Metalated Epoxides and Aziridines in Synthesis

The chemistry of a-metalated epoxides and aziridines (the a prefix will from now on not be included but should be assumed) has been reviewed previously [1], but in this chapter it is our intention to focus on those reactions involving them that are useful in synthesis, rather than just of pedagogical interest. Beginning with metalated epoxides, since the greater amount of work has involved them, we intend to present carefully chosen examples of their behavior that delineate the diverse nature of their chemistry. We will then move on to metalated aziridines, the chemistry of which, it will become apparent, closely mirrors that of their epoxide cousins. 

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

Following this, House and Ro presented the first experimental evidence for the existence of metalated epoxides. Treatment of cis- and trons-a-methyl- 3-(phenyl- 

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Metalated Epoxides and Aziridines in Synthesis 5.2.4.2 Silyl-stabilized Lithiated Epoxides... 

Stereoselective addition of allyl metal reagents to various functionalities is an important reaction in organic synthesis [32, 33]. The allylation of epoxides and aziridines with allyltin reagent is catalyzed by Lewis acids. Even though many Lewis acids have been reported to catalyze this reaction, Bi(OTf)3 is distinct because it avoids the formation of byproducts and is also environmentally more compatible. It catalyzes the reaction of aryl epoxides with tetraallyltin to afford the corresponding homoallyllic alcohol [34]. 

Enantioselective vanadium and niobium catalysts provide chemists with new and powerful tools for the efficient preparation of optically active molecules. Over the past few decades, the use of vanadium and niobium catalysts has been extended to a variety of different and complementaiy asymmetric reactions. These reactions include cyanide additions, oxidative coupling of 2-naphthols, Friedel-Crafts-type reactions, pinacol couplings, Diels-Alder reactions, Mannich-type reactions, desymmetrisation of epoxides and aziridines, hydroaminations, hydroaminoalkylations, sulfoxida-tions, epoxidations, and oxidation of a-hydroxy carbo) lates Thus, their major applications are in Lewis acid-based chemistiy and redox chemistry. In particular, vanadium is attractive as a metal catalyst in organic synthesis because of its natural abundance as well as its relatively low toxicity and moisture sensitivity compared with other metals. The fact that vanadium is present in nature in equal abundance to zinc (albeit in a more widely distributed form and more difficult to access) is not widely appreciated. Inspired by the activation of substrates in nature [e.g. bromoperoxidase. 

In the fifty or so years since the discovery of a-metalated epoxides, our understanding of their reactivity has advanced to such a level that their use in routine organic synthesis is now possible. Many research groups continue to examine their unusual reaction pathways and to develop these into synthetically useful processes. In contrast, the chemistry of a-metalated aziridines is still in its infancy and there are undoubtedly many interesting facets of their nature still to be explored and applied in organic synthesis. 

In this chapter, some of the essential aspects of the synthesis and characterization of copolymers derived from the coupling of C02 with various monomers, namely, epoxides, oxetanes, and aziridines, have been reviewed. In addition, the use of carbon disulfide as a resource for copolymer production was introduced, and the present understanding of the mechanistic aspects of processes involving cyclic ethers and C02 catalyzed by well-defined metal systems has been emphasized. This knowledge has led to the development of catalytic systems capable of controlling not only the product selectivity but also the regio- and stereoregularities of the resultant copolymers. 

Terminal epoxides of high enantiopurity are among the most important chiral building blocks in enantioselective synthesis, because they are easily opened through nucleophilic substitution reactions. Furthermore, this procedure can be scaled to industrial levels with low catalyst loading. Chiral metal salen complexes have also been successfully applied to the asymmetric hydroxylation of C H bonds, asymmetric oxidation of sulfides, asymmetric aziridination of alkenes, and the asymmetric alkylation of keto esters to name a few. 

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