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Chromium-Catalyzed Allylic Defluorinative Ketyl Olefin Coupling
Chang Zhang1, Zhiyang Lin1, Yufei Zhu1
1Hefei National Laboratory for Physical Science at the Microscale and Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, People's Republic of China.
This study introduces a chromium-catalyzed reaction coupling aldehydes and trifluoromethyl alkenes to create gem-difluorohomoallylic alcohols. The method is highly selective, tolerating various functional groups for broad synthetic utility.
Area of Science:
- Organic Chemistry
- Organometallic Chemistry
- Fluorine Chemistry
Background:
- Accessing fluorinated organic compounds is crucial for pharmaceuticals and materials.
- Developing selective methods for introducing fluorine atoms remains a synthetic challenge.
Purpose of the Study:
- To develop a novel chromium-catalyzed reaction for synthesizing gem-difluorohomoallylic alcohols.
- To explore the chemoselectivity and scope of the developed coupling reaction.
Main Methods:
- Chromium-catalyzed allylic defluorinative ketyl olefin coupling.
- Reaction between aldehydes and α-trifluoromethyl alkenes.
Main Results:
- Efficient synthesis of diverse gem-difluorohomoallylic alcohols.
- High chemoselectivity demonstrated, tolerating various reducible functional groups.
- Successful derivatization of the hydroxyl group in coupling products.
Conclusions:
- The developed method offers a novel and efficient route to valuable gem-difluorinated building blocks.
- The reaction's high chemoselectivity expands its applicability in complex molecule synthesis.
- Mechanistic studies suggest a C-C bond formation followed by beta-fluoro elimination pathway.
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In the first step of the mechanism, the acid protonates the carbonyl oxygen resulting in a resonance-stabilized cation, which subsequently loses an α-hydrogen to form an enol tautomer. The C=C bond in an enol is highly nucleophilic because of the electron-donating nature of the –OH group. Consequently, the double bond attacks an electrophilic halogen to form a...