The role of fluorine in the stereoselective tandem aza-Michael addition to acrylamide acceptors: an experimental and theoretical mechanistic study.
Aza-Michael additions of alpha-amino esters to fluorinated acceptors take place in a highly stereoselective manner, to give partially modified Psi[NHCH2]retropeptides incorporating a hydrolytically stable trifluoroalanine mimic. The reaction mechanism has been investigated experimentally and theoretically, in order to explain the effect of the trifluoromethyl group on the reactivity and the origins of the experimentally observed stereocontrol. The reaction is a two-step process, involving a tandem aza-Michael addition followed by a stereoselective hydrogen transfer. Both steps are base-catalyzed. The high level of stereocontrol is the result of a combination of electrostatic interactions and steric effects.
Fustero
Santos
S
Departamento de Química Orgánica, Universidad de Valencia, 46100 Burjassot, Valencia. santos.fustero@uv.es
Chiva
Gema
G
Piera
Julio
J
Volonterio
Alessandro
A
Zanda
Matteo
M
González
Javier
J
Ramallal
Antonio Morán
AM
D020106:Acrylamide / Q000737:chemistry*; D005461:Fluorine / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008958:Models, Molecular; D013237:Stereoisomerism
D020106:Acrylamide; D005461:Fluorine