Systematic Investigation of the Scope of Transannular C-H Heteroarylation of Cyclic Secondary Amines for Synthetic Application in Medicinal Chemistry.

Autor:	Li Z; Department of Medicinal Chemistry, Biotherapeutic and Medicinal Sciences, Biogen, Cambridge, Massachusetts 02142, United States.; Biogen Postdoctoral Scientist Program, Biogen, Cambridge, Massachusetts 02142, United States., Dechantsreiter M; Department of Medicinal Chemistry, Biotherapeutic and Medicinal Sciences, Biogen, Cambridge, Massachusetts 02142, United States., Dandapani S; Department of Medicinal Chemistry, Biotherapeutic and Medicinal Sciences, Biogen, Cambridge, Massachusetts 02142, United States.
Jazyk:	angličtina
Zdroj:	The Journal of organic chemistry [J Org Chem] 2020 May 15; Vol. 85 (10), pp. 6747-6760. Date of Electronic Publication: 2020 Apr 28.
DOI:	10.1021/acs.joc.0c00870
Abstrakt:	Transannular C-H heteroarylation of amines provides rapid access to complex scaffolds that are otherwise difficult to synthesize. Wide adaptation of this emerging reaction for medicinal chemistry requires a broad understanding of substrate scope and more robust experimental conditions. In this article, we report a new ligand to promote the transannular reaction of a range of fused- and bridged-bicyclic secondary amines with a broad set of heteroarenes. The method was also successfully applied to the arylation of one spiro-bicyclic amine, a class of substrates that has not been studied in the context of transannular C-H activation reactions. The broad application of this transannular C-H heteroarylation methodology is currently hampered by the difficulty of removing the directing group. The development of a new directing group that is easier to remove will expand the utility of this reaction.
Databáze:	MEDLINE
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