Noticeable difference in C-D and C-H bond strength is extensively used in various chemical and biomedical researches. The comparison of the C–H bond and C–D bond reactivity was applied in the study of reaction mechanisms [1]; the substitution of hydrogen by deuterium was also applied to alter the selectivity of the reactions [2] and for the management of pharmacoki¬netic profile of drugs [3]. The actual approvement of the first deuterated drug, deutetrabenazine [4], made the synthesis of new deuterated substances a demanded goal for organic and pharmaceutical chemistry.
The use of CaC2–D2O mixture for dideuteroacetylene generation in a two-chamber reactor (Scheme 1, path A) is a convenient synthetic path to D2-labeled pyrazoles [5], isoxazoles [6], triazoles, and pyridazines [7,8]. Reacting with alcohols, CaC2-H2O(D2O) mixture gives vinyl or trideuterovinyl ethers (Scheme 1, Path B) [9]. The latter can be applied as acetylene-D2 surrogates in [3+2] or [4+2] cycloaddition reactions leading to deuterated pyrazoles [9] or pyridazines (Scheme 1, Path B). A regioselective replacement of hydrogen to deuterium in vinyl ether allowed synthesis of a valuable building block, alkyl 1-deuterovinyl ether (Scheme 1, path C). The reaction of 1-deuterovinyl ether and nitrile imines was regioselective and led to 5-deuteropyrazoles in good to excellent yields [9].

References: [1] Shigenobu, M.; Takenaka, K.; Sasai, H. Angew. Chem., Int. Ed., 2015, 54, 9572.
[2] Miyashita, M.; Sasaki, M.; Hattori, I.; Sakai, M.; Tanino, K. Science, 2004, 305, 495.
[3] Harbeson, S. L.; Tung, R. D. Annu. Rep. Med. Chem., 2011, 46, 403.
[4] Mullard, A. Nat. Rev. Drug Discovery, 2017, 16, 305.
[5] Voronin, V.V.; Ledovskaya, M.S.; Gordeev, E.G.; Rodygin, K.S.; Ananikov V.P. J. Org. Chem., 2018, 83, 3819.
[6] Ledovskaya, M.S.; Rodygin, K.S.; Ananikov, V.P. Org. Chem. Front., 2018, 5, 226.
[7] Ledovskaya, M.S.; Voronin, V.V.; Rodygin, K.S.; Ananikov V.P. Org. Chem. Front., 2020, 7, 638.
[8] Ledovskaya, M.S.; Polynski, M.V.; Ananikov, V.P. Chem. Asian. J., 2021, Accepted Author Manuscript, DOI: 10.1002/asia.202100562.
[9] Ledovskaya, M.S.; Voronin, V.V.; Polynski, M.V.; Lebedev, A.N.; Ananikov, V.P. Eur. J. Org. Chem., 2020, 4571.