Enantioselective <i>N</i> -Heteroaryl C–H Functionalization for Piperidine-Azine Conjugation: Alkynes as Allylmetal Pronucleophiles in Dearomative Addition-Hydrogen Auto-Transfer

The first enantioselective N -heteroaryl C–H functionalizations via dearomative addition-hydrogen auto-transfer are described. Using a ruthenium catalyst assembled from RuHCl(CO)(PPh 3 ) 3, ( R )-Cy-BINAP and the piperidine-containing alkyne 1d as an allylmetal pronucleophile, electron-deficient N -heteroaromatic compounds 2a – 2p are converted to branched products of C–H allylation 6a – 6p with uniformly high levels of enantioselectivity. Using alkyne 1f, enantiomerically enriched azetidine-containing adducts 8a, 8l, 8m, 8o, and 8p are formed. Isolation of the dearomatized adduct dihydro - 6h derived from quinazoline 2h corroborates the proposed dearomative addition pathway. DFT calculations demonstrate that dearomative C═N addition assisted by azine C–H hydrogen-bonding to the chloride counterion of the ruthenium catalyst is the rate-, regio-, and enantioselectivity-determining step of the catalytic cycle and that the magnitude of the azine LUMO coefficient guides regioselectivity.