Intermolecular Diels−Alder Reactions of Brominated Masked o-Benzoquinones with Electron-Deficient Dienophiles. A Detour Method to Synthesize Bicyclo[2.2.2]octenones from 2-Methoxyphenols

• Published in: Journal of organic chemistry Vol. 67; no. 18; pp. 6493 - 6502
• Main Authors: Lai, Chien-Hsun, Shen, Yi-Ling, Wang, Min-Nen, Kameswara Rao, N. S, Liao, Chun-Chen
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 06.09.2002; Amer Chemical Soc
• Subjects: Alicyclic compounds; Alicyclic compounds, terpenoids, prostaglandins, steroids; Chemistry; Chemistry, Organic; Exact sciences and technology; Organic chemistry; Physical Sciences; Preparations and properties; Science & Technology; SODIUM; ETHERS; PI-METHANE REARRANGEMENT; FORMAL SYNTHESIS; STRATEGY; VANILLATE; CHEMISTRY; CEDRANOID SESQUITERPENES; (+/-)-COMPACTIN; TRIQUINANES; Debromination; Ether; Regioselectivity; Bromination; Benzoquinone derivatives; Diels Alder addition; Ketone; Stereoselectivity; Cyclization; Bicyclic compound; Phenols; Bromine Organic compounds; Dimer; Oxidation; Chemical synthesis; Ethylenic compound
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo020171h

Intermolecular Diels−Alder reactions of masked o-benzoquinones, i.e., 6,6-dimethoxy-2,4-cyclohexadienones 5−7 and 21−24 generated from 2-methoxyphenols 1−3 and 17−20, respectively, with electron-deficient dienophiles leading to highly functionalized bicyclo[2.2.2]octenones are described. The masked o-benzoquinones (MOBs) 5−7 underwent Diels−Alder cycloadditions with methyl acrylate, methyl methacrylate, and methyl vinyl ketone to provide bicyclo[2.2.2]octenones 13a−c to 15a−c (direct method) in low to moderate yields with the concomitant formation of considerable amounts of dimers 9−11. To retard dimerization and to improve the yields of the requisite bicyclo[2.2.2]octenones, a detour method comprised of sequential bromination of 2-methoxyphenols 1−4, oxidation and Diels−Alder reaction, and debromination has been developed. The oxidation of bromophenols 17−20 produced MOBs 21−24 which are stable enough to be isolated. The MOBs 21−24 underwent cycloaddition with electron-deficient dienophiles in a very efficient manner to afford the corresponding cycloadducts 25a−c to 28a−c in good to high yields without self-dimerization. When the cycloadducts 25a−c to 28a−c were treated with either Bu3SnH/AIBN or tributylammonium formate−palladium reagent, the corresponding debrominated products 13a−c to 16a−c were obtained in high to excellent yields. In general, the cycloadducts 13a−c to 15a−c were obtained in 20−40% higher yields via the detour method than those via the direct method. In both routes, the Diels−Alder reactions proceeded in a highly regio- and stereoselective manner to furnish a single cycloadduct in each case.