Transition-Metal-Free, Selective Reductive Deuteration of Terminal Alkynes with Sodium Dispersions and EtOD-d₁

Abstract

A transition-metal-free single electron transfer reaction has been developed for the synthesis of [D]-alkenes from terminal alkynes using sodium dispersions as the electron donor and EtOD- d as the deuterium source. Both reagents are cost-effective and bench-stable. This practical method exhibits remarkable terminal alkyne selectivity and exclusive alkene selectivity. Excellent deuterium incorporations and yields were achieved across a broad range of terminal alkynes without olefin isomerization. Of note, this reaction is highly solvent dependent. n-Hexane provides unique enhancement to this reductive deuteration process.

Selective Transfer Semihydrogenation of Alkynes with H2O (D2O) as the H (D) Source over a Pd‐P Cathode

“…Thee asy and efficient access to deuterated alkenes was af ascinating application of our strategy.U sing D 2 Oa st he low-cost and safe deuterium source could bypass the tedious handling process of expensive and flammable D 2 gas and other toxic deuterated reagents. [20] This electrochemical semideuteration of alkynes proceeded efficiently with D 2 O to generate the desired deuterated alkenes in good yields with up to 99 %d euterium incorporation and 99 % Z selectivity (for internal alkenes;T able 2, 3i and 3j). Here,t he trideuterated (D 3 )t erminal alkenes,t he important building blocks for the construction of avariety of targeted deuterated compounds,could be expediently synthesized by the electrocatalytic semihydrogenation of unlabeled alkynes with D 2 O (3a-h).…”

Recent Advances in the Synthesis of Deuterium‐Labeled Compounds

“…To reduce the cost and increase the feasibility of these reactions, some researchers have combined in situ generation of D 2 from other deuterium sources for the deuteration of unsaturated bonds. Han et al [13] . used a sodium dispersion as the electron donor and EtOD‐ d 1 as the deuterium source to form D 2 , which then added into a triple carbon bond to form deuterium‐labeled olefin.…”

“…Deuterium‐labeled [D 3 ]‐alkenes are easily prepared from terminal alkynes in a single step; however, other alkynes hardly undergo addition reactions in this process (Figure 1). This selective addition leads to remarkable selectivity of terminal deuterated olefins [13] …”

Recent Advances in the Use of Sodium Dispersion for Organic Synthesis

“…The An group extended this methodology to the selective deuteration of terminal alkynes using sodium dispersion (particle size 5-10 µm) and ethanol-d1 (Scheme 15). 39 The choice of solvent was crucial for this reaction: in hexane, the reaction proceeded in quantitative yield (>98%), while the use of Et2O, THF, or toluene resulted in <5% yield. They explained that solvents with low dielectric constant such as hexane should facilitate the reaction through an inner-sphere electron transfer mechanism.…”