Constructing densely functionalized Hajos–Parrish-type ketones with six contiguous stereogenic centers and two quaternary carbons in a formal [2 + 2 + 2] cycloaddition cascade

Abstract

A [2 + 2 + 2] annulation of 2-methylcyclopentane-1,3-dione and nitrostyrenes has been achieved via a cascade double Michael–Henry reaction that provides densely functionalized Hajos–Parrish-type ketones with two quaternary carbons and six contiguous stereogenic centers. An uncommon and intriguing example of the high self-disproportionation of enantiomers (SDE) in the crystallization of racemic 3i was observed. The spontaneous high resolution of racemic mixture of 3i into its enantiopure forms via regular crystallization without the need to utilize a chiral resolving agent or external stimuli has achieved. The structures of the appropriate derivatives, (±)-3a, (±)-5a, (±)-3f, and (−)-3i, were further confirmed by their single-crystal X-ray crystallographic analyses.