Asymmetric Strecker Reaction with Chiral Amines: a Catalyst‐Free Protocol Using Acetone Cyanohydrin in Water

Abstract

The synthesis of a series of new chiral α‐aminonitriles was achieved in a diastereoselective Strecker reaction in a one‐pot procedure with aldehydes, enantiopure amines, and acetone cyanohydrin in water. Primary and secondary amines derived from L‐α‐amino acids were used as sources of chirality. The reactions proceeded efficiently without any catalyst at room temperature. The diastereoselectivity of the process, and the configurational stability of new chiral α‐aminonitriles were investigated. The identification of labile intermediates by NMR analysis, and a proposed mechanism and a model for the asymmetric induction are reported. The chemical transformation of proline‐derived chiral α‐amino‐nitriles into chiral amino‐diacids, aminols, and amides is reported.

Spectroscopy for model heterogeneous asymmetric catalysis

“…One of the early examples of HeAC by immobilization of a homogeneous catalyst was reported in France by Kagan et al for a supported chiral rhodium complex in 1973 . Immobilization approaches have been strongly developed in the past, and there are various excellent reviews and scientific reports available on the topic.…”

A short synthesis ofd-[1-14C]-serine of high enantiomeric purity

“…Since Harada first reported the diastereoselective Strecker reaction using ( S )‐1‐phenylethylamine as the chiral auxiliary, many chiral 1‐arylethylamine derivatives, such as phenylglycinol, phenylglycinol methyl ether, phenylglycine methyl ester, 1‐phenylalaninol, and phenylglycine amide, have been introduced for this purpose. ( S )‐1‐phenylethylamine is an optimal chiral auxiliary for the Strecker synthesis with a defined stereochemical outcome: ( S )‐1‐phenylethylamine affords ( S )‐configurated α‐aminonitrile as the major diastereomer, 26a–c which gives ( S )‐configured α‐amino acids after hydrolysis.…”

Ag-Catalyzed Cyanomethylation of Amines Using Nitromethane as a C1 Source

“…The structure has been identified in numerous bioactive compounds including pharmaceuticals . It has been applied as a useful building block for the formation of α-amino acids, β-aminoalcohols, 1,2-diamines, and so on. − The Strecker reaction, a traditional three-component condensation method, is the first choice for the preparation of α-amino nitriles. , Imine or iminium electrophiles generated in situ from amines and carbonyl compounds reacted with cyanide to afford the corresponding α-amino nitriles. However, this methodology is not suitable for the synthesis of N -tertiary α-amino nitriles from secondary amines .…”