Nitrenium ions rearrangement reactions

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 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. 

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... 

The acid-catalyzed conversion of A-hydroxyanilines 177 intopara-hydroxyanilines 179 is well-known as the Bamberger rearrangement (see reviews in References 23,265-267). It is the opinion now that this intermolecular reaction follows a mechanism of monomolec-ular Svl nucleophilic substitution via intermediate nitrenium ion 178 (see review in Reference 268) (equation 70). 

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