Optimizing the Synthesis of Deuterated Isotopomers and Isotopologues of Cyclohexene using Molecular Rotational Resonance Spectroscopy

Despite advances in reactions such as hydrogen isotope
exchange
(HIE) and reductive deuteration, achieving controlled and selective
deuteration remains challenging. Moreover, the difficulty of developing
successful deuteration platforms is compounded by a lack of means
to assess the stereoisotopic purity of deuterated products. We previously
reported a highly regio- and stereoselective approach for generating
semideuterated cyclohexenes via tandem protonation (H+/D+) and reduction (H–/D–) sequences of a dihapto-coordinate tungsten-benzene complex. While
NMR and HRMS analyses suggested successful deuterium incorporation,
molecular rotational resonance (MRR) spectroscopy identified numerous
over-, under-, and mis-deuteration impurities. At the time of publication,
these impurities were attributed to H/D scrambling that could occur
during thermolysis of the tungsten-bound cyclohexene ligand prior
to MRR analysis. In this work, we describe the analysis of semideuterated
cyclohexenes using MRR spectroscopy with an improved thermolysis apparatus
that eliminates deuterium scrambling during analysis. Quantitative
analysis of both racemic and enantiopure samples enables the optimization
of deuteration conditions by providing multiple mechanistic insights
into the formation of impurities.