α,β-Deuterated amines
are crucial for the development
of deuterated drugs. We intend to introduce the novel tandem H/D exchange-single
electron transfer (SET) reductive deuteration strategy with high pot-
and reagent-economy by the synthesis of α,β-deuterated
amine using nitrile as the precursor. The H/D exchange of the −CH2CN group was achieved by D2O/Et3N, which
were also the required reagents in the tandem SmI2-mediated
SET reductive deuteration of the α-deuterated nitrile. The potential
application of this method was further showcased by the synthesis
of bevantolol-d
4.
We discovered that highly regioselective H/D exchange can be achieved on the α-position of the pentafluorophenyl (Pfp) ester using Et 3 N as the catalyst and D 2 O as the deuterium source. Our computational and experimental results showed that the Pfp group can significantly increase the acidity of the α-hydrogen of the ester. This mild reaction condition tolerated a variety of functional groups. 90% ~98% yields and 91% 98% deuterium incorporations were obtained with all the tested Pfp esters. Taking advantage of the high reactivity of Pfp esters, a series of valuable α-deuterio carboxylic acid derivatives, including herbicide, drugs and drug intermediates, have been synthesized using α-deuterio Pfp esters as precursors.
Deuterated polymers have wild applications but limited synthetic methods. In this study, we report an efficient two-step approach for the synthesis of deuterated polyesters and polyurethanes. Firstly, two practical single electron transfer (SET) reductive deuteration methods have been developed for site-selective introduction of C(sp3)–D into diol monomers. 9 deuterated diol monomers with high deuterium incorporations were synthesized under SmI2-D2O and/or Na-EtOD-d
1 SET reductive deuteration conditions. Then, 6 typical deuterated polyesters and polyurethanes were synthesized using those deuterated monomers under typical polymerization conditions. In all the synthesized polymers, high deuterium incorporation was fully maintained, which showcased the potential application of this approach for the synthesis of polymers with site-specific deuterium labelling.
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