Functionalization of C-H bonds in acetophenone oximes with arylacetic acids and elemental sulfur

Abstract

Fused thieno[3,2-d]thiazoles were synthesized via a coupling of acetophenone ketoximes, arylacetic acids, and elemental sulfur in the presence of Li₂CO₃ base. Functionalities including chloro, bromo, fluoro, trifluoromethyl, and pyridyl groups were compatible with reaction conditions. High yields and excellent regioselectivities were obtained even if meta-substituted ketoxime acetates were used. Ethyl esters of heteroarylacetic acids were competent substrates, which is very rare in the literature. Our method would offer a convenient protocol to afford polyheterocyclic structures from simple substrates.

Scheme 1. Retrosynthesis of 2-aryl benzothienothiazoles.

Scheme 2. Annulation of arylacetic acid derivatives^a. ^a1a (0.3 mmol), arylacetic acids (0.2 mmol), sulfur (0.6 mmol, 32 g mol⁻¹), Li₂CO₃ (0.3 mmol), DMSO (1 mL), 120 °C, 3–12 h. Yields are isolated yields. ^b2 mmol scale. ^cEthyl esters of arylacetic acids (0.2 mmol) were used.

Scheme 3. Scope of ketoxime acetates^a. ^aKetoxime acetates (0.3 mmol), phenylacetic acid 2a (0.2 mmol), sulfur (0.6 mmol, 32 g mol⁻¹), Li₂CO₃ (0.3 mmol), DMSO (1 mL), 120 °C, 3–12 h. Yields are isolated yields.

Scheme 4. Mechanistic consideration.

Scheme 5. Plausible mechanism.

Scheme 6. Directed C–H functionalization of 2-phenyl benzothienothiazole^a. ^aCondition: 3aa (0.2 mmol), Fe(NO₃)₃·9H₂O (0.4 mmol), anhydrous CuCl₂ (20 mol%), K₂S₂O₈ (0.4 mmol), 1,2-dichloroethane (3 mL), 100 °C, 8 h. Yield is isolated yield.