Copper -nitrene intermediates

Kwart and Kahn have found that benzenesulfonyl azide forms a complex with freshly reduced copper powder.189 190 This copper azide complex decomposes at a lower temperature than the pure sulfonyl azide. In refluxing methanol, benzene-sulfonamide (27) is isolated as the major product. In the presence of dimethyl sulfoxide, N-benzenesulfonyldimethyl-sulfoximine (28) is obtained in almost quantitative yield. In cyclohexene solution benzenesulfonamide (29), N-benzenesul-fonyl-7-azabicyclo[4.1.0]heptane (30), and 1-cyclohexenylben-zenesulfonamide (31) are isolated as the main reaction products. According to the authors, Schemes VII and VIII represent an acceptable interpretation of the experimental data.189 190 In pure alcohol, the decomposition should occur by two competitive reactions (Scheme VII) producing benzenesulfonamide together with a ketone and oxidized copper. These last two products have indeed been observed in the reaction mixture. In the presence of DMSO, it seems that a copper-nitrene intermediate is formed which is trapped by DMSO. In cyclohexene solution, the authors have observed that the aziridine (30) disappears from the product composition when DMSO is added. The yield of enamine 31, however, is... 

Copper Catalysts Copper is an excellent catalyst for nitrogen transfer reactions via copper-nitrene intermediates. Benzylic hydrocarbons are selectively converted to the corresponding sulfonamides [40]. The intermolecular amidation of saturated C—H bonds of cyclic ethers has been reported using TsNH2-PhI(OAc)2 or PhI=NTs as the nitrene source [41]. The copper-catalyzed amidation of unactivated sp3 C—H bonds adjacent to a nitrogen atom has also been achieved using tert-butyl hydroperoxide or... 

Goriya and Ramana reported the synthesis of substituted quinolones and indoles via a copper(l)-catalyzed SNAr/intramolecular nitrene insertion sequence.The azide anion displaces the bromide of 143 the resulting intermediate loses nitrogen to form a copper nitrene intermediate, which inserts across the C—H bond to form indole 144. The authors propose the copper plays a role in both the SnAt and nitrene formation/insertion steps (14CC7790). 

Whilst there are several examples of late transition-metal stabilised nitrenes in the literature (see below), very few experimental studies are available for copper-nitrene intermediates. These are proposed as important intermediates in copper-catal3 ed alkane amination and alkene aziridination reactions, therefore identification and characterisation is critical for providing new mechanistic insights. Ray et recently... 

Thus far, enantioselective intramolecular aziridination via metal nitrene intermediates has not been successful. Bromamine-T has recently been shown to be a viable source of nitrene for addition to alkenes in copper halide catalyzed reactions, " and so has iodosylbenzene (Phl=0) that forms 44 in situ. Conceptually, aziridination does not necessarily fall between cyclopropanation and epoxidation, as some have suggested. Instead, metal nitrene chemistry has unique problems and potential advantages associated with the electron pair at nitrogen that are yet to be fully overcome. 

A parallel development during this period was the identification of chiral bis(oxazolines) and bis(benzylidene)diaminocyclohexanes as useful ligands for copper-catalyzed, asymmetric tosylaziridination reactions with Phi = NTs (Scheme 64) [174,175]. Evidence for the likely formation of copper(III)-nitrene intermediates,cCu(III) = NTs , in such reactions was also reported [176]. 

More recently, the effect of substituents in the arenesulfonyl moiety on Cu(I)-catalyzed aziridinations of cyclohexene with a series of [(arenesulfonyl-imino)iodo]benzenes was evaluated (Scheme 65) [177]. Iminoiodanes possessing p-OMe,p-CF3, andp-N02 substituents gave higher yields of aziridines than the tosylimino analog. Product yields in these reactions are not simply related to relative rates of aziridination (p-MeO >p-Me >p-N02), and appear to reflect partitioning of the copper(III)-nitrene intermediates between aziridination of the C,C-double bond and reduction to the corresponding sulfonamides. 

The treatment of various sulfides with Phi = NTs in the presence of cuprous triflate leads to the corresponding N-tosylsulfimides (N-tosylsulfilimines) 21 [30]. The presence of the chiral bis(oxazoline) ligand 22 in the reaction medium results in coordination of the copper(III)-nitrene intermediate, L Cu(III) = NTs, and enables the enantioselective production of 21 (Scheme 12). Similar copper-catalyzed reactions of allylic sulfides with Phi = NTs lead to formal insertion of the NTs group into the carbon-sulfur bond of the substrates, and proceed via a [2,3]-rearrangement with allylic inversion, to give sulfonamides 23 [30]. 

For example, Jacobsen has studied the asymmetric aziridination of alkenes using (diimine)-copper(I)-catalysts 85. The results support the intermediacy of a discrete Cu(III)-nitrene intermediate and thus suggests mechanistic similarity (particularly regarding transition state geometry) to asymmetric cyclopropanation [95JA5889]. 

