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Synthesis of Bicyclo[1.1.1]pentane Bioisosteres of Internal Alkynes and para ‐Disubstituted Benzenes from [1.1.1]Propellane
Author(s) -
Makarov Ilya S.,
Brocklehurst Cara E.,
Karaghiosoff Konstantin,
Koch Guido,
Knochel Paul
Publication year - 2017
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201706799
Subject(s) - bicyclic molecule , propellane , chemistry , pentane , pyridine , transmetalation , medicinal chemistry , stereochemistry , organic chemistry , catalysis
We report a general preparation of arylated bicyclo[1.1.1]pentanes through the opening of [1.1.1]propellane with various arylmagnesium halides. After transmetalation with ZnCl 2 and Negishi cross‐coupling with aryl and heteroaryl halides, bis‐arylated bicyclo[1.1.1]pentanes are obtained. These bis‐arylated bicyclo[1.1.1]pentanes may be considered as bioisosteres of internal alkynes. Bioisosteres of tazarotene and the metabotropic glutamate receptor 5 (mGluR5) antagonist 2‐methyl‐6‐(phenylethynyl)pyridine were prepared and their physicochemical properties were evaluated.