Indium-Catalyzed Tandem Cyanomethylation/Cyclization of α-Alkynyl α,β-unsaturated Ketones with 3-Azido-2-methylbut-3-en-2-ol toward Trisubstituted Furans

Abstract

An indium-catalyzed cyanomethylation of α-alkynyl α,β-unsaturated ketones with 3-azido-2-methylbut-3-en-2-ol is presented. Furan-substituted propanenitriles were produced in yields of 29–97%. The reaction involves a nucleophile addition/cycloisomerization process.

Key word

furans - cyanomethylation - cyclization - alkynyl enones - azidomethylbutenol - cascade reaction

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• 8 InBr₃-Catalyzed Cyanomethylation/Cyclization of α-Alkynyl α-Enones with 3-Azido-2-methylbut-3-en-2-ol (2): General Procedure Under a N₂ atmosphere, a reaction tube equipped with a magnetic stirrer was charged with the appropriate alkynyl enone 1 (0.1 mmol), azido compound 2 (0.15 mmol), InBr₃ (15 mol%), and toluene (1.0 mL), and the mixture was stirred at 40 °C for 24 h. The mixture was then cooled to r.t. and directly subjected to flash column chromatography (silica gel) or preparative TLC. 3-(2-Methyl-5-phenyl-3-furyl)-3-phenylpropanenitrile (3a) Colorless oil; yield: 26.7 mg (73%). ¹H NMR (400 MHz, CDCl₃): δ = 7.61 (d, J = 8.0 Hz, 2 H), 7.34–7.37 (m, 4 H), 7.28–7.29 (m, 3 H), 7.22 (t, J = 7.7 Hz, 1 H), 6.57 (s, 1 H), 4.25 (t, J = 8 Hz, 1 H), 2.95–2.97 (m, 2 H), 2.31 (s, 3 H). ¹³C NMR (151 MHz, CDCl₃): δ = 152.14, 148.11, 140.98, 130.61, 128.97, 128.64, 127.46, 127.18, 127.11, 123.40, 121.38, 118.42, 104.53, 38.43, 24.73, 12.00. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₀H₁₈NO⁺: 288.1383; found: 288.1397.