title: From Heteroaromatic Acids and Imines to Azaspirocycles: Stereoselective Synthesis and 3D Shape Analysis.
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.
authors.affiliation: Department of Chemistry, University of York, York, UK.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Chambers
authors.affiliation: Department of Chemistry, University of York, York, UK.
authors.forename: Graeme
authors.initials: G
authors.lastname: Coulthard
authors.affiliation: Department of Chemistry, University of York, York, UK.
authors.forename: William P
authors.identifier: http://orcid.org/0000-0002-9169-5156
authors.initials: WP
authors.lastname: Unsworth
authors.affiliation: Department of Chemistry, University of York, York, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: O'Brien
authors.affiliation: Department of Chemistry, University of York, York, UK. richard.taylor@york.ac.uk.
authors.forename: Richard J K
authors.initials: RJ
authors.lastname: Taylor
keywords: 3D space; N-acyliminium ions; dearomatisation; lead identification; spirocycles