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From Heteroaromatic Acids and Imines to Azaspirocycles: Stereoselective Synthesis and 3D Shape Analysis
Author(s) -
Chambers Sarah J.,
Coulthard Graeme,
Unsworth William P.,
O'Brien Peter,
Taylor Richard J. K.
Publication year - 2016
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201600823
Subject(s) - stereoselectivity , chemistry , combinatorial chemistry , chemical space , organic chemistry , stereochemistry , drug discovery , catalysis , biochemistry
Heteroaromatic carboxylic acids have been directly coupled with imines using propylphosphonic anhydride (T3P) and NEt( i Pr) 2 to form azaspirocycles via intermediate N ‐acyliminium ions. Spirocyclic indolenines (3 H ‐indoles), azaindolenines, 2 H ‐pyrroles and 3 H ‐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.