GaCl3‑Mediated Cascade [2 + 4]-Cycloaddition/[4 + 2]-Annulation of Donor–Acceptor Cyclopropanes with Conjugated Dienes: Strategy for the Construction of Benzobicyclo[3.3.1]nonane Skeleton

• Published in: Journal of organic chemistry 2021-06, Vol.86 (12), p.8089-8100
• Main Authors: Belaya, Maria A, Knyazev, Daniil A, Borisov, Denis D, Novikov, Roman A, Tomilov, Yury V
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.1c00564

Structurally important benzobicyclo[3.3.1]­nonane derivatives were synthesized by a gallium trichloride mediated reaction of readily available donor–acceptor cyclopropanes (DACs) with 1,3-dienes as a one-pot cascade ionic [2 + 4]-cycloaddition/Friedel–Crafts-type cyclization process. At the first stage, DACs act as sources of formal gallium 1,2-zwitterionic complexes to give 6-benzylcyclohex-3-ene-1,1-dicarboxylates that are converted under certain conditions in the presence of GaCl3 to give benzobicyclo[3.3.1]­nonanes in 30–74% yields. The process is tolerant of varying substituents at different positions of the main framework. Further, potentially useful modifications of benzobicyclo[3.3.1]­nonane derivatives are demonstrated. 2-Cyclopropylbutadiene reacts with DAC at higher temperature more deeply with cleavage of three-membered rings in both cyclopropane substrates, and twofold alkylation of the Ph-substituent at ortho- and meta-positions, that leads to a 1,2,7,8,9,10-hexahydro-6H-7,10a-methanocycloocta­[cd]­indene skeleton. Cyclopropane-1,1-diesters containing a bulky substituent in the ester group react with isoprene in a different way to give bicyclic lactones containing a 2-oxabicyclo[2.2.2]­octan-3-one moiety.