Highly selective difluoromethylations of β-keto amides with TMSCF2Br under mild conditions

Submitting author affiliation:
Xinxiang Medical University, xinxiang, China

Beilstein Arch. 2021, 202135. https://doi.org/10.3762/bxiv.2021.35.v1

Published 20 Apr 2021

This preprint has not been peer-reviewed. When a peer-reviewed version is available, this information will be updated.


Without employing any transition metal and other additives, efficient methods for selective difluoromethylations of β-keto amides with TMSCF2Br reagent have been developed under alkaline and open-air conditions. This protocol allows a convenient access to various α-difluoromethyl β-keto amides with excellent yields (up to 93%) and high C/O regioselectivities (up to 99:1). The C/O selectivity of β-keto amides could be easily reversed and controlled by simply changing the base. This protocol can be easily scaled up and the C-difluoromethylation product could be reduced into amino-alcohol derivatives. Moreover, the first enantioselective electrophilic difluoromethylation of β-keto amides has been achieved by phase-transfer catalysis.

Keywords: Difluoromethylation, β-Keto amides, C/O selectivity, Asymmetric synthesis

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When a peer-reviewed version of this preprint is available, this information will be updated in the information box above. If no peer-reviewed version is available, please cite this preprint using the following information:

Wang, Y.; Wang, S.; Zhang, C.; Zhao, T.; Hu, Y.; Zhang, M.; Chen, P.; Fu, Y.; Lv, J. Beilstein Arch. 2021, 202135. doi:10.3762/bxiv.2021.35.v1

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