title: Mechanism and stereoselectivity of a dual amino-catalyzed robinson annulation: rare duumvirate stereocontrol.
abstract: Computational study of the mechanisms and stereoselectivities of a dual amino-catalyzed synthesis of cyclohexenones containing all-carbon γ-quaternary and ∂-tertiary stereocenters is reported. Extensive conformational search with density functional theory optimizations, the high-accuracy SCS-MP2/cc-pV∞Z energies, and PCM solvation corrections were used to characterize all intermediates and transition states. Six mechanisms were considered, all consistent with available experiments. The reaction proceeds via sequential Michael and Mannich conjugate additions whereby the primary amine activates the aldehyde and the catalyst activates the pentenone. We have discovered a rare duumvirate stereocontrol: the Michael reaction sets the enantioselectivity, but both the Michael and the Mannich reactions control the diastereoselectivity.
authors.affiliation: Department of Chemistry, Oregon State University, 153 Gilbert Hall, Corvallis, Oregon 97331, USA.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Pierce
authors.forename: Ryne C
authors.initials: RC
authors.lastname: Johnston
authors.forename: Subham
authors.initials: S
authors.lastname: Mahapatra
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
authors.forename: Rich G
authors.initials: RG
authors.lastname: Carter
authors.forename: Paul
authors.initials: P
authors.lastname: Ha-Yeon Cheong