Generation, Stability, Dimerization, and Diels−Alder Reactions of Masked o-Benzoquinones. Synthesis of Substituted Bicyclo[2.2.2]octenones from 2-Methoxyphenols

• Published in: Journal of organic chemistry Vol. 64; no. 11; pp. 4102 - 4110
• Main Authors: Liao, Chun-Chen, Chu, Chrong-Shyua, Lee, Tsung-Ho, Rao, Polisetti Dharma, Ko, San, Song, Ling-Duan, Shiao, Huey-Chin
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 28.05.1999; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; REARRANGEMENT; OXIDATION; ROUTE; HYPERVALENT IODINE; FORMAL SYNTHESIS; CIS-DECALINS; CHEMISTRY; CEDRANOID SESQUITERPENES; MODEL; DERIVATIVES
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo9901891

Diels−Alder reactions of labile and readily dimerizing masked o-benzoquinones, i.e., substituted 6,6-dimethoxy-2,4-cyclohexadienones with electron-deficient dienophiles that resulted in the development of an efficient and reliable one-pot method for the preparation of highly functionalized bicyclo[2.2.2]octenones, are described. Oxidation of 2-methoxyphenols 8, 9, 11, 13, and 14 with (diacetoxy)iodobenzene in methanol afforded the corresponding masked o-benzoquinones 1, 2, 4, 6, and 7, which are not stable enough to be isolated and are found to dimerize under reaction conditions in a highly regio- and stereoselective manner to provide the Diels−Alder dimers 22, 23, 25, 27, and 28 respectively. On the other hand, masked o-benzoquinones 3 and 5, derived from phenols 10 and 12, respectively, were found to be quite labile and provided a complex mixture of products. However, masked o-benzoquinones 1−7, when generated in the presence of dienophiles such as methyl acrylate, methyl methacrylate, and methyl vinyl ketone, underwent highly regio- and stereoselective intermolecular Diels−Alder reactions to furnish variously substituted bicyclo[2.2.2]octenones 15−21(a−c). While the Diels−Alder reactions of masked o-benzoquinone 5 were found to be low-yielding, masked o-benzoquinones 1−4, 6, and 7 provided the desired adducts in good to high yields. Attempts are made to explain the observed regio- and stereoselectivity of these Diels−Alder reactions in terms of frontier molecular orbital theory.