A New Approach to the S–H Insertion Reaction of α-Keto Esters and Thiols

Abstract

Sulfur-containing compounds are well known for their frequent occurrence in a large number of natural and synthetic molecules with relevant biological activity. An easy and highly efficient approach to sulfur-containing compounds, by S–H insertion reactions of α-keto esters with thiols, is reported. The substrate scope was remarkably wide, affording the corresponding products in up to 97% yield. Overall, the raw materials were readily available and the reaction conditions were mild in this synthetic method.

Key words

sulfur-containing compounds - S–H insertion reactions - α-keto esters - thiols

• References and Notes

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• 16 General procedure: P(NMe₂)₃ (0.15 mmol) was added to a solution of α-keto ester (2, 0.1 mmol) in dry DCM (0.5 mL) at –78 °C, and the resulting mixture was stirred for 5 min at the same temperature. Thiol (1, 0.1 mmol) was then added to the above solution at –78 °C. After being stirred for 5 min at –78 °C, the mixture was left to stir at room temperature for 8 h. After the reaction had finished, the solution was concentrated under reduced pressure, and the mixture was purified by flash column chromatography over silica gel (petroleum ether/ethyl acetate = 15:1 or 10:1) to afford the desired product 3, which was analyzed with ¹H NMR and ¹³C NMR spectroscopy (see Supporting Information). Typical data for representative compound 3aa: R_f = 0.30 (petroleum ether/ethyl acetate = 10:1), colorless oil (26.4 mg, 97% yield). ¹H NMR (600 MHz, CDCl₃) δ = 7.45 (d, J = 7.2 Hz, 2 H), 7.39–7.37 (m, 2 H), 7.35–7.29 (m, 3 H), 7.28–7.24 (m, 3 H), 4.90 (s, 1 H), 4.18–4.07 (m, 2 H), 1.16 (t, J = 7.2 Hz, 3 H). ¹³C NMR (150 MHz, CDCl₃): δ = 170.6, 135.7, 133.9, 132.7, 129.1, 128.8, 128.6, 128.4, 128.1, 61.9, 56.4, 14.1. HRMS (ESI): m/z calcd for C₁₆H₁₆O₂SNa [M + Na]⁺: 295.0763; found: 295.0769.