Base-Mediated Deuteration of Organic Molecules: A Mechanistic Insight

Abstract

A base-promoted, step-economical, and cost-effective strategy for introducing heavy isotopes into the organic molecules has been developed. The schemes involve the selective deuteration of various electronically distinct molecules that are formed because of deuterioamination, deuteriothiolation, deuteriophenoxylation, and deuterioalkoxylation as well as tandem cyclization using dimethyl sulfoxide (DMSO)-d 6 as a deuterium source. The reaction involves a metal-, ligand-, and additive-free route and provides a high level of deuterium incorporation in the presence of DMSO-d 6 as an inflammable and ecological reagent. The reaction is well tolerated across the electronically varied substrates for the successful incorporation of deuterium into the product. The proposed mechanistic pathway for various transformations has been well supported by NMR studies.

Potassium tert-butoxide promoted regioselective deuteration of pyridines

“…Although a dramatic retardation was observed, the reaction was not completely suppressed even at more than 5.0 equivalents of TEMPO. Then, we turned our attention to verifying the possibility of the carbanion pathway, 19 which had been studied kinetically in protic environments by This work suggested an acidic strength of 12 : 9.3 : 1.0 at the g-, b-, and a-positions on the pyridines, respectively. Thus, the substrate was treated with the in situ prepared dimsyl anion.…”

3D Printing to Increase the Flexibility of the Chemical Synthesis of Biologically Active Molecules: Design of On-Demand Gas Generation Reactors

“…Compared to the literature, one can easily highlight the advantages of atom-economic D-labeling through the use of C 2 D 2 . Alternative synthetic approaches to incorporate deuterium labels are based on base- or metal-catalyzed exchange reactions [ 81 , 82 , 83 , 84 , 85 , 86 ], D 2 -gas use [ 87 ], or previously labeled compounds [ 88 , 89 , 90 ]. Exchange reactions consume a significant amount of deuterated starting substrate when the desired product is mixed with a many-fold excess of a deuterated source several times [ 91 , 92 ].…”

Direct Synthesis of Deuterium-Labeled O-, S-, N-Vinyl Derivatives from Calcium Carbide

“…It is also consistent with the previous investigations where D-labeled alkenes and acetylenes were obtained through the treatment of the unlabeled ones with base-deuterated solvent mixtures. 20,30 A reverse D-H exchange process is also highly possible.…”

“…There are three general ways for alkenyl (vinyl) group deuterium labeling. The first one includes base- 20 or transition-metal-catalyzed 21 exchange reactions with the previously synthesized alkene and D 2 O, C 6 D 6 , or other deuterated reagent (Scheme 1, path a). The second method is a metalcatalyzed deuteration of alkynes with D 2 or H 2 -D 2 O mixture (Scheme 1, path b).…”