Dearomatization [4+2] Cycloaddition of Nonactivated Benzene Derivatives

Abstract

Dearomatization reactions have recently emerged as a powerful tool for the rapid buildup of molecular complexity. Here, an unparalleled thermal dearomatization [4+2] cycloaddition reaction between benzene derivatives and a 2H-phosphindole tungsten complex was reported. The unique reactivity of the in situ-generated 2H-phosphindole complex toward benzene was revealed by density functional theory calculations. We thus provide new insights into the dearomatization of nonactivated arenes and pave the way for the manipulation of the dearomatization for further applications.

Formation of Isolable Dearomatized [4 + 2] Cycloadducts from Benzenes, Naphthalenes, and N-Heterocycles Using 1,2-Dihydro-1,2,4,5-tetrazine-3,6-diones as Arenophiles under Visible Light Irradiation

“…While heteroaromatic compounds with attenuated aromaticity and electron-rich phenol derivatives are relatively susceptible to dearomative transformations, simple benzene derivatives are highly challenging substrates to dearomatize due to their high levels of aromaticity. Despite recent advances in dearomatization strategies for synthesizing valuable organic molecules, the development of methodologies that are able to selectively convert benzene rings into the corresponding saturated or partially saturated cyclic carbon skeletons under mild reaction conditions remains a formidably challenging task …”

“…As the introduction and their manipulation of functional groups on aromatic rings are well-established synthetic transformations, a wide range of substituted aromatics are also common starting materials in organic synthesis. Based on this background, dearomatization reactions that enable rapid construction of complex non-planar scaffolds from planar aromatic compounds have attracted great attention. − A major challenge in achieving such transformations derives from the requirement to overcome the stabilization of aromatic systems. While heteroaromatic compounds with attenuated aromaticity and electron-rich phenol derivatives are relatively susceptible to dearomative transformations, simple benzene derivatives are highly challenging substrates to dearomatize due to their high levels of aromaticity.…”

NHC-catalyzed enantioselective radical reactions of enal and pyridinium salt: mechanism and origin of regio- and stereoselectivities

“…In the present study, all computations were carried out using the Gaussian 16 program. 35 Due to the reliability of density functional theory in the mechanistic studies of organocatalytic reactions, [36][37][38][39][40][41][42][43] enzyme catalyzed reactions 44 and transition metal-catalyzed reactions, [45][46][47][48][49][50]…”

2H‐Phosphindole‐Enabled Dearomatization and [4+2] Cycloaddition of (Hetero)Arenes

“…[13] We recently described a preliminary thermal dearomatization [4 + 2] cycloaddition between 2H-phosphinidole and non-activated benzenoid hydrocarbons (Scheme 1d). [14] This metal-free dearomatization approach reveals the unique reactivity of 2H-phosphinidoles and provides rapid access to high-value three-dimensional polycyclic architectures. Therefore, it is exciting and necessary to reveal the reactivity and selectivity of 2H-phosphinidole towards other (hetero)arenes.…”

“…Stephan reported an intramolecular [4+2] cycloaddition of a phosphaalkene moiety with the N‐bound benzene ring [13] . We recently described a preliminary thermal dearomatization [4+2] cycloaddition between 2 H ‐phosphinidole and non‐activated benzenoid hydrocarbons (Scheme 1d) [14] . This metal‐free dearomatization approach reveals the unique reactivity of 2 H ‐phosphinidoles and provides rapid access to high‐value three‐dimensional polycyclic architectures.…”