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

Abstract

The asymmetric reduction of prochiral ketones and ketimines represents one of the most important and practical chemical transformations toward the synthesis of valuable chiral alcohols and amines. Among the existing strategies, organocatalyzed asymmetric reduction of carbonyls and imines using silicon hydrides is attractive due to low-cost, chemical stability, and easy handling in experiments. In this review, we wish to highlight the recent progress made in the past fifteen years in this field. Four catalytic systems of different activation modes are presented and discussed in detail. We aim to help shed light on common features that enable highly enantioselective silicon hydride reductions through organocatalysis and provide the design principles for the development of more effective catalytic systems.

Reductive Amination Revisited: Reduction of Aldimines with Trichlorosilane Catalyzed by Dimethylformamide─Functional Group Tolerance, Scope, and Limitations

“…The reductive amination was carried out under our standard conditions and proved to proceed uneventfully yet again, giving rise to amines 11a–p in ∼90% yields (Chart ). Reductive amination of the pyridine N -oxide derivative 2m proceeded with a concomitant reduction of the N -oxide group (with 2.5 equiv of Cl 3 SiH to reach completion), affording amine 11j (84%) …”

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

“…The integration of Equation ( 1) provides the kinetic model (Equation ( 2)). Although in one instance, nonlinear effects (NLE) have indicated the participation of two catalyst molecules in the mechanism [59], NLE data have confirmed in most instances the involvement of one single catalyst molecule in the mechanism, in particular for catalytic systems related to the ones in this study and involving a dual activation mechanism [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43].…”

“…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]. Although for axially chiral biscarboline-based alcohols, the participation of two molecules of HSiCl 3 has been included in the reaction mechanism, to consider the quantitative reaction of this reagent with alcohols to produce hydrogen, this could be discarded in our case, as this process was not observed [43].…”

“…Thus, the organocatalytic reduction of ketimines with trichlorosilane provides an efficient methodology for the asymmetric preparation of amines [24][25][26]. Different organocatalysts have been reported and evaluated against a series of benchmark ketimines [27][28][29][30][31][32][33] and related substrates, in particular enamines [34][35][36][37][38][39], to compare their reactivity and selectivity. Some of them have provided very good levels of asymmetric induction, but their development was often based on empirical approaches, where structural modifications were sequentially tested until the required level of chiral induction was achieved.…”

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

“…Herein describes our preliminary investigations in this area. Among the reported reducing agents that are amenable for organocatalysis (selected reviews; [27][28][29]), trichlorosilane is particularly attractive because it is a readily available, inexpensive and easy-to-handle liquid (selected reviews; [30][31][32]). Furthermore, it only produces innoxious NaCl and SiO2 as by-products upon quenching with aqueous NaOH or NaHCO3 solutions, which are easily separable from the reaction products (i.e., organic compounds).…”