“On Water” Organocatalyzed [4 + 2] Cycloaddition of Enones and Nitro Dienes for the Enantioselective Synthesis of Densely Substituted Cyclohexanones

An “on water” hydroquinine-based
primary amine–benzoic
acid organocatalyst system was found to be best suited to produce
3,4,5-trisubstituted cyclohexanones with a nitro group in the 4-position
from enones and nitro dienes under ambient conditions in good yield,
with good diastereoselectivity, and with excellent enantioselectivity.
An appreciable rate enhancement by water was observed compared to
organic solvents. Mechanistic analysis of the reaction suggests that
it followed an endo [4 + 2] cycloaddition with enamine
of enone as diene and nitro diene as dienophile.