DFT Study of PNP-Mn-Catalyzed Acceptorless Dehydrogenative Coupling of Primary Alcohols with Hydrazine to Give Alkene or Azine

A density functional theory (DFT) study has been carried out to gain insight into the acceptorless dehydrogenative coupling (ADC) reactions of primary alcohols with hydrazine to afford alkene or azine, catalyzed by PNP-Mn pincer catalyst. The reaction takes place via three stages: alcohol dehydrogenation to give aldehyde (stage 1), coupling of aldehyde with hydrazine to give hydrazone (stage 2), and further coupling of hydrazone with aldehyde to afford alkene or azine (stage 3). Stage 2 is the rate-determining step with a barrier of 31.7 kcal/mol, while stage 3 determines the chemoselectivity. In stage 3, the N–H addition of hydrazone to PNP-Mn gives a nucleophilic [Mn]–N¹H–N²C¹HR intermediate (i.e., IM7 or IM7a) featuring two nucleophilic sites at N¹ and C¹. The nucleophilic attack of aldehyde at C¹ leads to alkene, while the attack at N¹ gives azine. The kinetic competition between the two pathways controls the chemoselectivity of the reaction. If the alcohol is aromatic such as a benzyl alcohol, then the pathway initiated by nucleophilic attack at C¹ is kinetically more favorable, leading to alkene. For aliphatic alcohol, the pathway with the attack at N¹ wins, resulting in azine. The N₂ extrusion involved in alkene formation pathway takes place in stage 3 by dissociation of an anionic species (i.e., CHR–C­(OH)­HR, 8^–/8a^–) from the intermediate resulted from the C,C coupling. For the coupling of aromatic alcohol with hydrazine, the chemoselectivity of alkene originates from the electron-withdrawing effect of the aromatic group on the anionic fragment, which lowers the barrier for the dissociation. We expect these in-depth mechanistic insights to provide valuable guidance to mechanistic understanding and help to develop new ADC reactions.