Aziridine cis trans

There are at least two mechanisms available for aziridine cis-trans isomerism. The first is base-catalyzed and proceeds via an intermediate carbanion (235). The second mechanism can be either thermally or photochemically initiated and proceeds by way of an intermediate azomethine ylide. The absence of a catalytic effect and interception of the 1,3-dipole intermediate provide support for this route. A variety of aziridinyl ketones have been found to undergo equilibration when subjected to base-catalyzed conditions (65JA1050). In most of these cases the cis isomer is more stable than the trans. Base-catalyzed isotope exchange has also been observed in at least one molecule which lacks a stabilizing carbonyl group (72TL3591). 

Entry R Catalyst ligand Yield of cis-aziridines (%) ee of cis-aziridine (%) cis trans aziridine... 

Entry R R2 R3 Yield of trans aziridines (%) transxis aziridine ee (%) trans CIS... 

The cis alkenes are more reactive and more selective than their trans counterparts. As with the Evans system, this reaction is not stereospecific. Acyclic cis alkenes provide mixtures of cis and trans aziridines. cis-p-Methylstyrene affords a 3 1 ratio of aziridines favoring the cis isomer, Eq. 67, although selectivity is higher in the trans isomer. A fascinating discussion of this phenomenon, observed in this system as well as the Mn-catalyzed asymmetric oxo-transfer reaction, has been advanced by Jacobsen and co-workers (83). Styrene provides the aziridine in moderate selectivity, Eq. 68, not altogether surprising since bond rotation in this case would lead to enantiomeric products. 

Aziridines not substituted on the nitrogen atom react with nitrous acid to produce olefins.324 An N-nitroso compound is an intermediate (2-51) other reagents that produce such intermediates also give olefins. The reaction is stereospecific cis aziridines give cis olefins and trans aziridines give trans olefins.325 Aziridines carrying N-alkyl substituents can be converted to olefins by treatment with ferrous iodide326 or with m-chloroperbenzoic acid.327 An N-oxide intermediate (9-28) is presumably involved in the latter case. 

The triazoline diazo compound equilibrium may be considered to play a role in the cis-trans isomerization332 and oxidation (Scheme 119)284 of certain triazolines. Triazole formation by elimination of amine214 or alcohol405 is also postulated to involve intermediate diazo compounds (Scheme 123). Unlike normal triazolines, the inability of 1-fluorotriazolines to undergo thermolysis or photolysis reactions to yield aziridines is ascribed to the fact that the triazoline always exists in equilibrium with the diazo compound (Scheme 98).356 Spontaneous isomerizations of triazolines not... 

Another process worth mentioning is the cis-trans isomerization of aziridi-nyl ketones. The transformation of tnms-aziridines into the cis form was carried out in a methanol-acetone solution in the presence of triethylbenzylammonium hydrochloride [85]. However, the best yields of the cis isomer (up to 90%) were detected by the same authors when water was added to the reaction mixture [86]. The reverse transition from the trans configuration into the cis form is possible using methanolic solution of sodium methylate [87] or potassium hydroxide [35]. 

When 2 equiv (relative to catalyst) of 2,6-di-terf-butylhydroxytoluene (BHT, a radical reaction inhibitor) was added to the reaction, the yield of the reaction decreased by half. A radical trap experiment using cyclohexane was carried out in CCI4 as well, and together with 40% amination product, 12% of chlorocyclohexane was also detected. This result also suggests that a radical pathway is operative. When a 1 2.3 mixture of cis- and trans-2 pentene was reacted with PhI=NTs (Scheme 6.7), a 1 1.5 cis trans aziridine product was isolated, which suggests the mechanism may... 

Huisgen, R., Scheer, W., and Huber, H. (1967) Stereospecific conversion of cis-trans isomeric aziridines to open-chain azomethine ylides. Journal of the American Chemical Society, 89, 1753-1755. 

It is noteworthy that high stereospecificity was observed in all the aziridinations of trans- and cis-1,2-disubstituted olefins, although such reactions in the presence of metal catalysts and PhI=NTs did not always show high stereospecificity [4,9a-j]. Other trans- substituted styrene derivatives were examined, and gave excellent en-antioselectivities, as shown in Table 6.5. 

Addition of cyclopentene to JV-chloro carbamates gives lower yields and a smaller cis/trans ratio than cyclohexene. The addition of ethyl chlorocarbamate to l-methylcyclohexene was efficient and had better diastereoselectivity than the comparable addition to cyclohexene, however, the reaction did not occur with complete regioselectivity giving 5 and 6 8. The stereochemistry of the minor trans-isomers was shown by conversion to the corresponding aziridines. Ethyl bromocarbamate and /V-halo amides are less selective. 

Styrene cyclopropanation continues to attract much interest. Cationic complex CpFe(CO)2(THF) BF4" mediates carbene transfer from ethyl diazoacetate with high cis selectivity cis trans = 85 15) [38]. On the other hand, Tp Cu(C2H4), where Tp is hydrotris(3,5-dimethyl-l-pyrazolyl)borate, is one of the rare catalysts to promote carbene transfer from ethyl diazoacetate to alkenes and also to alkynes. While cyclopropanes are formed in high yield, cyclopropenes are obtained only in moderate yield [39]. The same complex also catalyzes nitrene transfer from PhI=NTs to alkenes to produce aziridines in high yields. 

While the electrocyclic ring-opening of aziridines to azomethine ylides is well known, the reverse reaction has also been studied as a route to aziridines . This process is implicit in the cis-trans equilibration of substituted aziridines <67JA1753, 7UA1779), and may be involved in the reaction of diazoalkanes with imines <84T2569>. Convincing evidence for the electrocyclization of... 

A procedure has been developed which extends the Darzens synthesis to the preparation of aziridine esters and amides (equation 29). Reaction of benzalaniline (80) and ethyl chloroacetate (in BuKDK/DME) results in the formation of the trans-aziridine (82a) in 29% yield analysis of the crude reaction mixture showed no more than 10% of the isomeric cis adduct (83a). Similarly, condensation of 2-chloro-N,N-diethylacetamide and (80) affords aziridines (82b) and (83b) in 65% yield. However, in this case the cis isomer predominates ( 90 10, cis trans). The formation of (83a R = OEt) as the major product is consistent with the overlap control model suggested by Zimmerman. Apparently, the decreased stability of the amide (81b) enolate relative to the ester (81a) enolate causes ki (cyclization) to become greater than k (addition Scheme 19) it follows that the stereochemical outcome is determined in the initial aldol step, and steric arguments are advanced to explain this outcome. 

---