Sequential Reactions Initiated by Oxidative Dearomatization. Biomimicry or Artifact?

Robert Robinson first introduced the concept of biomimetic synthesis in 1917 with a one-pot preparation of tropinone [1]. This remarkable transformation joins three reactants together capitalizing upon the reactive proclivities of polyketides. Because aromatic compounds themselves are the end point of polyketide biosynthetic sequences, which are followed by the action of a few specific tailoring decarboxylative and oxidative enzymes, it is hard to conclude that sequences commencing with dearomatization are indeed ‘biomimetic’ [2]. However, sequential reactions initiated by oxidative phenol dearomatization can often appear as ‘biomimetic’, reaching very complex molecular architectures in short order because the functionality and the stereoand regiochemical tendencies that are programmed into the polyketide intermediates are still efficacious in the corresponding phenol derivatives and in the reactions stemming from these compounds. In this chapter, we examine some of the sequential one-pot reactions initiated by oxidative dearomatization. This discussion is by no means a comprehensive treaty on this topic. However, we attempt to untangle this subject for the benefit of interested chemists by focusing on one-pot oxidative dearomatization sequences commencing from phenols that result in the formation or cleavage of three or more C–C, C–O or C–N bonds. In all of the following schemes, the intermediate formed by the initial oxidative dearomatization undergoes further chemical reactions involving the formation and breakage of two or more bonds. Thus, the examples presented are different from most rudimentary oxidative dearomatization reactions that most often result in the usual quinol and ketal adducts [3].