Deuteration of Alkynes Based on DCL™
Background & Overview
Deuterated organic compounds are synthetically interesting and synthetically challenging chemical entities. Alkyne motifs are present in many natural products and drugs, and are not only widely used in chemical synthesis, live-cell imaging of drugs, biomolecules, and materials science, but are also frequently used as highly reliable probes in the study of chemical transformation mechanisms. Additional deuterated molecules can be synthesized based on deuterated alkynes, eg, deuterated alkynes are hydrogenated to yield cis- or trans-deuterated alkenes or deuterated alkanes. Or ring trimerization of deuterated alkynes to obtain deuterated aromatics. Among all deuterated molecules, alkynes are the most widely used substrates for the preparation of deuterated triazopiperazines using ephedrine. Therefore, the development of high-value protocols with excellent deuterium incorporation levels is of great importance to both academia and the biotechnology, pharmaceutical, analytical, pharmaceutical and agrochemical industries.
Existing Strategy for the Synthesis of Deuterated Alkynes
In general, deuterated alkynes are currently obtained by conventional organic synthesis and catalyzed isotope exchange synthesis. Terminal alkynes can be deuterated in heavy water using reusable basic resins. Using this method, various monoaryl and alkyl substituted alkynes incorporate quantitative deuterium by efficient deuteration.
Fig.1 Deuteration of terminal alkynes using a basic resin.[3]
The use of Ru(II) pincer complexes is also an efficient method for the synthesis of deuterated alkynes. This protocol shows good functional group tolerance, in the case of efficient deuteration of aliphatic terminal alkynes, the arene C–H bonds are not deuterated.
Fig.2 Ru-Catalysed mono-deuteration of terminal alkynes.[3]
Both acid-base-promoted H/D exchange and transition metal-catalyzed isotope exchange are costly, which means they are not commercially available. BOC Sciences has developed a selective and cost-effective platform for deuterium-labeled compounds.
DCL™ in Undirected Deuteration of Alkynes
Our DCL™ technology platform is applicable to a range of structurally diverse aliphatic, heterocyclic and heteroatom alkynes, providing quantitative yields and excellent deuterium incorporation levels in minutes. Deuteration of terminal alkynes can make them synthetically "attractive", especially for the synthesis of deuterated building blocks and drug-like molecules. Our technology provides an efficient route for the synthesis of labeled pharmaceutical compounds.
In conclusion, DCL™ is an extremely mild, general-purpose, extremely practical, inexpensive and environmentally friendly protocol for the efficient conversion of terminal alkynes to their deuterated analogs; does not use low temperature, anhydrous solvents or strong base; and is useful to organic, inorganic, medicinal and agricultural chemists, etc.
References
- Chatterjee B and Gunanathan C. The ruthenium-catalysed selective synthesis of mono-deuterated terminal alkynes. Chemical Communications. 2016, 52(24): 4509-4512.
- Kumar S, et al. Base-Catalyzed Selective Deuteration of Alkynes. Asian Journal of Organic Chemistry, 2021, 10(9): 2365-2369.
- Prakash G, et al. C-H deuteration of organic compounds and potential drug candidates[J]. Chemical Society Reviews. 2022.
Customer Intellectual Property Protection
BOC Sciences has always regarded intellectual property as the most valuable asset of the company and its customers. We have signed non-disclosure agreements with customers and employees before the project starts, and provide synthetic route design and synthesis services in strict accordance with the terms of the non-disclosure agreement, striving to provide customers with target compounds in the shortest time possible.
