Palladium-catalyzed dehydrogenation serves as one of the vital methods for aromatic compound synthesis. During the past decades, significant progress has been made by using endo-cyclic olefins as starting materials; inexpensive oxidant or O₂ could be used to remove Pd-H generated in the catalytic cycle (Fig. 1a)^1-5. However, exo-cyclic olefins are rarely employed as substrates.  

In principle, a Pd-H species can simultaneously catalyze both olefin isomerization and allyl CH dehydrogenation under suitable conditions. This work found N-heterocyclic carbene (NHC) as a suitable ligand to regulate those competing reactivity. With the help of olefin additives, a modular dehydroaromatization system was established for a wide range of exo- and endo-cyclic substrates without strong oxidants and under mild physical conditions.

Fig. 1 Strategies in Pd-catalyzed dehydroaromatization (DHA) of cyclic alkenes. a AMS/quinone-assisted Pd(II) regeneration. b NHC-Pd(II)-H directed transfer-dehydroaromatization.

That change in active dehydrogenation species from PdX₂ to (NHC)PdRX also came with good functional group tolerance. Ester, amide, pinacol ester, phenol, epoxide, etc., were tolerated under the standard neutral condition (Fig. 2a). Diverse exo-cyclic structures, like methylene, vinyl, and allyl cyclohexanes with different degrees of substitution, including tri-/tetra-substituted olefins generated by chain-walking, were all compatible (Fig. 2b).

Fig. 2 Selected examples of TDHA reaction. a endocyclic olefin as substrates. b exocyclic olefins as substrates.

A suitable choice of regulator could manipulate the catalytic cycle, and the intermediates could be used for other valuable transformations. For instance, by using 1-morpholine cyclohexene as substrate, the corresponding substituted aniline or the Diels-Alder product were obtained optionally by simply changing the regulator under the standard condition (Fig. 3).

Fig. 3 Catalytic synthesis of a substituted aniline and dehydrogenative Diels-Alder product. a Synthesis of a substituted aniline. b Trapping the diene for the Diels-Alder reaction.

A highly chemoselective dehydrogenation of cyclic alkene over cyclic ketone was also achieved. If you want to know more about our work, please visit the following website: https://doi.org/10.1038/s41467-022-33163-6 .

Reference

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