Second-Generation One-Pot Enantioselective Heck-Matsuda Arylations of Unactivated Olefins Directly from Anilines and Nitroarenes

Author(s)

Leao, Luiz Paulo Melchior de Oliveira ; de Oliveira, Valdeir Carlos ; Chorro, Tomaz Henrique Duarte ; Gorbatov, Sergei Aleksandrovich ; Correia, Carlos Roque Duarte

• Document type: Journal article
• Source: ADVANCED SYNTHESIS & CATALYSIS; v. N/A, p. 12-pg., 2025-02-14.

Abstract

A highly improved second generation of the one-pot enantioselective Heck-Matsuda reaction directly from anilines and nitroarenes is reported. This practical arylation method, featuring 56 examples, relies on the in situ diazotization of anilines and 3-aminothiophenes, or from the in situ reduction-diazotization of nitrobenzene derivatives. The in situ diazotization of the aniline, directly or from the in-situ reduction of the nitroarene, synchronizes smoothly with the enantioselective Heck-Matsuda reaction under mildly acidic conditions, bypassing the synthesis and handling of some unstable and/or difficult-to-prepare arenediazonium salts. The protocol was applied to the desymmetrization of unactivated olefins leading to the synthesis of functionalized spirocyclopentenyl hydantoins, aryl cyclopentenes, and beta-aryl-gamma-lactones, in high yields (up to 99%) and er (up to 99:1). The efficiency of the method is showcased by the formal total synthesis of the bioactive compound VPC01091, a potential drug candidate for multiple sclerosis treatment at the gram scale in excellent yield (94%), in 97:3 er and 20>1 dr. (AU)

• 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: 23/00025-5 - Autosustenable enantioselective Heck-Matsuda reactions via in situ generated aryldiazonium salts directly from anilines or nitroaryl derivatives in a one-pot strategy.
• Grantee: Sergei Gorbatov
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• 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