Anticancer-active 3,4-diarylthiolated maleimides synthesis via three-component radical diarylthiolation

Abstract

Herein, we report an efficient and simple copper-catalyzed oxidative diarylthiolation of maleimides with sulfur powder and aryl boronic acids, in which S powder was used as a substrate and internal oxidant. The corresponding double C-S bonds coupling products were obtained in moderate to high yields under a simple catalytic system. Mechanistic studies indicated that copper-catalyzed radical thiolation of aryl boronic acids with S powder, and the resulting arylthiyl underwent radical addition with double bonds of maleimides.

Keywords: bisthiolation; copper-catalyzed; maleimides; radical thiolation; sulfur powder.

SCHEME 1

Strategies for diarylthiolated alkenes.

SCHEME 2

Scope of arylboronic acids^a. ^a) Reaction conditions unless specified otherwise: 1a (0.2 mmol), sulfur powder (0.6 mmol), 2 (0.6 mmol), CuI (10 mol%) and XPhos (12 mol%) in DMSO (2.0 ml) were stirred at 100°C under O₂ atmosphere for 24 h, isolated yields are given.

SCHEME 3

Scope of maleimides^a. ^a) Reaction conditions unless specified otherwise: 1 (0.2 mmol), sulfur powder (0.6 mmol), 2a (0.6 mmol), CuI (10 mol%) and XPhos (12 mol%) in DMSO (2.0 ml) were stirred at 100°C under O₂ atmosphere for 24 h, isolated yields are given.

SCHEME 4

Mechanism of study and proposal.

FIGURE 1

Anticancer activity of 3,4-diarylthiolated maleimides.