Application of deuterated THENA for assigning the absolute configuration of chiral secondary alcohols

Abstract

The structure of a constrained bicyclic CDA, 1,2,3,4-tetrahydro-1,4-epoxynaphthalene-1-carboxylic acid, THENA 1, was modified by replacing both exo-methylene protons with deuterium atoms. The modified CDA, THENA-d2 2, was successfully prepared and could be used to assign the absolute configuration of chiral secondary alcohols with good reliability. Compared with THENA, the multiplicity of the methylene proton signals in the 1H NMR spectra of THENA-d2 derivatives is less complicated and the new CDA thus offers simpler NMR spectra for data interpretation.

Recent Developments for the Deuterium and Tritium Labeling of Organic Molecules

“…A straightforward way to add deuterium atoms onto olefins relies simply on switching from gaseous hydrogen to gaseous deuterium (Scheme ). For instance, supported palladium on carbon was utilized in the synthesis of a bicyclic chiral derivatization agent . Similarly, an α,β-unsaturated ketone was deuterated with nickel boride during the synthesis of cis -perhydroazulene- d 1 .…”

“…For instance, supported palladium on carbon was utilized in the synthesis of a bicyclic chiral derivatization agent. 371 Similarly, an α,β-unsaturated ketone was deuterated with nickel boride during the synthesis of cis-perhydroazulene-d 1 . 372 From a homogeneous catalysis point of view, the Wilkinson catalyst has been applied in the synthesis of d 2 -amlexanox for the purpose of metabolic studies.…”

Deuteriodifluoromethylation and gem‐Difluoroalkenylation of Aldehydes Using ClCF2H in Continuous Flow

“…[1] In particular,the difluoromethyl group (CF 2 H) is al ipophilic hydrogen bond donor that can serve as ametabolically stable bioisostere for thiols,a lcohols and amines. [2] Deuteration is also an efficient tool to optimize drug pharmacokinetics, [1a, 3] and has widespread applications in organic synthesis, [4] structure determination, [5] mechanistic investigations, [6] and quantitative analyses. [7] Deutetrabenazine (Austedo) is the first deuterated drug to be approved by the U.S. Food and Drug Administration (FDA) in 2017 to treat both tardive dyskinesia and Huntingtonsd isease chorea (Figure 1a).…”