Synthesis of Bicyclo[1.1.1]pentane Bioisosteres of Internal Alkynes and para-Disubstituted Benzenes from [1.1.1]Propellane

被引：172

作者：

Makarov, Ilya S. ^{[1
]}

Brocklehurst, Cara E. ^{[2
]}

Karaghiosoff, Konstantin ^{[1
]}

Koch, Guido ^{[2
]}

Knochel, Paul ^{[1
]}

机构：

[1] Ludwig Maximilians Univ Munchen, Dept Chem, Butenandtstr 5-13,Haus F, D-81377 Munich, Germany

[2] Novartis Inst BioMed Res, Global Discovery Chem, 141 Klybeckstr, CH-4057 Basel, Switzerland

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2017年 / 56卷 / 41期

关键词：

arenes; bioisosteres; magnesium; nitrogen heterocycles; small ring systems; CROSS-COUPLING REACTIONS; DERIVATIVES; BRIDGEHEAD; INHIBITOR; BINDING;

D O I：

10.1002/anie.201706799

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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 ZnCl2 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.

引用

页码：12774 / 12777

页数：4

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