In Tandem Enantioselective Intramolecular Heck-Matsuda Reactions directly from Anilines

Author(s)

Duarte Chorro, Tomaz Henrique ; Scarpa de Souza, Edson Leonardo ; Koster, Otto Daolio ; Polo, Ellen Christine ; Carmona, Rafaela Costa ; Menezes da Silva, Vitor Hugo ; Batista Junior, Joao Marcos ; Duarte Correia, Carlos Roque

• Document type: Journal article
• Source: ADVANCED SYNTHESIS & CATALYSIS; v. 365, n. 2, p. 13-pg., 2023-01-11.

Abstract

A new enantioselective intramolecular strategy for the synthesis of enantioenriched bridged benzoxacines, unsaturated spirobenzofurans, 2,3-dihydrobenzofuran and 2,3-indoline acetate scaffolds in a tandem-like diazotization/Heck-Matsuda process directly from anilines has been developed. The process combines the in situ diazotization of the aniline, followed by the intramolecular Heck-Matsuda reaction, thus skipping the isolation and purification of potentially unstable or hard-to-synthesize aryldiazonium salts. The practicality and robustness of the sequence were demonstrated by the synthesis of 30 complex motifs in yields up to 91% and enantiomeric ratios up to 97:3, including quaternary stereocenters. The in-tandem processes from anilines were compared to conventional Heck-Matsuda reactions using pre-synthesized aryldiazonium salts. With few exceptions, the reactions starting directly from the anilines afforded better overall yields and enantioselectivity, demonstrating the efficiency of the method. (AU)

• 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: 18/16916-8 - Enantioselective and regioselective desymmetrizations directed by the substrate employing Heck-Matsuda reactions
• Grantee: Tomaz Henrique Duarte Chorro
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 19/25657-9 - Radical arilations of endocyclic encarbamates by fotoredox: development of the new method, derivatization, and synthetic applications
• Grantee: Edson Leonardo Scarpa de Souza
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 19/22319-5 - Vibrational circular dichroism spectral markers: facilitating absolute configuration assignment of natural products
• Grantee: João Marcos Batista Junior
• Support Opportunities: Regular Research Grants
• 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: 18/00271-8 - Enantioselective Synthesis of Heterocylces via Intramolecular and Desymmetrizations Reacions Using Arenediazonium Salts
• Grantee: Rafaela Costa Carmona
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• 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: 18/02945-6 - Preliminar studies and development of the sequential intramolecular Heck-Matsuda reaction using carbon dioxide
• Grantee: Otto Daolio Koster
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)