Michael Additions to Dehydroalanine Derivatives

Abstract

The Michael addition is one of the most important and generic synthetic tools for producing quaternary carbon atoms. However, there are few reports on the use of this conjugate addition of nucleophiles to α, β-dehydroamino acids [1–3]. The limited use of dehydroamino acids in these reactions can be assigned mainly to the fact that these compounds are poor Michael acceptors. However, we found that double acylation of the amino group of α, β-dehydroalanine derivatives greatly enhances the reactivity of these compounds towards nucleophilic addition. Thus, by addition of nitrogen and sulfur nucleophiles to these double acylated dehydroalanine derivatives, with potassium carbonate as base and acetonitrile as solvent, we were able to carry out high-yield syntheses of several β-substituted alanines [4]. The same method gave the corresponding β-substituted dehydroalanine derivatives when 4-toluenesulfonyl was substituted for one of the amine acyl groups [5]. In view of these results, we decided to expand the scope of this reaction to other nucleophiles.