Base‐Catalyzed Selective Deuteration of Alkynes

Abstract

Deuteration of organic molecules has gained considerable importance in medicinal chemistry. A mild concept of inducing 2H isotope stoichiometrically into terminal alkynes was developed in KOH‐DMSO‐d6 medium. The four pairs of substrate scopes, namely aromatic, aliphatic, dialkynes, and alcohol/amine‐substituted alkyne were readily switchable from hydrogen to deuterium. Mild reaction condition, no requirement of column chromatography; environment‐friendly nature of the protocol increases the synthetic utility of the developed chemistry. The procedure avoids the use of expensive transition‐metal catalysts and should find attention in academia as well as in pharmaceuticals.

Recent Developments for the Deuterium and Tritium Labeling of Organic Molecules

“…Besides, another base-catalyzed methodology using catalytic amounts of potassium hydroxide along with deuterated DMSO as deuterium source was published more recently and can be considered for the fast introduction of deuterium labels in alkynes under mild conditions …”

Alkali-metal bases in catalytic hydrogen isotope exchange processes

“…dihydroxylation, cyclopropanation and hydroamination). Related deuteroalkoxylation and deuteroamination of alkynes have also been reported with KO t Bu in DMSO- d 6 , 19 where the deuteration of the acidic terminal position of the alkyne 20 is combined with the addition across the triple bond of the alkoxide to prepare the corresponding deuterated vinyl ethers or amines.…”

Graphene Oxide Membrane Reactor for Electrochemical Deuteration Reactions

“…Substituted C–H bonds with heavier C–D bonds are in great demand in the pharmaceutical industry because drug molecules with C–D bonds exhibit improved stability against metabolic cleavage. Hydrogen–deuterium (H–D) substitution has received considerable attention since the U.S. Food and Drug Administration confirmed in 2017 the use of a deuterated drug, deuterobenazine (Austedo), for treating chorea associated with Huntington’s disease and tardive dyskinesia. − Deuterium-labeled alkynes, − alkenes, , alkanes, , amines, , and ketones are valuable in the biotechnology, pharmaceutical, and medical chemistry industries . Therefore, there is an urgent need to innovate new routes to produce various deuterium-labeled compounds with excellent efficiency.…”