Trichlorosilane mediated asymmetric reductions of the CN bond

Abstract

Chiral amines are key components in numerous bioactive molecules. The development of efficient and economical ways to access molecules containing this functional group still remains a challenge at the forefront of synthetic chemistry. Of the methods that do exist, the trichlorosilane mediated organocatalytic reduction of ketimines offers significant potential as an alternative strategy. In this perspective, we wish to highlight the progress made in the past decade in this field and offer a direct quantitative comparison to transition-metal mediated process.

Mechanistic investigations of the asymmetric hydrosilylation of ketimines with trichlorosilane reveals a dual activation model and an organocatalyst with enhanced efficiency

“…This is very similar to the behaviour with the simpler catalysts 3 and 4, however the reactivity is inverted, with catalyst 26 showing incomplete complexation being more active. Since no direct reaction with HSiCl 3 is possible here as corroborated by 29 Si NMR data, the changes in the 1 3 and an additional Brønsted base capable of reacting with HCl generated or present in the reaction (Fig. 12).…”

“…Upon addition of 1 equiv. of HSiCl 3 , the hydroxy catalyst 17 shows a rapid and complete change in the stretching frequency of the carbonyl group, whilst catalyst 26 shows a rapid but incomplete change, suggesting an equilibrium process. This is very similar to the behaviour with the simpler catalysts 3 and 4, however the reactivity is inverted, with catalyst 26 showing incomplete complexation being more active.…”

“…However, significant chemical shift changes were Si NMR spectra of reaction products as depicted in Scheme 1 with catalyst 17. observed in the imidazole and methine protons, in addition to those signals corresponding to the pyrrolidine ring. As in the case of the hydroxyl-catalyst 17, these changes may have resulted from protonation of the imidazole, in this case from adventitious HCl usually found in HSiCl 3 . The presence of HCl and protonation of the catalysts appeared to be a key factor in their activity, and related studies have also shown that additives such as water (to form HCl in situ), acetic acid, and benzoic acid can improve the catalytic activity.…”

“…Since the first chiral Lewis-base derived catalyst was reported in 2001, 1 there have been many variants of catalyst prepared and evaluated; 2,3 selected examples include formamides, [4][5][6][7] sulfinimides, 8,9 pyridines, [10][11][12] and organophosphorus compounds. [13][14][15] The main focus of research from this group has been using an imidazole derived catalyst that has been shown to function as efficiently as the reported analogous picolinoyl series, 16 in addition to being amenable to reductive amination protocols.…”

Stereoselective metal-free catalytic synthesis of chiral trifluoromethyl aryl and alkyl amines

“…11 In the last decade different classes of enantiomerically pure Lewis bases have been developed. 12 We started our investigation by screening different typologies of chiral activators, developed by us and other groups. The catalysts, shown in Fig.…”