Asymmetric Synthesis of Indoline from Achiral Phthalimide Involving Crystallization‐Induced Deracemization

Abstract

Abstract Asymmetric synthesis was performed by combining the photochemical reaction of an achiral substrate followed by crystallization‐induced deracemization. The results indicated that a fused indoline produced by photochemical intramolecular δ‐hydrogen abstraction and cyclization of N‐(5‐chloro‐2‐methylphenyl)phthalimide crystallized as a racemic conglomerate. Since this substrate has an aminal skeleton, racemization involving a ring‐opening and ring‐closing equilibrium process occurred under suitable conditions. Efficient racemization was observed in acetone containing a catalytic base, 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU). Crystallization‐induced dynamic deracemization by Viedma ripening from racemic indoline was performed with an excellent enantioselectivity of 99 % ee. Furthermore, one‐pot asymmetric synthesis of the indoline was achieved by the photochemical reaction of achiral phthalimide followed by continuous attrition‐enhanced deracemization converging to 99 % ee of enantiomeric crystals. This is the first example of asymmetric expression and amplification by photochemical hydrogen abstraction and crystallization‐induced dynamic deracemization.