Asymmetric synthesis of α-mercapto-β-amino acid derivatives: application to the synthesis of polysubstituted thiomorpholines

• Published in: Tetrahedron: asymmetry 2006-04, Vol.17 (7), p.1135-1145
• Main Authors: Candela-Lena, José I., Davies, Stephen G., Roberts, Paul M., Roux, Bruno, Russell, Angela J., Sánchez-Fernández, Elena M., Smith, Andrew D.
• Format: Article
• Language: English
• ISSN: 0957-4166; 1362-511X
• DOI: 10.1016/j.tetasy.2006.04.004

Tandem conjugate addition of a homochiral lithium amide to tert-butyl cinnamate and quenching with TsS t Bu gives access to homochiral anti-α-mercapto-β-amino acid and polysubstituted thiomorpholine derivatives. Tandem conjugate addition of homochiral lithium N-benzyl- N-(α-methyl- p-methoxybenzyl)amide to tert-butyl cinnamate and enolate trapping with TsS t Bu proceeds with high diastereoselectivity to give a homochiral anti-α- tert-butylthio-β-amino ester. Stepwise deprotection gives the corresponding free α- tert-butylthio-β-amino acid without epimerisation. Tandem conjugate addition of homochiral lithium N-allyl- N-(α-methylbenzyl)amide to tert-butyl cinnamate and enolate trapping with TsS t Bu followed by conversion of the S- tert-butyl group to a disulphide, and reduction with Lalancette’s reagent generates polysubstituted thiomorpholine derivatives.