Can the Crabbé Homologation Be Successfully Applied to the Synthesis of 1,3-Disubstituted Allenes?

Abstract

The Crabbé homologation of terminal alkynes could be applied to the synthesis of 1,3-disubstituted allenes using aldehydes, N,N-dicyclohexylamine, and a catalytic amount of copper(I) iodide. The key to this success was the employment of an excess of aldehyde and amine, and performing the reaction under microwave irradiation conditions.

Key words

allenes - copper - microwave - multicomponent reaction - propargylamines

References and Notes

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Typical Procedure for the Microwave-Assisted Crabbé Homologation
Alkyne 1a (65.0 mg, 0.500 mmol), aldehyde 2b (68 µL, 0.75 mmol), amine 3b (150 µL, 0.754 mmol), CuI (9.6 mg, 0.050 mmol), and toluene (1.0 mL) were mixed in a 2 mL process vial. The vial was sealed, and the reaction mixture was heated with microwaves to 200 ˚C for 2 h. After cooling, the mixture was filtered, and the filtrate was concentrated. The residue was purified by column chromatography on silica gel(hexane) to afford 5ab (46.8 mg, 50%) as a colorless oil. IR (CHCl₃): 1961 cm^-¹. ^¹H NMR (600 MHz, CDCl₃, TMS): δ = 7.27 (t, J = 7.6 Hz, 2 H), 7.20-7.16 (m, 3 H), 5.14-5.06 (m, 2 H), 2.72 (t, J = 7.6 Hz, 2 H), 2.32-2.27 (m, 2 H), 1.97-1.87 (m, 2 H), 1.38 (sext, J = 7.6 Hz, 2 H), 0.90 (t, J = 7.6 Hz, 3 H). ^¹³C NMR (150 MHz, CDCl₃): δ = 204.1, 141.9, 128.5, 128.2, 125.8, 91.3, 90.2, 35.5, 31.0, 30.7, 22.4, 13.6. MS (EI): m/z (%) = 186 (3.1) [M⁺]. HRMS: m/z calcd for C₁₄H₁₈: 186.1409; found: 186.1407.