Nitrenoids. copper

Various approaches to epoxide also show promise for the preparation of chiral aziridines. Identification of the Cu(I) complex as the most effective catalyst for this process has raised the possibility that aziridination might share fundamental mechanistic features with olefin cyclopropanation.115 Similar to cyclo-propanation, in which the generally accepted mechanism involves a discrete Cu-carbenoid intermediate, copper-catalyzed aziridation might proceed via a discrete Cu-nitrenoid intermediate as well. 

Decomposition of sulfonyl azides was shown to be catalyzed by copper in 1967 (72, 73). In the presence of alkenes, the reaction provides both aziridines and the C-H insertion products, albeit in low yields (73). In 1991, Evans et al. (74, 75) illustrated that both Cu(I) and Cu(II) salts were effective catalysts for nitrenoid transfer from [A-(/Moluenesulfonyl)imino]phenyliodinane (PhI=NTs) to a variety of acceptor alkenes. In the absence of ancillary ligands, reactions proceed best in polar aprotic solvents such as acetonitrile. Similar results are observed using both Cu(MeCN)4C104 and Cu(acac)2 as precatalysts, Eq. 53. 

As mentioned earlier, it was originally assumed that this reaction is mechanistically related to the copper-catalyzed diazo-transfer cyclopropanation. As such, the intervention of a metal complexed nitrenoid intermediate has been theorized as the principal mode of action. Mechanistic investigations in this reaction have paralleled the development of the asymmetric version and hence, will be discussed in concert. 

The groundwork for this study was laid in the bis(oxazoline)-copper-catalyzed cyclopropanation reaction reported by Evans, Masamune, Pfaltz, and their coworkers (32-34) (cf. Section II.A.6). Indeed, two of these early papers reported that the same catalysts were capable of effecting nitrenoid transfer to acceptor alkenes in moderate ee. 

PhI=NTs in MeCN affords a copper species that is indistinguishable by ultraviolet-visible (UV-vis) spectroscopy from an identical solution derived from Cu(OTf)2. Given the strong oxidizing nature of PhI=NTs, it seems likely that both catalysts proceed through a Cu(II) species. Beyond this, little can be said with certainty. If nitrenoid formation proceeds by a two-electron oxidation of the catalyst, one would need to invoke Cu(IV) as an intermediate in this process (77). This issue is resolved if one invokes the intervention of a bimetallic complex in the catalytic cycle. However, attempted observation of a nonlinear effect revealed a linear relationship between ligand enantiopurity and product ee (77, 78). 

Treatment of a solution of 55cCu(OTf)2 complex with a stoichiometric amount of PhI=NTs in CH2C12 resulted in rapid uptake of the insoluble iodinane. This complex, when treated with styrene, provided aziridine in quantitative yield in the same selectivity (37% ee) as the catalytic reaction (in CH2C12 at 25°C, 36% ee), Eq. 59. Addition of toluene at -78°C resulted in deposition of the complex as an oil. Analysis of the supernatant liquid revealed that <5% Phi was present, suggesting that the iodobenzene was still part of the complex. Unfortunately, this material resisted repeated attempts at crystallization. Whatever its true nature, it seems that this complex is not a classical copper nitrenoid (77). 

The initial screen of potential catalysts by these workers revealed that several Lewis acids are capable of effecting nitrenoid transfer to alkenes. In particular, SmLOf-Bu, a species that is unlikely to participate in redox processes, was found to work well for 7ra s-p-methylstyrene aziridination. Although the generality of this catalyst fell far short of the copper system, it raises the intriguing possibility that the Cu(II) species formed in the aziridination acts at least in part as a Lewis acid. The considerable Lewis acidity of cationic Cu(II) complexes has since been extensively exploited (cf. Section V). 

In addition to cyclopropanation and nitrenoid transfer, a number of other asymmetric group-transfer reactions have been reported using catalytic amounts of copper complexes. Each of these is relatively underexplored compared to the work described above. 

Uemura and co-workers (91) demonstrated that copper catalysts effectively transfer nitrenoid groups to sulfides generating chiral sulfimides. A complex obtained from CuOTf and 55d catalyzes nitrenoid transfer to prochiral sulfides to afford products such as 139 in moderate to poor enantioselectivities (<71% ee, Eq. 78). Nitrenoid transfer occurs selectively to the sulfur atom of allylic sulfides generating allylic sulfenamide (140) in moderate selectivity, after [2,3] sigmatropic rearrangement of the initial sulfimide 141, Eq. 79. 

Pancralistatin, [29], The first asymmetric total synthesis of (+)-pancratistatin (94) was reported by Hudlicky 130,26], Thus the bromo olefin 114 (Scheme 15), obtained by a-addition of copper nitrenoid generated from (N-tosyiimino) phenyliodinane to 45, was debrominated to the olefinic aziridine 117. The latter underwent Irons 1,2-ring opening with diarylcyancuprate... 

The transition metal-mediated nitrenoid transfer to olefins represents a very concise route to the aziridine structure very often, however, an excess of the olefinic substrate is required for preparatively useful yields. In this arena, Andersson and co-workers have studied the copper-catalyzed aziridination of olefins using [A -(arenesulfonyl)imino]phenyliodinanes 446 as nitrene precursors, and have reported on conditions which give good to excellent yields of aziridines 447 without the constraint of having to use an excess of alkene (Scheme 116). 

