Quantum chemical study on enantioselective reduction of keto oxime ether with borane catalyzed by oxazaborolidine. Part 4. The reduction process in which oxime is reduced first and carbonyl is reduced through an intermediate containing a B(2)–N(3)–B BH2–O CO–C CO–C CN–N CN 7-membered ring

Abstract

As the fourth part of quantum chemical study on enantioselective reduction of keto oxime ether with borane catalyzed by chiral oxazaborolidine, the reduction path in which oxime is reduced first and the carbonyl is reduced through an intermediate containing a B(2)–N(3)–B BH2–O C  O–C C  O–C C  N–N C  N 7-membered ring is discussed by means of density functional theory (DFT) method in this paper. The structures of the main intermediary and transition states are optimized completely at the B3LYP/6-31g(d) level. The harmonic frequencies of all the structures are calculated, and corresponding vibrational modes are decided. The reduction path discussed in this paper mainly goes through the formation of the catalyst-borane adduct 2, catalyst-borane-keto oxime ether adduct 3b, adduct 4b* with a B(2)–N(3)–B BH2–O C  O–C C  O–C C  N–N C  N 7-membered ring and adduct 5b*. As shown from the studies on transition states, the controlling steps for the chirality of products are the transfers of hydride from the borane moiety to the oxime carbon and carbonyl carbon. From the energy point of view, the reaction should mainly go through 1→2→TS 1b-1→3b-1→TS 2b-1→4b*-1→TS 5b-1→5b*-1 and get cyclic(1S,2R)- cis amino-alcohols, which is in accordance with the experiment.