Chemo- and Diastereoselectivity in the Dimethyldioxirane Oxidation of 2,3-Dihydro-4H-1-benzothiopyran-4-ones and 4H-1-Benzothiopyran-4-ones. Unusual Reactivity of 4H-1-Benzothiopyran-4-one 1-Oxides¹

Abstract

The oxidation of the 1-thiochromanones 1-3 by dimethyldioxirane (DMD) produced the corresponding sulfoxides 4-6 or sulfones 7-9; their relative amounts depended on the amount of oxidant used. A low diastereoselectivity was observed in the sulfoxidation of the 2-substituted 1-thiochromanones 2 and 3, due to the small steric differentiation during the DMD attack. An unusual reactivity pattern was found in the DMD oxidation of the 1-thiochromones 10-12, in that the sulfoxides 13-15 were more reactive toward the electrophilic oxidizing agent than the corresponding sulfides. The observed anomaly may be explained in terms of transannular stabilization of the transition structure (TS) for the sulfone formation, promoted through favorable conformational effects in the sulfoxide. Higher sulfoxide/sulfone ratios were found in solvents of greater hydrogen bond donor capacity, which is in accordance with the postulated stabilizing effect.

Selective and mild oxidation of sulfides to sulfoxides or sulfones using H2O2 and Cp′Mo(CO)3Cl as catalysts

“…2,6a,c To gain some mechanistic insight on the sulfoxidation reactions, kinetic experiments were performed where p-ClC 6 H 4 SCH 3 and C 6 H 5 SOCH 3 (1:1) were in competition for the oxidant (Table 3). 17,18 A much higher oxidative reactivity of p-ClC 6 H 4 SCH 3 was observed, as expected. 19,20 When H 2 O 2 is used as oxidant, the protic solvent MeOH favors the chemoselective formation of sulfoxide (entries 1 and 2), as in other catalytic systems 18,21a and this has certainly permitted the straightforward synthesis of sulfoxides in Table 2.…”

“…8b The use of MeOH produces a dramatic slowing effect on the reaction (entry 13), perhaps due to the coordination of this solvent to the Mo(VI) center. 14 The benzothiophenic compounds DBTP and 4,6-DMDBTP (entries [17][18][19][20] could be oxidized in good yields, under very mild conditions. In literature, the oxidation of thiophene derivatives to their sulfones is known to take place over a limited range of metal catalysts and large excess of H 2 O 2 and higher reaction temperatures are typically used.…”

H32, a non-quinone sulfone analog of vitamin K3, inhibits human hepatoma cell growth by inhibiting Cdc25 and activating ERK

“…A solution of H28 (1-sulfone-3-methyl-4-naphthoquinone), 20 obtained from ChemDiv Inc, San Diego, CA in methylene chloride was treated with bromine. The reaction mixture was stirred under an atmospheric pressure of argon for 30 min at room temperature.…”

Synthesis of 2-(substituted-phenyl)-5-(aminomethyl)- and (thiomethyl)-1,3,4-oxadiazoles. Oxidation of thiomethyl-oxadiazole derivatives by dimethyldioxirane

“…This reactivity pattern is characteristic of DMD oxidation although exceptional deviations have also been reported. 17 It is noteworthy that a complete decomposition of the starting 6,7 sulfides without the formation of considerable amount of any sulfoxide or sulfone was found in the attempted oxidation by hydrogen peroxide in acetic acid. Once again, these results demonstrate the synthetic value of DMD in oxygen transfer under mild and neutral conditions.…”