Aggregation-Induced Asymmetric Synthesis (AIAS) Leading to More Selective Formation of 2,3-Dihydrobenzofuran Based on Various Sulfur Ylides

Abstract The 2,3-dihydrobenzofuran scaffold represents a key structural motif in many bioactive natural products and pharmaceutical compounds. Herein, we report an efficient [4 + 1] annulation of chiral salicyl N-phosphonyl imine with sulfur ylides under aggregation-induced conditions to access functionalized trans-2,3-dihydrobenzofuran derivatives. Systematic modulation of the THF/EtOH cosolvent ratios enable tunable diastereoselectivity, with diastereomeric ratios improving progressively as solvent polarity increased. Aggregation-induced emission (AIE), aggregation-induced polarization (AIP), and dynamic light scattering (DLS) analyses confirm the formation and evolution of chiral aggregates, providing mechanistic insight into the origin of aggregation-induced synthesis. Overall, this work highlights the application of aggregation-induced asymmetric synthesis (AIAS) to enhance stereocontrol and expand the synthetic toolbox for accessing functionalized 2,3-dihydrobenzofuran scaffolds.