- Title
- Facile amidinations of 2-aminophenylboronic acid promoted by boronate ester formation
- Creator
- Pappin, Brighid B.; Garget, Taylor A.; Healy, Peter C.; Simone, Michela I.; Kiefel, Milton J.; Houston, Todd A.
- Relation
- Organic & Biomolecular Chemistry Vol. 17, Issue 4, p. 803-806
- Publisher Link
- http://dx.doi.org/10.1039/C8OB02696C
- Publisher
- Royal Society of Chemistry
- Resource Type
- journal article
- Date
- 2019
- Description
- Amidine synthesis by amine addition to nitriles normally requires high temperatures or harsh catalysts. Here, we report that boronate esters can facilitate amidination of proximal amines with moderate heating. With amidines present in a number of drugs and the synthetic handle provided by the boron, this chemistry should find useful applications.Amidines are important pharmacophores in many drugs (e.g., pentamidine and quetiapine) and drug-like molecules.1 These can be constructed from the reaction of nitriles and amines with strong Lewis acid activation of the cyano group by catalysts such as AlCl3.2 Reaction of nitriles with aniline in the presence of AlCl3 and BCl3 can result in electrophilic aromatic substitution by the nitrile ortho to the amine as originally reported by Sugasawa.3 The iminium intermediates can then be hydrolysed to the corresponding ketones. When this chemistry is carried out by addition of AlCl3 and BCl3 sequentially, amidination occurs first followed by boron substitution at the ortho position as outlined in Scheme 1.4 The boron is likely delivered in an intramolecular manner following complexation with the amidine. We have discovered an amidination reaction that creates the same amidine-boronate system through a different pathway and developed it into a simple synthetic transformation.
- Subject
- boron acids; chemistry; amidine product
- Identifier
- http://hdl.handle.net/1959.13/1469110
- Identifier
- uon:48151
- Identifier
- ISSN:1477-0520
- Language
- eng
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