Mechanistic insights to define the directional role of hydrogen-bonding network between aryl oximes and propargyl alcohols in Rh(III) catalysis

The mechanism of the Cp*Rh(OAc)2-catalyzed C−H activation/annulation of acetophenone oxime and secondary propargyl alcohol was studied theoretically. Four elementary steps are involved as follows: C−H activation via concerted-metalation-deprotonation (CMD) mechanism, regioselective alkyne insertion, β-OH elimination and metal-free 6π electrocyclization. Importantly, density functional theory (DFT) calculations reveal that β-H elimination is inferior to β-OH elimination that is assisted by the directional hydrogen-bonding network between the two hydroxyl groups of the substrates. This noncovalent interaction also contributes to tuning the regioselectivity of alkyne insertion. Furthermore, the metal-free 6π electrocyclization rather than Rh-assisted cyclization gave the final product, isoquinoline N-oxides. The computationally supported mechanistic features were further validated by exploring substrate effects via replacing acetophenone oxime with O-methyl oxime and secondary propargyl alcohol with allyl alcohol, allenol and tertiary propargyl alcohol, respectively.