Conformations of Oxocane

by Meyer, Walter L.; Taylor, Patterson W.; Reed, Scott A.; Leister, Marvin C.; Schneider, Hans-Jorg; Schmidt, Gunter; Evans, Frederick E.; Levine, Robert A.

Conformational analysis of oxocane (oxacyclooctane) has been examined by molecular mechanics (MM2), variable-temperature C-13 NMR, and lanthanide-induced shift (LIS) H-1 and C-13 NMR. MM2 calculations find the BC-3 conformer and its enantiomer BC-7 to be favored, with the four next best forms and their energies relative to BC-3 being BC-1 (1.1 kcal/mol), TBC-1 (1.1), BC-4 (1.5), and TCC-1 (1.6). Barriers to pseudorotational interconversion of BC-3 and BC-7 are calculated to be 5.0 kcal/mol through BC-5 and 6.7 kcal/mol through BC-1. The former would allow fast BC-3/BC-7 equilibration even at -170-degrees-C, which would leave reported low-temperature H-1 NMR spectra compatible with a BC-3 structure as well as BC-1. Calculated barriers for BC ring inversion and interconversion of the BC family with the crown family (TCC-1) are 8.2 and 8.5 kcal/mol, respectively. A new two-step synthesis of oxocane and its 2,2,7,7-d4 analogue is reported, the latter allowing unequivocal assignment of chemical shifts. C-13 NMR spectra of oxocane between 138 and 290 K show BC-family/crown-family interconversion in the vicinity of 215 K (DELTA-G double-ended-dagger = 10.0 +/- 0.3 kcal/mol), with the crown family comprising 4% of the equilibrium at 174 K (DELTA-G-degrees = 1.1 +/- 0.1 kcal/mol). The H-1 and C-13 LIS induced by Yb(fod)3 on oxocane agree well with BC-3 and BC-7 being the predominant conformers at room temperature but do not acceptably fit a BC-1 structure. Thus, all available data from calculation and experiment are in accord with BC-3 being the favored conformation of oxocane.

Journal of Organic Chemistry
Start Page
0022-3263; 1520-6904