Organocatalytic asymmetric hydroxymethylation of isoindolinones with paraformaldehyde

Activated 3-substituted isoindolinones have been investigated as nucleophiles in the organocatalytic asymmetric cross-aldol reaction with formaldehyde for the synthesis of derivatives with tetrasubstituted stereocenters. Among the tested catalysts, bifunctional chiral tertiary amines led to the target products in high yields and moderate enantioselectivity, while chiral ammonium salts, tested under phase-transfer conditions, were less effective. Graphical abstract: [Figure not available: see fulltext.]