Palladium-Catalyzed [3 + 2] Annulation of Alkynes with Concomitant Aromatic Ring Expansion: A Concise Approach to (Pseudo)azulenes

Abstract

The construction of (pseudo)­azulenes represents an appealing yet challenging task in organic synthetic chemistry. Herein, we disclose a palladium-catalyzed [3 + 2] annulation technique of alkynes with concomitant aromatic ring expansion driven by a diboron reagent and iodide, affording a concise approach to azulenes (7-fused-5 bicycle) and pseudoazulenes (6-fused-5 bicycle). Compared with the documented synthetic strategies, the route to (pseudo)­azulenes developed herein is applicable for both homo- and cross-annulation processes and exhibits a broad substrate scope. It is worth noting that this transformation is not only suitable for the ring expansion of the phenyl moiety to afford azulenes but also applicable to the ring expansion of the electron-rich five-membered heterocycles to deliver pseudoazulenes. Experimental and computational investigations on the mechanism support the formal trans-palladium-boration across the alkyne, cis-addition of the alkyne, dearomative spiroannulation, and aromatic ring expansion process.

Linear Nonalternant Isomers of Acenes Fusing Multiple Azulene Units

“…By contrast, the latter provides an opportunity to build azulene from simple nonazulene precursors with diverse structural modifications which facilitates the incorporation of azulene unit into polymer backbones [20, 21] and fused PAHs [22–31] . Despite the in situ generated fused azulene units can be achieved through Scholl reaction, [23, 28, 32] oxidative aromatization, [25, 26] and on‐surface synthesis, [33–35] there are relatively few general methods [36] for constructing azulene skeletons from small building blocks, most of which involve multi‐step synthesis. Several strategies starting from seven‐membered ring [37–41] and five‐membered ring [20, 42, 43] precursors, respectively, have been well established to prepare a diverse range of azulene derivatives with various substituents, while the construction of fused azulene units in PAHs from small nonazulene subunits remains very challenging.…”

Modular Synthesis of Structurally Diverse Azulene‐Embedded Polycyclic Aromatic Hydrocarbons by Knoevenagel‐Type Condensation

“…In addition to commencing the synthesis of these fascinating molecules from the parent azulene, [7] a surge of methods have been recently developed by us and others to in situ construct azulene subunits in the large π‐systems either by on‐surface synthesis [8] or by in‐solution chemistry (Figure 1a), such as the Scholl‐type cyclization, [9a–c] intramolecular Friedel‐Craft reaction followed by aromatization, [10] alkyne annulation, [11] Pd‐catalyzed [5+2] annulation [12] and photo‐induced cyclization, [13] etc. Despite significant recent progress, the above transformations usually require multi‐step synthesis of the specific precursors, and some products result from unpredicted rearrangement [9a,c] or insertion reactions [11d,e] . For example, the most commonly used Scholl reaction [14] under acidic conditions with 2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone (DDQ)/acid or FeCl 3 to prepare non‐alternant PAHs is sometimes difficult to be predicted, [9a,c] and is not a controllable tool for the construction of acid‐sensitive pentagon‐heptagon system [15] .…”

Direct Access to Functionalized Azulenes and Pseudoazulenes via Unconventional Alkyne Cyclization Reactions

“…Further, the biggest problem is the control of the selectivity, in particular for the inter‐ and intramolecular dimerization reaction of alkynes. Currently, only the fluorine substitution effect on the benzenoid rings [24] and relatively higher reactivity of arylalkynes over alkylalkynes [25] provides partial solutions for this issue. New design of active catalytic systems based on further investigations on the reaction mechanism may afford new solutions.…”

“…[24b] Recently, You and coworkers described a palladium-catalyzed [3 + 2] annulation technique of alkynes with concomitant aromatic ring expansion driven by a diboron reagent and iodide, affording a concise approach to azulenes and pseudoazulenes. [25] Besides examples on pseudoazulenes derived from heteroaryl alkynes for the first time, this new catalytic system is also effective to promote cross-annulation between two different alkynes including internal aliphatic and monoaryl alkynes (Scheme 9). Experimental and computational investigations on the mechanism revealed a pivotal role of the iodide ion in triggering the reaction and driving the cis-trans isomerization of boroalkenyl palladium species.…”