Direct Synthesis of α‐Aryl‐α‐Trifluoromethyl Alcohols via Nickel Catalyzed Cross‐Electrophile Coupling
A nickel‐catalyzed reductive cross‐electrophile coupling between the redox‐active N‐trifluoroethoxyphthalimide and iodoarenes is documented. The protocol reproduces a formal arylation of trifluoroacetaldehyde under mild conditions in high yields (up to 88 %) and with large functional group tolerance...
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Published in | Angewandte Chemie International Edition Vol. 61; no. 47; pp. e202211732 - n/a |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
WEINHEIM
Wiley
21.11.2022
Wiley Subscription Services, Inc John Wiley and Sons Inc |
Edition | International ed. in English |
Subjects | |
Online Access | Get full text |
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Summary: | A nickel‐catalyzed reductive cross‐electrophile coupling between the redox‐active N‐trifluoroethoxyphthalimide and iodoarenes is documented. The protocol reproduces a formal arylation of trifluoroacetaldehyde under mild conditions in high yields (up to 88 %) and with large functional group tolerance (30 examples). A combined computational and experimental investigation revealed a pivotal solvent assisted 1,2‐Hydrogen Atom Transfer (HAT) process to generate a nucleophilic α‐hydroxy‐α‐trifluoromethyl C‐centered radical for the Csp2−Csp3 bond forming process.
A nickel catalyzed synthesis of α‐aryl‐α‐trifluoromethyl alcohols B is presented that exploits the condensation of iodoarenes and the redox active ether A via cross‐electrophile coupling. A mechanistic study was conducted using a comprehensive computational investigation that was also supported by ad hoc control experiments and showed that the key 1,2‐HAT (Hydrogen Atom Transfer) event results in the formation of a C‐centered radical C′ that mimics the reactivity of trifluoroacetaldehyde. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1433-7851 1521-3773 1521-3773 |
DOI: | 10.1002/anie.202211732 |