After successful application of the silver catalyst shown in olefin aziridination (Section 6.1.1), He and coworkers showed that intramolecular amidation was possible with both hydrocarbon-tethered carbamates and sulfamate esters.24 They found that only the Bu3tpy silver complex could catalyze efficient intramolecular amidation, while other pyridine ligands gave either dramatically lower yields or complicated product mixtures. In an interesting control study, both copper and gold were also tested in this reaction. Both the copper and gold Bu tpy complexes can mediate olefin aziridination, but only silver can catalyze intramolecular C-H amidation, indicating that the silver catalyst forms a more reactive metal nitrene intermediate. 

The reaction of A -[A -(benzoylimino)-A -phenylsulfonyl]amide 429 with iodosylbenzene 426 leads efficiently to nitrene intermediates that convert olefins 411 into aziridines 430 in good yields, through a copper(ll)-mediated (Cu(OTf)2) reaction. Owing to the stereogenic sulfur atom present in the molecules, the reactions proceed with some degree of diastereoselectivity (Scheme 111) <2004OL3573>. 

An electrophilic metal-carbene complex intermediate has been proposed in the cyclopropanation reaction, whereas a paramagnetic copper nitrene species, which behaves as an electrophilic, nitrogen-centered radical, is proposed as the intermediate for the aziridination reaction.45 [Cu(Tp GF3 2)(C2H4)] is a good aziridination catalyst, readily converting a variety of olefins into the corresponding A-tosyl aziridines.46... 

Pyrolysis of the compounds 250 yields nitrene intermediates, which undergo a wide range of insertion reactions.502 529 W-Cyanopyrroles, which are obtained from the pyrolysis of tetrazolopyridines, also arise from nitrene intermediates via ring contraction.512,530 Mass spectral studies have indicated that the first step in the gas-phase pyrolysis of fused tetrazolopyridines and pyrimidines involves tautomerism to the azide with subsequent nitrene formation.523 Copper compounds have been found to catalyze the generation of nitrene intermediates from the compounds 250 and 244.531 The compounds 250 also undergo cycloaddition reactions through the azido form.511... 

Mechanistic studies of copper-catalyzed aziridinations have demonstrated that copper nitrene species are the key intermediates in this reaction [802-804]. 

A copper-sulphonyl nitrene complex has been postulated as an intermediate in the reaction of chloramine-T with DMSO and with dioxan 45>. In the absence of copper powder, only a small yield of sulphoximine (6%) was obtained in DMSO. Again, no sulphonylaniline or azepine... 

On the other hand, thermolysis of ferrocenylsulpkonyl azide (14) in aliphatic solvents may lead to the predominant formation of the amide (16) 17>. A 48.4% yield of (16) was obtained from the thermolysis in cyclohexane while an 85.45% yield of 16 was formed in cyclohexene. Photolysis of 14 in these solvents led to lower yields of sulphonamide 32.2% in cyclohexane, 28.2% in cyclohexene. This suggests again that a metal-nitrene complex is an intermediate in the thermolysis of 14 since hydrogen-abstraction appears to be an important made of reaction for such sulphonyl nitrene-metal complexes. Thus, benzenesulphonamide was the main product (37%) in the copper-catalyzed decomposition of the azide in cyclohexane, and the yield was not decreased (in fact, it increased to 49%) in the presence of hydroquinone 34>. On the other hand, no toluene-sulphonamide was reported from the reaction of dichloramine-T and zinc in cyclohexane. 

The aziridines are the nitrogen analogs of the epoxides and undergo similar electrophilic reactions. No biological data were obtained for these compounds nor were they used as precursors to any CA-4, 7, analogs. They have been included since the synthesis is noteworthy, and they could be interesting intermediates. Xu et al. stereoselectively aziridinated chalcones using the nitrene precursor (PhINTS) and a copper catalyst to form compound 141 (Scheme 36) [82],... 

In 1993, Jacobsen and Evans simultaneously reported that [7V-(p-tolylsulfonyl)imino]phenyliodinane (TsN=IPh, 195) is an efficient asymmetric nitrene transfer reagent to alkenes in the presence of a catalytic amount of a copper(i) salt and a chiral diimine ligand or a chiral bis(oxazoline) ligand (Equation (31)). Mechanistic study by Jacobsen and co-workers suggests that a discrete copper(iii) nitrene complex is an intermediate responsible to the reaction. ... 

Evans et al. proposed that an imino-copper species in the 3+ oxidation state (Cu3+=NTs) should be the key intermediate in copper-catalyzed aziridinations [75b]. This proposal was supported by Jacobsen s study on the dependence of enantioselectivity on the nitrene precursors and/or the substrate structures with two iminoiodoarenes, PhI=NTs and 2,3,4-Me3-6-(r-Bu)C6HI=NTs), in the presence of CuPF6-33a complex and four olefins [80b]. This study disclosed that enantioselectivity did not depend on the iminoiodoarene, but on the olefins used, that is, the finding excludes the possibility that a Cu-Arl=NTs adduct is a key intermediate. It has also been observed that the photochemical aziridination with tosyl azide (TsN3) catalyzed... 

The enol form of mandelic acid (101) has been generated by flash photolysis of phenyldiazoacetic acid in aqueous solution.101 The enol forms by hydration of the intermediate carbene (102). The reaction of chloramine-T (TsNClNa O) with methyl p-tolyl sulfide to give the corresponding sulfimide (103) appears to proceed via a nitrene-transfer mechanism in the presence of copper(I) and a second nitrogen ligand (such as acetonitrile).102... 

---