Nitrilium ions intramolecular Ritter reaction

Fused or spiro sugar oxazolines have been synthesized by treating D-fructopyranose or D-fructofuranose 1,2-0-acetonides with nitriles in triflic acid773 (Scheme 5.73). First the activation of the anomeric center takes place with simultaneous isopropy-lidene cleavage to form the oxocarbenium ion intermediate, which is attacked by the nitrile. The resulting nitrilium ion is then trapped by the hydroxyl group in an intramolecular Ritter-like reaction to yield the final product. 

As an alternative to amide formation, intramolecular cyclizadons involving the nitrilium ion lead to a variety of heterocyclic systems (Section 1.9.2). Since carbenium ions, or their equivalents, may be produced by means other than strong acid, a number of valuable extensions of the original reaction are possible (Section 1.9.3). In addition, nitrilium and imidate species are also available through other processes, implying that the Ritter reaction has close mechanistic relationships with other well-established reactions and with the chemistry of the isonitriles. These aspects are explored in Section 1.9.4. 

Evidence supporting the involvement of nitrilium ion intermediates is available from the large number of heterocyclic derivatives obtained by intramolecular trapping reactions. Furthermore, independently generated nitrilium salts undergo hydrolysis to Ritter products (Scheme 3). 

In 1952, Ritter and Murphy reported cases of intramolecular Ritter behavior resulting in formation of dihydroisoquinolines from reactions of methyleugenol with nitriles such as veratronitrile (equation 30). Such reactions involve nucleophilic attack by the aromatic ring on the nitrilium ion and are enhanced by... 

Both nitronium and nitrosonium salts are effective initiators but with quite different results. Thus, propene and nitronium fluoroborate react to produce the secondary a-nitrocarbenium ion which undergoes Ritter reaction with acetonitrile to yield amide (118). Under similar conditions, nitrosonium fluoroborate leads to heterocyclic products. Intramolecular reaction of the nitroso and nitrilium groups, followed by prototropic shifts, affords the iV-hydroxy imidazolium salt (119). This may be either neutralized to produce the iV-oxide or reduced to the imidazole (120 Scheme SS). 

However, a considerable difference should be noted between a-hydroxyalkyl nitrilium ions 24 which contain an intramolecular nucleophilic center (OH group), and N-alkylnitrilium ions 26 which are the intermediates of a Ritter reaction. The transformation of ions 24 into the A -acyliminium ions 25 (equation 11) is evidently an intramolecular rearrangement (see Sections V.B and V.C), while the nitrilium salts 26 can be converted into ions 25 only by an oxidative dehydrogenation of amides 27 (equation 12). 

Intramolecular reaction of a nitrile group and a carbenium ion can produce a cyclic nitrilium intermediate leading to Ritter-type products after reaction with an external nucleophile (Scheme 15). Geome-... 

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