Second‐Generation One‐Pot Enantioselective Heck‐Matsuda Arylations of Unactivated Olefins Directly from Anilines and Nitroarenes
Year: 2025
Type: article
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 β ‐aryl‐ γ ‐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 .
Source: Advanced Synthesis & Catalysis
Authors: Luiz Paulo Melchior de Oliveira Leão, Valdeir Carlos de Oliveira, Tomaz Henrique Duarte Chorro, Sergei Aleksandrovich Gorbatov, Carlos Roque Duarte Correia
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: bronze
Awards: G2275071777, G2823776494, G3572101131, G407438531, G47252533, G6191138830, G6807018335, G6822879463, G8174336396, 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, G8955683106
OpenAlex ID: W4407129724