Seven‐Membered Heterocycles: Azepines, Benzo Derivatives and Related Systems

Evidence for the formation of Michael adducts from reactions of (E,E)-muconaldehyde with glutathione and other thiols

Based on the literature published during last 12 years, this chapter covers different aspects of the chemistry of oxepines and oxepanes from the simplest compounds formed in metabolism of aromatic hydrocarbons to complicated fused O-heterocyclic systems of marine origin. Some structural features, chemical properties, and reaction mechanisms of base systems are discussed concisely. Ring syntheses of oxepines and oxepanes are treated in detail. Especial attention is paid to modern cyclization procedures like ring-closing metathesis and transformations of different carbo- and heterocyclic compounds to oxepines and oxepanes, particularly to novel variants of Baeyer–Villiger reaction with cyclohexanones and manifold reactions leading from epoxides to seven-membered O-heterocycles. A separate section is devoted to brief summary of syntheses of particular classes of compounds under discussion. Finally, important compounds and applications of natural and synthetically prepared oxepines and oxepanes are demonstrated.

Oxepanes and Oxepines

Epoxidations, heteroatom oxidations, and Y-H insertions constitute the best investigated oxidations by dioxiranes. This article concerns epoxidation of the double bonds in the cumulenes, such as allenes, acetylenes, and arenes; the oxidation of heteroatom functionalities, mainly lone pairs on sulfur, on nitrogen, and on oxygen as the deoxygenation of N-oxides; the oxidation of C = Y functionalities, Y-H insertions such as in C-H alkanes, and Si-H silanes; and the oxidation of organometallic substrates including metal and ligand-sphere oxidation.


Keywords:

Dioxirane oxidations;
Allenes;
Alkynes;
Arenes;
Heteroatom substrates;
Alkanes;
Silanes;
Organometallic compounds;
Mechanisms;
Nitrogen;
Sulfur;
Selenium;
Phosphorus;
Oxygen;
Halogens;
Method comparisons;
Experimental procedures

Dioxirane Oxidations of Compounds other than Alkenes

The very rapid benzene oxide/oxepin equilibrium plays an important role in the metabolism of benzene by cytochrome P450. Although it is the benzene oxide valence tautomer that is attacked by nucleophiles and rearranges to phenols in acidic media, it is the oxepin valence isomers that suffer one-electron oxidation. However, some other reactions are more competitive and also furnish useful illustrations of the Curtin–Hammett principle. For example, while oxepin and benzene oxide are comparable in energy, the only reaction product with maleic anhydride is the Diels–Alder adduct with benzene oxide. Density function theory (B3LYP/6-31G*) calculations are employed for study of three sets of benzene oxide/oxepin equilibria and Diels–Alder reactions with maleic anhydride and dimethylazodicarboxylate as well as epoxidation by dioxirane. Comparisons are made between theory and published experimental data.

Dhananjaya Nauduri

Papers

Direct observation by 1H NMR of 4,5-benzoxepin-2,3-oxide and its surprisingly rapid ring-opening rearrangement to 1H-2-benzopyran-1-carboxaldehyde☆