Visible-Light Photoredox-Catalyzed Decarboxylation of α-Oxo Carboxylic Acids to C1-Deuterated Aldehydes and Aldehydes

Abstract

The synthesis of high-value-added C1-deuterated aldehydes would improve the availability of deuterated lead compounds for deuterium-labeled drug discovery. Herein, we develop a metal-free synthesis of C1-deuterated aldehydes with D2O from α-oxo carboxylic acids at ambient temperature. Via visible-light photoredox-catalyzed decarboxylation, stoichiometric reductants and oxidants were avoided. Various functional groups were tolerated and resulted in C1-deuterium aldehydes in up to 92% yield and 91–97% D incorporation under mild conditions. This method is also applied to the synthesis of various aldehydes. Primary mechanistic studies indicate that the catalytic pathway occurs via a reductive quenching pathway followed by hydrogen atom transfer.

Isocyanides as Catalytic Electron Acceptors in the Visible Light Promoted Oxidative Formation of Benzyl and Acyl Radicals

“…The hydrogen atom source was identified via formation of the labelled 20-D (87 % yield, 98 % deuteration) when water was replaced by deuterium oxide (D 2 O, Scheme 7a). [46] The high percentage of deuterium labeling led to exclude the role of TIS as a hydrogen atom donor.…”

Synthesis and Spectroscopic Characterization of Furan-2-Carbaldehyde-d

“…Hence, deuteration is an important research issue in medicinal chemistry as well [10,11]. In addition, 2 H-, and even 14 C-and 18 Oisotope derivatives of furfural, especially of the aldehyde group, have been synthesized before [10,12]. As early as 1973, D.J.…”

“…More recently, two methods for the direct H/D exchange via a photo-redox reaction or an N-heterocyclic carbene (NHC) catalyzed reaction were described. The scope of these methods includes a wide range of aldehyde substrates, but furfural (2) is missing in both cases [18,19]. Shinada et al summarized methods for the formation of deuterated aldehydes [20], but they did not mention a straightforward synthesis for 1.…”

Photosynthesis of C-1-Deuterated Aldehydes via Chlorine Radical-Mediated Selective Deuteration of the Formyl C–H Bond

“…The rapid growth of deuterated drug research has stimulated the development of practical and reliable methodologies for constructing deuterated drugs and their key building blocks. , Aldehydes not only are widely present in natural products and drug molecules but also play a pivotal role in chemical and pharmaceutical synthesis, often termed the “transit station” of organic transformations . Therefore, significant effort has been invested in the effective and practical production of C-1-deuterated aldehydes, , where hydrogen–deuterium exchange (HDE) of aldehydes is the ideal approach owing to its high synthesis efficiency. Currently, there are four mainly catalytic systems for activating the C–H bond of aldehydes to enable HDE.…”