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. 2024 Feb 16;26(6):1261-1264.
doi: 10.1021/acs.orglett.4c00095. Epub 2024 Feb 1.

Addition of Carboxylic Acids to gem-Difluoroalkenes for the Synthesis of gem-Difluoromethylenated Compounds

Yuwei Zong  1 , Gavin Chit Tsui  1
Affiliations

Addition of Carboxylic Acids to gem-Difluoroalkenes for the Synthesis of gem-Difluoromethylenated Compounds

Yuwei Zong et al. Org Lett. .

Abstract

We herein describe a straightforward protocol for the synthesis of carboxylic esters containing a gem-difluoromethylene unit. Readily available carboxylic acids can act as nucleophiles to add regioselectively to tetrasubstituted or trisubstituted β,β-difluoroacrylates (formal hydroacetoxylation) for the construction of RCO2-CF2 bonds. Thermal conditions are sufficient without the use of catalysts or additives.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Hydrofunctionalization of gem-Difluoroalkenes
Scheme 2
Scheme 2. Initial Results
Scheme 3
Scheme 3. Addition of Carboxylic Acids to Tetrasubstituted gem-Difluoroalkenes
Unless specified otherwise, reactions were carried out using 0.2 mmol of 1 for 48 h. Isolated yields. Condition A: 10 equiv of carboxylic acid at 75 °C. Condition B: 3.0 equiv of carboxylic acid at 150 °C.
Scheme 4
Scheme 4. Addition of Carboxylic Acids to a Trisubstituted gem-Difluoroalkene
Unless specified otherwise, reactions were carried out using 0.2 mmol of 3a for 24 h. Isolated yields.
Scheme 5
Scheme 5. Addition of Sulfonic Acids to a Trisubstituted gem-Difluoroalkene
See this image and copyright information in PMC

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