Enantioselective, Noncovalent, Substrate-Directable Heck-Matsuda and Oxidative Heck Arylations of Unactivated Five-Membered Carbocyclic Olefins

Author(s)

de Oliveira, Juliana Manso ^[1] ; Angnes, Ricardo Almir ^[1] ; Khan, Ismat Ullah ^{[2, 1]} ; Polo, Ellen Christine ^[1] ; Heerdt, Gabriel ^[1] ; Servilha, Bruno M. ^[3] ; Menezes da Silva, Vitor H. ^[1] ; Braga, Ataualpa A. C. ^[3] ; Duarte Correia, Carlos Roque ^[1]

Affiliation

^[1] Univ Estadual Campinas, Dept Organ Chem, Chem Inst, CP 6154, BR-13083970 Campinas, SP - Brazil

^[2] Quaid I Azam Univ, Dept Chem, Islamabad 45320 - Pakistan

^[3] Univ Sao Paulo, Dept Fundamental Chem, Ave Lineu Prestes 748, Bl 05 Sup Sl 0552, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: CHEMISTRY-A EUROPEAN JOURNAL; v. 24, n. 45, p. 11738-11747, AUG 9 2018.
• Web of Science Citations: 11

Abstract

Highly diastereo- and enantioselective, noncovalent, substrate-directable Heck desymmetrizations of cyclopentenyl olefins containing hydroxymethyl and carboxylate functional groups are presented. These conformationally unbiased cyclic olefins underwent effective arylations in yields of up to 97 %, diastereoselectivity up to >20:1, and enantiomeric excesses of up to 99%. Noncovalent directing effects were shown to be prevalent in both Heck-Matsuda and oxidative Heck reactions, allowing the preferential formation of cis-substituted aryl cyclopentenes containing two stereocenters, including quaternary stereocenters. These results further validate the internal out-of-coordination-sphere iondipole interaction concept directing the reaction diastereo-selectivity to the cis-Heck product. This approach is complementary to existing methods using bis-phosphine monoxide ligands to give the opposite trans-diastereoisomer. The applicability of the method is showcased by the straightforward synthesis of a potent phosphodiesterase 4 inhibitor in a diastereo-and enantioselective manner. The reaction is operationally simple and has broad scope with regard to the nature of the arenediazonium salt and boronic acid employed. The mechanism and origin of stereoselectivity were investigated with control experiments and DFT calculations that fully supported the stabilizing internal out-of-coordination-sphere ion-dipole interaction between the resident functional group and cationic palladium. (AU)

• FAPESP's process: 17/18207-1 - Evaluating new palladium chiral catalysts and application in enantioselective Heck-Matsuda reaction development in new olefinic models: computational studies
• Grantee: Vitor Hugo Menezes da Silva
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/00544-0 - Substrate controlled Heck reactions using arenediazonium salts and the development of the enantioselective version of the Heck-Matsuda reaction.
• Grantee: Juliana Manso de Oliveira Silva
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 14/25770-6 - New frontiers in cross-coupling reactions promoted by palladium: combining enantioselective catalysis, C-H activations, new materials and in flux reactions aiming at high efficiency and sustainability in synthetic processes
• Grantee: Carlos Roque Duarte Correia
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery
• Grantee: Glaucius Oliva
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 15/01491-3 - Theoretical study of cross-coupling reactions: homogeneous and heterogeneous catalysis
• Grantee: Ataualpa Albert Carmo Braga
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/04963-6 - Molecular dynamics of cellulose enzymatic hydrolysis and QM / MM simulations of chemical reactions in biomolecular systems
• Grantee: Gabriel Heerdt
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/25849-9 - Application of the enantioselective Heck-Matsuda reaction for substrate oriented regioselective desymmetrizations
• Grantee: Ricardo Almir Angnes
• Support Opportunities: Scholarships in Brazil - Doctorate