Thiolate-Initiated Metal-Free Synthesis of Cyclopentenones via a Halogen-Stabilized Vinyl Carbanion

Abstract

A metal-free synthesis of cyclopentenones is described. The mechanism proceeds via a halogen-stabilized carbanion generated by the nucleophilic attack of a thiolate on a haloalkyne moiety. The sp²-hybridized carbanion undergoes cyclization to an embedded ester carbonyl, yielding the cyclopentenone. The reaction exhibits a broad tolerance toward functional groups and proceeds under mild conditions.

Keywords

Metal-free - Cyclization - sp²-Hybridized intermediate - Vinyl-carbanion - Halogen-stabilized carbanion - Cyclopentenone - Haloalkyne

• References

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• 36 Procedure for the Preparation of Cyclopentenone 14a. In a preheated Schlenk tube, haloalkyne 12c (61 mg, 0.24 mmol, 1.0 eq.) was dissolved in 2.4 mL dry DMSO. Thiophenol 13a (29 mg, 27.0 μL, 0.26 mmol, 1.1 eq.) was then added to the reaction mixture, followed by activated potassium carbonate (36 mg, 0.26 mmol, 1.1 eq.) and stirred at room temperature for 1 h. The reaction was quenched with 60 mL water and the resulting aqueous phase was extracted three times with 20 mL ethyl acetate. The organic phases were washed with 60 mL saturated NaHCO₃ solution and dried over MgSO₄. Excess solvent was removed under reduced pressure. The crude product was adsorbed on Celite and purified by chromatography to yield the desired cyclopentenone 14a in 75% yield. R_f = 0.17 (n-pentane/DEE 1:1). ¹H NMR (400 MHz, CDCl₃): δ = 7.60–7.58 (m, 2 H, CH_ar), 7.53–7.43 (m, 3 H, CH_ar), 2.48–2.45 (m, 2 H, CH₂CS), 2.40–2.37 ppm (m, 2 H, CH₂CO). ¹³C NMR (101 MHz, CDCl₃): δ = 196.9 (C=O), 171.7 (CCl), 135.8 (C_arH), 130.7 (C_arH), 129.8 (C_arH), 127.0 (C_arS), 126.4 (CH₂CS), 33.4 (CH₂CS), 29.1 ppm (CH₂CO)