Enantioselective Michael addition of alpha-substituted cyanoacetates to vinyl ketones catalyzed by bifunctional organocatalysts.
A highly enantioselective Michael addition of alpha-substituted cyanoacetates to vinyl ketones was accomplished in the presence of simple bifunctional thiourea/tertiary amine organocatalysts. A number of alpha-aryl or alkyl cyanoacetates have been successfully applied to give multifunctional compounds with an all-carbon-substituted quaternary stereocenter in excellent enantioselectivities (82-97 % ee) and yields (61-99 %). The optical pure adducts could be smoothly converted to variously structured beta(2,2)-amino acid esters. Moreover, an interesting reaction model involving multiple hydrogen-bonding interactions amongst the thiourea/tertiary amine catalyst and the reactants has been proposed based on the absolute configuration of the adduct and computational studies.
Liu
Tian-Yu
TY
Key Laboratory of Drug-Targeting of Education Ministry and Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
Li
Rui
R
Chai
Qian
Q
Long
Jun
J
Li
Bang-Jing
BJ
Wu
Yong
Y
Ding
Li-Sheng
LS
Chen
Ying-Chun
YC
D000085:Acetates / Q000737:chemistry*; D000596:Amino Acids / Q000737:chemistry; D002384:Catalysis; D018360:Crystallography, X-Ray; D003486:Cyanides / Q000737:chemistry*; D004583:Electrons; D007659:Ketones / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D013237:Stereoisomerism
D000085:Acetates; D000596:Amino Acids; D003486:Cyanides; D007659:Ketones