Asymmetric Synthesis of Indolines Bearing a Benzylic Quaternary Stereocenter through Intramolecular Arylcyanation of Alkenes

Abstract

Enantioselective intramolecular arylcyanation of olefins is achieved by a Ni(cod)₂/chiral phosphinoxazoline/AlMe₂Cl catalyst to give chiral, substituted indoline derivatives bearing a benzylic quaternary stereocenter in high yields with good to excellent enantioselectivities.

Key words

asymmetric synthesis - carbocyanation - C-C bond activation - nickel - indoline

References and Notes

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General Experimental Procedure: An aryl cyanide (0.50 mmol) and a solution of AlMe₂Cl (1.04 M in hexane, 0.20 mL, 0.20 mmol) were added sequentially to a solution of Ni(cod)₂ (13.8 mg, 50 µmol) and a ligand (50 µmol) in 1,2-dimethoxyethane (0.50 mL) prepared in a 3 mL vial under an argon atmosphere in a dry-box. The vial was sealed with a screw-cap, taken outside the dry-box and heated at 100 ˚C for the time specified Table  [¹] . The resulting mixture was filtered through a silica gel pad, concentrated in vacuo, and purified by flash column chromatography on silica gel to give the corresponding arylcyanation products in the yields listed in Table  [¹]

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The presented conditions were completely ineffective for N-methyl-N-(2-cyanophenyl)methacrylamide