Epoxides and Aziridines in Click Chemistry

Aziridines and Epoxides in Organic Synthesis. Andrei K. Yudin Copyright 2006 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN 3-527-31213-7 

Although beyond the scope of the present discussion, another key realization that has shaped the definition of click chemistry in recent years was that while olefins, through their selective oxidative functionalization, provide convenient access to reactive modules, the assembly of these energetic blocks into the final structures is best achieved through cydoaddition reactions involving carbon-het-eroatom bond formation, such as [l,3]-dipolar cydoadditions and hetero-Diels-Al-der reactions. The copper(i)-catalyzed cydoaddition of azides and terminal alkynes [5] is arguably the most powerful and reliable way to date to stitch a broad variety 

Epoxides are often encountered in nature, both as intermediates in key biosynthetic pathways and as secondary metabolites. The selective epoxidation of squa-lene, resulting in 2,3-squalene oxide, for example, is the prelude to the remarkable olefin oligomerization cascade that creates the steroid nucleus [7]. Tetrahydrodiols, the ultimate products of metabolism of polycyclic aromatic hydrocarbons, bind to the nucleic acids of mammalian cells and are implicated in carcinogenesis [8], In organic synthesis, epoxides are invaluable building blocks for introduction of diverse functionality into the hydrocarbon backbone in a 1,2-fashion. It is therefore not surprising that chemistry of epoxides has received much attention [9]. 

The past thirty years have witnessed great advances in the selective synthesis of epoxides, and numerous regio-, chemo-, enantio-, and diastereoselective methods have been developed. Discovered in 1980, the Katsuki-Sharpless catalytic asymmetric epoxidation of allylic alcohols, in which a catalyst for the first time demonstrated both high selectivity and substrate promiscuity, was the first practical entry into the world of chiral 2,3-epoxy alcohols [10, 11]. Asymmetric catalysis of the epoxidation of unfunctionalized olefins through the use of Jacobsen s chiral [(sale-i i) Mi iln] [12] or Shi s chiral ketones [13] as oxidants is also well established. Catalytic asymmetric epoxidations have been comprehensively reviewed [14, 15]. 

Owing to the aforementioned importance of epoxides, methods for their preparation have been the focus of intense studies during the last five decades. While this vast area is addressed in more details elsewhere in this volume, brief comments about procedures that have been found particularly convenient in click chemistry context are offered below. 

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Epoxides and Aziridines in Click Chemistry Table 12.11 Arylsulfonyl aziridines ... 

Click chemistry is a chemical concept enunciated by Barry Sharpless, Scripps Research Institute, USA, in 2001, which highlights the importance of using a set of powerful, highly reliable, selective reactions under simple reaction conditions to join small molecular units together quickly for the rapid synthesis of new compounds via heteroatom links and create molecular diversity. Several types of reactions have been identified that fulfill the criteria- thermodynamically favored reactions that lead specifically to one product such as nucleophilic ring opening reactions of epoxides and aziridines, nonaldol type carbonyl reactions, additions to carbon-carbon multiple bonds, Michael additions, and cycloaddition reactions. The best-known cHck reactions are the copper-catalyzed reaction of azides and alkynes or the so-called CuAAC reaction and the thiol-ene reaction. 

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