Asymmetric synthesis of 2-arylindolines and 2,2-disubstituted indolines by kinetic resolution.

Kinetic resolution of 2-arylindolines (2,3-dihydroindoles) was achieved by treatment of their N - tert -butoxycarbonyl (Boc) derivatives with n -butyllithium and sparteine in toluene at –78 °C followed by electrophilic quench. The unreacted starting materials together with the 2,2-disubstituted products could be isolated with high enantiomer ratios. Variable temperature NMR spectroscopy showed that the rate of Boc rotation was fast (ΔG ‡ ≈ 57 kJ/mol at 195 K). This was corroborated by DFT studies and by in situ ReactIR spectroscopy. The enantioenriched N -Boc-2-arylindolines were converted to 2,2-disubstituted products without significant loss in enantiopurity. Hence either enantiomer of the 2,2-disubstituted products could be obtained with high selectivity from the same enantiomer of the chiral ligand sparteine (one from the kinetic resolution and the other from subsequent lithiation–trapping of the recovered starting material). Secondary amine products were prepared by removing the Boc group with acid to provide a way to access highly enantioenriched 2-aryl and 2,2-disubstituted indolines.