C-H activations catalysed by Pd(II) and Rh(III): methodological and mechanistic studies to the synthesis of diarylethane and congeners and evaluations of its biological activity

• Grant number: 10/11068-7
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): October 01, 2010
• Effective date (End): February 28, 2015
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Carlos Roque Duarte Correia
• Grantee: Francisco de Azambuja
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated scholarship(s): 13/14209-9 - Development of a new intermolecular asymmetric Fujiwara-Moritani reaction: a new synthetic tool to obtain biologically active moieties, BE.EP.DR

Abstract

New Pd(II) and Rh(III) catalysed C-H activations methods were developed to the obtaining of potential biologically active molecules, particularly 1,1- e 1,2-diarylethanes. With palladium, the Fujiwaras hydroarylation of alkynes was investigated as a fast, mild and direct method to the synthesis of -aryl--heteroaryl acrylates. Initially, the mechanism of this reaction was studied using nuclear magnetic resonance and mass spectrometry to elucidate the catalyst role and the key factors controlling the stereoselectivity. After, the reaction conditions were optimized in order to prepare the -aryl--heteroaryl acrylates in good yields and selectivities. The palladium was also applied as catalyst to the Heck-Matsuda arylations employed as the key step to the synthesis of non-symmetric diaryl maleic anhydrides. From such compounds new combretastatin A4 analogs were produced. These new compounds and the Fujiwara adducts were tested against several human tumor cells. The results were much better to the Fujiwara products, especially to kidney and ovary tumor cell lines. In contrast, the diaryl maleic anhydrides derivatives showed very low activity for all kinds of cells tested. This absence of activity was attributed to unfavorable steric interactions detected in preliminary docking studies. Last, the C-H activations catalysed by 1,2,3,4,5-pentamethylciclopentadienylrhodium(III) ([Cp*Rh(III)]) were explored in two different projects: 1) the C-H activation/1,3-diyne strategy to the synthesis of adjacent bis-heterocycles and 2) -halo/pseudohaloketones as oxidized alkyne equivalents to the selectively preparation of monosubstituted N-heterocycles, in particular the isoquinolone core.

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)

GODOI, MARLA N.; DE AZAMBUJA, FRANCISCO; MARTINEZ, PABLO DAVID G.; MORGON, NELSON H.; SANTOS, VANESSA G.; REGIANI, THAIS; LESAGE, DENIS; DOSSMANN, HELOISE; COLE, RICHARD B.; EBERLIN, MARCOS N.; et al. Revisiting the Intermolecular Fujiwara Hydroarylation of Alkynes. EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, v. 2017, n. 13, p. 1794-1803, APR 3 2017. (10/00257-3, 08/00122-0, 10/11068-7, 11/23832-6)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

AZAMBUJA, Francisco de. C-H activations catalysed by Pd(II) and Rh(III): methodological and mechanistic studies to the synthesis of diarylethane and congeners and evaluations of its biological activity. 2015. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Instituto de Química Campinas, SP.