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.