(1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)methanone synthesis

 To a solution of indole (11 g, 95 mmol) in 30 mL of dichloromethane at ambient temperature was added 105 mL of a 1 M solution of ethyl magnesium bromide in tetrahydrofuran (THF) (105 mmol) δropwise via syringe pump. After the addition was complete, the solution was stirred for 15 min at which time 105 mL of a 1 M solution of ZnCl2 in Et2O (105 mmol) was added. The mixture was stirred for an additional 30 min, and then 2,2,3,3-tetramethylcyclopropane carbonyl chloride (95 mmol) in 50 mL of dichloromethane was added via cannula. The mixture was stirred for 6 h at ambient temperature and then was quenched with 50 mL of saturated, aqueous NH4Cl and diluted with 50 mL of dichloromethane. The layers were separated, and the aqueous layer was extracted with dichloromethane (3 × 30 mL). The combined organics were washed with 20 mL of H2O and then were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified via column chromatography (SiO2, 50% ethyl acetate/ hexanes) to give 9.7 g of the major regioisomer (1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)methanone (40 mmol, 42% yield) and 6.1 g of the minor regioisomer of 1-[(2,2,3,3-tetramethylcyclopropyl) carbonyl]-1H-indole (25 mmol, 27% yield). 1H NMR (major product) (300 MHz, CD3OD) δ ppm 1.32 (s, 6 H), 1.33 (s, 6 H), 2.14 (s, 1 H), 7.12-7.24 (m, 2 H), 7.38-7.46 (m, 1 H), 8.02 (s, 1 H), 8.19-8.25 (m, 1 H); 1H NMR (minor product) (300 MHz, CD3OD) δ ppm 1.29 (s, 6 H), 1.34 (s, 6 H), 1.94 (s, 1 H), 6.66 (dd,J =3.7, 0.7 Hz, 1 H), 7.16-7.32 (m, 2 H), 7.51-7.58 (m, 1 H), 7.67 (d, J = 3.7 Hz, 1 H), 8.32-8.39 (m, 1 H); MS (major and minor regioisomers) (DCI/NH3) m/z 242 (M + H) + .