Dynamic Kinetic Resolution in Enantioselective Reductive Amination ofα-Branched Aldehydes by Lewis Base Organocatalyzed Hydrosilylation

Abstract

Dynamic kinetic resolution (DKR) represents one of the most efficient strategies to prepare optically active compounds which have shown great potential in asymmetric synthesis. β‐Branched chiral amines widely exist in pharmaceutic chemicals and natural products. In this paper, an enantioselective reductive amination of α‐branched aldehydes via dynamic kinetic resolution has been presented. In the presence of a readily acessible chiral Lewis base catalyst derived from the intermediate of chloramphenicol, the reactions provided various β‐branched chiral amines with moderate to good yields (up to 92 %) in low to moderate enantioselectivities (up to 56 %).

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

“…kinetic resolution. [73] In the presence of a readily accessible catalyst 40 b, the reactions furnished various β-branched amines in moderate to excellent yields (up to 92 %), but only low to moderate enantioselectivities (up to 56 % ee) were obtained. Different from the case above, molecular sieves were added to the reaction mixture to remove water, which led to the dramatically increased yield without losing in enantioselectivity.…”

“…The interesting finding indicated that trace amount of water could react with trichlorosilane to generate HCl that promoted the tautomerization of the enamine to reactive imine, which was the real species participated in the reduction. The acetal‐based picolinoyl catalysts were also applied to the asymmetric reductive amination of α‐branched aldehydes via dynamic kinetic resolution [73] . In the presence of a readily accessible catalyst 40 b , the reactions furnished various β‐branched amines in moderate to excellent yields (up to 92 %), but only low to moderate enantioselectivities (up to 56 % ee) were obtained.…”

Organocatalytic Dynamic Kinetic Resolution: An Update

“…Earlier in 2017, an enantioselective reductive amination of α‐branched aldehydes evolving through DKR was described by Zhang et al [57] . It involved the asymmetric three‐component reaction between α‐branched aldehydes 198 , aromatic amines 6 and triethylsilane as the reductant agent.…”

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

“…The resulting kinetic profiles are presented in Figure 3. Chang-ing the solvent from CH 2 Cl 2 to CHCl 3 in this kind of reaction often provides lower ee values and slower reaction rates [54,[56][57][58], but slower kinetics can enable more accurate NMR kinetic analyses and reduce the contribution of the uncatalyzed reaction. The rate constants were calculated considering a simultaneous contribution of the uncatalyzed and catalyzed reactions with first-order rate equations in both substrate and reagent, in agreement with most mechanistic studies (Scheme 2 and Equation ( 1)) [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42].…”