Catalytic Mechanism Study on the 1,2‐ and 1,4‐Transfer Hydrogenation of Ketimines and β‐Enamino Esters Catalyzed by Axially Chiral Biscarboline‐Based Alcohols

Abstract

Abstract Axial N ‐O alcohols, which have two large carboline moieties connected to the axis were synthesized and used in catalytic enantioselective 1,2‐ and 1,4‐transfer hydrogenations of total 26 ketimines and β‐enamino esters. Excellent levels of enantioselectivity ranging from 91% to 99% were achieved by using catalyst (a S )‐( S )‐3,3′‐bis(( S )‐2‐(hydroxymethyl)pyrrolidine‐1‐carbonyl)‐9,9′‐dimethyl‐9 H ,9′ H ‐[1,1′‐bipyrido[3,4‐ b ]indole] 2‐oxide. Interestingly, a mixture of (a S )‐( S )‐3,3′‐bis(( S )‐2‐(hydroxymethyl)pyrrolidine‐1‐carbonyl)‐9,9′‐dimethyl‐9 H ,9′ H ‐[1,1′‐bipyrido[3,4‐ b ]indole] 2‐oxide and (a R )‐( S )‐3,3′‐bis(( S )‐2‐(hydroxymethyl)pyrrolidine‐1‐carbonyl)‐9,9′‐dimethyl‐9 H ,9′ H ‐[1,1′‐bipyrido[3,4‐ b ]indole] 2‐oxide was also able to provide high enantioselectivities up to 95% that is the same as that using pure (a S )‐( S )‐3,3′‐bis(( S )‐2‐(hydroxymethyl)pyrrolidine‐1‐carbonyl)‐9,9′‐dimethyl‐9 H ,9′ H ‐[1,1′‐bipyrido[3,4‐ b ]indole] 2‐oxide. A plausible catalytic mechanism was suggested and total four kinds of transition states (TS) including almost 60 TS structures were investigated using density functional theory (DFT) with different basis sets such as 6‐311G(2d,p). The predicted activation energy data are consistent with the experimental results. magnified image