Dienamine-Catalyzed Nitrone Formation via Redox Reaction

Abstract

The first catalytic method to directly introduce nitrone functionality onto aldehyde substrates is described. This reaction proceeds by an unprecedented organocatalytic redox mechanism in which an enal is oxidized to the γ-nitrone via dienamine catalysis, thereby reducing an equivalent of nitrosobenzene. This reaction is a unique example of divergent reactivity of an enal, which represents a novel strategy for rapidly accessing small libraries of N,O-heterocycles. Alternatively, divergent reactivity can be suppressed simply by changing solvents.

Old tricks, new dogs: organocatalytic dienamine activation of α,β-unsaturated aldehydes

“…Very recently, Brenner-Moyer and colleagues reported the first γ-site-selective catalytic reaction to directly introduce nitrone functionality to α,β-unsaturated aldehydes via dienamine intermediate S using catalyst 14 ( Scheme 17 ). 30 This work represents an unprecedented and useful example of an organocatalytic redox reaction, in which the alkyl and aryl substituted enal ( 65 ) is oxidized to the corresponding γ-nitrone ( 67 ) with moderate yields and diastereoselectivities, thereby reducing the corresponding nitrosoaryl derivative to N -arylhydroxylamine. Supported by experimental and theoretical studies, the authors proposed a plausible mechanism, in which the reaction starts with the condensation of the enal 65 with catalyst 14 , to form an iminium ion intermediate, which is in equilibrium with the dienamine intermediate ( S ) via the loss or gain of a proton.…”

Nitrone/Imine Selectivity Switch in Base‐Catalysed Reaction of Aryl Acetic Acid Esters with Nitrosoarenes: Joint Experimental and Computational Study

“…The feasibility of the enolate addition to the dimer of nitrosobenzene [27] was evaluated via the calculation of the electrofilicity index ω as proposed by Parr. [28] It was found that the monomer had ω = 1.99 eV, whereas the dimer had ω = 1.55 eV (M06-2X/6-311 + G(d,p) level).…”

“…[12] They proved to be useful in the Au/Ag-catalysed 1,2-iminonitronation of propargylic esters to give α-imidoyl nitrones (Scheme 1 B(i)), [13] or in the organocatalytic addition of the γ-nitrone group onto the α,β-unsaturated aldehydes (Scheme 1 B(ii)). [14] Interestingly, an umpo-lung strategy (Scheme 1 B(iii)), alternative to route A (i), has been devised using α-keto methyl esters under stoichiometric amounts of phosphines to produce ketonitrones. [15] The latter are versatile building blocks to prepare imines, fumarates and isoxazolines.…”

“…A less explored approach to nitrones involves the use of nitrosoarenes as the reagents, a class of versatile and readily available electrophiles [12] . They proved to be useful in the Au/Ag‐catalysed 1,2‐iminonitronation of propargylic esters to give α‐imidoyl nitrones (Scheme 1 B(i)), [13] or in the organocatalytic addition of the γ‐nitrone group onto the α,β‐unsaturated aldehydes (Scheme 1 B(ii)) [14] . Interestingly, an umpolung strategy (Scheme 1 B(iii)), alternative to route A(i), has been devised using α‐keto methyl esters under stoichiometric amounts of phosphines to produce ketonitrones [15] .…”

Visible-light-promoted nitrone synthesis from nitrosoarenes under catalyst- and additive-free conditions

“…Recently, Lattanzi and Mazzanti et al developed the constructed arylnitrones from aryl acetates and nitrosoarenes in the presence of catalytic amount of 2-tert-butylimino-2-diethylamino-1,3-dimethylperhydro-,3,2-diazaphosphorine (BEMP) as catalyst (Scheme 1b) [30]. Moreover, other types of nitrone construction from nitrosoarenes using transition metal-and dienamine catalytic strategy have also be realized [31][32][33][34][35][36][37][38]. Despite these elegant progresses, to the best of our knowledge, catalyst and additive-free synthesis of nitrones from nitrosoarenes has not yet been discovered.…”