Diels-Alder Reactions of Substituted Cyclohexa-2,4-dienones with Alkenes and Alkynes

Abstract

Substituted cyclohexa-2,4-dienones, generated in situ by pyrolysis of the appropriate dimer, participated in Diels-Alder reactions with various dienophiles to afford bicyclo[2.2.2]octenone and bicyclo[2.2.2]octadienone derivatives in high yields.The structural complexity of natural products demands the development of new and efficient strategies to construct complex polycyclic frameworks from simple starting materials with high selectivities. 2 Occasionally, tandem, 3 cascade, 4 or multicomponent reactions 5 are developed to achieve this objective.Substituted cyclohexa-2,4-dienones, 6 i.e. 2, constitute a synthetically useful class of compounds. These compounds can be generated by in situ oxidation of the readily available o-alkoxy phenols using hypervalent iodine reagents 7 in the presence of an alcohol or a salicyl alcohol using the Adler-Baker oxidation (NaIO 4 ). 8 Alternatively, when the substituted cyclohexa-2,4-dienones dimerized faster than trapped, thermolysis 9 of dimer 3 is a convenient source of 2 (Scheme 1).Substituted cyclohexa-2,4-dienones have been shown to be efficient 4p-components in Diels-Alder reactions undergoing regio-and stereoselective cycloaddition processes with electron-poor as well as electron-rich dienophiles. 10 Other 2p-components used in these reactions have been heteroaromatic compounds such as furan, 11 pyrrole, 12 and thiophene 13 derivatives. The resulting bicyclo[2.2.2]octenone derivatives have been used as starting materials for the synthesis of different targets, including polysubstituted cyclohexenes, 14 cis-decalins, 15 bicyclo[2.2.2]derivatives, 16 and triquinanes, 17 as key steps in several complex total syntheses of natural products. 18 We report herein our results of utilizing dimers 3, as a source of substituted cyclohexa-2,4-dienones 2, to synthesize various bicyclo[2.2.2]octenone and bicyclo[2.2.2]octadienone derivatives. The required dimer 3a was obtained in 50-62% yield by the oxidation of o-eugenol 19 with (diacetoxy)iodobenzene in MeOH at room temperature, while, dimer 3b was obtained in 65-70% yield when salicyl alcohol 1b was subjected 8 to sodium meta-periodate oxidation in aqueous acetonitrile.The substituted cyclohexa-2,4-dienones 2 generated in situ by the pyrolysis of dimer 3 in o-xylene in a sealed tube at 230°C (sand bath), furnished Diels-Alder cycloadducts in the presence of appropriate dienophile as shown in Table 1. Cycloadduct 4a, 20 as a single isomer, was obtained in 95% yield, when styrene was allowed (at 230°C in a sealed tube) to undergo reaction with masked o-benzoquinone (2a), generated in o-xylene by thermolysis of dimer 3a (Scheme 2). The oxidation of o-eugenol with (diacetoxy)iodobenzene in the presence of styrene at room temperature was found to be sluggish, it produced substantial amounts of dimer 3a and some desired product 4a. Similarly, cycloadduct 4b, as a single isomer, was produced in 52% yield when styrene was allowed (at 230°C in sealed tube) to react with spiroepoxycyclohexa-2,4-dienone (2b), generated by thermolysis of dim...