Epoxides, ring-opening, asymmetric synthesis

The asymmetric epoxidation of electron-poor cinnamate ester derivatives was highlighted by Jacobsen in the synthesis of the Taxol side-chain. Asymmetric epoxidation of ethyl cinnamate provided the desired epoxide in 96% ee and in 56% yield. Epoxide ring opening with ammonia followed by saponification and protection provided the Taxol side-chain 46 (Scheme 1.4.12). 

In the total synthesis of phalarine, the dihydrobenzo[Z>] furan core shown below was constructed by treatment of the substrate with TFA, followed by a CSA-catalyzed rearrangement <07AGE1448>. Asymmetric total synthesis of bisabosquals was also achieved via an epoxide-ring opening reaction <07T10018>. 

Advances in the chemistry of ring-fused oxiranes during the period under review (1995-2007) principally involve new or expanded methods of asymmetric synthesis including metallosalen-catalyzed, and chiral dioxirane- and iminium salt-mediated processes. Developments in the reactivity of such species include extensive work in the area of epoxide ring opening and advances in the chemistry of lithiated epoxides. 

Wu, M. H. Jacobsen, E. N., An Efficient Formal Synthesis of Balanol via the Asymmetric Epoxide Ring Opening Reaction. Tetrahedron Lett. 1997, 38, 1693. 

The ready availability of achiral and racemic epoxides from simple alkene precursors renders epoxide ring-opening an appealing approach to asymmetric synthesis. The inherent strain-induced reactivity of epoxides can be enhanced by coordination of the epoxide oxygen to a Lewis acid, thereby creating the possibility for chiral Lewis acids to catalyze enantioselective ring opening events. 

The preparation of the C33-C35 segment [137] began with the Horner-Emmons olefination of wo-butyraldehyde, reduction, and asymmetric epoxida-tion [39] leading to epoxy alcohol 234 (Scheme 33). Dithiane epoxide ring opening (regioselectivity 12 1), primary alcohol reduction, and secondary alcohol protection completed the synthesis of this segment ( 235). 

The evolution of an asymmetric synthesis of the differentially 2,6-anhydro-octitol ring of the altohyrtins has been described. An intramolecular epoxide ring opening was the key step in the synthesis, the epoxide itself being obtained via substrate-controlled epoxidation of the corresponding alkene (Scheme 5 see also Chapter 2). ... 

SCHEME 35.5. A combination of asymmetric epoxidation and regioselective intramolecular epoxide ring-opening strategies for the total synthesis of (—)-dysiherbaine. 

The asymmetric oxidation of organic compounds, especially the epoxidation, dihydroxylation, aminohydroxylation, aziridination, and related reactions have been extensively studied and found widespread applications in the asymmetric synthesis of many important compounds. Like many other asymmetric reactions discussed in other chapters of this book, oxidation systems have been developed and extended steadily over the years in order to attain high stereoselectivity. This chapter on oxidation is organized into several key topics. The first section covers the formation of epoxides from allylic alcohols or their derivatives and the corresponding ring-opening reactions of the thus formed 2,3-epoxy alcohols. The second part deals with dihydroxylation reactions, which can provide diols from olefins. The third section delineates the recently discovered aminohydroxylation of olefins. The fourth topic involves the oxidation of unfunc-tionalized olefins. The chapter ends with a discussion of the oxidation of eno-lates and asymmetric aziridination reactions. 

This approach provides a new method for carbohydrate synthesis. In the synthesis of tetritols, pentitols, and hexitols, for example, titanium-catalyzed asymmetric epoxidation and the subsequent ring opening of the thus formed 2,3-epoxy alcohols can play an essential role. 

Several methods have been developed for the synthesis of the taxol side chain. We present here the asymmetric construction of this molecule via asymmetric epoxidation and asymmetric ring-opening reactions, asymmetric dihydroxylation and asymmetric aminohydroxylation reaction, asymmetric aldol reactions, as well as asymmetric Mannich reactions. 

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