Mechanism and Stereoselectivity of a Dual Amino-Catalyzed Robinson Annulation: Rare Duumvirate Stereocontrol

作者：Pierce Matthew D; Johnston Ryne C; Mahapatra Subham; Yang Hua; Carter Rich G; Cheong Paul Ha Yeon^*

来源：Journal of the American Chemical Society, 2012, 134(33): 13624-13631.

DOI：10.1021/ja3018219

Computational study of the mechanisms, and stereoselectivities of a dual amino catalyzed synthesis of Cyclohexenones containing all carbon gamma-quaternary and partial derivative-tertiary stereocenters is reported. Extensive conformational search with density functional theory optimizations, the high accuracy SCS-MP2/cc-pV infinity 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.

• 出版日期2012-8-22