Ethers, methyl 2 + 2 cycloaddition reactions

Vinyl ethers undergo many cycloaddition reactions similar to those which take place with enamines. In general, however, these cycloaddition reactions with vinyl ethers take place less readily than those with enamines. These reactions include cycloaddition of vinyl ethers with ketene (200-205), phenyl isocyanate (206), sulfene (207,208), methyl acrylate (209), diethyl acetylenedicarboxylate (210), and diphenylnitrilimine (183). 

More recently, further developments have shown that the reaction outlined in Scheme 4.33 can also proceed for other alkenes, such as silyl-enol ethers of acetophenone [48 b], which gives the endo diastereomer in up to 99% ee. It was also shown that / -ethyl-/ -methyl-substituted acyl phosphonate also can undergo a dia-stereo- and enantioselective cycloaddition reaction with ethyl vinyl ether catalyzed by the chiral Ph-BOX-copper(ll) catalyst. The preparative use of the cycloaddition reaction was demonstrated by performing reactions on the gram scale and showing that no special measures are required for the reaction and that the dihydro-pyrans can be obtained in high yield and with very high diastereo- and enantioselective excess. 

The reactivity of the prototype o-QM as heterodiene in Diels-Alder cycloaddition reactions with several substituted alkenes such as methyl vinyl ether (MVE), styrene,... 

On the basis of available experimental data, it is impossible to choose a definite pathway of elimination of silanol. However, study of silylation of methyl P -nitropropionate (411) with BSA in the presence of trapping agents rigorously proved that silyl nitronate D is initially formed. This compound can be detected in the [3 + 2]-cycloaddition reaction with methyl acrylate product (413). If silylation of AN (411) is performed in the presence of ethyl vinyl ether, a-nitrosoalkene E can be successfully trapped in as heterodiene a Diels-Alder reaction. Dihydroox-azine (414) is formed, and its silylation affords isolable product (415). 

With this revision in our original plans, both alkenes and allenes were found to undergo efficient cycloadditions to produce cyclooctenone products in a new [6+2] cycloaddition process. This novel cycloaddition has been shown to proceed efficiently with alkenes tethered with sulfonamide, ether, or geminal diester Hnkers (Tab. 13.15, see page 294). Isomerization of the olefin, a potential competing reaction in this process, is not observed. Methyl substitution of either alkene in the substrate is well tolerated, resulting in the facile construction of quaternary centers. Of mechanistic importance, in some cases cycloheptene byproducts were isolated from [6+2] cycloaddition reactions in addition to the expected cyclooctenone products (that is, entries 3 and 4). 

Nitrile oxides react with the methyl enol ethers of (Rs)-l -fluoro-alkyl-2-(p-tolylsulfinyl)ethanones to produce (45,5/f,/fs)-4,5-dihydroisoxazoles with high regio-and diastereo-selectivity.87 In the 1,3-dipolar cycloaddition of benzonitrile oxide with adamantane-2-thiones and 2-methyleneadamantanes, the favoured approach is syn, as predicted by the Cieplak s transition-state hyperconjugation model.88 The 1,3-dipolar cycloaddition reaction of acetonitrile oxide with bicyclo[2.2.l]hepta-2,5-diene yields two 1 1 adducts and four of six possible 2 1 adducts.89 Moderate catalytic efficiency, ligand acceleration effect, and concentration effect have been observed in the magnesium ion-mediated 1,3-dipolar cycloadditions of stable mesitonitrile oxide to allylic alcohols.90 The cycloaddition reactions of acryloyl derivatives of the Rebek imide benzoxazole with nitrile oxides are very stereoselective but show reaction rates and regioselectivities comparable to simple achiral models.91. 

Figure 2 Thermal and (Lewis) acid catalyzed LUMOdjoe-controlled [4-I-2] cycloaddition reaction of acrolein and methyl vinyl ether AM I results (Table 5)...

For example, the three-component domino inter-[4- -2]/inter-[3- -2] cycloaddition reaction of the D-galactose-derived heterodiene 538 with ethyl vinyl ether and methyl vinyl ketone took place with total chemo-, regio-, facial-, and stereoselectivity to give a single nitrosoacetal 539 in 70% yield (Equation 89) <1998CC459>. 

Similarly, reaction of 1,4-diacetoxy-l,3-butadiene with methyl glyoxalate afforded glu-curonate glycal [228] and a 2,3-unsaturated isomer. Cycloaddition reactions performed on substrates with inverse electronic properties (e. g., enol ether as a dienofile and unsaturated carbonyl compound as a heterodiene) afford not only the expected products but also ones having high endo selectivity [229,230] as exemplified below by olivose 126 synthesis (O Scheme 43). 

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