Publisher Summary This chapter presents the syntheses and reactions of five-membered heterocyclic ring systems containing oxygen and nitrogen atoms. The use of primary nitroalkanes as nitrile oxide precursors in 1,3-dipolar cycloadditions (1,3-DCs) with active methylene compounds is precluded because of competitive interactions between the commonly used dehydrating agents and enolic dipolarophiles. On the other hand, the treatment of activated nitro compounds and dipolarophiles with tertiary amines, such as N-methylpiperidine (NMP), in the presence of a Cu(II) salt did allow the synthesis of highly functionalized isoxazoles by cycloaddition/condensation reactions. A solid-phase nitrile oxide-alkyne click reaction is used to form isoxazole conjugated oligonucleotides. The Mg(II)-mediated, hydroxyl-directed nitrile oxide cycloaddition to allyl alcohols is used for the production of dipolarophiles, such as homoallylic alcohols and monoprotected homoallylic diols. The process is anti-diastereoselective and can be used to synthesize a variety of isoxazolines as polyketide building blocks.