Synthesis of Nβ-Substituted α,β-Diamino Acids via Stereoselective N-Michael Additions to a Chiral Bicyclic Dehydroalanine

The highly diastereoselective 1,4-conjugate additions of several nitrogen nucleophiles to chiral bicyclic dehydroalanines have been assessed effectively at room temperature in good to excellent yields without needing any catalyst or additional base. This methodology is general, simple, oxygen and moisture tolerant, high-yielding, totally chemo- and stereoselective. This procedure offers an efficient and practical approach for the synthesis of Nβ-substituted α,β-diamino acids, such as 1-isohistidine, τ-histidinoalanine, β-benzylaminoalanine, β-(piperidin-1-yl)alanine, β-(azepan-1-yl)alanine, and fluorescent and ciprofloxacin-containing amino acid derivatives.We thank the Ministerio de Ciencia, Innovacion y Universidades (RTI2018-099592-B-C21 and RTI2018-099592-B-C22 projects) and the Ministerio de Economia y Competitividad (RYC-2013-14706 to G.J.-O.). N.M. and P.O. thank Universidad de La Rioja for a grant. We also thank Universidad de La Rioja (Beronia cluster) for computer support