Abstract Compared to parent oxygenated five- and six-membered rings, oxepanes
represent a rare structure found in Nature. Nevertheless, natural products with
significant biological activities possess either only one seven-membered ring or
one or multiple oxepane subunits fused to other oxygenated heterocycles. Therefore, a large number of methods have been designed to access these structures with
a special attention on metal-catalysed coupling reactions.
Keywords Cyclisation • Epoxides • Lactones • Metal-induced cyclisations •
Metathesis • Oxepanes • Oxepins • Oxidation • Palladium-catalyzed coupling •
Prins reaction • Radical cyclisation • Ring enlargement • Ring opening • Samarium
diiodide
1 Introduction
Compared to the corresponding five- and six-membered cyclic ethers, the homologous oxepanes and oxepins are less common in Nature. Some of them depicted in
Figs. 1 and 2 exhibit a large variety of pharmaceutical properties. Therefore, due to
their usually low abundance, synthetic chemists have developed a large panel of
methods to reach them. In this chapter, the access to various seven-membered
oxacycles including oxepanes, oxepins or benzoxepines will be described, and, to
a less extent, the synthesis of polycyclic structures reported in different reviews
[1–6].
2 Ring Expansion of Oxygenated Structures
For steric and also entropic reasons, the direct formation of seven-membered rings
from acyclic structures is usually difficult. Therefore, the ring expansion of
dihydropyranes into oxepanes has emerged as a powerful and high-yielding
method.
2.1 Cyclopropanation and Ring Opening of Bicyclo[4.1.0]
heptanes
The synthesis of heptanoside 2 has been achieved according to a two-step procedure. D-Glucal derivatives can be easily converted to bicyclo[4.1.0]heptanes by a
diastereoselective addition of a dibromocarbene to the double bond. By heating 1 in
toluene, in the presence of silver acetate, the cleavage of a carbon–bromide bond
occurred and is followed by an electrocyclic ring opening. The corresponding
carbocation was next trapped by various nucleophiles. The best results were
obtained with sodium acetate. Noteworthy, in refluxing toluene and in the absence
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O. Piva
represent a rare structure found in Nature. Nevertheless, natural products with
significant biological activities possess either only one seven-membered ring or
one or multiple oxepane subunits fused to other oxygenated heterocycles. Therefore, a large number of methods have been designed to access these structures with
a special attention on metal-catalysed coupling reactions.
Keywords Cyclisation • Epoxides • Lactones • Metal-induced cyclisations •
Metathesis • Oxepanes • Oxepins • Oxidation • Palladium-catalyzed coupling •
Prins reaction • Radical cyclisation • Ring enlargement • Ring opening • Samarium
diiodide
1 Introduction
Compared to the corresponding five- and six-membered cyclic ethers, the homologous oxepanes and oxepins are less common in Nature. Some of them depicted in
Figs. 1 and 2 exhibit a large variety of pharmaceutical properties. Therefore, due to
their usually low abundance, synthetic chemists have developed a large panel of
methods to reach them. In this chapter, the access to various seven-membered
oxacycles including oxepanes, oxepins or benzoxepines will be described, and, to
a less extent, the synthesis of polycyclic structures reported in different reviews
[1–6].
2 Ring Expansion of Oxygenated Structures
For steric and also entropic reasons, the direct formation of seven-membered rings
from acyclic structures is usually difficult. Therefore, the ring expansion of
dihydropyranes into oxepanes has emerged as a powerful and high-yielding
method.
2.1 Cyclopropanation and Ring Opening of Bicyclo[4.1.0]
heptanes
The synthesis of heptanoside 2 has been achieved according to a two-step procedure. D-Glucal derivatives can be easily converted to bicyclo[4.1.0]heptanes by a
diastereoselective addition of a dibromocarbene to the double bond. By heating 1 in
toluene, in the presence of silver acetate, the cleavage of a carbon–bromide bond
occurred and is followed by an electrocyclic ring opening. The corresponding
carbocation was next trapped by various nucleophiles. The best results were
obtained with sodium acetate. Noteworthy, in refluxing toluene and in the absence
284
O. Piva