Aziridines from carbenes

Diels-Alder additions in water. It also catalyzes aldehyde olefination with N2C(C02Et)2 and PPhs as oxygen sink. Its catalyzed decomposition of N2C(C02Et)2 leads to carbene transfer reactions allowing for the formation of epoxides from aldehydes and ketones, aziridines from imines and cyclopropanation. 

Aziridinium ylides appear to be the initial products from the reaction of aziridines with carbenes. - The ylides (531) derived from N-substituted... 

Aziridine Formation with Chalcogen-Ylides from Carbene Sources... 

Synthesis of aziridines by treatment of carbenes with imines was reported by Jacobsen [56]. A metallocarbene 104 derived from ethyl diazoacetate and copper fluorophosphate was treated with N-arylaldimines to form aziridines with reasonable diastereoselectivities (>10 1 in favor of cis) but with low enantioselectivities (about 44% ee). This was shown to result from a competitive achiral reaction path-... 

Aziridines can be prepared directly from double-bond compounds by photolysis or thermolysis of a mixture of the substrate and an azide. The reaction has been carried out with R = aryl, cyano, EtOOC, and RSO2, as well as other groups. The reaction can take place by at least two pathways. In one, the azide is converted to a nitrene, which adds to the double bond in a manner analogous to that of carbene addition (15-62). Reaction of NsONHC02Et/ CuO [Ns = A(/7-toluenesulfonyl-inimo)] and a conjugated ketone, for example, leads to the A-carboethoxy aziridine derivative.Calcium oxide has also been used to generate the nitrene.Other specialized reagents have also been used." ... 

Some fragmentation reactions from cyclopropyl carbenes and aziridine derivatives are as follows ... 

Interestingly, sulfonium ylides generated from electrophilic carbene complexes and sulfides can react with carbonyl compounds, imines, or acceptor-substituted alkenes to yield oxiranes [1320-1325], aziridines [1321,1326,1327] or cyclopropanes [1328,1329], respectively. In all these transformations the thioether used to form the sulfonium ylide is regenerated and so, catalytic amounts of thioether can be sufficient for complete conversion of a given carbene precursor into the... 

The prochiral aziridine 1 is easily prepared from cyclooctene. Paul Muller of the University of Geneva has shown (Helv. Chim. Acta 2004,87,227) that metalation of 1 in the presence of the chiral amine sparteine leads to the bicyclic amine 3 in 15% , by way of intramolecular C-H insertion by the intermediate chiral carbene 2. The sparteine can be recovered and recycled. 

The nitrene transfer from PhI=NTos to alkenes catalyzed by the CpFe(CO)2+ fragment gave better results (85% for styrene) [25], but the characteristics of the chemistry of the cationic intermediates as postulated by the reaction mechanism are closely connected to the alternative formation of aziridines by a carbene transfer... 

An IV-heterocyclic carbene (similar to that in Scheme 15) has proved to be an effective catalyst for the nucleophilic ring opening of IV-tosylaziridines by silylated nucleophiles (MesSiX, X = N3, Cl, I).45 Yields range from 89 to 99% for reaction at the least substituted carbon, except when a phenyl group on one of the carbons of the aziridine ring induces predominant attack at the benzyl carbon. The stereochemistry is consistent with the SN2 mechanism and THF was found to be the best solvent for the reaction. 

The chemistry of ammonium ylides formed from the reaction of cyclic amines with carbenes was found to be dependent on the ring size of the amine.52 For example, treatment of 1-benzylazetidine (104) with ethyl diazoacetate in the presence of a copper (II) catalyst afforded pyrrolidine 106 in 96% yield. This result is consistent with ammonium ylide formation followed by ring expansion. In contrast, treatment of 1 -phenethylaz-iridine (107) under identical conditions gave the fragmentation product 109 in quantitative yield. Similar results were observed for the reaction of aziridine 107 with dichlorocarbene.53 On the other hand, reaction of 1-phenethylpyrrolidine with ethyl diazoacetate in the presence of a... 

J0rgensen and coworkers reported the preparation of A-tosyl aziridines 19-20 by the net carbene addition (via a diazo compound) to A-tosyl iminoesters with either copper or silver catalysts.13,14 It was noted that the copper catalysts were generally superior, although a catalyst derived from AgSbF6 and (R)-Tol-BINAP provided the corresponding aziridine 19 from 16 and trimethylsilyl diazomethane 17 (R = TMS) in excellent chemical yield with high levels of diastereoselectivity, but unfortunately the enantioselectivity was poor (Scheme 8.3). This success with trimethylsilyldiazo-... 

Depending on the mode of generation, a carbene may be initially formed in either the singlet or triplet state, irrespective of its stability. Common methods used for the generation of carbenes include photolytic, thermal, or metal catalyzed decomposition of diazocompounds, elimination of halogenfrom gem-dihalides, elimination of Hx from CHX3, decomposition of ketenes, thermolysis of a-halo-mercury compounds and cycloelimination of shelf stable substrates such as cyclopropanes, epoxides, aziridines and diazirines. 

Another set of related carbenes are the five-membered cyclic aminooxy and dioxy derivatives (46) and (47) prepared from aziridines or epoxides and ReX(CO)5 or ReX(CO)3(PPh3)2. 

Loss of nitrogen from these aziridines occurs on photolysis and pyrolysis, and a number of the subsequent reactions have been formulated as reactions of the carbenes F2C and (CF3)2C , which have also been discussed earlier see Chapter 6, Section IIIA. 

Analogous to epoxides, aziridines can be prepared by the methylenation of imines. In this case, ethyl diazoacetate is the most common source of carbenes. For example, the imine derived from p-chlorobenzaldehyde 148 is converted to the c/j-aziridinyl ester 149 upon treatment with ethyl diazoacetate in the presence of lithium perchlorate <03TL5275>. These conditions have also been applied to a reaction medium of the ionic liquid l-n-butyl-3-methylimidazolium hexafluorophosphate (bmimPFe) with excellent results <03TL2409>. An interesting enantioselective twist to this protocol has been reported, in which a diazoacetate derived from (TJ)-pantolactone 150 is used. This system was applied to the aziridination of trifluoromethyl-substituted aldimines, which were prepared in situ from the corresponding aminals under the catalysis of boron trifluoride etherate <03TL4011>. 

The most commonly used of these three bond classes is the formation of bond b . Formation of bond b typically occurs through an intramolecular alkylation of a nitrogen atom. A second highly prevalent method for the formation of the type I structure is the formation of bonds b and c from addition of a nitrogen across a carbon-carbon double bond. A final rarely used route is the formation of bonds c and e through the intramolecular addition of a carbene across and carbon-nitrogen double bond. Methods in which bond a is formed are rare in terms of simple fused-ring aziridines but several examples can be found in Section 1.02.7 in the discussion of the mitomycin family of alkaloids (Scheme 1). 

A ring-contraction reaction is rarely used to produce an aziridine. A Wolff ring contraction of a carbene generated from 6-diazopenicillanate 21 forms the intermediate ketene, which is then trapped by imines to give spiroaziridines 22 (86CC584). 

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. 

Aziridines. A CuOTf complex of ferrocenyldiimine is effective for nitrene transfer from TsN=IPh (and also carbene from diazoacetic esters) to alkenes. 

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