Manganese-Catalyzed α-Trideuteromethylation of Sulfones

Abstract

Recent advancements in deuteration techniques have garnered significant attention from both academia and industry. Herein, we report a manganese-catalyzed α-trideuteromethylation of sulfones with CD₃OD as a deuterating reagent via a deuterium autotransfer strategy under mild conditions. Our approach yields target compounds with 60–96% efficiency and deuteration levels up to 99%. This methodology stands out due to its reliance on accessible deuterium sources, an earth-abundant transition-metal catalyst, and mild conditions.

Key words

manganese - homogeneous catalysis - deuterated methanol - α-trideuteromethylation - deuterium autotransfer

Publication History

Received: 25 February 2025

Accepted after revision: 08 April 2025

Accepted Manuscript online:
08 April 2025

Article published online:
28 May 2025

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• 36 Manganese-Catalyzed α-Trideuteromethylation of Sulfones; General Procedure: In a nitrogen-filled glove box, an oven-dried Schlenk pressure tube (10 mL) containing a stirring bar was charged with [Mn] (1.0 mol%). Dry and degassed 1,4-dioxane (0.5 mL) and NaOtBu (50 mol%) were added and the mixture was stirred at room temperature for 5.0 min. Compound 1 (0.25 mmol) and CD₃OD (2.5 mmol) were then added in sequence. The tube was brought out of the glovebox and heated at 120 °C for 12 h. Upon reaction completion, the reaction mixture was cooled to ambient temperature, concentrated in vacuo, and purified by column chromatography on silica gel (100–200 mesh) using PE/EtOAc as the eluent to afford the final product. ((1-Phenylethyl-1,2,2,2-d ₄)sulfonyl)benzene (3) The procedure was followed using (benzylsulfonyl)benzene (0.25 mmol, 58.1 mg), CD₃OD (2.5 mmol, 102 μL) stirred at 120 °C for 12 h. Purification by column chromatography (PE/EtOAc = 10:1) gave 3 (56.3 mg, 90%) as a white solid. ¹H NMR (600 MHz, CDCl₃): δ = 7.64–7.48 (m, 3 H), 7.42–7.37 (m, 2 H), 7.31–7.27 (m, 1 H), 7.27–7.22 (m, 2 H), 7.15–7.11 (m, 2 H), 4.22 (s, 0.15 H). ¹³C NMR (150 MHz, CDCl₃): δ = 136.8, 133.7, 133.6, 129.4, 129.2, 128.8, 128.7, 128.4, 66.2–65.0, 13.7–12.7 HRMS (ESI): m/z [M + NH₄]⁺ calcd for C₁₄H₁₄D₄O₂NS: 268.1304; found: 268.1301.