Chromium(III)-Catalyzed C(sp2)-H Alkynylation, Allylation, and Naphthalenation of Secondary Amides with Trimethylaluminum as Base

Among base metals used for C-H activation reactions, chromium(III) is rather unexplored despite its natural abundance and low toxicity. We report herein chromium(III)-catalyzed C(sp(2))-H functionalization of an ortho-position of aromatic and alpha,beta-unsaturated secondary amides using readily available AlMe3 as a base and using bromoalkynes, allyl bromide, and 1,4-dihydro-1,4-epoxynaphthalene as electrophiles. This redox-neutral reaction taking place at 70-90 degrees C, requires as low as 1-2 mol % of CrCl3 or Cr(acac)(3) as a catalyst without any added ligand, and tolerates functional groups such as aryl iodide, boronate, and thiophene groups. Stoichiometric and kinetics studies as well as kinetic isotope effects suggest that the catalytic cycle consists of a series of thermally stable but reactive intermediates bearing two molecules of the amide substrate on one chromium atom and also that one of these chromate(III) complexes takes part in the alkynylation, allylation, and naphthalenation reactions. The proposed mechanism accounts for the effective suppression of methyl group delivery from AlMe3 for ortho-C-H methylation.