NMR and Computational Studies of the Configurational Properties of Spirodioxyselenuranes. Are Dynamic Exchange Processes or Temperature-Dependent Chemical Shifts Involved?

Abstract

Spirodioxyselenurane 4a and several substituted analogs revealed unexpected (1)H NMR behavior. The diastereotopic methylene hydrogens of 4a appeared as an AB quartet at low temperature that coalesced to a singlet upon warming to 267 K, suggesting a dynamic exchange process with a relatively low activation energy. However, DFT computational investigations indicated high activation energies for exchange via inversion through the selenium center and for various pseudorotation processes. Moreover, the NMR behavior was unaffected by the presence of water or acid catalysts, thereby ruling out reversible Se-O or benzylic C-O cleavage as possible stereomutation pathways. Remarkably, when 4a was heated beyond 342 K, the singlet was transformed into a new AB quartet. Further computations indicated that a temperature dependence of the chemical shifts of the diastereotopic protons results in convergence upon heating, followed by crossover and divergence at still higher temperatures. The NMR behavior is therefore not due to dynamic exchange processes, but rather to temperature dependence of the chemical shifts of the diastereotopic hydrogens, which are coincidentally equivalent at intermediate temperatures. These results suggest the general need for caution in ascribing the coalescence of variable-temperature NMR signals of diastereotopic protons to dynamic exchange processes that could instead be due to temperature-dependent chemical shifts and highlight the importance of corroborating postulated exchange processes through additional computations or experiments wherever possible.

Synthesis, Structure and Antioxidant Activity of Cyclohexene-Fused Selenuranes and Related Derivatives

“…It is due to the diastereotopic nature of the methylene protons. A similar pattern has been reported by Back and coworkers for 9a [35]. The 77 Se-NMR spectrum of compound 22 exhibits a signal at 908 ppm.…”

Effects of Methoxy Substituents on the Glutathione Peroxidase-like Activity of Cyclic Seleninate Esters

“…Typical Procedure for the Preparation of Allyl Aryl Selenides: [4-Methoxy-2-(prop-2-en-1-ylselanyl)phenyl]methanol (20). Diselenide 14 (200 mg, 0.463 mmol) was dissolved in 18 mL of THF−ethanol (5:1) and cooled to 0 °C.…”

“…room temperature and, unexpectedly, split into new AB quartets upon further heating, as a result of temperature-dependent chemical shifts of the exo and endo protons. 20,21 Chart 1 Scheme 2…”

Cyclic Seleninate Esters, Spirodioxyselenuranes and Related Compounds: New Classes of Biological Antioxidants That Emulate Glutathione Peroxidase

“…This results in the observed singlet, followed by divergence of shifts at still higher temperatures to regenerate an ew set of doublets. [51] While several of the cyclic seleninates and spiroselenuranes describeda bove have improveda ctivity compared to ebselen in the indicated assays,m ost display equally poor solubility in water.I no rder to improves olubility,s elenides 36 and 38 were prepared, representing the reduced form of spiroselenuranes 37 and 39,r espectively. [52,53] These compounds retain one arylseleniumb ond in order to resist metabolic conversion into toxic inorganic species, but display much improved solubility properties.…”

“…Computational studies revealed that as the temperature is increased, higher vibrational levels become populated, which changes the chemical shifts of the diastereotopic hydrogens, such that the shifts converge around room temperature. This results in the observed singlet, followed by divergence of shifts at still higher temperatures to regenerate a new set of doublets …”