Nitrile oxide precursor

Thermal dehydrochlorination of hydroximoyl chlorides affords nitrile oxides (50-52). O-Ethoxycarbonylbenzohydroximoyl chloride, generating benzonitrile oxide, was used as a stable nitrile oxide precursor, which was efficiently used in... 

Macrocycles containing isoxazoline or isoxazole ring systems, potential receptors in host—guest chemistry, have been prepared by multiple (double, triple or quadruple) 1,3-dipolar cycloadditions of nitrile oxides, (prepared in situ from hydroxamoyl chlorides) to bifunctional calixarenes, ethylene glycols, or silanes containing unsaturated ester or alkene moieties (453). This one-pot synthetic method has been readily extended to the preparation of different types of macrocycles such as cyclophanes, bis-calix[4]arenes and sila-macrocycles. The ring size of macrocycles can be controlled by appropriate choices of the nitrile oxide precursors and the bifunctional dipolarophiles. Multiple cycloadditive macrocy-clization is a potentially useful method for the synthesis of macrocycles. 

New isoxazoline derivatives of a-tocopherol, the main component of vitamin E, have been synthesized in a facile, two-step sequence consisting of nitration followed by 1,3-dipolar cycloaddition. 5-Nitromethyl-a-tocopheryl acetate, obtained from a-tocopheryl acetate by direct nitration in one step, act as the nitrile oxide precursor in the reaction with various alkenes. The facile conversion proceeds in the presence of equimolar amounts of PhNCO and catalytic amounts of triethylamine to give isoxazolines, 446 (489). 

Nitrile oxide precursors have been prepared by the reaction of an isocyanate and an alkyl nitroacetate. These precursors release alkanol and carbon dioxide when heated, to liberate the highly reactive nitrile oxide species. An improved synthetic procedure has been developed to afford novel cross-linking agents based on difunctional, trifunctional and aliphatic precursors. Application of these agents to polymer cross-linking has been demonstrated (527). 

Benzofurazans are thermally more stable but can be cleaved photolytically. For example, benzo-furazan itself in benzene affords cyanoisocyanate (17) and azepine (18), the latter being formed by reaction of the solvent with the putative intermediate acylnitrene (19) (Scheme 5) further supporting evidence for the proposed pathway is provided by trapping the nitrile oxide precursor with dimethyl acetylenedicarboxylate and isolation of the methylurethane derivative of the isocyanate <75JOC2880>. Photolysis of diphenylfurazan yields benzonitrile, diphenylfuroxan and 3,5-diphenyl-1,2,4-oxadiazole. 

TABLE 6.1. CYCLOADDITIONS TO 1-HEXENE USING FUROXANS AS NITRILE OXIDE PRECURSORS"... 

Nitroacetal 77 was used as the nitrile oxide precursor in a synthesis of (-l-)-hepialone (82). Curran s group carried out a 1,3-dipolar cycloaddition to... 

TABLE 6.10. CYCLOADDITIONS OF CHIRAL NITRILE OXIDES (PRECURSORS SEE TABLE 6.9) WITH ACHIRAL ALKENES... 

Kumaran, G., Kulkarni, G. H. Afacile conversion of nitro olefins to functionalized hydroximoyl chlorides as nitrile oxide precursors. Tetrahedron Lett. 1994, 35, 5517-5518. 

Solid-supported nitrile oxides have the main advantage over those prepared in solution that formation of dimers is avoided. Thus, a 96-member library of 3-hydroxymethyl isoxazoles (265) [298] has been prepared from nitroethanol on a modified tetrahydropyranyl linker (263) as nitrile oxide precursor. The cycloaddition step was then performed by generating the nitrile oxide under the Mukaiyama conditions in the presence of alkynes (Scheme 59). As expected, the presence of dimer furoxane was never detected. 

The synthesis of a series of isoxazoles 15 and isoxazolines 15a on the solid phase has been reported by Pei and Moos [50] via [3 + 2] cycloaddition of alkenes and alkynes with highly reactive nitrile oxides. The cycloaddition reactions of resin-bound peptoids were carried out in toluene at 100°C or in DCM-H2O at room temperature, depending on the precursors of the nitrile oxides. Benzaldehyde oxime and various nitroalkyl compounds were selected as nitrile oxide precursors. The nitrile oxides were generated in situ by reacting the nitroalkyl compounds with phenyl isocyanate and triethylam-ine or by oxidizing the oximes with sodium hypochlorite in the presence of triethylamine (Fig. 7). 

One of the most important reactions of hydroxamoyl chlorides involves dehydrochlorination to nitrile oxides, and the renewed interest in the 1,3-cycloaddition reactions has focused attention again on the nitrile oxide precursors. 

Zagozda and Plenkiewicz reported a synthesis of enantiopure isoxazolines 103 via 13DC of optically active nitrile oxides 101 with MVK and acrylate 102 (Scheme 28) [ 122], The nitrile oxide precursor 100 was prepared from ni-troalkenes 99a,b by Baker s yeast promoted reduction. While the Mukaiyama procedure (PhNCO, EtsN) was satisfactory for the generation of nitrile oxide 101 in some cases, the Hassner method (B0C2O, DMAP) provided better results in other cases. Although yields were satisfactory (35-55%), stereoselectivity remained low (<65 35). 

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