Asymmetric -mediated dearomatization

Anisole and its derivatives have thus far demonstrated the widest variety of [Os]-mediated dearomatization reactions. These transformations have included substitutions, asymmetric tandem addition sequences, and a variety of cyclizations. 

In this chapter, an overview of dearomatization tactics employed in organic synthesis is presented. The material is organized according to mechanistic considerations and includes discussion of conventional as well as transition metal-mediated dearomatization reactions, with particular emphasis accorded to asymmetric processes. This chapter highlights the most common dearomatization reactions encountered in synthesis (with the exclusion of the Birch reduction—the topic of another chapter in this volume) and is not meant to provide a comprehensive treatise on the subject. Only dearomatization reactions of carbocyclic arenes are discussed. 

Kuending, E.P., Laxmisha, M.S., Gannas, R.. Tchertchian, S., and Liu, R. (2005) Chromium-mediated dearomatization application to the synthesis of racemic 15-acetoxytubipofuran and asymmetric synthesis of both enantiomers. Helv. Chim. Acta, 88,1063-1080. 

Fig. 22 Quideau s asymmetric hydroxylative naphthol dearomatization via an in situ w-CPBA-mediated generation of a chiral binaphthyl iodane...

Phenolic oxidations are pivotal steps frequently involved in the biosynthesis of natural products, which possess a variety of important biological activities. Therefore, a continuing interest exists in such transformations, in particular in asymmetric oxidative protocols. Kita et al. performed asymmetric dearomatization of naphthols 43 mediated by chiral hypervalent iodine(III) reagents, 33 and 45 having a rigid spirobiindane backbone (Scheme 20) [66, 67]. A series of other ortho-functionalized spirobiindane reagents of type 46 were synthesized. Intramolecular oxidative substitution of 43 afforded five-membered spirolactone 44 with good levels of enantioselectivity (up to 92% ee). Conformationally flexible iodoarenes employed in this study produced almost racemic products. Catalytic use of these chiral catalysts with wCPBA as cooxidant afforded the chiral spirolactones without detrimental effects on the ee values. 

In 2008 Kita developed a procedure for the asymmetric dearomatization of naph-thols via the formation of ortho-spirolactones using a C2-symmetrical chiral precatalyst 36 (Figure 19.11) and co-oxidant mCPBA with acetic acid [115] (Scheme 19.16). This reaction proceeds via the mCPBA/acetic acid-mediated oxidation of precatalyst 36 to the hypervalent iodine(III) active catalytic species 37. Ishihara has taken this work further with the development of the conformationally more flexible chiral organo-iodine precatalyst 38 [116], offering increased enantioselectivity at... 

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