Recent Advances in Organocatalytic Methods for the Synthesis of Deuterated Aldehydes

Abstract

Formyl-selective deuteration of aldehydes is one of the important synthetic methods in the field of medicinal chemistry. Aldehyde-d is often used as an important building block for pharmaceutical and drug synthesis due to its versatile reactivity and applicability. Due to the recent interest and development in the use of deuterated pharma drugs, there is an urgent need for simple and practical synthetic methods that are effective in producing a broad range of highly deuterated (up to 99% D) functionalized aryl, heteroaryl, alkyl, and alkenyl aldehyde moieties. Organocatalytic processes mediated by NHC have recently been used to achieve selective deuterium labelling processes; this system is frequently used to analyze drug distribution, metabolism, absorption, and excretion (ADME). Moreover, deuterated pharmaceutical compounds are designed to develop therapeutic effectiveness and reduce significant side effects and toxicity by increasing the half-life of the isotope drug response. Remarkably, in 2019-2022, NHC-mediated various catalytic approaches have been dramatically developed. One such method is a practical and mild synthesis of functionalized deuterated aldehydes, drug molecules, therapeutic agents, small and complex natural products, and their analogues using a green method in the presence of water-d as a cheap reagent. These modern methods prepared deuterated drug scaffolds such as 3-formyl rifamycin, midecamycin, menthol, ibuprofen, naproxen, etc. In this concern, we could provide a succinct description of the NHC-organocatalyzed modern synthetic strategies, as well as a mild greener approach for the functional group-selective deuterium isotopic labeling of various formyl compounds using commercially available deuterium sources (D2O and CD3OD).