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Honggen Wang’s Research Group Made New Progress in Divergent Synthesis of Difluorinated Alkylborons

Last updated :2018-11-13

Source: School of Pharmaceutical Sciences
Written by: School of Pharmaceutical Sciences
Edited by: Wang Dongmei

The research group of Prof. Honggen Wang from the School of Pharmaceutical Sciences at Sun Yat-sen University published a paper entitled “gem-Difluorination of Alkenyl N-methyliminodiacetyl Boronates: Synthesis of α- and β-Difluorinated Alkylborons” in Angewandte Chemie International Edition (Angew. Chem. Int. Ed. 2018, DOI: 10.1002/anie.201810204. IF: 12.102) on October 24th, 2018. Prof. Honggen Wang is the corresponding author, and Ph.D. student Wen-Xin Lv and Prof. Qingjiang Li are the co-first authors.

Organofluorine compounds are widely used in pharmaceutical, agrochemical and material sciences. The geminal, or 1,1-difluoroalkyl groups (CF2), possessing specific steric and electronic properties, are of particular importance in medicinal chemistry. They can act as chemically and metabolically inert bioisosteres for alcohols, thiols, and other polar functional groups, bringing about modulated bioavailability, lipophilicity and improved binding affinity. While organofluorines are particularly useful, organoborons also play an important role in modern organic chemistry due to their versatility for involvement in diverse chemical transformations. In recent years, there has been an increase in the number of boron-containing drugs in which the boron motif is the key pharmacophore. Given the medicinal importance of difluoroalkyl groups and boron-containing moieties, gem-difluorinated alkylboron compounds should serve as intriguing synthons for organofluorines and may find applications in medicinal chemistry.

Migratory gem-difluorination of alkenyl MIDA boronates and its synthetic applications
Prof. Wang’s research group has a continued interest in the field of construction of boron and/or fluorine containing molecules (see also: J. Am. Chem. Soc. 2017, 139, 3537; Angew. Chem. Int. Ed. 2017, 56, 14707; Angew. Chem. Int. Ed. 2016, 55, 10069.). Reported herein is a migratory geminal difluorination of aryl-substituted alkenyl N-methyliminodiacetyl (MIDA) boronates using commercially available Py·HF as the fluorine source and hyperiodine (PIDA) as the oxidant. The protocol offers an unprecedented opportunity for the synthesis of α- and β-difluorinated alkylboron compounds. Mild reaction conditions (room temperature), broad substrate scope, easy handles and safety operations (under air, 1 min) were observed. Importantly, the utility of these products is demonstrated by further transformations of the C-B bond to other valuable difluorinated compounds.

This work is supported by the National Natural Science Foundation of China (21472250 and 21502242), and the Key Project of Chinese National Programs for Fundamental Research and Development (2016YFA0602900).

Link to the paper: https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.201810204