Photocatalytic Transition‐Metal‐Free Direct 3‐Acetalation of Quinoxaline‐2(1H)‐ones

Abstract

Comprehensive Summary A general transition‐metal‐free visible‐light‐promoted 3‐acetalation reaction of quinoxaline‐2(1H)‐ones was developed under mild conditions. By employing 1,2,3,5‐tetrakis(carbazol‐9‐yl)‐4,6‐dicyanobenzene (4CzIPN) as an inexpensive photocatalyst, and glyoxylic acid acetal as a radical source, various acetalated quinoxaline‐2(1H)‐ones were constructed in moderate to good yields. Moreover, the versatility of this protocol is highlighted by the successful application in the late‐stage modification of drug molecules and the various functionality transformations. The excellent antitumor activity of the acetalated product demonstrated that this streamlined and sustainable approach could have emerged as a powerful strategy for structural modification in medicinal chemistry.

Recent advances in the photocatalytic synthesis of aldehydes

“…In 2022, Yu et al developed a visible-light-induced 4CzIPN-catalyzed procedure for the direct decarboxylative acetalation of quinoxaline-2(1 H )-ones 37 and glyoxylic acid acetal 1 (Scheme 12). 36 Unlike those in the previous reports, this procedure is conducted under an air atmosphere and shows a broad substrate scope and excellent functional group tolerance. Importantly, this method is successfully applied in the late-stage modification of bioactive molecules.…”

Acetal Radicals: Synthetic Access and Applications

“…[25] It should be noted that the oxidation potentials of carboxylates are generally high (E pa [RCO 2 À / RCO * ] = + 1.1 to + 1.6 V vs SCE), and in turn require a highly oxidizing photocatalyst. [26] Decarboxylation strategies have been employed to access both cyclic and acyclic acetal radicals for the coupling into alkenes, [27][28][29] imines, [30] N-heterocycles, [12,31,32] and aryl halides [33] (Scheme 3). The acyclic diethoxy variant can be easily accessed from the hydrolysis of ethyl diethoxyacetate.…”

Solvent-Controllable C–F Bond Activation for Masked Formylation of α-Trifluoromethyl Alkenes via Organo-Photoredox Catalysis

“…In this scenario, diethoxy-acetic acid represents an outstanding delegate with broad synthetic applications. Since the pioneering work from Wang and co-workers, various alkenes including electron-deficient alkenes and styrenes were successfully hydroformylated to afford aliphatic aldehydes via decarboxylic functionalization of diethoxy-acetic acid . Notably, Wei and co-workers communicated the decarboxylative masked formylation reaction of α-trifluoromethyl alkenes with diethoxylacetic acid (Scheme d) .…”