Aziridine cyclization reactions, nitrogen nucleophiles

Melchiorre and co-workers reported the first asymmetric aziridination of a,p-unsaturated ketones using the primary amine-amino acid salt 91 (Scheme 5.39) [68]. The reaction occurred via first nucleophilic addition of A-centered nucleophile (iminium catalysis) followed by intramolecular cyclization (enamine catalysis). Essential factors for the success of the current reaction included the proper selection of nitrogen nucleophile and the addition of solid NaHCO. Under the optimized conditions, a range of cyclic or acyclic enones can be incorporated in the protocol to afford either A-CBz or A-Boc aziridines with excellent diastereo- and enantioste-reocontrol (Scheme 5.39). 

A systematic review of synthetic approaches to fused azirines is provided in CHEC-III . One of the most common routes to aziridines of this type involves a cyclization via nucleophilic attack of a nitrogen on an exocyclic sp3-hybridized carbon as exemplified in Scheme 1 <2003TL7997, 2003TA1969>. Another general approach to fused azirines involves DielsAlder reactions of carboxylate-substituted 2/7-azirines (e.g., Scheme 2) < 1997S271, 1998J(P1)2969, 2005S555, CHEC-III(1.02.3.2.2)121>. 

Path C Aziridine formation. P-Tosyl derivatives of serine and threonine compounds protected on nitrogen by trityl or tosyl groups, can cyclize to aziridines in strongly basic media (272, 288, 289, 387). In the case of serine derivatives, this reaction is observed only when either the Ca-H acidity is reduced (amides) or the nitrogen atom retains high nucleophilicity (N-trityl derivatives). The tendency of threonine derivatives to form aziridines is much stronger, and less dependent on these factors. Thus, treatment of N,0-ditosylthreonine ester with bases yields primarily the aziridine (272). ... 

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