Nitrile oxides isoxazoline ring cleavage

Isoxazolines, derived from alkenes and nitrile oxides, undergo ring cleavage with lithium di-isopropylamide to form enoximes (Scheme Subsequent... 

Lorsbach et al. have studied the synthesis of isoxazoline-functionalized isoquinolines (Scheme 11.37). A resin-bound isoxazoline ring was obtained by reacting resin-bound aUtenes with nitrile oxides. The traceless cleavage of the heterocycles was then carried out under alkahne conditions. Ehmination of the resin released aromatized isoquinoline from the solid support. 

A rapid access to carbocyclic nucleosides, containing a fused isoxazoline ring has been proposed, starting from cyclopentadiene. The route involves a het-ero Diels-Alder cycloaddition reaction of nitrosocarbonylbenzene followed by a 1,3-dipolar cycloaddition of nitrile oxides, cleavage of the N-0 tether and transformation of the heterocyclic aminols into nucleosides via construction of purine and pyrimidine heterocycles (457). 

An efficient synthetic route to (10Z)- and (10 )-19-lluoro-la,25-dihydroxy vitamin D3 has been developed (488). The key feature of this pathway is the introduction of a 19-fluoromethylene group to a (5 )-19-nor-10-oxo-vitamin D derivative. The 10-oxo compound 445 has been obtained via a 1,3-dipolar cycloaddition reaction of (5 )-la,25-dihydroxyvitamin D with in situ generated nitrile oxide, followed by ring cleavage of the formed isoxazoline moiety with molybdenum hexacarbonyl. Conversion of the keto group of (5 )-19-nor-10-oxo-vitamin D to the E and Z fluoromethylene group has been achieved via a two-step sequence, involving a reaction of lithiofluoromethyl phenyl sulfone, followed by the reductive de-sulfonylation of the u-lluoro-j3-hydroxysulfone. The dye-sensitized photoisomerization of the (5 )-19-fluorovitamin D affords the desired (5Z)-19-fluorovitamin D derivatives, (10Z)- and (10 )-19-fluoro-la,25-dihydroxy-vitamin D3. 

In the great major tiy of applications that use the intramolecular nitrile oxide-alkene cycloaddition, the intention is to prepare intermediates for the synthesis of natural products or related compounds. The most popular transformations of these isoxazolines are the following ring cleavage modes ... 

Aliphatic nitro compounds are versatile building blocks and intermediates in organic synthesis,14 15 cf. the overview given in the Organic Syntheses preparation of nitroacetaldehyde diethyl acetal.16 For example, Henry and Michael additions, respectively, lead to 1,2- and 1,4-difunctionalized derivatives.14 18 1,3-Difunctional compounds, such as amino alcohols or aldols are accessible from primary nitroalkanes by dehydration/1,3-dipolar nitrile oxide cycloaddition with olefins (Mukaiyama reaction),19 followed by ring cleavage of intermediate isoxazolines by reduction or reduction/hydrolysis.20 21... 

Ring fused products can be elaborated from isoxazolines (80S757). Several nitrocyclo-alkenes (516) were prepared and reacted with phenyl isocyanate to generate the intermediate nitrile oxides which underwent internal cycloaddition to afford the tricyclic isoxazolines (517). Cleavage of the N—O bond by hydrogenation in the presence of a catalytic amount of Raney nickel and subsequent hydrolysis afforded the /3-ketol (518 Scheme 113). 

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