Microwave‐Assisted Rapid One‐Pot Synthesis of Fused and Non‐Fused Indoles and 5‐[¹⁸F]Fluoroindoles from Phenylazocarboxylates

Abstract

Substituted indoles can be prepared from phenylazocarboxylates through a rapid one-pot sequence featuring a microwave-assisted Fischer indole synthesis as a key step. Considering that the phenylazocarboxylates may beforehand be modified by mild nucleophilic aromatic substitution, including the introduction of [ F]fluoride, the overall strategy offers an attractive new access to 5-[ F]fluoroindoles.

Use of Vinyl Sulfides in Fischer Indole Reactions

“…Yield: 137 mg (0.465 mmol, 93%); Rf = 0.59 (30% EtOAc/Hex); Mp: 106-107 C. (44) General Procedure B, 1-phenyl-2-ethylthio-propene 5b (90 mg, 0.50 mmol, E/Z ~70:30), 4-fluorophenylhydrazine hydrochloride 6a (85 mg, 0.53 mmol), TsOH‧H2O (103 mg, 0.541 mmol), EtOH (5 mL), reflux, 12 h. Flash chromatography (10→50% EtOAc/Hex) provided the known indole 8b (CAS: 2143937-00-0) an amber oil. Yield: 93 mg (0.41 mmol, 82%); Rf = 0.48 (30% EtOAc/Hex).…”

Recent Advances in the Microwave Assisted Synthesis of Benzofuran and Indole Derivatives

“…Microwave assisted strategy for the synthesis of substituted indoles from phenylazocarboxylates was reported. 60 This new methodology offers a unique synthetic approach to 18 F-substituted indoles. tert-Butyl-4-[ 18 F]fluorophenylazocarboxylate on treatment with a wide variety of ketones including phenylacetone, 2-indanone and 2-tetralone underwent the reaction successfully furnishing the corresponding 5-fluoroindole derivatives in moderate to good yields.…”

Synthesis of Heteroarene‐Fused Cyclopentadienes and Related Compounds Suitable for Metallocene Preparation

“…The reductive condensation of a tert-butyl(4-fluorophenyl)azocarboxylate with 2-indanone that also included a Fischer rearrangement resulted in 2-fluoro-5,6-dihydroindeno[2,1-b]indole 529 in 58% yield. [243] In addition to 2-indanone, indene oxide has been used as a starting compound; the reaction sequence involving a Meinwald rearrangement and Fischer indolization resulted in 522 and 523 in moderate to good yields (Scheme 72). [244] N-Substituted 5,6-dihydroindeno [2,1-b]indoles that are of immediate interest for metallocene synthesis were obtained via the alkylation of N-unsubstituted compounds by alkyl halides (Scheme 73A).…”