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从杂芳族酸和亚胺到氮杂螺环：立体选择性合成与三维形状分析

From Heteroaromatic Acids and Imines to Azaspirocycles: Stereoselective Synthesis and 3D Shape Analysis.

作者信息

Chambers Sarah J, Coulthard Graeme, Unsworth William P, O'Brien Peter, Taylor Richard J K

机构信息

Department of Chemistry, University of York, York, UK.

出版信息

Chemistry. 2016 May 4;22(19):6496-500. doi: 10.1002/chem.201600823. Epub 2016 Mar 23.

DOI:10.1002/chem.201600823
PMID:26918778
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5071705/
Abstract

Heteroaromatic carboxylic acids have been directly coupled with imines using propylphosphonic anhydride (T3P) and NEt(iPr)2 to form azaspirocycles via intermediate N-acyliminium ions. Spirocyclic indolenines (3H-indoles), azaindolenines, 2H-pyrroles and 3H-pyrroles were all accessed using this metal-free approach. The reactions typically proceed with high diastereoselectivity and 3D shape analysis confirms that the products formed occupy areas of chemical space that are under-represented in existing drugs and high throughput screening libraries.

摘要

通过丙基膦酸酐（T3P）和二异丙基乙胺，杂芳族羧酸已与亚胺直接偶联，通过中间体N-酰基亚胺离子形成氮杂螺环化合物。使用这种无金属方法可以得到螺环吲哚啉（3H-吲哚）、氮杂吲哚啉、2H-吡咯和3H-吡咯。反应通常以高非对映选择性进行，三维形状分析证实所形成的产物占据了现有药物和高通量筛选库中代表性不足的化学空间区域。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4509/5071705/7dadcaf67583/CHEM-22-6496-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4509/5071705/570c2e1821d7/CHEM-22-6496-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4509/5071705/c79a8b8e07c1/CHEM-22-6496-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4509/5071705/03dc03f43c12/CHEM-22-6496-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4509/5071705/0da7fe059e7e/CHEM-22-6496-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4509/5071705/0b8a0b8a45bb/CHEM-22-6496-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4509/5071705/2729f87582a3/CHEM-22-6496-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4509/5071705/7dadcaf67583/CHEM-22-6496-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4509/5071705/570c2e1821d7/CHEM-22-6496-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4509/5071705/a9b1bf06d010/CHEM-22-6496-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4509/5071705/520aa904c0f2/CHEM-22-6496-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4509/5071705/c79a8b8e07c1/CHEM-22-6496-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4509/5071705/03dc03f43c12/CHEM-22-6496-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4509/5071705/0da7fe059e7e/CHEM-22-6496-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4509/5071705/0b8a0b8a45bb/CHEM-22-6496-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4509/5071705/2729f87582a3/CHEM-22-6496-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4509/5071705/7dadcaf67583/CHEM-22-6496-g005.jpg

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