Dimethyl sulfoxide as a mild oxidant in S–P(O) bond construction: simple and metal-free approaches to phosphinothioates

Abstract

A direct metal-free oxidative S–P(O) coupling reaction for the preparation of phosphinothioates starting with readily available thiols (or disulfides) and P(O)H compounds using DMSO as a mild oxidant is presented.

Influence of reaction conditions on the oxidation of thiol groups in model peptidomimetic oligoureas

“…Such differences in reaction kinetics could be caused by different hydrogen bond compositions within the different mixtures of DMSO and MeOH . Furthermore, the hydrogen bond between the MeOH molecule and the DMSO molecule causes a reduction of the electron density on the sulfur atom, which makes the attack of the thiol group on DMSO more accessible …”

“…Figure 3A which makes the attack of the thiol group on DMSO more accessible. 22,23 Different results were obtained for the dimerisation reaction of 1 in DMSO/MeOH mixtures when 140 eq of the tertiary amine DIPEA (at 40°C) was included in the experiment. Increasing amounts of DMSO clearly accelerated the formation of dimer 3 in the presence of 140 eq DIPEA, with the fastest reaction rate observed in pure DMSO ( Figure 3B).…”

A Robust Methodology for the Synthesis of Phosphorothioates, Phosphinothioates and Phosphonothioates

“…Methods for the preparation of S-alkyl products with low molecular weight sidechains (e. g. S-methyl or S-ethyl) are conspicuously absent in the literature, despite the pervasiveness of these motifs in organophosphorus chemistry. S-Alkyl organophosphorus compounds prepared via non-metal-catalysed methods typically employ the corresponding thiocyanate, [17] disulfide, [18] thiol [19] or sulfonyl chloride [20] as starting materials which, for complex substrates, may not be readily available. These methods may also suffer from limited substrate scope with respect to the organophosphorus precursor.…”

Synthesis of Thiophosphates by Coupling of Phosphates with Bunte Salts under Mild Conditions

“…1 H NMR (400 MHz, CDCl3) δ 7.38 -7.29 (m, 10H), 7.26 (d, J = 5.0 Hz, 5H), 5.07 (dd, J = 11.7, 8.6 Hz, 2H), 4.98 (dd, J = 11.7, 8.6 Hz, 2H), 3.97 (d, J = 13.9 Hz, 2H). 13 5 Compound 3ag was obtained in 40% yield (25.9 mg) according to general procedure 3 as colorless oil. 1 H NMR (400 MHz, CDCl3) δ 7.90 -7.81 (m, 4H), 7.55 -7.49 (m, 2H), 7.46 (dd, J = 7.6, 3.5 Hz, 4H), 7.25 (s, 1H), 7.20 (d, J = 4.0 Hz, 4H), 4.02 (d, J = 9.2 Hz, 2H).…”