Five-membered rings nitrile oxide intramolecular cycloadditions

An intramolecular nitrile oxide cycloaddition reaction of a 1,3-dioxolane monocyclic precursor provided the construction of the two five-membered rings of the isoxazoline (32), a precursor to prostaglandin F2a (Equation (12)) <84JOC230l>. 

The reaction forms the five-membered ring in a single step it is a cycloaddition, in which the alkyne is using its HOMO to attack the LUMO of the nitrile oxide (see Chapter 34 for an explanation). If the alkyne has an electron-withdrawing group, mixtures of isomers are usually formed as the HOMO of the nitrile oxide also attacks the LUMO of the alkyne. Intramolecular reactions are usually clean regardless of the preferred electronic orientation if... 

The use of diphenylmethylenecyclopropanes, as opposed to methylenecyclo-propanes, greatly enhances the Pd°-induced [3 + 2] cycloaddition with alkenes to produce five-membered rings. A one-carbon ring-contraction route to cyclopentanes involves a high-pressure version of the known 1,3-dipolar addition of azides to O-silylated enolates, which removes some of the previously observed steric limitations of the reaction, so that the adduct (47) fragments, as shown, to produce the ring-contracted product (48). The intramolecular nitrile oxide... 

A total synthesis of functionalized 8,14-seco steroids with five- and six-membered D rings has been developed (467). The synthesis is based on the transformation of (S)-carvone into a steroidal AB ring moiety with a side chain at C(9), which allows the creation of a nitrile oxide at this position. The nitrile oxides are coupled with cyclic enones or enol derivatives of 1,3-diketones, and reductive cleavage of the obtained cycloadducts give the desired products. The formation of a twelve-membered ring compound has been reported in the cycloaddition of one of the nitrile oxides with cyclopentenone and as the result of an intramolecular ene reaction, followed by retro-aldol reaction. 

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