Dearomative 1,4-difunctionalization of naphthalenes via palladium-catalyzed tandem Heck/Suzuki coupling reaction

Abstract

Dearomative functionalization reactions represent an important strategy for the synthesis of valuable three-dimensional molecules from simple planar aromatics. Naphthalene is a challenging arene towards transition-metal-catalyzed dearomative difunctionalization reactions. Reported herein is an application of naphthalene as a masked conjugated diene in a palladium-catalyzed dearomative 1,4-diarylation or 1,4-vinylarylation reaction via tandem Heck/ Suzuki sequence. Three types of 1,4-dihydronaphthalene-based spirocyclic compounds are achieved in excellent regio-and diastereoselectivities. Key to this transformation is the inhibition of a few competitive side reactions, including intramolecular naphthalenyl C-H arylation, intermolecular Suzuki cross-coupling, dearomative 1,2-difunctionalization, and dearomative reductive-Heck reaction. Density functional theory (DFT) calculations imply that the facile exergonic dearomative insertion of a naphthalene double bond disrupts the sequence of direct Suzuki coupling, leading to the tandem Heck/Suzuki coupling reaction. The observed regioselectivity towards 1,4-difunctionalization is due to the steric repulsions between the introduced aryl group and the spiro-scaffold in 1,2-difunctionalization.

Palladium-Catalyzed Cascade Dearomative Spirocyclization and C−H Annulation of Aromatic Halides with Alkynes

“…Recently, the endocyclic C=C bonds of (hetero)­arenes have been regarded as nonclassic olefins to enable the dearomative difunctionalization reactions . In this regard, Jia and You reported the catalytic dearomative 1,4-difunctionalization of naphthalenes by capturing the in situ formed π-allyl-palladium species with a second coupling partner (Scheme b). , Inspired by this dearomative difunctionalization strategy, we envisioned that the catalytic Heck-type dearomative spiroannulation of polycyclic aromatic halides with diaryl acetylenes could be achieved without the assistance of an alkyl group, by intercepting the alkyl palladium intermediates with the attached aryl rings on the carbon–carbon triple bonds. The implementation of this rational design relied on the development of a highly efficient and selective catalytic system that enables the thermodynamically unfavored dearomatization process rather than nonspirocyclization and a following C–H annulation process as the termination reaction of the cascade course.…”

Palladium-Catalyzed Asymmetric Domino Heck/Carbocyclization/Suzuki Reaction: A Dearomatization of Nonactivated Naphthalenes

“…45 Very recently, elegant examples of Pd-catalyzed dearomative 1,4-difunctionalization of naphthalenes for the diastereoselective formation of 1,4-dihydronaphthalene-based spirocycles have emerged (Scheme 1b). 46,47 Based on our recent interest in the field, 35,48 we hypothesized that the β-naphthyl group might be activated by the key alkyl-Pd species in domino Heck reaction through an intramolecular coordination interaction (Scheme 1c). As such, an intramolecular dearomative migratory insertion of the nonactivated naphthyl ring into the alkyl-Pd bond might be achieved in certain cases.…”

Spirocyclizative Remote Arylcarboxylation of Nonactivated Arenes with CO 2 via Visible-Light-Induced Reductive Dearomatization

“…In contrast, only limited important advances have been made in the dearomatization of electronically unbiased aromatics such as naphthalene and benzene derivatives that possess high resonance stabilization energy. 6,[25][26][27][28][29][30][31][32][33][34][35] Of particular note, the You's group and the Hong and Jia's group simultaneously reported two types of elegant highly diastereoselective 1,4-difunctionalization reactions of 1-naphthamides via palladium-catalyzed dearomatization at slightly elevated temperature. 25,26 Therefore, the dearomatization of non-activated arenes remains challenging, and the development of a mild and complementary protocol for dearomatization of non-activated arenes is highly desirable.…”