Metalated Aziridines

The first example of a metalated aziridine appeared in 1972. Treatment of azir- 

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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. 

The chemistry of metalated aziridines is far less developed than the chemistry of metalated epoxides, although from what is known [lb], it is obvious that their chemistry is similar. Like metalated epoxides, metalated aziridines can act as classical nucleophiles with a variety of electrophiles to give more highly substituted aziridines (Scheme 5.56, Path A). A small amount is known about how they can act as electrophiles with strong nucleophiles to undergo reductive alkylation (Path B), and undergo C-H insertion reactions (Path C). 

As well as for metalated epoxides, the trifluoromethyl moiety also proved an effective organyl-stabilizing group for metalated aziridines. Lithiated aziridine 241 reacted stereoselectively with carbonyl-containing electrophiles, and phenyl disulfide and chlorotrimethylsilane were also trapped in good yield (Scheme 5.60) [70b, 85],... 

Sulfonylaziridine 243 was halogenated in carbon tetrahalides in the presence of KOH as base [86] (Scheme 5.61). Although other examples of electrophile trapping of sulfonyl- and phosphonyl-stabilized metalated aziridines exist, the reactions were not stereoselective [87]. 

Florio et al. have employed heteroaromatic rings as organyl-stabilizing groups for metalated aziridines as well as for metalated epoxides. Regioselective deprotonation of aziridine 246 with n-BuLi, followed by addition of Mel, gave aziridine 247 (Scheme 5.62) [88]. 

Reports of the generation and subsequent electrophile trapping of nonstabilized metalated aziridines appeared before those for metalated epoxides. Desulfinylation of sulfinylaziridine 250 with EtMgBr gave metalated aziridine 251, which, remarkably, could be kept at 0 °C for 1 h before quenching with D2O (Scheme 5.64). The deuterated aziridine 252 (E = D) was obtained in excellent yield, but acetaldehyde was the only other electrophile found to be trapped efficiently [90],... 

Desilylation of a,P-aziridinylsilanes is a route to nonstabilized metalated aziridines. Treatment of 254 with CsF in the presence of PhCHO furnished substituted aziridine 255 in good yield (Scheme 5.65). Interestingly, the isomeric aziridine 256 gave azirine 257 on treatment with CsF, presumably via a phenyl-stabilized metalated aziridine [91]. 

The (3-elimination of epoxides to allylic alcohols on treatment with strong base is a well studied reaction [la]. Metalated epoxides can also rearrange to allylic alcohols via (3-C-H insertion, but this is not a synthetically useful process since it is usually accompanied by competing a-C-H insertion, resulting in ketone enolates. In contrast, aziridine 277 gave allylic amine 279 on treatment with s-BuLi/(-)-spar-teine (Scheme 5.71) [97]. By analogy with what is known about reactions of epoxides with organolithiums, this presumably proceeds via the a-metalated aziridine 278 [101]. 

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. 

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