Toluene → Indole

Participants

Reaction Conditions

Reaction Steps

A solution of potassium N,N-bis(trimethylsilyl)amide in toluene (0.50 M, 24.7 mL, 12.3 mmol, 1.1 equiv) was added dropwise via syringe to a stirred solution of the enone 5 (4.24 g, 11.2 mmol, 1 equiv, dried by azeotropic distillation with toluene, 3 mL) in tetrahydrofuran (31.3 mL) at −78° C. and the reaction solution was stirred at −78° C. for 30 min. A solution of the isopropyl sulfonate ester 6 (4.99 g, 16.2 mmol, 1.45 equiv, prepared immediately prior to use, dried by azeotropic distillation with toluene, 3 mL) in tetrahydrofuran (3.0 mL) was then added dropwise via cannula to the cold reaction solution. The flask containing the sulfonate ester 6 was rinsed with two 3.0-mL portions of tetrahydrofuran, which were transferred to the reaction flask via cannula. Upon completion of the addition, the reaction flask was immersed in a −35° C. bath and the reaction solution was stirred at this temperature 30 h. The product solution was then partitioned between saturated aqueous sodium bicarbonate solution (100 mL) and ethyl acetate (200 mL). The layers were separated, and the organic layer was washed with saturated aqueous sodium chloride solution (100 ml). The washed solution was dried over sodium sulfate. The dried solution was filtered and the filtrate was concentrated. The residue obtained was purified by flash-column chromatography on silica gel (deactivated with 10% triethylamine-ethyl acetate, eluting with 10% ethyl ether-hexanes initially, grading to 20% ethyl ether-hexanes, 5%-steps) to furnish the alkylation product 7 as a white foam (4.37 g, 70%).

Provenance & Evidence