Nitrenoid intermediate

Recently, Scott et al. have reported that a Cu complex bearing an axially chiral ligand (49) is an excellent catalyst for aziridination of 2,2-dimethylchromene and cinnamate esters (Scheme 36), though it is also less efficient for the reactions of simple olefins.157,158 On the basis of DFT investigation of the nitrenoid intermediate (50), one of the oxygen atoms of the A -sulfonyl group has been proposed to be interacting with the nitrene N-atom.158... 

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. 

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. 

Investigations into the mechanism of this reaction revealed several interesting facts (61). Compelling evidence was presented that a discreet Cu nitrenoid was involved in the catalytic cycle. Photolysis of a solution of tosyl azide and styrene in the presence of the catalyst afforded aziridine with the same enantioselectivity as obtained from the PhI=NTs reaction, Eq. 69. Since photolysis of tosyl azide is known to extrude dinitrogen and form the free nitrene, the authors argue that this is indicative of a common Cu-nitrenoid intermediate in this reaction. 

Table 7 Heterocyclic Rings Prepared from Nitrenoid Intermediates ...

Table 7 Heterocyclic rings prepared from nitrenoid intermediates ...

Hydroxylamine derivatives add to activated double bonds in the presence of a base to give aziridines where intermediates of the type illustrated above have not been isolated or observed. These reactions may proceed via stereospecific addition of nitrenoid intermediates to the double bonds. However, in some instances, both isomeric aziridines are produced and these are included in Table 21 of the Tabular Survey since the possibility exists that they are formed by a Michael addition/cyclization process. An example is shown in Eq. 172.495... 

Subsequent studies demonstrated, however, that these photoinduced ring fissions are remarkably solvent-dependent. For example, in water or methanol virtually quantitative yields of benzoxazoles are obtained, whereas with a low concentration of water or methanol in acetonitrile (or hexane), 3-substituted indoxazenes yield only o-hydroxyamides and -esters indoxazene itself gives salicylonitrile.64 These transformations are rationalized in terms of ring cleavage of the indoxazene to the polar (or nitrenoid) intermediate (46), which by rearrangement gives either benzoxazoles (see Section II,C,4) or, as outlined in Scheme 4, the salicylic acid derivatives (47). 

The la type classification also applies to a group of reactions attributable to nitrene or related (nitrenoid) intermediates. Although not as prominent as carbonyl condensation reactions, these reactions are especially useful for carbazole synthesis. These are formally insertion reactions but mechanistic scrutiny frequently reveals that the reactions are more complicated than a one step insertion process (Scheme 29). 

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... 

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). 

Du Bois has extensively studied and developed the chemistry of carbamates that permit stereoselective C-H functionalization reactions via putative nitrenoid intermediates [22, 93, 101-106]. Thus, in the presence of diacetoxyiodobenzene, MgO, and 5 mol% Rli2(OAc)4, substrates such as 194 were converted into products that arise from C-H insertion (Equation 33) [102]. The amination was observed to proceed stereoselectively to give the corresponding product oxazolidinones (cf. 195) as single regio- and dia-stereomers. 

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