The diastereomers of 5-deuterio-2-hexanol, prepared stereospecifically from acetol and lactic acid by using fermentation procedures, have been subjected to the Barton reaction with Ag2CO3/Br2 in pentane over the temperature range –8.65 to 30.05 °C. The derived 2,5-dimethyltetrahydrofuran deuterium incorporation yields both the C-5 diastereotopic hydrogen stereoselectivity and the isotope effect (kH/kD) for the intramolecular hydrogen-transfer step. The isotope effect is classically temperature dependent, 5.82 (±0.07), 30.05; 6.01 (±0.22), 20.55; 6.81 (±0.17), 10.55; 6.90 (±0.08), 1.65; 7.47 (±0.49), –8.65 °C, while the stereoselectivity is small, 1.23 (1.65 °C), and temperature independent. Molecular mechanics calculations show that conformations with linear arrangements of C5, H, and O show small steric energy differences between the diastereotropic hydrogens at C-5. Calculations of isotope effects and their temperature dependencies for model transition states match the experimental data for only C5, H, and O angles greater than 150°. The Hofmann–Loeffler–Freitag reaction of the cation radical of 5-deuterio-2-aminohexane exhibits an isotope effect (kH/kD= 1.20) and stereoselectivity (ka/kb = 1.54/1), both at 25 °C, for the comparable γ-hydrogen-transfer step suggesting a more acute angle of transfer than for the alkoxy radical.
ASJC Scopus subject areas
- Colloid and Surface Chemistry