A highly selective decarboxylative deuteration of carboxylic acids

Abstract

In this paper, we report a moderate and practical method for precise deuteration of aliphatic carboxylic acids by synergistic photoredox and HAT catalysis. The reaction delivers excellent D-incorporation (up to...

Technological Innovations in Photochemistry for Organic Synthesis: Flow Chemistry, High-Throughput Experimentation, Scale-up, and Photoelectrochemistry

“…The incorporation of deuterium atoms into organic compounds is a field of increased interest, where methods providing high selectivity and high deuterium incorporation are especially valued. 615 The photocatalytic decarboxylative deuteration method, developed by Zhu et al, 616 fulfills the requirements of high selectivity, high D-incorporation, broad functional group tolerance, and importantly, easy scalability in flow. A batch protocol was first developed, with D 2 O as deuterium source and thiol as hydrogen atom transfer catalyst.…”

Radical deuteration

“…In 2019, Glorius et al 29 Despite their significance, the deuteration of oxime esters is atom uneconomical, and the development of the photocatalytic direct decarboxylative deuteration was still highly desired. In 2021, Zhu et al 30 described a scalable, practical and sitespecific deuteration of aliphatic carboxylic acids by dual photoredox and thiol catalysis. In this protocol, benzylic and a-heteroatom carboxylic acids (101) realized the direct decarboxylative deuteration by employing Mes-Acr-Me as the photocatalyst, 2,4,6-collidine as the base and TRIP thiol as the HAT catalyst.…”

Highly selective single and multiple deuteration of unactivated C(sp3)-H bonds

“…Then the hydrogen atom of the remote C(sp 3 )-H is transferred to the N-radical and a carbon-centered radical ( 11 ) is produced via a six-membered ring intermediate ( 10 ). In a HAT catalytic cycle analogous to our previous work 16 , 17 , RSD is generated in-situ from RSH and excess D 2 O as a result of the distinction in the pK a values. Subsequently, the nucleophilic alkyl radical ( 11 ) undergoes deuterium atom transfer (DAT) from RS-D, furnishing the desired product ( 3c ).…”

“…As the use of strong base KO t Bu failed in this deuteration reaction, we exclude the deprotonation-electron transfer pathway 33 and a plausible mechanism based on our previous work on synergistic catalyzed deuteration 16 , 17 , 45 – 53 is proposed in Fig. 5 .…”