Perillaketones, synthesis

These cycloadducts, at their most elementary level, are excellent intermediates for the synthesis of 3-substituted furan derivatives. For example, Kawanisi and coworkers reported a synthesis of perillaketone 174 in which the critical step was a Paterno-BUchi photocycloaddition between furan and 4-methylpentanal in the presence of methanesul-fonic acid (Scheme 39)82. This reaction furnished two initial photoadducts, 172 and 173. The unexpected product 173 presumably arises from a Norrish Type II cleavage of 4-methylpentanal to give acetaldehyde, and subsequent cycloaddition with furan. The desired cycloadduct 172 was then converted uneventfully to 174 via acid-catalyzed aromatization and oxidation. 

Many papers from the patent literature on pyrethroids and juvenile hormones cannot be included in this Report. Papers have reported the synthesis and activity of monoterpenoid juvenoids, including geranyl pyridyl ethers " and geranyl alkyl ethers and amines and their epoxides. Further papers in this section include a report of the potent lung toxicity of perillaketone, the observation that the malodorous water contaminant 2-methylisoborneol has the l-R-exo configuration, and that fenchyl methyl L-aspartylaminomalonate is 2 x 10" times sweeter than sucrose. ... 

A recent synthesis of 3-substituted furan derivatives illustrates an important application of the furan-carbonyl photocycloaddition. Zamojski has reported the rearomatization of oxetane (115) in the presence of p-toluenesulfonic acid to 3-furylmethanol derivative (116). Synthesis of (117), itself a substrate for the intramolecular photocycloaddition reaction (Section 2.4.6), involved a similar rearomatization process (PPTS/CHjClj) and capitalized upon the chemoselectivity observed in the ketone-furan photocycloaddition. Similarly, a synthesis of perillaketone (118) by Kawanisi involved irradiation of a carbonyl compound and furan. A complication in the rearomatization is that acid also catalyzes the reversion of the photoadduct to starting materials to circumvent this problem the photoreaction was run in the presence of acid, so that rearomatization would occur in situ and the products of competitive reversion would promptly recombine. 

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