Asymmetric Formal [5 + 3] Cycloadditions with Unmodified Morita–Baylis–Hillman Alcohols via Double Activation Catalysis

The discovery of
a previously unreported activation mode and reaction
pathway is important but challenging for the development of asymmetric
organocatalysis. Here we disclosed a formal [5 + 3] cycloaddition
reaction of unmodified Morita–Baylis–Hillman alcohols
from 2-cyclopentenone and aldehydes with cyclic azomethine imines.
A double catalytic system, combining chiral primary amine from cinchona
alkaloid and achiral 2-mercaptobenzoic acid, has proved to be crucial
for the chemoselectivity and enantioselectivity, through covalently
dual activation of the sterically hindered enone substrates. A spectrum
of tricyclic frameworks bearing substantial substitutions were produced
in moderate to high yields with good stereoselectivity (up to 98%
ee, >19:1 dr). Assisted by the experimental observations, a plausible
catalytic mechanism is proposed; moreover, the key intermediates suggested
have been detected and elucidated by high-resolution mass spectrometry
analysis.