Hydrogen bonding, nitrile oxide cycloadditions

A number of examples involving nitrile oxide cycloadditions to cyclic cis-disubstituted olefinic dipolarophiles was presented in the first edition of this treatise, notably to cyclobutene, cyclopentene, and to 2,5-dihydrofuran derivatives (15). The more recent examples discussed here also show, that the selectivity of the cycloaddition to 1,2-cis-disubstituted cyclobutenes depends on the type of substituent group present (Table 6.8 Scheme 6.41). The differences found can be explained in terms of the nonplanarity (i. e., pyramidalization) of the double bond in the transition state (15) and steric effects. In the cycloaddition to cis-3,4-diacetyl-(197) and cis-3,4-dichlorocyclobutene (198), the syn-pyramidalization of the carbon atoms of the double bond and the more facile anti deformability of the olefinic hydrogens have been invoked to rationalize the anti selectivity observed. 

The same authors also reported the solid-phase version of the above hydrogen-bond-directed cycloaddition in which complete diastereoselectiv-ity was observed during the nitrile oxide cycloaddition step [ill]. However,... 

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). 

Now we have the 1,3-dipolar cycloaddition. A nitrile oxide is formed from the nitro compocu by dehydration with PhNCO (the full mechanism is on p. 934) and cycloaddition can occur c- with the regio- and stereoselectivity shown because of the short tether. We have shown the nkrr oxide approaching from the bottom face of the alkene so that all three hydrogens are up. ReductL of the C=N bond then occurs from the top (outer, exo-, convex face) of the bowl-shaped molecal... 

De la Hoz recently described, in a book chapter, selected reports highlighting particularly interesting [3+2] cycloaddition reactions of nitrile oxides, and their applications [3j]. Earlier examples of controlled MAOS are limited and can be found in the most recent review article by Bougrin [13c]. From these, and for the sake of completeness, some of the most significant examples can also be found in this review. The application of microwaves to the cycloaddition reactions of allyl alcohols with nitrile oxides not only achieved a substantial reduction in reaction time and improved yields, but also altered the regioselectivity of the cycloaddition in favor of the non hydrogen bond-directed cycloadduct [83]. 

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