Isoxazolium salts reactions with nucleophiles

Isoxazoles are susceptible to attack by nucleophiles, the reactions involving displacement of a substituent, addition to the ring, or proton abstraction with subsequent ring-opening. Isoxazolium salts are even more susceptible to attack by a variety of nucleophiles, providing useful applications of the isoxazole nucleus in organic synthesis. Especially useful is the reductive cleavage of isoxazoles, which may be considered as masked 1,3-dicarbonyl compounds or enaminoketones. 

Isoxazolium salts can be prepared by reaction with alkyl iodides or sulfates, although the low basicity of isoxazoles and their sensitivity to nucleophilic attack may necessitate special care. Isoxazolium salts containing bulky Af-substituents can be prepared by the reaction of isoxazoles with alcohols in the presence of perchloric acid. For example, the reaction of 3,5-dimethylisoxazole (53) with some alcohols in the presence of 70% perchloric acid gave isoxazolium salts, (54a) in 29%, (54b) in 57% and (54c) in 82% yield 79AHC(25)147, 68JOC2397). Attempts to quaternize 3,5-dimethyl-4-nitroisoxazole failed 71JCS(B)2365). 

Isoxazolin-5-one, 2,3-dimethyl-4-substituted photolysis, 6, 14 Isoxazolinones synthesis, 5, 132 Isoxazolin-3-ones alkylation, 6, 43 synthesis, 6, 106, 129 Isoxazolin-4-ones synthesis, 6, 106-107 Isoxazolin-5-ones alkylation, 6, 39 4,4-dialkyl substituted reaction with Grignard reagents, 6, 40 reactions with bases, 6, 41 synthesis, 6, 103-105 Isoxazolium bisulphate, 2,3,5-trimethyl-hydrogen exchange, 6, 21 Isoxazolium salts deprotonation, 5, 71 as hardeners for gelatin, 1, 363 nucleophilic cleavage, 6, 31 nucleophilic reactions, 6, 28-29 4/f-pyran synthesis from, 3, 761 reactions... 

B. Reactions of Isoxazoles and Isoxazolium Salts with Nucleophiles.170... 

Isoxazolium salts can be prepared by appropriate general methods, although the low basicity of the isoxazoles and their sensitivity to nucleophilic attack may necessitate special care. The explosive nature of isoxazolium perchlorates must be noted.125 The preparation of isoxazolium salts containing bulky N-substituents can be very difficult, and the particular utility of such compounds in synthesis (see Section III,B,2) has prompted the development of new methods for preparing them. A noteworthy route involving the reaction of the isoxazole with a carbenium ion, formed from a suitable alcohol, is exemplified in Eq. (18).30,126... 

Nucleophiles other than carboxylate ions have been less widely studied in reactions with 3-unsubstituted isoxazolium salts, but they can in general be rationalized in terms of the ketoketenimine intermediate. Examples are shown in Scheme 12. Many of these reactions were recorded in the earlier literature, but the structures of the products were in some cases not established until spectroscopic methods became available.165 The application of... 

Nucleophiles react with isoxazoles and even faster with isoxazolium salts, but differently in each case and usually with ring cleavage. A special and synthetically useful reaction of isoxazoles unsubstituted in the 3-position is the ring-opening by bases, e.g. ... 

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