Dearomative Addition-Hydrogen Autotransfer for Branch-Selective N-Heteroaryl C-H Functionalization via Ruthenium-Catalyzed C-C Couplings of Diene Pronucleophiles.

A novel mechanism for N-heteroaryl C-H functionalization via dearomative addition-hydrogen autotransfer is described. Upon exposure to the catalyst derived from RuHCl(CO)(PPh3)3 and Xantphos, dienes 1a-1g suffer hydroruthenation to form allylruthenium nucleophiles that engage in N-heteroaryl addition-β-hydride elimination to furnish branched products of C-C coupling 3a-3s and 4a-4f. Oxidative cleavage of isoprene adducts 3j, 3k, 3l, and 3n followed by ruthenium-catalyzed dynamic kinetic asymmetric ketone reduction provides enantiomerically enriched N-heteroarylethyl alcohols 6a-6d and, therefrom, N-heteroarylethyl amines 7a-7d. Density functional theory calculations correlate experimentally observed regioselectivities with the magnitude of the N-heteroaryl LUMO coefficients and corroborate rate-determining dearomative allylruthenium addition. In the presence of 2-propanol and trifluoroethanol, dearomatized adducts derived from pyrimidine 2a and quinazoline 2n were isolated and characterized.