Photocatalytic Decarboxylative Reduction of Carboxylic Acids and Its Application in Asymmetric Synthesis

Abstract

The decarboxylative reduction of naturally abundant carboxylic acids such as α-amino acids and α-hydroxy acids has been achieved via visible-light photoredox catalysis. By using an organocatalytic photoredox system, this method offers a mild and rapid entry to a variety of high-value compounds including medicinally relevant scaffolds. Regioselective decarboxylation is achieved when differently substituted dicarboxylic acids are employed. The application of this method to the synthesis of enantioenriched 1-aryl-2,2,2-trifluoroethyl chiral amines starting from natural α-amino acids further testifies to the utility of the developed photocatalytic decarboxylative reduction protocol.

Hydrodecarboxylation of Carboxylic and Malonic Acid Derivatives via Organic Photoredox Catalysis: Substrate Scope and Mechanistic Insight

“…Wallentin et al have also demonstrated the ability for an acridinium photooxidant to decarboxylate protected amino acids and phenyl acetic acid derivatives in dichloroethane, but alkyl-substituted acids were not possible. 24 …”

“…22–24 These methods often utilize stoichiometric amounts of a terminal oxidant and hydrogen atom donor. 22,23 …”

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

“…Wallentin and co-workers have described a method for the reductive decarboxylation of amino acids, using bis(4-chlorophenyl)disulfide (empirical name – dichlorodiphenyl disulfide, abbreviated as DDDS), 2,6-lutidine and acridinium salts under blue LED irradiation, providing access to precious, non-commercially available and multifunctional amine building blocks in one step (Scheme 2) [40]. …”

Facile Preparation of Peptides with C-Terminal <i>N</i>-Alkylamide <i>via</i> Radical-Initiated Dethiocarboxylation

“…However, this protocol requires protecting almost all of the reactive functional groups present on the substrates, except for the C-terminal carboxylic acid, followed by the deprotection of those groups after the condensation. Yoshimi and colleagues 9) and several others [10][11][12] recently reported a new off-resin protocol for converting side-chain-protected peptides to the corresponding peptide alkylamides via a photo-induced radical decarboxylation reaction (Chart 1D). However, these methods require the protection of the non-C-terminal side-chains to avoid the occurrence of decarboxylation and photo-induced side reactions.…”

“…19) We synthesized derivatives of N-terminal human RFamide-related peptide-1 (hRFRP-1) (1-11) 21) consisting of non-protected residues, some of which are not compatible with previous methods. [9][10][11][12] The radical dethiocarboxylation of peptide thioacid 5a was initially investigated under the reaction conditions typically used for the desulfurization of a cysteine residue. The progress of this reaction was monitored by HPLC (Fig.…”