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

  1. Yakun WangORCID Logo,
  2. Shuaifei Wang,
  3. Conghui Zhang,
  4. Ting Zhao,
  5. Yanqin Hu,
  6. Mingwei Zhang,
  7. Pengli Chen,
  8. Yang Fu and
  9. Jieli Lv

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

  • Preprint

Abstract

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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