Synthesis of 3,4,5‐Trisubstituted Isoxazoles from Morita–Baylis–Hillman Acetates by an NaNO₂/I₂‐Mediated Domino Reaction

Abstract

An efficient NaNO2 /I2 -mediated one-pot transformation of Morita-Baylis-Hillman (MBH) acetates into alkyl 3-nitro-5-(aryl/alkyl)isoxazole-4-carboxylates is described. In a cascade event, initial Michael addition of NaNO2 to the MBH acetate furnishes the allylnitro intermediate which undergoes I2 -catalyzed oxidative α-CH nitration of the nitromethyl subunit followed by [3+2] cycloaddition to afford the title compounds. Structural elaborations of these highly substituted isoxazoles by SN Ar reactions and hydrogenolysis allows access to useful products.

Synthesis of N‐Heterocycles by Dehydrogenative Annulation of N‐Allyl Amides with 1,3‐Dicarbonyl Compounds

“…[18] Thereaction begins with the anodic oxidation of 3 (E p/2 = 0.52 Vv s. SCE) into the corresponding radical cation 3C + .Meanwhile,H 2 Oisreduced at the cathode to produce H 2 and HO À ,t he latter of which then deprotonates the 1,3-dicarbonyl compound I [E p/2 (2) > 2.0 Vv s. SCE] to generate the more oxidizable anion II (E p/2 = 0.31 Vv s. SCE, R = OMe). [24] Scheme 4. [24] Scheme 4.…”

Direct Transformation of Arylamines to Aryl Halides via Sodium Nitrite and N‐Halosuccinimide

“…We have been studying the applicationso fN aNO 2 and I 2 for preparing useful products in the realmso fs ynthetic chemistry. [12] During the course of one of our studiesr elated to metalfree oxidativen itrationo fa-carbont oc arbonyl in acetophenonesw ith NaNO 2 /I 2 ,w ed iscovered that the reaction of 4'aminoacetophenone insteado fp roducing the expected product, at hiohydroximic acid, afforded4 '-iodoacetophenone in 62 %y ield. [12c] This result suggested that 4'-aminoacetophenone underwent nucleophilics ubstitution of the aminog roup with I 2 rathert han nitration of the a-carbono ft he carbonyl group.…”

Applications of Sodium Nitrite in Organic Synthesis

“…Our group developed a NaNO 2 /I 2 ‐mediated one‐pot transformation of MBH acetates 90 to substituted 3‐nitroisoxazoles 91 (Scheme ) . The procedure that has broad substrate scope and is scalable, proceeds via a cascade process wherein Michael addition of NO 2 – onto MBH acetate 90 affords the allylnitro derivative LXX which transforms into LXXI by liberation of a proton (Scheme ).…”