Aziridines nucleophilic attack

Treatment of cyclic vinylaziridine 105 with organocuprates of the R2CuLi type proceeds in a highly syn-selective manner (Scheme 2.29) [46], The syn stereochemistry of the reaction reflects the effect of the acetonide group, which directs the nucleophilic attack to the less hindered a-face. The formation of SN2 products 109 from the cyclic (chlorovinyl)aziridine 107 can be explained by assuming a syn-SN2 ... 

O Brien et al. provided the first examples of olefin formation by reductive alkylation of aziridines [97]. Treatment of aziridine 267 with s-BuLi gave olefin 270 in 76% yield (Scheme 5.68). For the formation of olefin 270 they suggest a reaction pathway that proceeds in a manner analogous to that proposed for epoxides [36] namely, nucleophilic attack of s-BuLi on lithiated aziridine 268 to form dilithiated species 269, which eliminates Li2NTs (TsNH2 was observed as a product of this reaction) to yield olefin 270. 

Aziridines have been synthesized, albeit in low yield, by copper-catalyzed decomposition of ethyl diazoacetate in the presence of an inline 260). It seems that such a carbenoid cyclopropanation reaction has not been realized with other diazo compounds. The recently described preparation of 1,2,3-trisubstituted aziridines by reaction of phenyldiazomethane with N-alkyl aldimines or ketimines in the presence of zinc iodide 261 > most certainly does not proceed through carbenoid intermediates rather, the metal salt serves to activate the imine to nucleophilic attack from the diazo carbon. Replacement of Znl2 by one of the traditional copper catalysts resulted in formation of imidazoline derivatives via an intermediate azomethine ylide261). 

Typically, the stereospecific formation of quaternary centers is as problematic as selective nucleophilic attack at the more substituted carbon of aziridines. Interestingly, a copper mediated methodology has been reported that does both <060L5105>. Although N-tosyl aziridines show favorable results, A-nosyl aziridines gave the best results. The reaction of 89 with a variety of phenols yielded 90 in moderate yields. 

Several new syntheses of the oxazolidinone ring have been published. Treatment of spoxyurethane 184 with a strong base induced the cyclisation to oxazolidinone 185 which, trough an olefine methathesis afforded 186 . Treatment with iron salt of acyl azide 187 afforded an aziridine, which, upon nucleophilic attack of a chloride ion, was transformed in the final oxazolidinone 188 <00CC287>. 

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). 

Nucleophilic attack on azirines at the C = N double bond is useful for the preparation of substituted aziridines (B-83MI ioi 02,84CHEC-i(7)47). The C = N bond is more electrophilic than a normal imine due to the strain of the three-membered ring. 

A general type of [3 + 3] heterocyclization involves initial nucleophilic attack on the electrophilic three-membered heterocycle by a 1,3-electrophile-nucleophile. Aziridines (330) with either a-mercapto ketones (329) or with a mixture of a ketone and sulfur give 5,6-dihydro-1,4-thiazines (330 — 331 — 332). Azirines (333) can be used for the preparation of pyrazinones (334) from ot-amino esters R2CH(NH2)C02Et and of 1,4-oxazinones from a-hydroxy esters (83TL1153). 

The cis and trans isomers of 18 behave somewhat differently in this reaction the trans isomer reacts faster at the stage of the aziridine cycle nucleophilic attack, whereas for another isomer this stage is inhibited by an adjacent cis substituent (Scheme 1.14). Such inhibition of the cyclization stage results in the formation of acyl hydrazone 56 as a by-product as well as the formation of pyrazole 55 from the intermediate aminopyrazoline by a rapid trans elimination. In the case of tnms-aziridinyl ketone 18, the slowest step is the cis elimination of RNH2, isolating 4-alkylaminopyrazines 54 in most cases. 

The attempts to isolate the intermediate 1,2-A-sulfonylaziridine 53 were unsuccessful. Nucleophilic attack of the acceptor 9 at C-l opens the aziridine the nitrogen rearranges to the C-2 position and yields the desired tetrasaccharide 18. 

When A-tosylaziridines were reacted with amines or thiols in acetonitrile in the presence of 5 mol% DABCO,50 the nucleophile attacked regiospecifically at the least substituted carbon of the aziridine ring. When a benzyl carbon was present in the aziridine ring, both possible products were obtained although the major product was from attack at the benzyl carbon. The catalytic role of DABCO (which may form an ammonium zwitterion which can deprotonate the nucleophile) is under investigation. 

In the presence of trifluoroacetic acid, these aziridines undergo protonation at room temperature and ring opening at reflux in methanol, diethyl ether or hexane under nucleophilic attack of the trifluoroacetate anion followed by acyl exchange to give the corresponding a-silyl-(i-aminoalcoho] derivative.316... 

---