Sodium hypochlorite, nitrile oxide generation

Oxidation of aldoximes 327 with sodium hypochlorite or NBS is one of the best-known methods for generation of nitrile oxides (Equation 73) <1999BCJ2277>. 

Dihydro- and tetrahydrofuroisoxazoline rings were constructed by intramolecular cycloaddition of nitrile oxides or nitrones, generated from oximes . Thus, oxime 30 and sodium hypochlorite afforded furoisoxazolines 31 (equation 14). Similarly, furanyl or thienyl oximes 32 in the presence of NaOCl afforded tricyclic products 33 in 35-90% yields (equation 15). Nitrostyrenes (ArCH=CHN02) and various nucleophiles (for example, allyl mercaptan) also generated hydroximoyl chlorides which underwent similar cycloaddition leading to bicycUc tetrahydrothiophene and tetrahydrofuran derivatives ... 

The Brown allylboration was used in the enantioselective total synthesis of (-)-calicheamicinone 3318 (Scheme 3.1o). Thus the lactol 34, readily prepared from tetronic acid, was treated with the allylborane d35 to give 36 in a highly stereoselective manner (95% ee, > 98% de). Compound 36 was converted to the aldoxime 37 by standard chemistry. Generation of the nitrile oxide with aqueous sodium hypochlorite was accompanied by spontaneous [3 + 2]-dipolar cycloaddition to afford 38 in 65% yield. 

The nitrile oxides can be generated by various methods. Generation from bromoaldoximes in a chloroform/sodium hypochlorite biphase medium is efficient. ... 

Similar [3 4-2] cycloadditions with C-aryl nitrile oxides and other terminal fiuoroalkylated al-kenes (RF = C2F5, C6F13) and fiuoroalkylated alkynes provide high yields of cycloadducts.86,87 The nitrile oxides can be generated by various methods. Generation from bromoaldoximes in a chloroform/sodium hypochlorite biphase medium is efficient.86... 

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). 

A stereocontrolled total synthesis of (+)-vinblastine (329), a prominent alkaloid used in cancer chemotherapy, was reported by the Fukuyama/ Tokuyama team and features an INOC reaction for the preparation of a key reaction intermediate utilized in their synthesis (2010CR101). Thus, the oxidation of oxime 323 with sodium hypochlorite generated the expected nitrile oxide 324 which imderwent a subsequent 1,3-dipolar cycloaddition to produce isoxazoline 325 as a single isomer (Scheme 59). The INOC proceeded via a six-membered chairlike transition state (i.e., 324) to furnish 325 with the desired stereochemistry. After reductive cleavage of the N—O bond in isoxazoftne 325 with zinc dust in acetic acid, a... 

The addition of nitrile oxides to various olefins was studied by several groups. Similarly to ketenes, the dipolar compounds must be generated in the presence of the other partner, and several methods were used for this purpose. The first one consists of the oxidation of oximes (Z) or ( ), in a biphasic system with aqueous sodium hypochlorite (Fig. 4). Sonication provided a large rate increase, and the reaction was completed in hours instead of days. This result is most probably explained by an efficient emulsification (Ch. 4, p. 108). In a few cases, minor changes in stereoselectivity occur in the irradiated reactions. 

Nitrile oxides have been used extensively in heterocyclic synthesis. They are readily generated from oximes, using sodium hypochlorite under phase-transfer conditions, in high yields. They are versatile, lending themselves to one-pot procedures and reaction in situ with dipolarophiles. Lee discusses a wide variety of their reactions, notably the intramolecular reaction in which the benzopyran derivatives (48) are formed in yields that are more than double those previously reported. 

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