Benzaldehyde → 5-Benzyl-1H-indole

Participants

Reaction Steps

5-Bromo-1-triisopropylsilylindole (2.0 g, 5.68 mmol) was dissolved in THF (dry, 30 mL) and the solution cooled to -70° C. tert-Butyllithium (1.7M in hexane; 10.7 mL, 18.2 mmol) was added, and by the time addition was complete, a permanent yellow coloration had been produced. After a further 1 hr at -65° C. benzaldehyde (0.658 g, 6.20 mmol) was added and the mixture stirred at ca -65° C. for 1 hr before warming gradually to room temperature H2O and NaCl were added to the mixture which was then extracted (3×) with Et2O, and the extracts were combined, washed (H2O, 3× and then saturated aqueous NaCl) and dried (MgSO4). Evaporation gave a gum which was chromatographed (silica gel; hexane/Et2O; 0-30%). Recovered starting material, 0.437 g (22%) eluted first; followed by the product: phenyl(1-triisopropylsilylindol-5-yl)methanol, a gum which solidified on standing, 0.61 g (28%; several fractions containing contaminated product were subsequently obtained). The pure product (0.6 g, 1.58 mmol) was dissolved in THF (10 mL) and treated with tetra-n-butylammonium fluoride solution (1.0M in THF; 3.0 mL) at room temperature. The mixture was stirred for 1.5 hr and then partitioned between Et2O and saturated aqueous NaCl. After re-extracting the aqueous layer (Et2O; 2×), the combined ethereal layers were washed with saturated aqueous NaCl, dried (MgSO4) and evaporated to a gum which was chromatographed (silica gel; hexane/Et2O; 0-50%), giving: phenyl(indol-5-yl)methanol, as an almost colourless gum, 0.347 g (98%). This material was hydrogenated in EtOH (25 mL) over Pd-C (5%; a total of 0.30 g was added over the reaction period, in two portions), at 45 psi, for ca 40 hr. The catalyst was filtered off, and the filtrate evaporated to a gum which was chromatographed (silica gel; hexane/Et2O; 0-50%). The required product: 5-benzylindole, was obtained as an off white solid, 0.135 g (44%), as well as 5-benzylindoline 0.03 g, (10%) and unreacted starting material, 0.013 g (4%).

Provenance & Evidence