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 <i>N</i>-heteroaryl C-H functionalizations via dearomative addition-hydrogen auto-transfer are described. Using a ruthenium catalyst assembled from RuHCl(CO)(PPh₃)₃, (<i>R</i>)-Cy-BINAP and the piperidine-containing alkyne <b>1d</b> as an allylmetal pronucleophile, electron-deficient <i>N</i>-heteroaromatic compounds <b>2a</b>-<b>2p</b> are converted to branched products of C-H allylation <b>6a</b>-<b>6p</b> with uniformly high levels of enantioselectivity. Using alkyne <b>1f</b>, enantiomerically enriched azetidine-containing adducts <b>8a</b>, <b>8l</b>, <b>8m</b>, <b>8o</b>, and <b>8p</b> are formed. Isolation of the dearomatized adduct <i>dihydro</i>-<b>6h</b> derived from quinazoline <b>2h</b> 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.