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

Towards Enantiomerically Pure Unnatural α-Amino Acids via Photoredox Catalytic 1,4-Additions to a Chiral Dehydroalanine

[Image: see text] Chemo- and diastereoselective 1,4-conjugate additions of anionic and radical C-nucleophiles to a chiral bicyclic dehydroalanine (Dha) are described. Of particular importance, radical carbon photolysis by a catalytic photoredox process using a simple method with a metal-free photocatalyst provides exceptional yields and selectivities at room temperature. Moreover, these 1,4-conjugate additions offer an excellent starting point for synthesizing enantiomerically pure carbon-β-substituted unnatural α-amino acids (UAAs), which could have a high potential for applications in chemical biology