Michael Additions versus Cycloaddition Condensations with Ethyl Nitroacetate and Electron‐Deficient Olefins

Abstract

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.

Acid–Base‐Catalysed Condensation Reaction in Water: Isoxazolines and Isoxazoles from Nitroacetates and Dipolarophiles

“…* Heating the reaction mixture is favourable for the condensation reaction, particularly when this reaction is in competition with the conjugate addition. [31] This suggests that the release of the water is the rate-determining step and not the cycloaddition. However, at 100 8C the decomposition of nitroacetate is detrimental.…”

“…(2)]. [26][27][28][29][30][31] Whereas the former method requires anhydrous conditions and dehydrating reagents in stoichiometric amounts, [32,33] the latter condensation reaction in chloroform relies on the acid-catalysed deAbstract: 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".…”

Reactivity of [60]Fullerene with Primary Nitro Compounds: Addition or Catalysed Condensation to Isoxazolo[60]fullerenes

“…We have previously shown that compounds containing electron‐deficient double bonds, on treatment with “active” primary nitro compounds (i.e., bearing an EWG geminal to the nitro group) in chloroform, undergo either cycloaddition/condensation to give isoxazole derivatives 2 or conjugate addition to yield 3 , depending on the catalyst employed and the Michael acceptor (Scheme ) 29…”

“…Nitroalkanes did not react under these conditions. However, we have previously shown that on addition of a Cu II salt to the base, the cycloaddition/condensation predominated in chloroform and not only active nitro compounds but also nitroalkanes underwent condensation selectively 29,30. Their reactions in various solvents with catalytic Cu II are reported in Table 2.…”

Base‐ and Copper‐Catalysed Condensation of Primary Activated Nitro Compounds with Enolisable Compounds

“…Nitro compounds with enhanced acidity and dipolarophiles condense to form the product by organocatalysis. [20][21][22][23] 1,4-Diazabicyclo[2.2.2]octane (DABCO) gives the best results if used alone, but the reaction becomes faster on addition of a Cu II salt. With a Cu II salt, other tertiary amines like triethylamine (TEA) or N-methylpiperidine (NMP) appear to be more suitable and cycloaddition/condensation reactions occur even with nitroalkanes.…”