Synthetic Studies on Trifluoroacetylindoles

Comprehensive Synthesis of Photoreactive (3-Trifluoromethyl)diazirinyl Indole Derivatives from 5- and 6- Trifluoroacetylindoles for Photoaffinity Labeling

“…Construction of a (trifluoromethyl)diazirinyl moiety on indole at the 5-or 6-position began by treating the corresponding bromide derivatives (1a and 1b) with potassium hydride−t-BuLi followed by treatment with trifluoroacetylated reagents. Trifluoroactylations of 5-or 6-bromoindole with trifluoroacetic anhydride 5 with potassium hydride−t-BuLi were not effective (30−60%), and replacement of potassium hydride with sodium hydride did not influence the isolated yield. Replacement of trifluoroacetic anhydride with ethyl trifluoracetate or trifluoroacetyl piperidine improved the yield of the products (2a and 2b; ∼80%), because the leaving groups did not decrease the reaction mixture basicity.…”

“…2,2,2-Trifluoro-1-(1H-indol-5-yl)ethanone (2a). 5 A solution of 5-bromoindole 1a (1.57 g, 8.00 mmol) in THF (8 mL) was added dropwise to a suspension of potassium hydride (1.09 g, 30% suspension in mineral oil, 8.00 mmol) in THF (16.0 mL) at 0 °C under N 2 . After being stirred for 1 h at 0 °C, the mixture was cooled to −78 °C and a solution of t-BuLi (10 mL of 1.7 M pentane solution, 17.0 mmol) was added dropwise over a period of 15 min.…”

Preparation of 5-Heteroaryl Substituted 1-(4-Fluorophenyl)-1H-indoles via Palladium-Catalyzed Negishi and Stille Cross-Coupling Reactions

“…The rearrangement of 3-and 5-lithioindoles to the thermodynamically more stable 2-lithioindoles has been reported in the literature. 17 Such rearrangements were avoided by lateral protection of the indole 2-position by the introduction of bulky protecting groups at the indole N-1-position 17,18 or by generation of the indole N-1-anion prior to halogen metal exchange. 19 Apparently the presence of the weak orthodirecting fluorine 20,21 in the 4-fluorophenyl substituent at N-1 makes the protons in the C-3¢ position more reactive compared to the proton in the indole 2-position.…”