title: An efficient and scalable one-pot double Michael addition-Dieckmann condensation for the synthesis of 4,4-disubstituted cyclohexane beta-keto esters.
abstract: 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.
authors: Department of Medicinal Chemistry, Amgen Incorporated, 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.
authors: Michael R
authors: MR
authors: DeGraffenreid
authors: Sarah
authors: S
authors: Bennett
authors: Sebastien
authors: S
authors: Caille
authors: Felix
authors: F
authors: Gonzalez-Lopez de Turiso
authors: Randall W
authors: RW
authors: Hungate
authors: Lisa D
authors: LD
authors: Julian
authors: Jacob A
authors: JA
authors: Kaizerman
authors: Dustin L
authors: DL
authors: McMinn
authors: Yosup
authors: Y
authors: Rew
authors: Daqing
authors: D
authors: Sun
authors: Xuelei
authors: X
authors: Yan
authors: Jay P
authors: JP
authors: Powers
mesh_terms: D003512:Cyclohexanones / Q000737:chemistry*; D004952:Esters / Q000737:chemistry*
chemical_list: D003512:Cyclohexanones; D004952:Esters