Mechanistic and Kinetic Factors of ortho‐Benzyne Formation in Hexadehydro‐Diels‐Alder (HDDA) Reactions

Abstract

With the rapid development of the hexadehydro-Diels-Alder reaction (HDDA) from its first discovery in 1997, the question of whether a concerted or stepwise mechanism better describes the thermally activated formation of orthobenzyne from a diyne and a diynophile has been debated. Mechanistic and kinetic investigations were able to show that this is not a black or white situation, as minor changes can tip the balance. For that reason, especially, linked yne-diynes were studied to examine steric, electronic, and radical-stabilizing effects of their terminal substituents on the reaction mechanism and kinetics. Furthermore, the influence of the nature of the linker on the HDDA reaction was explored. The more recently discovered photochemical HDDA reaction also gives ortho-arynes, which display the same reactivity as the thermally generated ones, but their formation might not proceed by the same mechanism. This minireview summarizes the current state of mechanistic understanding of the HDDA reaction.

Advances in the synthesis of nitrogen-containing heterocyclic compounds byin situbenzyne cycloaddition

“…), and their varieties are diverse (Scheme 1b). 9,10 In 1902, Stoermer and Kahlert et al reported the existence of the benzene species by treating 3-bromobenzofuran with a strong base in ethanol solution, 11 the usual strategy for the preparation of benzyne intermediates is to remove two adjacent atoms or groups from the benzene ring. Due to the instability, benzyne intermediate must be generated in situ from appropriate precursors under suitable reaction conditions, including thermo-synthesis, oxidation, deprotonation, halogen-metal exchange, C-Si bond cleavage by uoride source or decarboxylation by transition metal-catalyzed (Scheme 1c).…”

On the aromaticity and stability of benzynes in the ground and lowest‐lying triplet excited states

“…In particular, didehydrogenated benzene biradicals (see Scheme 1) participate in important reactions such as the Bergman cyclization in which a 1,4‐didehydrobenzyne ( p ‐benzyne) biradical is involved 5–29 . Additionally, the more stable o ‐benzyne isomer also participates as an intermediate in various organic reactions, such as Diels–Alder, the formation of epoxides, and the synthesis of various organic compounds 4,30–39 …”