Synthesis of 2-substituted indolines using sequential Pd-catalyzed processes

Abstract

A concise route to enantiomerically pure 2-substituted indolines 4a–g and a 2-substituted tetrahydroquinoline 4h has been developed by application of the Pd-catalyzed coupling of amino functionalised organozinc reagents with 2-bromoiodobenzene, followed by Buchwald's palladium-catalyzed intramolecular amination reaction. The yields in the initial coupling are modest (36–52%), but the cyclisation yields are satisfactory (63–87%). The stereochemical integrity of a representative example was established by chiral phase HPLC.