Nitrenium ions, rearrangement

In the course of studies on cyclopropanone—)5-lactam conversions, Wasserman and coworkers developed a route to the nocardicins by taking advantage of the reactivity of primary amines with cyclopropanone. The unusual susceptibility of the carbonyl group of cyclopropanone to attack by nucleophiles is well exemplified in this synthesis which involves the addition of the highly hindered malonate derivative (156) to generate the cyclopropanol adduct (157). The hindered amine (156) was previously found to be completely unreactive as a nucleophile in a displacement reaction with dibromoester (158) in an attempt to form the azetidine carboxylate (159). The further conversion of the amino malonate adduct (157) to the -lactam through a nitrenium ion rearrangement is illustrated in Scheme 59. 

The nitrenium ion rearrangement is characteristic of bicyclic N-haloamines catalyzed by Ag+ ions. As shown in Equation (6.151), it again involves a transition state with a pentacoordinate carbon. ... 

It is now apparent that nitrenium ions occur in a variety of contexts including the so-called Bamberger rearrangement (i.e., acid-catalyzed isomerization of N-hydroxyaniline 14 to 4-aminophenol 15, Fig. 13.9), and the aforementioned catabolism of arylamines. The earlier workers, however, for the most part did not explicitly consider the possibility of such a species. Heller et al. were the first to present kinetic evidence for such an intermediate. Interestingly, they chose to represent it as the iminocyclohexadienyl cation (16), With the customary ellipsis of allowing a single valency structure to represent mesomeric systems. ... 

Figure 13.8. Nitrenium ion formation versus concerted rearrangement.

Figure 13.11. Nitrenium ions in the rearrangment and elimination of benzhydryl azides.

It is important to note that for methyl nitrenium ion the singlet state is not predicted at higher levels of theory to show a potential energy minimum. Rather this species is a transition structure that eliminates H2 without a barrier (Fig. 13.15). It seems likely that the difficulties encountered in attempting to study alkyl nitrenium ions might be traced to their propensity to rearrange or eliminate. 

The situation is different for alkylarylnitrenium ions. Haley first demonstrated that a A -l-adamantyl-A -(2-benzoylphenyl) nitrenium ion 62 (Fig. 13.36) could be generated by photolysis of an anthranilium ion." In this case, rearrangement of the adamantyl ring, to give products from hydrolysis of 63, competes with addition reactions, giving 64. Similar experiments carried out on A -tert-butyl-A -arylni-trenium ions also showed that the 1,2-shift of a methyl group competes with additions of nucleophiles to the aryl ring. In the latter cases, the formation of the alkylarylnitrenium ion was verified by LFP. 

Although 68e could not be prepared, the less reactive pivalic acid ester analogues 71a-d (Scheme 29) were synthesized. Hydrolysis rate constants at 40°C were pH independent from pH 1.0 to 7.0 and k i,s correlated with to give a of —6.0. The products derived from 71a-c are summarized in Scheme 29. These products are consistent with a nitrenium ion mechanism. In particular, the products and product ratios derived from the meta-hxomo ester 71b were consistent with those previously reported for 68e and the Bamberger rearrangement of N-(3-bromophenyl)hydroxylamine, with the exception of the rearrangement products. The rearrangement products 72 appear to be derived from intramolecular aminolysis of 73. These... 

The para-nitro ester 71d generated only 4-nitroaniline (70%) and 4,4 -dinitroazoxybenzene (10%) when it underwent decomposition (Scheme 29). These products could have been derived from either a triplet nitrene or a triplet nitrenium ion precursor. Homolysis of the N—O bond to generate radical intermediates was ruled out because of the nearly quantitative yield of pivalic acid derived from 71d. The pivaloxy radical would have undergone rapid decarboxylation to generate CO2 and the rert-butyl radical under these conditions. Since no rearrangement product was observed, it was tentatively concluded that this ester underwent direct decomposition to 4-nitrophenyl-nitrene without the intermediacy of a nitrenium ion. ... 

The application of the azide clock methodology to nitrenium ions was made by Fishbein and McClelland who showed that NJ trapped a reactive intermediate identified as the nitrenium ion 75m, during the Bamberger rearrangement of N-(2,6-dimethylphenyl)hydroxylamine (Scheme 33)7 Kinetic studies showed that the NJ-solvent partitioning occurred after the rate-limiting step of the reaction so an Sn2 process could be eliminated. The selectivity ratio, was determined to be 7.5 M . Assuming that k is... 

The mechanism of Scheme 34 quantitatively explains the yields of rearrangement, solvent-derived and N3-derived products of hydrolysis of hydroxylamine or hydroxamic acid esters that yield selective nitrenium ions (log 5 One of the characteristics of these hydrolysis reactions is the... 

Mechanism A proposes initial attack by N-7 of d-G on the nitrenium ion to generate the N-7 adduct 110, followed by an intramolecular rearrangement to form the cationic C-8 intermediate 111. The evidence for the mechanism includes the precedent of other electrophiles, including carbocations, that usually react at N-7 of d-G," and the reported isolation of 113 (Scheme 50) and its reduction with NaBH4 into 114." Novak and co-workers were not able to isolate an adduct similar to 113 from the reaction of 76n and 76o... 

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