Isoxazoles reactions with enamines

Chloroximes and enamines have provided aminoisoxazolines which could readily be converted to isoxazoles with acid (610-612). Pyrrazoles were usually obtained from addition of chlorohydrazones to enamines (610,613). The intermediate aminopyrazolines could only be isolated from the reaction of the cyclopentenyl enamine system. Pyrazoles were also obtained from the reactions of enamines with a-diazoketones and a-diazoesters (614). 

A novel ring opening reaction of isoxazoles led to the formation of functionalized pyrroles <06S1021>. For example, treatment of isoxazole 52 with DBU led to the formation of pyrrole 53. A solid-phase synthesis of 3-amino-2,5-dicarboxylates was accomplished by transformation of pyrrol-3-one 54 <06JCC177>. The reaction between 54 and secondary amines led to the corresponding resin-bound aminopyrroles after enamine formation and loss... 

Nitro-3-phenylisoxazole-5-carboxylates (290) act as heterocyclic 1-azadiene components in [4 + 2] cycloaddition reaction with some enamines affording bicyclo derivatives 295 probably via a stepwise ionic cycloaddition involving the Michael adducts 292 as primary intermediates. Further intramolecular attack by the isoxazole nitrogen on the immonium carbon followed by elimination of the amine and aromatization of dihydropyridine 293 afforded 294, which was transformed into pyridine 295 by simple reduction164 (equation 63). 

There are no reports of simple isoxazoles participating in [4 + 2] cycloadditions in which the isoxazole nucleus functions as a heteroaromatic 1-azadiene system. However, one of the early reports of the successful participation of a 1-azadiene system in [4 + 2] cycloadditions does include the Diels-Alder reactions of benzisoxazoles (Chapter 9, Section 1, Table 9-1, entries 1-7).61 An additional report has detailed the participation of substituted 4,5-dihydro-3-vinylisoxazoles in [4 + 2] cycloadditions (Chapter 9, Section 1, Table 9-1, entry 8).62a Isoxazolium salts react with enamines to provide pyridinium salts via a [4+ + 2] reaction (Chapter 9, Section 10).62b... 

Strategies that lead to the formation of isoxazoles during cleavage from an insoluble support include the oxidative cleavage of /V-(4-alkoxybenzyl)isoxazolidincs with DDQ to yield isoxazolines (Entry 14, Table 15.16), the nucleophilic cleavage of 2-acyl enamines with hydroxylamine (Entry 15, Table 15.16), and the acidolysis of 2-cyano-phenols etherified with an oxime resin (Entry 17, Table 15.16). The required oxime ethers for the latter synthesis were prepared by reaction of the corresponding 2-fluorobenzonitriles with Kaiser oxime resin [203],... 

Azine approach. Enamines when used as dipolarophiles with nitrile oxides form isoxazoles. With cyclic enamines such as (89) fused isoxazoles are formed the nitrile oxide in this reaction is generated in situ from benzhydroxamoyl chloride (64JOC1582). 

Structure 159 has been erroneously assigned to the product of the reaction between 3-benzoyl-3-methyl-47/-isoxazol-5-one 157 and SOCI2 (53GA192). In reality, the compound has the structure of isoxazolone 158 (74HCA1934). The reactions of chloro compound 158 with ammonia, phenylenediamine, and phenylhydrazine produce enamine 160, isoxazolo[5,4-e]1.4-diazepine 161, and isoxazolo[5,4-c]pyrazole 162, respectively (59ZOB3446). The formation of 161 and 162 represents examples of substitution at the keto group in position 5 (Scheme 71). 

Photochemical addition of dimethyl acetylenedicarboxylate to the enamine H2Ca C -NH-CE=>CH2 (E => COOMe) yields the bridged cyclohexene (90), irtiich decomposes at 90 °C in a retro-Diels-Alder reaction to ethylene and the ester (91). The adducts (92 R = PhCO or COOBu ") of perf luorobut-2-yne, CP CHCCF, to N-substituted pyrroles have been degraded to 3,4-bls(trlfluoromethyl)pyrroles (93) by two methods in the former, the adducts were first hydrogenated at the unsubstituted double bond and then heated to eliminate ethylene,idille in the latter, the adducts were treated with mesitonitrile oxide, 2,4,S-Me C H CEN -0, which removed the ethylene unit in the form of the isoxazole (94). ... 

---