Aminoxylation of Thioalkynes through Radical-Polar Crossover

Published as part of the ISySyCat2019 Special Issue

Abstract

A one-pot procedure for the aminoxylation of thioalkynes for the direct formation of α-functionalized thioesters under mild reaction conditions is reported. A ketenethionium ion is the key intermediate, which is generated in situ by Brønsted acid mediated protonation and undergoes a radical-polar crossover.

Key words

thioalkynes - aminoxylation - radical-polar crossover - thioester

• References and Notes

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• 11 General Procedure for the Synthesis of 2 To a solution of the thioalkyne (1.00 equiv) in CH₂Cl₂ (0.1 M) in a flame-dried Schlenk tube, trifluoromethanesulfonic acid (1.10 equiv) was added, and the mixture was stirred for 15 min at 0°C. TEMPO (3.00 equiv) was added in one portion, and the resulting solution was allowed to warm up to 25 °C and stirred over 16 h. The reaction was quenched by addition of a saturated aqueous solution of NaHCO₃. The product was extracted with CH₂Cl₂, and the resulting organic phase was dried over Na₂SO₄, filtered, and the solvent was evaporated under reduced pressure. The product was purified by flash chromatography on silica gel using heptane methyl-tert-butyl ether as eluent.
• 12 Analytical Data for Compound 2c ¹H NMR (400 MHz, CDCl₃): δ = 3.75 (d, J = 8.8 Hz, 1 H), 2.28 (s, 3 H), 1.65–1.40 (br, 6 H), 1.30 (br, 3 H), 1.18 (br, 6 H), 1.12–1.06 (m, 1 H), 1.03 (br, 3 H) 0.75–0.45 (m, 4 H). ¹³C NMR (151 MHz, CDCl₃): δ = 201.4, 94.5, 40.3 (2 C), 34.4, 33.5, 20.4, 20.1, 17.1, 15.1, 10.9, 7.5, 2.05 (quaternary carbons in the TEMPO moiety not visible in ¹³C NMR). HRMS (ESI+): m/z calcd for (C₁₅H₂₈N₂OS⁺) [M + H]⁺: 286.1835; found: 286.1830. IR (neat): ν_max = 3005, 2972, 2929, 2359, 1684, 1465, 1376, 900 cm^–1.