Recent advances in [4 + 4] annulation of conjugated heterodienes with 1,4-dipolar species for the synthesis of eight-membered heterocycles

Abstract

Eight-membered heterocycles are important but their synthesis is usually challenging. This review summarizes the recent advances in [4 + 4] annulation of conjugated heterodienes with 1,4-dipolar species for assembling eight-membered heterocycles.

Palladium-catalyzed [4 + 4] cycloaddition of 2-pyrones with 2-alkylidenetrimethylene carbonates: access to bridged eight-membered oxygen heterocycles

“…The [4 + 4] cycloaddition is an efficient means to access eight-membered heterocycles. 9 However, previous examples of [4 + 4] cycloadditions show that only aza-dienes acted as partners in reactions with ADTMCs, as reported independently by Lin, 8 b Archambeau, 8 a Duan 8 c and Huang 8 d for the synthesis of non-bridged eight-membered rings, and reactions of ADTMC with all-carbon-based conjugated dienes for the construction of bridged eight-membered oxygen heterocycles has never been utilized (Scheme 2a). Undoubtedly, selecting the appropriate diene partner to react with ADTMC is the key factor for realizing this type of [4 + 4] cycloaddition.…”

Editorial: Heterodienes in organic synthesis

“…Due to their electron-deficient nature, heterodienes react only with electron-rich dienophiles via an inverse-electron demand Diels–Alder reaction ( Baiazitov and Denmark, 2013 ; Png et al, 2017 ). Third, being highly polarized 1,4-synthons, heterodienes are convenient partners for stepwise [4 + 1]- [4 + 3]- and [4 + 4]- and other [4 + n]-annulation processes involving ylides, carbenoids, and related species ( Selvaraj et al, 2020 ; Ushakov et al, 2022 ; Wang et al, 2024 ). Additionally, they are commonly involved in multi-component condensation reactions that lead to the formation of valuable heterocyclic scaffolds ( Attanasi et al, 2009 ; Lopes et al, 2018 ; Heredia-Moya et al, 2022 ).…”