Origin of the enantioselectivity in organocatalytic Michael additions of β-ketoamides to α,β-unsaturated carbonyls: a combined experimental, spectroscopic and theoretical study.
The organocatalytic enantioselective conjugate addition of secondary β-ketoamides to α,β-unsaturated carbonyl compounds is reported. Use of bifunctional Takemoto's thiourea catalyst allows enantiocontrol of the reaction leading either to simple Michael adducts or spirocyclic aminals in up to 99 % ee. The origin of the enantioselectivity has been rationalised based on combined DFT calculations and kinetic analysis. This study provides a deeper understanding of the reaction mechanism, which involves a predominant role of the secondary amide proton, and clarifies the complex interactions occurring between substrates and the catalyst.
Aix Marseille Université, Centrale Marseille, CNRS, iSm2 UMR 7313, 13397, Marseille (France). Fax: (+33) 491-289-187.
Adrien
A
Quintard
Diana
D
Cheshmedzhieva
Maria Del Mar
Mdel M
Sanchez Duque
Anouk
A
Gaudel-Siri
Jean-Valère
JV
Naubron
Yves
Y
Génisson
Jean-Christophe
JC
Plaquevent
Xavier
X
Bugaut
Jean
J
Rodriguez
Thierry
T
Constantieux
D000475:Alkenes / Q000737:chemistry; D000577:Amides / Q000737:chemistry*; D002384:Catalysis; D008958:Models, Molecular; D009570:Nitriles / Q000737:chemistry*; D013057:Spectrum Analysis; D013237:Stereoisomerism; D013890:Thiourea / Q000737:chemistry
D000475:Alkenes; D000577:Amides; D009570:Nitriles; C520957:beta-ketoamide; D013890:Thiourea
Michael addition; density functional calculations; enantioselectivity; organocatalysis; reaction mechanisms