Ethers, vinyl reaction with nitrile oxides

It was found that 2-propenyloxymagnesium bromide reacts much more readily with nitrile oxides than other known dipolarophiles of electron-deficient, electron-rich, and strained types, including 3-buten-2-one, ethyl vinyl ether, and norbomene, respectively (147). Therefore, this BrMg-alkoxide is highly effective in various nitrile oxide cycloaddition reactions, including those of nitrile oxide/Lewis acid complexes. 

However, most asymmetric 1,3-dipolar cycloaddition reactions of nitrile oxides with alkenes are carried out without Lewis acids as catalysts using either chiral alkenes or chiral auxiliary compounds (with achiral alkenes). Diverse chiral alkenes are in use, such as camphor-derived chiral N-acryloylhydrazide (195), C2-symmetric l,3-diacryloyl-2,2-dimethyl-4,5-diphenylimidazolidine, chiral 3-acryloyl-2,2-dimethyl-4-phenyloxazolidine (196, 197), sugar-based ethenyl ethers (198), acrylic esters (199, 200), C-bonded vinyl-substituted sugar (201), chirally modified vinylboronic ester derived from D-( + )-mannitol (202), (l/ )-menthyl vinyl ether (203), chiral derivatives of vinylacetic acid (204), ( )-l-ethoxy-3-fluoroalkyl-3-hydroxy-4-(4-methylphenylsulfinyl)but-1 -enes (205), enantiopure Y-oxygenated-a,P-unsaturated phenyl sulfones (206), chiral (a-oxyallyl)silanes (207), and (S )-but-3-ene-1,2-diol derivatives (208). As a chiral auxiliary, diisopropyl (i ,i )-tartrate (209, 210) has been very popular. 

Nitrile oxides are relatively electron-deficient compounds that react smoothly with electron-rich vinyl ethers. Jenkins and co-workers (171) investigated the reactions of L-menthyl-, 8-phenylmenthyl- and S)-endo- >omy vinyl ethers with nitrile oxides, but generally the de values were <33%. However, use of the chiral vinyl ether 114 in the reaction with a number of alkyl and benzonitrile oxides provided product 115 with de values of up to 66% (Scheme 12.38). It is proposed that the syn-staggered conformation is preferred for the vinyl ether 114 as indicated... 

Intermediate formation of nitrile oxides is, also proposed in reactions of nitroacetylene with furan and vinyl ethers (Scheme 1.9) (93) and of lithium (phenyl)acetylide with N2C>4 (94). 

However, this interaction should also be increased by alkyl substituents, which lower the alkene IP, or, equivalently, raise the alkene HOMO energy. Experimentally, there is either no change in rate, or a small decrease, as the IP of the alkene decreases. Thus, an apparent contradiction is revealed in these examples dipole LUMO-alkene HOMO control nicely accounts for regioselectivity and the nitrile oxide substituent effect, but does not explain the decrease in rate for increasing alkyl substitution. More potent electron-donors do, indeed, accelerate the reaction, but only feebly. For example, butyl vinyl ether reacts 2.1 times faster than ethylene with BNO at 0 °C, while styrene reacts only 1.2 times faster than ethylene with BNO, in spite of the low IP of styrene (8.48 eV)72. ... 

Isoxazoles have also been obtained through an elimination reaction (Scheme 11.40). Cycloaddition of nitrile oxide to resin-bound vinyl ether gave resin-bound 2-isoxazoUne, which aromatized to isoxazole after the elimination of the polymer support. A regioselective reaction gave isoxazoles in high purity and with 36—83% yield. Enhanced diversity was obtained with the Suzuki coupling reactions to the R group prior to the cycloadditions. 

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