Acid-catalyzed nitronate cycloaddition reactions. Useful syntheses and simple transformations of 3-acyl- and 3-alkenylisoxazolines

Abstract

Nitronic esters derived from primary nitro ketones, ethyl nitroacetate, and (phenylsulfonyl)nitromethane react with dipolarophiles in the presence of nonaqueous protic and Lewis acids to give nitrile oxide cycloadducts. a-Nitro ketones, ethyl nitroacetate, and (phenylsulfonyl)nitromethane give nitrile oxide cycloadducts in the presence of p-toluenesulfonic acid, although conditions are necessarily more vigorous. The anions of phenylnitromethane and 1-nitropropane react similarly under mild conditions, the latter in poor yield. The methyl nitronic ester of (phenylsulfonyl)nitromethane undergoes direct cycloaddition to 1-hexene in neutral media to give diastereomeric isoxazolidines. 3-(a-Hydroxyalkyl)isoxazolines are readily prepared by reduction of 3-carbethoxyisoxazolines with sodium borohydride and by carbonyl addition to 3-acylisoxazolines with alkyllithium reagents. 3-Alkenylisoxazolines, which can be prepared from either 3-(hydroxyalkyl)isoxazolines or 3-sulfonylisoxazolines, undergo reversible [4 + 2]-cycloaddition with tetracyanoethylene.The diverse reactions of nitro compounds, nitronate salts, and nitronic esters with aqueous acid have been under study for over a century.1 Aldehydes and ketones are most commonly obtained (the Nef reaction). Under strongly acidic conditions, hydroxamic acids are formed instead; these may further hydrolyze to carboxylic acids and hydroxylamine (the Meyer reaction). Hydroxamic acid formation has been shown to proceed through hydrolysis of a nitrile oxide intermediate.2 Surprisingly little synthetic use has been made of this demonstration. Furoxans (1,2,5-oxadiazole 2-oxides) have been prepared from several nitro compounds under strongly acidic conditions,3 but extensive studies of nitrile oxide cycloadditions to added dipolarophiles are conspicuously lacking.

1,4‐Diazabicyclo[2.2.2]octane (DABCO) as an Efficient Reagent for the Synthesis of Isoxazole Derivatives from Primary Nitro Compounds and Dipolarophiles: The Role of the Base

“…The enhanced reactivity of 1a and 1b compared to nitro compounds 1c, 1d and 1f has already been noticed and is related to the ability of the carbonyl group to enolize. [51] Phenylsulfonylnitromethane (1d) appears particularly sluggish in this reaction.…”

1,2,5‐Oxadiazole (Furazan) Derivatives from Benzoylnitromethane and Dipolarophiles in the Presence of DABCO: Structure and Intermediates

“…We therefore prepared this com- pound from benzoylnitromethane (1) following a literature procedure [14] and submitted it to the same reaction conditions (DABCO, water and chloroform at 60°C). Without the dipolarophile, benzoic acid was the sole identified product, whereas in the presence of the dipolarophiles norbornene (2a), styrene (2b) or phenylacetylene (2c) furoxan 7 was mainly converted into the furazans 5a (70 %) 5b (50 %), and 5c (41 %), respectively.…”

Formation of isoxazole derivatives via nitrile oxide using ammonium cerium nitrate (CAN): a novel one-pot synthesis of 3-acetyl- and 3-benzoylisoxazole derivatives

“…Wade and co-workers 26 reported that acid-catalyzed nitronate cycloaddition reactions gave 4,5-dihydroisoxazole and isoxazole derivatives from nitro compounds and dipolarophiles. In this reaction, nitronic esters were transformed from primary nitro ketones in the presence of nonaqueous protonic and Lewis acids or a strong acid.…”