Oxirane, three-membered ring

This chapter will deal exclusively with three-membered rings containing the hetero atoms O, S and N, and fused to the steroid skeleton. Because of the conformational requirements in steroids, not all of the usual methods of synthesis of three-membered rings are applicable to the fused ring system. For the synthesis of steroids to which an aziridine, oxirane or thiirane is attached either in the side chain or at a ring position but not directly fused to the nucleus, the methods discussed in this chapter, as well as others, are applicable. 

Alkenes are oxidized to give epoxides on treatment with a peroxyacid (RCO H), such as mefn-chloroperoxybenzoic acid. An epoxide, also called an oxirane, is a cyclic ether with an oxygen atom in a three-membered ring. For example ... 

The one group of cyclic ethers that behaves differently from open-chain ethers contains the three-membered-ring compounds called epox.id.es, or oxiranes,... 

In the case of the oxiranes, the insertion is promoted by the strain of the three-membered ring. Insertion of the metal atom produces a surface-adsorbed four-membered metallaoxacyclobutane, and this process decreases the ring strain. 

Epoxides are cyclic ethers with three-membered rings (IUPAC oxiranes). 

It should be noted that the unusual high-field positions of H and IJC signals in three-membered rings like cyclopropane, oxirane, thiirane, and aziridine have been rationalized in terms of ring currents (69,70). 

The tin-lithium exchange is also suitable for the generation of a-lithiated oxiranes 53245-247 jjyg jQ jjjg enhanced acidity of a carbon atom incorporated into a three-membered ring, the metalation of epoxides by treatment with various alkyllithium reagents of lithium amide bases also permits one to obtain carbenoids 53 in situ (equation 35) °. 

Epoxides. Epoxides or oxiranes are quite reactive metabolically. These three-membered rings will readily open in the presence of most nucleophiles. They will react with most biopolymers, including proteins and nucleic acids. Compounds with epoxides have very short half-lives and tend to be toxic. 

Unique among cyclic ethers are those with three-membered rings, the epoxides or oxiranes. Their large ring strains make them highly reactive. 

The addition of diazo compounds generally leads to three membered rings, although in special cases, linear adducts with an intact diazo group [//0 or l,3,4-oxadiazol-3-ines [111] can be isolated Most diazo compounds are unstable and yield oxirans and azindmes [112,113,114] Azindmes are obtained exclusively on reaction of certain polyfluonnated acyl imines with diazomethane [115]... 

The three-membered ring of analogous oxirane derivatives offers three acceptor sites for a H-bonding substituent, viz. the ring C—C bond, the vicinal C—O bond and the oxygen atom, of which the latter seems to be preferred (see References 69, 76 and works cited therein). 

Oxacyclopropane (oxirane), the simplest cyclic ether, is an outstanding exception to the generalization that most ethers are resistant to cleavage. Like cyclopropane, the three-membered ring is highly strained and readily opens under mild conditions. Indeed, the importance of oxacyclopropane as an industrial chemical lies in its readiness to form other important compounds. The major products derived from it are shown in Figure 15-5. 

Recently, considerable interest has been shown in the photochemistry of a,/9-epoxyketones.16 Although the photochemistry of this system is undoubtedly the result of an n->ir excitation in the carbonyl function, the orbital overlap with the bent bonds of the three-membered ring, for which there is considerable evidence,16 is also implicated in the process. The major product of irradiation of an a,/8-epoxyketone is the corresponding /8-diketone, the result of oxirane ring cleavage and migration of a /9-substituent to the a-position [Eq. (3)]. Other photoproducts arise mainly from the /9-diketone. 

The parent saturated three-membered ring systems containing nitrogen, or oxygen, or sulphur as the heteroatom are known as aziridine (1), oxirane (2) and thiirane (3). 

Three membered rings are all strained and the parent systems may be endothermic (AH°f. cyclopropane 35 oxirane -78 aziridine 92 thiirane 52 kJ/mole). Some molecules with small distorted rings (of high strain energy) are explosively unstable. Individual entries are ... 

Oxetanes are generally much more stable to nucleophilic attack than the more strained three-membered ring oxiranes. However, activation of the oxygen atom by a Lewis acid increases the electronegativity of the adjacent carbon atom and renders oxetanes susceptible to attack from a nucleophile accompanied by subsequent ring opening. 

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