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Abstract

In this work, two new atom-economic approaches for the synthesis of α-amino acids and their derivatives have been developed. First, a wide variety of preformed N-benzyl aldimines was reacted with acetylcyanide in the presence of Schreiner thiourea catalyst to obtain different N-acyl α-amino nitrile products. Then Jacobsen thiourea catalysts were found to be highly enantioselective catalysts for this novel reaction giving the products with excellent enantioselectivities. The substrate scope was broad and one optically active N-acyl α-amino nitrile product was converted to the desired α-amino acid without losing enantiopurity. This report was the first catalytic asymmetric acylcyanation of imines.
Then a one-pot three-component variant of the acylcyanation reaction starting from different aldehydes, amines and acylcyanides was developed. Schreiner thiourea and Jacobsen thiourea catalysts were again the best catalysts for the non-asymmetric and asymmetric versions respectively giving a diverse array of products. Thus the first organocatalytic asymmetric three-component Strecker type reaction was developed.
A novel synthesis of cyclic amidines was achieved when ketimines were reacted with acetylcyanide in the presence of phenylphosphinic acid catalyst.
Besides the acylcyanation, a new catalytic three-component Ugi reaction from aldehydes, primary amines and isocyanides was designed and phenyl phosphinic acid (as a new motif for organocatalysis) was found to be the most efficient catalyst for this novel reaction affording a wide variety of α-amino amide products. This reaction could potentially be made asymmetric; however, so far low enantioselectivities were obtained with some new chiral phosphinic acid catalysts. Nevertheless, this is the first approach towards a catalytic asymmetric Ugi reaction.