Selective Functionalization of Benzo-FusedN-Heterocycles by Using In Situ Trapping Metalations

Author(s)

Nishimura, Rodolfo H. V. ; Murie, Valter E. ; Vessecchi, Ricardo ; Clososki, Giuliano C.

• Document type: Journal article
• Source: CHEMISTRYSELECT; v. 5, n. 36, p. 6-pg., 2020-09-30.

Abstract

We have prepared some benzo-fusedN-heterocycles derivatives by regioselective metalation of quinoline, isoquinoline, quinoxaline, and quinazoline with LiTMP in the presence of zinc chloride. Applying this strategy to synthesize an analog of the antitumor verubulin illustrates its relevance for medicinal chemistry. Computational calculations of the pK(a)values of the aromatic hydrogens have helped us to rationalize substrate reactivity and metalation regioselectivity by the complex-induced proximity effect concept. (AU)

• FAPESP's process: 18/14150-8 - Selective aromatic functionalization: Methodological Studies and new applications in the synthesis of BIOATIVE compounds
• Grantee: Giuliano Cesar Clososki
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/23604-1 - Computational chemistry: a tool to studies of mass spectrometry, reactivity and fragmentation/reaction mechanisms of organic compounds
• Grantee: Ricardo Vessecchi Lourenço
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/01466-9 - Directed functionalization of quinazolines and quinazolinones aiming the synthesis of bioactive substances
• Grantee: Rodolfo Hideki Vicente Nishimura
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 15/21364-6 - Applicantion of Organometallic Reagents in the Directed Functionalization of Quinolines Aimming the Synthesis of Medicinal Interest Compounds
• Grantee: Valter Eduardo Murie
• Support Opportunities: Scholarships in Brazil - Doctorate