Aminoalkylation of [1.1.1]Propellane Enables Direct Access to High-Value 3-Alkylbicyclo[1.1.1]pentan-1-amines

被引：58

作者：

Hughes, Jonathan M. E. ^{[1
]}

Scarlata, David A. ^{[1
]}

Chen, Austin C. -Y. ^{[2
,4
]}

Burch, Jason D. ^{[3
]}

Gleason, James L. ^{[1
]}

机构：

[1] McGill Univ, Dept Chem, 801 Sherbrooke West, Montreal, PQ H3A 2K6, Canada

[2] Incept Sci, 6175 Nancy Ridge Dr, San Diego, CA 92121 USA

[3] Incept Sci, 7150 Frederick Banting St, St Laurent, PQ H4S 2A1, Canada

[4] Pipeline Therapeut, 10578 Sci Ctr Dr,Suite 200, San Diego, CA 92121 USA

来源：

ORGANIC LETTERS | 2019年 / 21卷 / 17期

基金：

加拿大自然科学与工程研究理事会;

关键词：

BIOLOGICAL EVALUATION; DERIVATIVES; BRIDGEHEAD; DESIGN;

D O I：

10.1021/acs.orglett.9b02426

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Bicyclo[1.1.1]pentanes are effective bioisoteres for aromatic rings, tert-butyl groups, and alkynes. Here we report the first method to synthesize 3-alkylbicyclo[1.1.1]pentan-1-amines directly from [1.1.1]propellane via sequential addition of magnesium amides and alkyl electrophiles. The mild reaction conditions tolerate a variety of important functional groups and enable efficient incorporation of several pharmaceutically relevant amines onto the bicyclo[1.1.1]pentane scaffold. This method's utility is highlighted by its ability to significantly streamline the syntheses of several important bicyclo[1.1.1]pentan-1-amine building blocks.

引用

页码：6800 / 6804

页数：5

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