Metalations under flow conditions.

• Grant number: 18/08856-5
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: September 01, 2018
• End date: January 31, 2019
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Giuliano Cesar Clososki
• Grantee: Rodolfo Hideki Vicente Nishimura
• Supervisor: Paul Knochel
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Ludwig Maximilian University of Munich (LMU Munich), Germany
• Associated to the scholarship: 15/01466-9 - Directed functionalization of quinazolines and quinazolinones aiming the synthesis of bioactive substances, BP.DR

Abstract

The directed metalation and halogen-metal exchange are among the most used strategies to generate polyfunctionalized organometallic compounds. However, the high ionic character of the species involved require specific reaction conditions, e. g., low temperature. In this context, continuous flow micro-reactors have become an important tool for this purpose, since this equipment allows a more efficient heat exchange. In this way, organometallic synthesis has benefited from this technology and a range of organometallic reactions have been performed quite easily in flow, whereas their conduction in batch has proven to be difficult and often difficult to scale-up. Thus, in this proposal, we wish to concentrate our efforts in the functionalization under flow conditions of new heterocyclic systems and olefinic building blocks using Br/Li exchange or sodiation as the strategy to achieve the corresponding organometallic intermediate and after reaction with various electrophiles (E-X) leading to valuable products of type Het-E.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

VICENTE NISHIMURA, RODOLFO HIDEKI; WEIDMANN, NIELS; KNOCHEL, PAUL. Preparation of Diorganomagnesium Reagents by Halogen-Lithium Exchange of Functionalized Heteroaryl Halides and Subsequent in situ Trapping with MgCl2 center dot LiCl in Continuous Flow. SYNTHESIS-STUTTGART, v. 52, n. 20, p. 11-pg., 2020-10-16. (18/08856-5)

WEIDMANN, NIELS; NISHIMURA, RODOLFO H. V.; HARENBERG, JOHANNES H.; KNOCHEL, PAUL. Halogen-Lithium Exchange of Sensitive (Hetero)aromatic Halides under Barbier Conditions in a Continuous Flow Set-Up. SYNTHESIS-STUTTGART, v. 53, n. 03, SEP 2020. (18/08856-5)