and environmentally friendly. There is no need for pre-functionalization (i.e., α-halogenation or silyl enol ether formation) or the use of specialized arylating agents (i.e., diaryliodonium salts). DFT calculations suggest that the in situ-generated enolate undergoes direct C-C bond formation with the nitroarene followed by regioselective O2-mediated C-H oxidation.

Publication types

  • Research Support, Non-U.S. Gov't