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Facile Approach to C ‐Glucosides by Using a Protecting‐Group‐Free Hiyama Cross‐Coupling Reaction: High‐Yielding Dapagliflozin Synthesis
Author(s) -
Vaňková Karolína,
Rahm Michal,
Choutka Jan,
Pohl Radek,
Parkan Kamil
Publication year - 2021
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202101052
Subject(s) - dapagliflozin , aryl , chemistry , glucal , protecting group , coupling reaction , combinatorial chemistry , group (periodic table) , halide , organic chemistry , stereochemistry , catalysis , diabetes mellitus , type 2 diabetes mellitus , medicine , endocrinology , alkyl
Access to unprotected (hetero)aryl pseudo‐ C ‐glucosides via a mild Pd‐catalysed Hiyama cross‐coupling reaction of protecting‐group‐free 1‐diisopropylsilyl‐ d ‐glucal with various (hetero)aryl halides has been developed. In addition, selected unprotected pseudo‐ C ‐glucosides were stereoselectively converted into the corresponding α‐ and β‐ C ‐glucosides, as well as 2‐deoxy‐β‐ C ‐glucosides. This methodology was applied to the efficient and high‐yielding synthesis of dapagliflozin, a medicament used to treat type 2 diabetes mellitus. Finally, the versatility of our methodology was proved by the synthesis of other analogues of dapagliflozin.