An Unprecedented Organocascade Synthesis of Functionalized Bicyclic Nitrones from 2‐Aminomalonate Derived Nucleophiles and 1‐Nitro‐1,3‐Enynes via Allenes Formation and Subsequent Rearrangement

Abstract

An efficient organocatalytic cascade reaction for synthesising functionalized bicyclic nitrones is reported. The reaction of dielectrophilic ethyl 2-(nitromethylene)-4-arylbut-3-ynoate and (E)-diethyl 2-((2hydroxybenzylidene)-amino)malonates to give a unique nitrone scaffold in the presence of a catalytic amount of DABCO is described. The working mechanism was proposed to proceed with allene formation followed by intramolecular cyclization and the rearrangement of an oxygen atom in the nitro group. A broad range of substrates was accessed in this facile chemical transformation, in which the bicyclic nitrones were isolated in moderate to good yields (19% to 79%) with excellent diastereoselectivity (> 20:1 dr).

Oxaazabicyclooctene Oxides, Another Type of Bridgehead Nitrones: Diastereoselective Assembly from Acetylene Gas, Ketones, and Hydroxyl Amine

“…11 Recently, a synthesis of bicyclic nitrones from iminomalonate derivatives and 1-nitro-1,3enynes in the presence of DABCO has been published. 12 Despite the efforts directed to preparation of nitrones, the chemistry and application of this important class of compounds still requires invention of more original synthetic approaches. Among the suitable materials for the design of functionalized nitrones of special complexity, acetylene gas might occupy a prominent place.…”

“…To access cyclic nitrones, the oxidation of cyclic amines or hydroxylamines, , intramolecular condensation of hydroxylamino-carbonyl derivatives, , and cyclizations of unsaturated oximes are employed . Recently, a synthesis of bicyclic nitrones from iminomalonate derivatives and 1-nitro-1,3-enynes in the presence of DABCO has been published …”

Palladium-Catalyzed Formal (3 + 2) Cycloaddition Reactions of 2-Nitro-1,3-enynes with Vinylaziridines, -epoxides, and -cyclopropanes

“…Related to nitroalkenes, 2-nitro-1,3-enyne substrates 5 are a valuable class of electron-deficient unsaturated reactants that have proven to be excellent Michael acceptors. − To date, they have not been shown to undergo (3 + 2) cycloaddition reactions with Pd-stabilized zwitterionic dipoles. It was speculated that they could act as partners in Pd-catalyzed (3 + 2) cycloadditions with vinylaziridines, vinylepoxides, and vinylcyclopropanes, given that these processes proceed via an initial Michael-type attack by a Pd-stabilized zwitterionic dipole.…”