Modular Design of Chiral Conjugate-Base-Stabilized Carboxylic Acids: Catalytic Enantioselective [4 + 2] Cycloadditions of Acetals

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available 1,2-amino alcohols provide the framework for
a new generation of chiral carboxylic acid catalysts that rival the
acidity of the widely used chiral phosphoric acid catalyst (S)-TRIP. Covalently linked thiourea sites stabilize the
carboxylate conjugate bases of these catalysts via anion-binding,
an interaction that is largely responsible for the low pKa values. The utility of the new catalysts is illustrated
in the context of challenging [4 + 2] cycloadditions of salicylaldehyde-derived
acetals with homoallylic and bishomoallylic alcohols, providing polycyclic
chromanes in a highly enantioselective fashion.