Copper-Catalyzed Synthesis of Masked (Hetero)Aryl Sulfinates

Abstract

Catalysis using substoichiometric copper facilitates the synthesis of masked (hetero)aryl sulfinates under mild, base-free conditions from aryl iodides and the commercial sulfonylation reagent sodium 1-methyl 3-sulfinopropanoate (SMOPS). The development of a tert-butyl ester variant of the SMOPS reagent allowed the use of aryl bromide substrates. The sulfones thus generated can be unmasked and functionalized in situ to form a variety of sulfonyl-containing functional groups.

Scheme 1

(a) TBSOMS-Na as a sulfonylation agent. (b) SMOPS as a sulfonylation agent. (c) This work: copper-catalyzed synthesis of aryl sulfones.

Scheme 2. Selected Optimization Studies

Scheme 3. (a) (Hetero)Aryl Iodide and (b) (Hetero)Aryl Bromide Coupling Scope

(a) Iodide coupling reaction conditions: 4 (0.2 mmol, 1.0 equiv), SMOPS (2) (0.24 mmol, 1.2 equiv), CuI (10 mol %), L3 (10 mol %), DMSO (0.13 M), 50 °C, 24 h. Reaction performed on 0.5 mmol scale. (b) Bromide coupling reaction conditions: 6 (0.2 mmol, 1.0 equiv), STOPS (3) (0.24 mmol, 1.2 equiv), CuI (10 mol %), L4 (10 mol %), DMSO (0.13 M), 70 °C, 24 h. 20 mol % CuI used, the corresponding alcohol was isolated after oxidation (7g*, see the Supporting Information).

Scheme 4. Functionalization of Masked (Hetero)Aryl Sulfinates

Reaction conditions: 5a or 7a (0.2 mmol, 1.0 equiv), NaOMe (30% w/w in MeOH, 0.2 mmol, 1.0 equiv), DMSO (0.1 M), 15 min, rt. General reaction conditions, then tert-butyl bromoacetate (0.4 mmol, 2.0 equiv). General reaction conditions, then NFSI (0.3 mmol, 1.5 equiv). General reaction conditions, then NCS (0.4 mmol, 2.0 equiv) and morpholine (0.4 mmol, 2.0 equiv).