In the arena of alternative nitrene sources, a flurry of activity has centered around the use of the readily available chloramine-T 469. Komatsu and co-workers have reported on the successful aziridination of alkenes using 469, catalyzed either by substoichiometric amounts of iodine (e.g., 470—>471) <1998T13485> or a combination of 5% cuprous chloride and 5 A powdered molecular sieves (e.g., 472 —> 473) < 1998TL309>. In certain cases, better yields are obtained using the bromo analog, presumably due to the more facile formation of the copper nitrenoid complex (Scheme 122) <1998TL4715>. 

The reaction is proposed to proceed via an intermediary copper nitrenoid species as known from the related copper-catalyzed aziridination of olefins [54]. A tentative transition state model for the stereochemical outcome of the oxidation ofp-tolyl methyl sulfide was suggested in which the approach of the sulfide was directed by a n-K interaction between the phenyl ring of ligand 30 and the aryl group of the sulfide. However, to date the exact mechanism remains unclear. 

Animations in this area involve anions of both it-excessive and it-deficient heterocycles, which are generated from the halo compounds or by direct metalation. Most of the animating reagents seem to be applicable except that phenylthiomethyl azide (32) fails with the 2-lithium or 2-copper derivatives of furan, thiophene, N-methylpyrrolc, and (V-methylindole.274 Similarly, chloramine and O-methylhydroxylaminc, but not phenyl azide, fail to aminate 2-lithio-1-methylimidazole 66 and the MeN(Li)OMe nitrenoid does not react with 2-lithiothiophene.97 The reactions that appear to be most widely applicable to heterocyclic carbanions are shown in Eqs. 73,100,101 74,316 and 75.358... 

Nitrenoids. In situ oxidation of CI3CCH2OSO2NH2 by PhIO gives the nittene that can be debvered to alkenes to form aziridines by azolecarbene-coordinated copper species. Cleavage of C=C bond. Adduct of Phl=0 with tetrafluoroboric acid serves as ozone equivalent in its capacity of cleaving alkenes to dialdehyde in the presence of 18-crown-6. ... 

Direct preparation of an aziridine from an alkene is possible by reaction of the alkene with a nitrene or metal nitrenoid species. Nitrenes can be generated thermally or photochemically from azides, although their reaction with alkenes to give aziridines is often low yielding and is complicated by side reactions. Oxidation of iV-amino-phthalimide or related hydrazine compounds (e.g. with Pb(OAc>4 or by electrolysis) and reaction with an alkene has found some generality. The metal-catalysed reaction of nitrenes with alkenes has received considerable study. A variety of metal catalysts can be used, with copper(II) salts being the most popular. For example, styrene was converted to its A-tosyl aziridine 72 by reaction with [A-(tosyl)imino]phenyliodinane (PhI=NTs) and copper(II) triflate (5.75). ... 

Copper nitrenoids that participate in C—H bond insertion reactions have also been studied for a long time. In 1997, the first asymmetric reaction was reported by Katsuki and co-workers. Their design was derived from the Kharash-Sosnovsky reaction (Scheme 1.52, top), the Cu-catalyzed allylic... 

Copper-catalyzed decomposition of tosyl azide or chloramine T in the presence of DMSO leads to A -tosylsulfoximines (149-151). The configuration of sulfur is retained (150). Thus, the nitrenoid intermediates are trapped by the... 

In 2008, Kim and Chang reported on the catalytic aziridination of styrenes and other olefins by 2-pyridylsulfonamide and PhROAc), using copper complexes [86]. These reactions do not require preformed (arylsulfonylimino)iodobenzenes PhlNS02Ar. During investigations of the mechanism, a copper PhINS02Ar complex was detected by ESI-MS as a major species (Scheme 21). A chelated nitrenoid complex derived from an unusual hypervalent iodine intermediate (Scheme 22) was proposed, based on Hammett plot analysis, kinetics and computational studies. 

A comparative study of the aziridination of styrene using a variety of arenesulfonyl azides and a Cu(acac>2 catalyst has shown that pyridine-2-sulfonyl azide and related snbstituted pyridines are particularly efficient. It seems likely that the nitrogen atom of the pyridine ring coordinates to the copper ion and drives the formation of an internally stabihzed nitrenoid intermediate. The method has been used to achieve aziridination of a range of substituted styrenes 29 in good yield and without the need for the alkene to be present in large excess (Scheme 6.15). 

To expand the utility of the direct use of sulfonamide as a nitrogen source, several effective catalyst systems have been reported. Chang and coworkers developed the alkene aziridination using 5-methyl-2-pyridinesulfonamide and Phi (OAc)2 catalyzed by Cu(tfac)2 (tfac = trifluoroacetylaceto-nate) without external ligands or bases (Scheme 2.26) [39]. It was postulated that the coordination of pyridyl N atom to the copper center was the driving force for the formation of copper nitrenoid 20. Indeed, replacement of the pyridyl N atom to CH suppressed the reaction. 

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