Aromaticity-Driven Access to Cycloalkyl-Fused Naphthalenes

Abstract

We report the efficient synthesis of cycloalkyl-fused naphthalenes through the [4 + 2]-cycloaddtion/decarboxylative aromatization of alkyne-tethered aryne insertion adducts. These scaffolds were difficult to synthesize using conventional reactions. The reaction proceeds via the formation of a benzopyrylium intermediate followed by intramolecular [4 + 2] cycloaddition and a subsequent decarboxylation pathway. This method is also compatible with allene-tethered substrates to afford similar products. In addition, the one-pot synthesis of polysubstituted naphthalenes via aryne insertion/benzannulation has also been developed in good yield.

Highlighting the Rich Chemistry of the Allenone Moiety

“…Arene‐tethered allenyl ketones 364 have been recently employed to build cyclohexanes fused to a benzene unit in systems 365 in one operational step (Scheme 66a) [179] . The cascade reaction is proposed to start with the coordination of BF 3 ⋅Et 2 O to the ketone moiety of 364 , promoting the oxycyclization towards intermediates 366 .…”

“…Arene-tethered allenyl ketones 364 have been recently employed to build cyclohexanes fused to a benzene unit in systems 365 in one operational step (Scheme 66a). [179] The cascade reaction is proposed to start with the coordination of BF moiety of 364, promoting the oxycyclization towards intermediates 366. Then, benzopyrylium formation and [4 + 2] cycloaddition with the participation of the terminal allenic double bond and the diene moiety of 367 conduct to bridged polycycles 368, which finally have provided fused polycycles 365 after decarboxylation (Scheme 66a).…”

“…Then, benzopyrylium formation and [4 + 2] cycloaddition with the participation of the terminal allenic double bond and the diene moiety of 367 conduct to bridged polycycles 368, which finally have provided fused polycycles 365 after decarboxylation (Scheme 66a). [179] In a different contribution, the cyclohexene motif has been generated in cyclohexenones 370 through a palladium-catalyzed decarboxylative cyclization of γ-allenones 369 (Scheme 66b). [180] The reaction of 1,2-allenyl ketones and vinyl ketones with or without the intervention of a second nucleophile, has provided a quick route to build saturated or partially unsaturated cyclic structures.…”

“…The cascade reaction is proposed to start with the coordination of BF 3 ⋅Et 2 O to the ketone moiety of 364 , promoting the oxycyclization towards intermediates 366 . Then, benzopyrylium formation and [4+2] cycloaddition with the participation of the terminal allenic double bond and the diene moiety of 367 conduct to bridged polycycles 368 , which finally have provided fused polycycles 365 after decarboxylation (Scheme 66a) [179] . In a different contribution, the cyclohexene motif has been generated in cyclohexenones 370 through a palladium‐catalyzed decarboxylative cyclization of γ‐allenones 369 (Scheme 66b) [180] …”

Radical Cascade Bicyclization/Aromatization of 1,7‐Enynes with 1,3‐Dicarbonyl Compounds towards 2,3‐Dihydro‐1H‐cyclopenta[a]naphthalenes

“…[12] Recently, Chandrasekhar and coworkers reported an elegant work to assemble cyclopentane-fused naphthalenes by using the Lewis-acid-catalyzed intramolecular [4 + 2] cycloaddition/aromatization of alkyne-, allene-, and alkene-tethered aryne insertion adducts (Scheme 1b). [13] Whereas the above-mentioned protocols provide approaches to obtain 2,3-dihydro-1Hcyclopenta[a]naphthalenes, they often suffer some limitations, such as the need for noble metal catalysts, or a preassembled naphthalene skeleton, or harsh reaction conditions, or a multi-step manipulation, etc. Therefore, to develop a straightforward and practical synthetic methodology for the construction of structurally diverse 2,3-dihydro-1H-cyclopenta[a]naphthalenes is highly desirable in organic synthesis and medicinal chemistry.…”