Photo‐Induced Functionalization of para‐Benzoquinones: Access to Dihydroquinoxalines with a Tetrasubstituted Carbon Stereocenter

Abstract

Visible light induced activation of para‐benzoquinone, and its sequential coupling with alkynes and ortho‐phenylenediamines/ortho‐aminophenols is reported. The protocol provides a route for synthesizing value‐added quinoxaline derivatives with tetrasubstituted carbon stereocenter at room temperature in 36–75% yields. Mechanistic investigation suggests that the reaction proceeds via in‐situ generation of para‐quinone methide through direct excitation of para‐benzoquinone in blue light.

Catalytic vs. uncatalyzed [2 + 2] photocycloadditions of quinones with alkynes

“…We believed that the electron-withdrawing effect of the exocyclic carbonyl group in the expected products would benefit their stability and avoid the introduction of bulky stabilizing groups ( i.e. aryl and tert -butyl 7,15 ), which may not be desired in further synthetic applications. First, a model reaction between p -benzoquinone and diphenylacetylene in acetonitrile under irradiation with blue light-emitting diodes (LEDs) showed that p -QM 1a can be obtained in 82% isolated yield (Scheme 2).…”

“…The synthesis of cyclobutenes by [2 + 2] photocycloaddition of quinones with alkynes does not typically require any additional reagents, 7,10,15 although trifluoroacetic acid and potassium persulfate were recently reported as necessary additives for certain transformations of this type. 12 To evaluate the role of these reagents, we first attempted to perform [2 + 2] cycloadditions between such quinones and alkynes by the action of blue light alone (Scheme 3).…”

“…Recent studies have shown that [2 + 2] photocycloadditions of quinines with alkynes can work in tandem with catalytic 1,6-conjugate addition of nucleophiles to the in situ formed p -QMs. 15 To address the less studied uncatalyzed addition, we first performed reactions of p -QM 1a with carbon and heteroatom nucleophiles under catalyst-free conditions (Scheme 4). Thus, 1,6-conjugate addition of thiophenol and aniline proceeded rapidly at room temperature even in the absence of Zn(OTf) 2 , 15 a providing adducts 3a , its benzo analogue 3b , and 3c in high yields ( 3c was found to be unstable and isolated as the O -acetate derivative 3c′ ).…”

“…Over the past decade, several catalytic photoreactions involving quinones and alkynes have been developed, enabling the synthesis of structurally diverse products: aryl ketones, 11,12 indoles, 13 naphthofurans 14 and various carbonyl compounds with a sterically hindered quaternary stereocenter in the α-position. 15 Given that these photocatalytic methods have already demonstrated high potential in diversity-oriented synthesis and target-oriented synthesis aimed at pharmaceuticals and their precursors, the development of purely photochemical versions of such processes may help to minimize the generated waste, synthesis costs, and the risks associated with product contamination by transition metals. To achieve this, some of the aforementioned catalytic transformations relied on uncatalyzed photointeraction between quinones and alkynes to generate p -QMs as intermediates, 15 although the subsequent uncatalyzed reactions with nucleophiles were found problematic.…”

“…15 Given that these photocatalytic methods have already demonstrated high potential in diversity-oriented synthesis and target-oriented synthesis aimed at pharmaceuticals and their precursors, the development of purely photochemical versions of such processes may help to minimize the generated waste, synthesis costs, and the risks associated with product contamination by transition metals. To achieve this, some of the aforementioned catalytic transformations relied on uncatalyzed photointeraction between quinones and alkynes to generate p -QMs as intermediates, 15 although the subsequent uncatalyzed reactions with nucleophiles were found problematic. 15 a , e , f However, other reports excluded 12,13 or did not consider 11,14 such an interaction as part of the primary or secondary reaction pathway.…”