Rapid Assembly of Saturated Nitrogen Heterocycles in One-Pot: Diazo-Heterocycle "Stitching" by N-H Insertion and Cyclization
Rapid Assembly of Saturated Nitrogen Heterocycles in One-Pot: Diazo-Heterocycle "Stitching" by N-H Insertion and Cyclization
复制标题
一锅法快速组装饱和氮杂环：通过 N-H 插入和环化实现重氮杂环“缝合”
DOI：
10.1002/ange.201812925
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发表时间：
2018
影响因子：
--
通讯作者：
Boddy A
中科院分区：
文献类型：
--
作者：
Boddy A
在生物学相关的化学空间中提供快速获得新的杂环结构的方法为药物发现提供了重要的机会。在此，描述了用于制备带有酯和不同芳基取代基的2，2-二取代的氮杂环丁烷、吡咯烷、哌啶和氮杂环庚烷的策略。一锅铑催化的N-H插入和环化序列使用重氮化合物将线性1，m-卤代胺（m=2-5）缝合在一起，以优异的产率快速组装4-、5-、6-和7-元饱和氮杂环。超过50个例子，包括与重氮化合物衍生的生物活性化合物的例子。产物可以被官能化以提供α，α-二取代的氨基酸并应用于片段合成。
Methods that provide rapid access to new heterocyclic structures in biologically relevant chemical space provide important opportunities in drug discovery. Here, a strategy is described for the preparation of 2,2‐disubstituted azetidines, pyrrolidines, piperidines, and azepanes bearing ester and diverse aryl substituents. A one‐pot rhodium catalyzed N–H insertion and cyclization sequence uses diazo compounds to stitch together linear 1,m‐haloamines (m=2–5) to rapidly assemble 4 ‐, 5 ‐, 6 ‐, and 7 ‐membered saturated nitrogen heterocycles in excellent yields. Over fifty examples are demonstrated, including examples with diazo compounds derived from biologically active compounds. The products can be functionalized to afford α,α‐disubstituted amino acids and applied to fragment synthesis.