Catalytic asymmetric 1,2-addition of α-isothiocyanato phosphonates: Synthesis of chiral β-hydroxy- or β-amino-substituted α-amino phosphonic acid derivatives

Article abstract of DOI:10.1002/anie.201308514

α-Amino phosphonic acid derivatives are considered to be the most important structural analogues of α-amino acids and have a very wide range of applications. However, approaches for the catalytic asymmetric synthesis of such useful compounds are very limited. In this work, simple, efficient, and versatile organocatalytic asymmetric 1,2-addition reactions of α-isothiocyanato phosphonate were developed. Through these processes, derivatives of β-hydroxy-α-amino phosphonic acid and α,β-diamino phosphonic acid, as well as highly functionalized phosphonate-substituted spirooxindole, can be efficiently constructed (up to 99 % yield, d.r. >20:1, and >99 % ee). This novel method provides a new route for the enantioselective functionalization of α-phosphonic acid derivatives. Correct chirality critical: Organocatalytic asymmetric Adol-type and Mannich-type reactions of α-isothiocyanato phosphonate have been realized. Michael addition was also applicable under the same catalytic conditions. This versatile approach provides a new route for the synthesis of diverse highly optically active functionalized α-amino phosphonic acid derivatives. Copyright