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

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 (aS)-2oxide. Interestingly, a mixture of (aS)-(S)-3,3'-bis ((S)-2-(hydroxymethyl)pyrrolidine-1-carbonyl)-9,9'dimethyl- 9H,9'H-[1,1'-bipyrido[3,4-b]indole] 2oxide and (aR)-(S)-3,3'-bis((S)-2-(hydroxymethyl) pyrrolidine-1-carbonyl)-9,9'-dimethyl-9H,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 (aS)-(S)-3,3'-bis((S)-2-(hydroxymethyl)pyrrolidine-1-carbonyl)-9,9'dimethyl- 9H,9'H-[1,1'-bipyrido[3,4-b]indole] 2oxide. 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.

The Development of Organocatalytic Asymmetric Reduction of Carbonyls and Imines Using Silicon Hydrides

“…The catalyst 61 with a tertiary butyl group, exhibited highly catalytic efficiency (Scheme 25c). In the same year, axially chiral N‐O alcohols, bearing two carboline moieties, were synthesized and utilized in the enantioselective reduction of ketimines and β‐amino esters [103] . In the presence of 5 mol% catalyst 62 , excellent yield and enantioselectivity were achieved (Scheme 25).…”

Rational Design of Simple Organocatalysts for the HSiCl3 Enantioselective Reduction of (E)-N-(1-Phenylethylidene)aniline

“…This study, however, did not provide any computational studies on these systems to reveal at a molecular level the activation mode proposed. A different mechanistic proposal, involving the participation of two molecules of trichlorosilane, has been recently reported by Dong et al in the case of axially chiral biscarboline-based alcohols [43].…”

“…To carry out a more rational catalyst design, better insight on the mechanisms for this process is needed to understand the effects of structural modifications. However, only a few computational or experimental systematic mechanistic studies are available, and, in most instances, tentative models are elaborated in order to understand the observed enantioselectivity at the molecular level [40][41][42][43]. In the seminal work of Schreiner and co-workers, a detailed evaluation of the possible mechanism of this reaction using density function theory calculations (B3PW91/cc-pVDZ) was reported [40].…”

Evaluation of 3,3′-Triazolyl Biisoquinoline N,N′-Dioxide Catalysts for Asymmetric Hydrosilylation of Hydrazones with Trichlorosilane

“…Since Matsumura's seminal work, that employed N-formylproline-derived catalysts [33,34], and the milestone achieved by Malkov and Kočovský with their N-methyl-L -valine-based catalysts [35][36][37], numerous chiral Lewis-base catalysts have been reported for the asymmetric hydrosilylation of ketimines with trichlorosilane (selected reviews; [30][31][32], selected references; [38][39][40][41][42][43][44][45]). While the majority of these catalysts are amide-based Lewis-bases, other kinds of Lewis-bases are also reported, which includes pyridine N-oxides (selected references; [46][47][48][49][50][51]), phosphine oxides (selected references; [52][53][54]), and sulfinamides (selected references; [55,56]). Despite a plethora of reports in this area, the Lewis-base-catalyzed trichlorosilane-mediated reduction of ketimines currently remains limited to N-aryl and alkyl protected ones (Scheme 1, Equation ( 2)).…”

“…Since Matsumura's seminal work, that employed N-formylproline-derived catalysts [33,34], and the milestone achieved by Malkov and Kočovský with their N-methyl-L-valine-based catalysts [35][36][37], numerous chiral Lewis-base catalysts have been reported for the asymmetric hydrosilylation of ketimines with trichlorosilane (selected reviews; [30][31][32], selected references; [38][39][40][41][42][43][44][45]). While the majority of these catalysts are amide-based Lewis-bases, other kinds of Lewisbases are also reported, which includes pyridine N-oxides (selected references; [46][47][48][49][50][51]),…”