Direct Asymmetric Addition of Heteroatom Nucleophiles to Imines

Abstract

The direct asymmetric addition of heteroatom nucleophiles to imines represents one of the most efficient tools for the formation of carbon‐heteroatom bonds and has received much interest recently. The review is devoted to the asymmetric addition reactions of non‐carbon nucleophiles to imines. The present review is divided into five main sections: reactions with N‐nucleophiles; reactions with P‐nucleophiles; reactions with O‐nucleophiles; reactions with S‐nucleophiles; reactions with Se‐nucleophiles. It has been seen that chiral catalysts such as quinines, BINOLs, chiral phosphoric acids as well as various Brønsted and Lewis acids are the source of asymmetry of the presented reactions of asymmetric addition of non‐carbon nucleophiles to imines.

Zn(ii)-catalysed enantioselective addition of alcohols and tert-butyl hydroperoxide to isatin-derived N-Boc ketimines

“…4 Despite the progress in enantioselective addition of oxygen-based nucleophiles to aldimines, examples of reactions affording enantiomerically pure N,O aminals from ketimines are still rare. 5…”

Catalytic Enantioselective Construction of an α-Thio-Substituted α-Aminonitriles-Bearing Tetrasubstituted Carbon Center

“…Changing the cyclohexyl moiety to the sterically encumbering benzhydryl moiety was also tolerated, giving the product without loss of either the yield or enantioselectivity ( 4ap : 94%, 96% ee). Tertiary thiols, which have far been restricted in previous reports, ,, presumably due to high steric hindrance and higher p K a compared to other thiols (approximately p K a = 18 in DMSO), 2q is a suitable reaction substrate for the protocol, although longer reaction time was required ( 4aq : 59%, 89% ee). Benzenethiol 2r was also found to be a suitable coupling partner for the reaction albeit with moderate enantioselectivity probably because of the racemic background reaction ( 4ar : 87%, 60% ee).…”

“…There are also examples of these urea-type HBD catalysts controlling the chirality of remote sites . Furthermore, we have previously developed catalytic enantioselective reactions of imines with thiols . In this context, we envisaged a novel strategy for the synthesis of α-thio-substituted α-aminonitriles with a tetrasubstituted carbon center via enantioselective thiol addition to the α-iminonitrile using HBD catalysis (Scheme d).…”

Enantioselective Transformations in the Synthesis of Therapeutic Agents

“…The transition metal-catalyzed asymmetric addition reaction represents an efficient process for the formation of carbon–carbon or carbon–heteroatom bonds. − As the formation of a stereogenic center and chemical bond occurs within one-step, this method is usually more efficient than the corresponding multistep synthetic process and can often compete with enzymatic processes by ensuring high stereoselectivity, generality, and enabling access to both enantiomers of therapeutic agents for biological screening and drug development.…”