Aziridine ring review

This review summarizes the application of aziridines as intermediates to the synthesis of natural products that do not contain an aziridine ring. 

Reactions of substituents attached to the nitrogen atom of aziridines have been reviewed aziridine ring. Only those reactions of A-substituents which do not result in ring-opening will be covered below. 

A soln. of l-cyclohexyl-2-phenyl-3-p-toluoylaziridine and p-nitrophenyl isothiocyanate refluxed 17 hrs. in dry benzene -> 3-cyclohexyl-5-p-nitrophenylamino-2-phenyl-4-p-toluoyl 4-thiazoline. Y 54%. J. W. Lown,G. Dallas, and T. W. Maloney, Can. J. Chem. 47, 3557 (1969) aziridine ring expansion, review, s. F. N. Gladysheva, A. P. Sineokov, and V. S. Etlis, Russ. Chem. Rev. 39, 118 (1970) (Eng. transL) heterocyclics by aziridine ring expansion, review, s. J. W. Lown, Record Chem. Progr. 32, 51 (1971). 

In this review, the results of early studies in this area will be presented first in order to estabhsh the background and context of the recent studies of pyridinium salt photocychzation and bicychc aziridine ring-opening reactions. The overall aim of the presentation is to show how these processes can be used as key steps in synthetic routes to simple, yet interesting natural and non-natural products. 

During our research in this field of small-ring heterocycles we found that functionahzed aziridines are attractive chiral catalysts, e.g., in the diethylzinc addition to aldehydes. Aspects of such uses of aziridines will be discussed as well. This overview does not pretend to be an exhaustive coverage of all existing literature on small-ring aza-heterocycles as that would require a separate monograph. Instead, emphasis is put on functionahzed three-membered aza-heterocycles, that were investigated in the author s laboratory [1], and relevant related literature. The older literature on these heterocycles is adequately summarized in some extensive reviews [2]. Chiral aziridines have been reviewed recently by Tanner [3], by Osborn and Sweeney [4], and by McCoull and Davis [5]. 

The majority of reactions of aziridines deal with acid-catalyzed ring opening with various nucleophiles. In this review only reactions with aziridine-2-car-boxylic esters are summarized (for other types of aziridines, see ref. [3]). 

The highly strained and reactive 2iT-azirines have been extensively studied for various synthetic purposes, such as ring expansion reactions, cycloaddition reactions, preparation of functionalized amines and substituted aziridines. The older literature on azirines in synthesis has extensively been reviewed [69]. Concerning azirines with defined chirality only scarce information is available. Practically all reactions of azirines take place at the activated imine bond. Reduction with sodium borohydride leads to cz5-substituted aziridines as is shown in Scheme 48 [26,28]. 

Various EADIs have been synthesized using different synthetic routes [30-34], One of the widely used methods of preparation of E-alkene peptide bond isosteres involving ring opening of vinyl aziridines by cuprates has recently been reviewed [35,36],... 

For a review of a nitrogen analog, see Boeckman Walters Adv. Heterocycl. Nat. Prod. Synth. 1990,1, 1-41. "For reviews of ring expansions of aziridines, see Heine Mech. Mol. Migr. 1971, 3, 145-176 Dermer Ham Ethylenimine and Other Aziridines Academic Press New York, 1969, pp. 282-290. See also Wong et at.. Ref. 114, pp. 190-192. 

Direct nucleophilic attack at a ring carbon atom of an aziridine is best accomplished when an electron-withdrawing group is present on the nitrogen atom. Examples are shown in Schemes 17 and 18. For reviews see (91C0S(6)65,94AG(E)599). 

This chapter is concerned with all compounds having a three-mcmbered ring containing two carbon atoms and one nitrogen atom. The parent compound of this heterocyclic system is the unsaturated ring, which has two isomeric forme, I-azirine (1) and 2-azirine (IJ). Very few authentic examples of the azirines are known, and this review ib therefore concerned almost wholly with the chemistry of the saturated derivative, aziridine (111). 

Asymmetric epoxidation, dihydroxylation, aminohydroxylation, and aziridination reactions have been reviewed.62 The use of the Sharpless asymmetric epoxidation method for the desymmetrization of mesa compounds has been reviewed.63 The conformational flexibility of nine-membered ring allylic alcohols results in transepoxide stereochemistry from syn epoxidation using VO(acac)2-hydroperoxide systems in which the hydroxyl group still controls the facial stereoselectivity.64 The stereoselectivity of side-chain epoxidation of a series of 22-hydroxy-A23-sterols with C(19) side-chains incorporating allylic alcohols has been investigated, using m-CPBA or /-BuOOH in the presence of VO(acac)2 or Mo(CO)6-65 The erythro-threo distributions of the products were determined and the effect of substituents on the three positions of the double bond (gem to the OH or cis or trans at the remote carbon) partially rationalized by molecular modelling. 

Silver is often used as a halophile. In the context of six-electron species, the role of silver atoms in carbene, nitrene, and silylene transfer reactions, including aziridination, CH insertion, ring expansion, and silacyclopropanation, has been reviewed.9... 

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