An efficient and scalable one-pot double Michael addition-Dieckmann condensation for the synthesis of 4,4-disubstituted cyclohexane beta-keto esters.
A simple, scalable, and efficient one-pot methodology for the synthesis of 4,4-disubstituted cyclohexane beta-keto esters from benzylic nitriles or esters and methyl acrylate promoted by potassium tert-butoxide is described. The process relies on a tandem double Michael addition-Dieckmann condensation reaction, which results in the formation of three discrete carbon-carbon bonds in a single pot, including a quaternary center. The method allows for the convenient and rapid synthesis of a variety of 4-aryl-4-cyano-2-carbomethoxycyclohexanone and 4-aryl-2,4-biscarbomethoxycyclohexanone building blocks for use in natural products synthesis and medicinal chemistry.
DeGraffenreid
Michael R
MR
Department of Medicinal Chemistry, Amgen Incorporated, 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.
Bennett
Sarah
S
Caille
Sebastien
S
Gonzalez-Lopez de Turiso
Felix
F
Hungate
Randall W
RW
Julian
Lisa D
LD
Kaizerman
Jacob A
JA
McMinn
Dustin L
DL
Rew
Yosup
Y
Sun
Daqing
D
Yan
Xuelei
X
Powers
Jay P
JP
D003512:Cyclohexanones / Q000737:chemistry*; D004952:Esters / Q000737:chemistry*
D003512:Cyclohexanones; D004952:Esters