Stereoselective synthesis of functionalized azepines via gold and palladium relay catalysis

Abstract

We report herein a gold/palladium bimetallic relay catalytic strategy for the efficient synthesis of furan-fused azepines in moderate to high diastereoselectivities and excellent enantioselectivities. In this procedure, enynamides were activated...

Gold-based enantioselective bimetallic catalysis

“…Very recently, the research group of Yang, Deng and co-workers developed a gold/palladium catalytic system for the asymmetric [4+3] cycloaddition reaction of enynamide 16a and cyano-trimethylenemethane (TMM) 16b to afford the furan fused azepine 16c (Scheme 16). 29 The screening of chiral phosphoramidite ligands at palladium complexes revealed that ligand L14 increases the enantioselectivity as well as diastereoselectivity of the reaction (97% ee and 13 : 1 dr). To understand the reaction mechanism, the authors performed the reaction in a stepwise manner; in this regard, enynamide 16a was first reacted with PPh 3 AuCl/AgPF 6 to give azadiene 16e , which was then treated with 16b in the presence of Pd 2 (dba) 3 / L14 affording the desired product 16c with 90% yield and 97% ee.…”

“…Very recently, the research group of Yang, Deng and coworkers developed a gold/palladium catalytic system for the asymmetric [4+3] cycloaddition reaction of enynamide 16a and cyano-trimethylenemethane (TMM) 16b to afford the furan fused azepine 16c (Scheme 16). 29 The screening of chiral phosphoramidite ligands at palladium complexes revealed that Scheme 13 Enantioselective Au/Pd catalysis: synthesis of furan-fused nine-membered heterocycles. 18b and dioxo pyrrolidine 18d (Scheme 18b).…”

Palladium-catalyzed asymmetric [4 + 3] cycloaddition of acyclic α,β-unsaturated imines with trimethylenemethane donors: access to chiral non-fused azepines

“…12 It was not until 2020 that the catalytic asymmetric version of this reaction using (benzo)furan- or indole-derived azadienes as four-atom synthons was independently reported by Trost, 13 Shao, 14 and our group (Scheme 1b). 15 In the aforementioned reactions, these substrates are limited to (benzo)furan- or indole-derived azadienes, which leverage a ring structure and the aromatic driving force to achieve the excellent regioselectivity of cyclic azadienes as four-atom synthons. However, the use of acyclic azadienes for the Pd-catalyzed asymmetric [4 + 3] cycloaddition of TMM donors to generate non-fused azepine derivatives has yet to be investigated.…”

Asymmetric synthesis of spirofuro[2,3-b]azepine-5,3′-indoline derivativesviacycloisomerization/[4 + 3] annulation process under Au/N-heterocyclic carbene relay catalysis

“…For example, they have been employed by the groups of Chi 13 and Moreau 14 for the enantioselective [4 + 2] cycloaddition reactions, respectively. Under the catalysis of chiral Pd complex, Zhao 15 and Deng 16 groups have achieved the asymmetric [4 + 5] and [4 + 3] variants with excellent control of selectivity. Meanwhile, our group has also found that under the catalysis of Au( i ), the formal [4 + 3] cycloaddition of 1 with three-atom synthons (derived from α-bromohydroxymates and allylic sulfur ylides) 17 provides new avenues for the effective construction of highly functionalized azepines.…”