Asymmetric Intramolecular Dearomatization of Nonactivated Arenes with Ynamides for Rapid Assembly of Fused Ring System under Silver Catalysis

Abstract

Arene dearomatization is a straightforward method for converting an aromatic feedstock into functionalized carbocycles. Enantioselective dearomatizations of chemically inert arenes, however, are quite limited and underexplored relative to those of phenols and indoles. We developed a method for diazo-free generation of silver-carbene species from an ynamide and applied it to the dearomatization of nonactivated arenes. Transiently generated norcaradiene could be trapped by intermolecular [4 + 2] cycloaddition, synthesizing polycycles with five consecutive stereogenic centers. This protocol constitutes the first highly enantioselective reaction based on the diazo-free generation of silver-carbene species. Mechanistic investigations revealed a dearomatization followed by two different classes of pericyclic reactions, as well as the origin of the chemo- and enantioselectivity.

Theoretical study on the mechanism, chemo- and enantioselectivity of the Ag- vs. Rh-catalyzed intramolecular carbene transfer reaction of diazoacetamides

“…6 However, the field of silver-catalyzed asymmetric carbene transfer reactions has developed very slowly 7–11 because of the linear and triangular coordination modes, 12 the competitive Lewis acid-catalyzed pathway and the free carbene pathway. 13 Since 1996, Burgess, 14 Jørgensen 13 and others 10,11,15,16 have investigated the asymmetric carbene transfer reaction catalyzed by silver salts, but have not achieved satisfactory results. In 2017, Nemoto's research group successfully realized the first silver-catalyzed, highly enantioselective carbene transfer reaction through the intramolecular reaction model.…”

Spirocyclizative Remote Arylcarboxylation of Nonactivated Arenes with CO 2 via Visible-Light-Induced Reductive Dearomatization

“…In contrast, only limited important advances have been made in the dearomatization of electronically unbiased aromatics such as naphthalene and benzene derivatives that possess high resonance stabilization energy. 6,[25][26][27][28][29][30][31][32][33][34][35] Of particular note, the You's group and the Hong and Jia's group simultaneously reported two types of elegant highly diastereoselective 1,4-difunctionalization reactions of 1-naphthamides via palladium-catalyzed dearomatization at slightly elevated temperature. 25,26 Therefore, the dearomatization of non-activated arenes remains challenging, and the development of a mild and complementary protocol for dearomatization of non-activated arenes is highly desirable.…”

Visible-Light-Mediated Cyclopropanation Reactions of 3-Diazooxindoles with Arenes

“…The Buchner reaction represents one of the most powerful methods of transforming stable aromatic rings to much more reactive systems . Typically, precious transition-metal catalysts are required to access a metal carbene intermediate, which then undergoes a cyclopropanation reaction with arenes . In contrast, the visible-light-mediated metal-free Buchner reaction has remained vastly underexplored until very recently.…”