1,3-dipolar cycloaddition reactions aliphatic nitrile oxides

Diaz-Ortiz described the microwave-induced 1,3-dipolar cycloadditions of mesi-tonitrile oxide to aliphatic and aromatic nitriles under solvent-free conditions. The adducts were obtained in shorter reaction times and better yields than with classical methods [84]. By the same approach, Corsaro reported the successful cycloaddition of arylnitrile oxides to naphthalene or aromatic polycyclic dipolaro-philes under solvent-free microwave activation [85]. In the same report, the yields of bis-cycloadducts were also improved by microwave exposure [85]. 

Diaz-Ortiz described the microwave-induced 1,3-dipolar cycloadditions of the me-sitonitrile oxide 10 with aliphatic and aromatic nitriles in solvent-free conditions [99]. The procedure allowed the corresponding heterocyclic adducts, the 1,2,4-oxadia-zoles 187, to be obtained in a domestic oven. The reaction times were shorter and the yields better than those seen with the classical homogeneous reactions (Scheme 9.57). 

Aliphatic nitro compounds are versatile building blocks and intermediates in organic synthesis,14 15 cf. the overview given in the Organic Syntheses preparation of nitroacetaldehyde diethyl acetal.16 For example, Henry and Michael additions, respectively, lead to 1,2- and 1,4-difunctionalized derivatives.14 18 1,3-Difunctional compounds, such as amino alcohols or aldols are accessible from primary nitroalkanes by dehydration/1,3-dipolar nitrile oxide cycloaddition with olefins (Mukaiyama reaction),19 followed by ring cleavage of intermediate isoxazolines by reduction or reduction/hydrolysis.20 21... 

Carreira has demonstrated that the hydroxy-directed nitrile oxide cycloaddition reaction is a general synthetic approach to polyketide fragments, with the intermediate isoxazolines functioning as latent, masked aldol adducts [65], The 1,3-dipolar cycloadditions have been shown to tolerate a large variety of alcohol substrates, including aliphatic allylic, homoallylic, and cyclic allylic alcohols [65-67], A demonstration of the versatility of the approach was reported in the synthesis of erythronolide A (58, Scheme 18.12) [67], This synthetic effort took advantage of two sequential hydroxy-directed nitrile oxide cycloadditions to provide fragments 55 and 57, both of which were obtained with excellent yields and diastereoselectivity (dr2 98 2). 

The dipolar cycloaddition of nitrile oxides with species containing unsaturation is a very attractive means of forming crosslinks in polymer systems, since the reaction is rapid and yields thermally stable links. Latent nitrile oxide precursors can be prepared by reaction of an isocyanate and an alkyl nitroacetate. These precursors release alkanol and carbon dioxide when heated to liberate the highly reactive nitrile oxide species. An improved synthetic procedure is developed to afford novel crosslinking agents based on difunctional, trifunctional and aliphatic precursors. Application of these agents to polymer crosslinking is demonstrated. 9 refs. 

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