Ortho-Cyclization in Asymmetrically Substituted Arylnitroso Oxides

Abstract

The mechanism of the photooxidation of a number of asymmetrically substituted phenyl azides in acetonitrile was studied. The key intermediates of this reaction are the corresponding nitroso oxides, the unimolecular consumption of which occurs via the cis form when the terminal oxygen atom of the NOO moiety reacts with the ortho position of the aromatic ring. As a result, it is opened to form a nitrile oxide. In the case of 3-methylphenyl azide, the reaction proceeds via the cis/syn form of nitroso oxide with a regioselectivity of 91%. The methoxy substituent at the para position changes the direction of the ortho-cyclization so that it occurs via the cis/anti form of nitroso oxide independently on the nature of a meta substituent. Nitrile oxides, which are formed as a result of these transformations of nitroso oxides, are stabilized by [3 + 2] cycloaddition with acetonitrile to give 1,2,4-oxadiazoles. The observed regioselectivity of the ortho-cyclization of nitroso oxides was explained using theoretical methods. Its cause consists in the extra-stabilization of the transition state of the reaction of the cis/anti form due to a stereoelectronic effect of the para-methoxy substituent.

Interplay of the Ring and Steric Strains in the Highly Substituted Cyclopropanes

“…4,5 The intramolecular ortho-cyclization of aromatic nitroso oxides is another interesting example of the SE-determining reactivity, in this case, in the form of the inverted steric effect. 6,7 The presence of both electron-donating and electronaccepting substituents R at the reaction center pronouncedly accelerates ortho-cyclization. The observed effect (Scheme 2) is induced with the steric repulsion of the NOO group and ortho-substituent, which disturbs the planar structure of nitroso oxide and makes it closer to the structure of the transition state.…”

“…The intramolecular ortho-cyclization of aromatic nitroso oxides is another interesting example of the SE-determining reactivity, in this case, in the form of the inverted steric effect. , …”

Comprehensive Study of the Mechanism of the “Aromatic Nitroso Oxide–Olefin” Interaction as a Function of the Reagents’ Structure

“…The obvious progress in the chemistry of RNOO was also supported by our laboratory. Thus, the papers − thoroughly consider the structure, spectral properties, generation methods, reactivity, and mechanisms of various transformations of aromatic nitroso oxides ArNOO. The experimental and theoretical results of these studies are summarized in a review, from which it follows that ArNOO are highly active species with a characteristic lifetime of several seconds and a high chemical potential.…”