A very efficient synthesis of 2,3-diaryl-β-amino acid derivatives is realized by a TiCl4/triethylamine-catalyzed Mannich-like reaction of arylacetic or arylthioacetic esters with arylimines. The presence on the arylacetic moiety of an ortho-heteroatom group able to coordinate to the titanium center is of dramatic importance for the outcome of the reaction and to tune the syn/anti diastereoselection. In particular, with o-F-, o-Cl-, and o-Br-arylacetates, the syn adduct was isolated as the largely prevalent isomer. When (-)-8-phenylmenthyl (2-fluorophenyl)acetate was used, the condensation with imines resulted in high diastereo- and enantioselectivity. In agreement with the stereochemical results and NMR studies, a conceivable reaction mechanism was proposed. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Syn/anti switching by specific heteroatom-titanium coordination in the Mannich-like synthesis of 2,3-diaryl-β-amino acid derivatives

F. Foschi;D. Nava;
2014

Abstract

A very efficient synthesis of 2,3-diaryl-β-amino acid derivatives is realized by a TiCl4/triethylamine-catalyzed Mannich-like reaction of arylacetic or arylthioacetic esters with arylimines. The presence on the arylacetic moiety of an ortho-heteroatom group able to coordinate to the titanium center is of dramatic importance for the outcome of the reaction and to tune the syn/anti diastereoselection. In particular, with o-F-, o-Cl-, and o-Br-arylacetates, the syn adduct was isolated as the largely prevalent isomer. When (-)-8-phenylmenthyl (2-fluorophenyl)acetate was used, the condensation with imines resulted in high diastereo- and enantioselectivity. In agreement with the stereochemical results and NMR studies, a conceivable reaction mechanism was proposed. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Amino acids; C-C coupling; Diastereoselectivity; Synthetic methods; Titanium; Organic Chemistry; Physical and Theoretical Chemistry
Bonetti, A.; Clerici, F.; Foschi, F.; Nava, D.; Pellegrino, S.; Penso, M.; Soave, R.; Gelmi, M. L.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11383/2086291
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 14
  • ???jsp.display-item.citation.isi??? 13
social impact