Aziridine ring intermediate

N-Acylaziridine-2-carboxylates readily rearrange to oxazolines under thennal, acidic, or nucleophilic conditions [91, 123-127]. Treatment of trans-aziridine-2-car-boxylate 176 (Scheme 3.63) with Nal in acetonitrile, for example, resulted in ring-expansion product 177 through the so-called Heine reaction. The reaction involves initial opening of the aziridine ring by iodide and subsequent oxazoline ring-closure by Sn2 displacement of the resultant iodide intermediate [127]. 

Aziridines are important compounds due to their versatility as synthetic intermediates. In addition, aziridine rings are present in innumerable natural products and biologically active compounds. Nitrene addition to alkenes is one of the most well established methods for the synthesis of aziridines. Photolysis or thermolysis of azides are good ways to generate nitrenes. Nitrenes can also be prepared in situ from iodosobenzene diacetate and sulfonamides or the ethoxycarbonylnitrene from the A-sulfonyloxy precursor. 

BCNU is synthesized by treating phosgene with ethyleneimine without the addition of a base to take up the HCl liberated. Reaction of the intermediate urea (46) in situ with hydrogen chloride serves to open the aziridine rings to afford sym-bis-2-chlorethylurea (47). This is nitrosated with sodium nitrite in formic acid to give BCNU (48). 

Similarly, in a 1,3-dipolar cycloaddition of DMAD to the conformationally locked cyclic a-alkoxycarbonylnitrone (727), bicyclic ring systems, containing a nitrogen atom at the bridgehead position have been synthesized. A mechanistic interpretation of the origin of the fused pyrroles (729) includes the intermediate formation of the aziridine ring in (728) (Scheme 2.303) (820). 

The preparation of the required t/ireo-3-methylcysteine component in this synthesis, used the stereoselective ring opening of aziridinesJ62-63 It was shown to be possible to maintain stereospecificity of the reaction using the aziridine ring as an intermediate. 

In the initial phases of this effort a means for introducing appropriate functionality in the C-l/C-2 positions from an unsubstituted precursor such as 80 that would eventually lead to an aziridine ring in the final target compound(s) was needed. When considering the oxidation of simple hexahydro-8-oxo-1 //-pyrrolo[ 1,2-a] indoles using DDQ, two mechanistic pathways are possible leading to either of the carbocationic intermediates 81 or 82 via hydride abstraction at C-5 or C-1, respectively (Scheme 12).69 Proton loss from 81 would ultimately lead to the phenolic product 83 whereas nucleophilic trapping of intermediate 82 by alcohols would afford the C-l-substituted ethers 84. Oxidative transformations at... 

The intermediate bicyclic vinyl dihydro triazoles were generally not isolated, as they are unstable. By thermal decomposition, the vinylaziridines were converted to regioisomeric bicyclic pyrrolines 1 and/or 2, with different substitution patterns, depending on the nature of the substituents. Under the same conditions a 1,5-homodienyl shift can take place to give a monocyclic pyrroline 3. Nucleophilic displacement by iodide ion, however, regioselectively cleaves the C-N bond of the aziridine ring, giving 2 exclusively. 

An interesting use of the bond e disconnection for the synthesis of perfluoro aziridines was reported <1999CC47>. Treatment of perfluoro imine 65 with an excess of PhLi provides the aziridine 67 in good yield (Equation 20). This reaction is believed to go through intermediate 66 after an initial addition of 2 equiv of PhLi. A subsequent nucleophilic attach of the nitrogen anion to displace a fluorine results in aziridine ring formation. The ease with which this strained system forms is attributed to relief of the 1,3-diaxial interactions found in intermediate 66. In addition, an X-ray structure of aziridine 67 was obtained. 

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