Base-Controlled Regioselective Functionalization of Chloro-Substituted Quinolines

Author(s)

Murie, Valter E. ^[1] ; Nishimura, Rodolfo H. V. ^{[2, 1]} ; Rolim, Larissa A. ^[3] ; Vessecchi, Ricardo ^[2] ; Lopes, Norberto P. ^[1] ; Clososki, Giuliano C. ^{[2, 1]}

Affiliation

^[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Nucleo Pesquisas Prod Nat & Sintet, Ave Cafe S-N, BR-14040903 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, Dept Quim, Ave Bandeirantes 3900, BR-14040901 Ribeirao Preto, SP - Brazil

^[3] Univ Fed Vale Sao Francisco, Colegiado Ciencias Farmaceut, Ave Jose de Sa Manicoba S-N, BR-56304205 Petrolina, PE - Brazil

• Document type: Journal article
• Source: Journal of Organic Chemistry; v. 83, n. 2, p. 871-880, JAN 19 2018.
• Web of Science Citations: 6

Abstract

We prepared a number of di- and trifunctionalized quinolines by selective metalation of chloro-substituted quinolines with metal amides followed by reaction with different electrophiles. Metalation of the C-3 position of the quinolinic ring with lithium diisopropylamide at -70 degrees C is easy to achieve, whereas reaction with lithium magnesium and lithium zinc amides affords C-2 or C-8 functionalized derivatives in a regioselective fashion. These complementary methods could be rationalized by DFT calculations and are convenient strategies toward the synthesis of bioactive quinoline derivatives such as chloroquine analogues. (AU)

• FAPESP's process: 15/01466-9 - Directed functionalization of quinazolines and quinazolinones aiming the synthesis of bioactive substances
• Grantee: Rodolfo Hideki Vicente Nishimura
• Support type: 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 type: Scholarships in Brazil - Doctorate
• FAPESP's process: 15/12811-9 - DIRECTED FUNCTIONALIZATION OF ARENES AND HETEROARENES AIMIMNG THE SYNTHESIS OF SUBSTANCES OF MEDICINAL INTEREST
• Grantee: Giuliano Cesar Clososki
• Support type: 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 type: Regular Research Grants