Hydroximinoyl chlorides

A concise and efficient asymmetric synthesis of L-( + )-carbafuranomycin 452, a novel analog of L-( + )-furanomycin, which is an unusual antibiotic amino acid of great interest, due to its activity as an isoleucine antagonist, has been reported (496). The synthesis starts with the 1,3-dipolar cycloaddition of a chiral nitrile oxide (obtained in situ from hydroximinoyl chloride 453 via slow addition of NEt3) with cyclopentadiene. Then methylation of cyclopentenyl acetate 454,... 

Vinyl boronates 228 undergo 1,3-dipolar cycloaddition with aryl hydroximinoyl chloride 229 to furnish the imine-oxide 231. The boronate moiety is highly labile under the reaction conditions and it undergoes protonolysis to yield isoxazolines 232. Alternatively, the boronates could be oxidized with hydroperoxides or sodium percarbonate to furnish the 4-hydroxyisoxazolines 233 in good yield (Scheme 39) <2000T965>. 

Besides carbonyl and alkynone condensation [94, 95] of hydroxylamine, the (2-i-3)-cycloaddition of aromatic nitrile oxides, a class of propargyl type 1,3-dipoles, is a very general access to isoxazoles [96, 97]. Since aromatic nitrile oxides tend to be very unstable, it is favorable to generate them in situ by dehydrochlorlnation of the corresponding hydroximinoyl chlorides with a suitable base. If triethylamine is the base, this step can be expected to be fully compatible with a preceding alkynone formation. 

Nitrile oxides could also be prepared from nitroalkanes by reaction with (Boc)20 in the presence of catalytic amounts of DMAP at room temperature under N2 [276]. Alternatively they could also be prepared via base-induced dehydrohalogenation from hydroximinoyl chlorides, which can be either purchased or generated hy chlorination of the corresponding aldoximes with N-chlorosucdnimide. 

Dimerization of nitrile oxides is one of the most important methods of synthesis of 1,2,5-oxadiazole iV-oxides (furoxans). However, this process can also lead to formation of symmetrical 1,4,2,5-dioxadiazines. The dipyridyl dioxadiazine 20 was obtained in 59% yield by treatment of 2-pyridyl hydroximinoyl chloride hydrochloride with triethylamine and pyridine in ethanol <2003EJI405>. The coumarin nitrile oxide 196 was dimerized with pyridine in ethanol to give the dioxadiazine 197 in 66% yield (Scheme 34). When a chloroform solution of the nitrile oxide 196 was heated at reflux in the absence of base, the furoxan 198 was produced in 70% yield (Scheme 34). Attempted purification of 196 by recrystallization caused dimerization into furoxan 198 <1998JHC619>. 

Trisubstituted isoxazoles 14 with ferrocenyl groups in 4- and 5-position can be synthesized utilizing acid chlorides 4, terminal alkynes 5, and hydroximinoyl chlorides 13 in a sequence consisting of modified Sonoga-shira cross-coupling I and cyclocondensation. Hydroximinoyl chlorides 13 are employed as synthetic equivalents of the corresponding aromatic nitrile... 

The desired products were obtained at rt after a few hours in high yields (72-89%). The basic conditions generate 1,3-dipoles from several aryl hydroximinoyl chlorides 232, which smoothly undergo 1,3-dipolar cycloaddition with the previously formed Knoevenagel condensation product. 

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