Project Summary The frustrating complexity of deuteration chemistry, a very limited number of deuterated building blocks available and high cost of making them hamper access to highly sought deuterated bioactive molecules. Therefore, practical synthesis of versatile deuterated building blocks and `privileged' structures will facilitate the construction of deuterated molecules of interest for their biological studies and drug discovery. We wish to develop a new aminocatalytic activation mode termed `ammonium catalysis' for deuterated molecule synthesis. We challenge the dogma of amine moieties in adducts resulting from nucleophilic additions to iminum ions can serve as leaving groups in ensuing reactions. In situ release of the presumed amine from the addition products will create a new scenario for aminocatalytic direct functionalization of aldehydes. It will be demonstrate that a number of unprecedented efficient catalytic cascade reactions will be realized by the new organic catalysts and new reactivities. These cascade processes produce a fascinating array of highly valued novel complex `privileged' benzopyrans and hydroquinolines with regioselective incorporation of deuterium at metabolically labile sites. In addition, the first binary photo- and organo-catalytic formylation reaction and NHC carbene promoted H/D exchange process with simple non-deuterated aldehydes will be developed for low cost synthesis of fundamentally important deuterated aldehydes and enals. Furthermore, practical chiral amine-catalyzed enantioselective H/D exchange-α-functionalization cascade reactions for synthesis of chiral deuterated highly valued building blocks such as (amino)sugars, amino acids, alcohols, amines etc. will be developed. Finally, new trimethylsulfoxonium iodide promoted CH3/CD3 exchange reactions for synthesis of synthetically and medicinally valued deuterated methyl, cyclopropanes, epoxides, aziridines and therapeutics will be accomplished. These deuterated building blocks and molecular architectures and drugs serve as valuable tools for biomedical researchers to use for biomolecule constructions and biological and drug discovery studies.