Base-catalysed condensation reactions of nitroacetic esters with dipolarophiles to give isoxazole derivatives proceed faster, and often with higher yields, in the presence of water than in organic solvents such as chloroform. Kinetic profiles show that induction times are greatly reduced when the reaction is performed "in water" or "on water". Any specificity of the base related to H-bonding ability observed in chloroform is lost in water: all bases either organic or inorganic give the same result that is simply depending on concentration. A 0.1 molar ratio of base to nucleophile gives the best conversion, whereas addition of one equivalent of base or strong acid prevents the reaction from occurring. These results fit into a reaction sequence in which reversible addition to a dipolarophile is followed by acid-catalysed irreversible dehydration of the cycloadduct. This is a remarkable example of a condensation reaction occurring in water because of irreversible acid-catalysed water elimination. The reaction has been successfully applied to dipolarophiles containing a wide variety of functional groups, including carboxylic acids and ammonium salts, under mild conditions. This new click-style reaction is expected to be compatible with biological environments.

1,4-Diazabicyclo[2.2.2]octane (DABCO) or other suitable Nbases cause primary activated nitro compounds to condense with alkenes to yield isoxazolines or with alkynes to give isoxazoles. As the molar ratio of the base with respect to the dipolarophile decreased, the reaction became slower, but the nitro compound became more resistant to hydrolytic cleavage. The best results were achieved with a molar ratio of base in the range of 0.05-0.1. The reactions were carried out in chloroform at 60°C; for ethyl nitroacetate and phenylnitromethane, ethanol at 80°C can be employed with better

Primary nitro compounds have not been employed as nitrile oxide precursors in reactions with active methylene compounds because the reagents commonly used as dehydrating agents also react with these dipolarophiles. However, the CuII‐catalysed cycloaddition/condensation procedure has been shown to be viable with these substrates, leading directly to the expected polyfunctional isoxazoles provided nitro compounds with enhanced acidity (“activated”) were used. In the absence of added dipolarophiles, these nitro compounds underwent self‐condensation to the corresponding furoxans. However, as well as 3,4‐dibenzoylfuroxan, benzoylnitromethane predominantly gave the isomer 3‐benzoyl‐4‐nitro‐5‐phenylisoxazole, the structure of which was confirmed by crystallographic analysis. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Ethyl nitroacetate (1) reacts with electron-poor olefins in the presence of a base to give either the Michael adducts 3 or the isoxazoline cycloadducts 4, resulting from water elimination. The proportions of the two products depend on the reaction conditions and change in the course of the process. Kinetic profiles for the two reactions show that the cycloaddition-condensations require long induction times that dramatically decrease upon addition of a copper salt to the catalytic system: the drops in the induction time cause increases in the proportion of cycloadducts 4, which are often the sole reaction products. This is the first report on the selective formation of products 3 and 4 from primary nitro compounds through modulation of the catalytic system.

Alkenes or alkynes bearing a wide variety of functional groups including carboxylic acids and ammonium salts are subjected to optimized conditions.