Photoinduced Hydrocarboxylation via Thiol-Catalyzed Delivery of Formate Across Activated Alkenes

Sara N. Alektiar and Zachary K. Wickens*

*Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States, Email: wickenswisc.edu

S. N. Alektiar, Z. K. Wickens, J. Am. Chem. Soc., 2021, 143, 13022-13028.

DOI: 10.1021/jacs.1c07562

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Abstract

A photochemical process for the preparation of carboxylic acids from formate salts and alkenes proceeds in high yields across diverse functionalized alkene substrates with excellent regioselectivity. This operationally simple and redox-neutral hydrocarboxylation can be readily scaled in batch at low photocatalyst loading (0.01% photocatalyst).

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Proposed Thiol-Catalyzed Radical Chain Mechanism

4DPAIPN

General Procedure A – Standard Conditions

Potassium formate (92.5 mg, 1.1 equiv, 1.10 mmol) and 4DPAIPN (0.8 mg, 0.001 equiv, 1.00 µmol) were added to a 20 mL scintillation vial (oven-dried, cooled in desiccator). Alkene* (1 equiv, 1.00 mmol), methyl thiosalicylate (2.8 µL, 0.02 equiv, 20.00 µmol), and 15 mL of DMSO were added to the vial and capped with a teflon cap. With fan cooling, irradiate with a 467 nm Kessil lamp for 2 h.

*If alkene has an inhibitor present, filter off the inhibitor by passing through ~1 in basic alumina immediately prior to use.

For product isolation: Reaction mixture was transferred to a 500 mL sep funnel with 2x2 mL EtOAc, 2x2 mL 10% HCl 20% brine aq solution, 2x2 mL EtOAc. 250 mL 10% HCl 20% brine aq solution was added and the mixture was extracted 3x100 mL EtOAc. Combined organic layers were washed with brine, dried over Na₂SO₄ and MgSO₄, and concentrated. The product was then purified via column chromatography (gradient of EtOAc and 1% AcOH in hexanes). To remove residual AcOH after purification, the product was azeotroped with benzene.

Key Words

hydrocarboxylations, photochemistry, organocatalysis, 1,4-keto carboxylic acids

ID: J48-Y2021