Conformational analysis of halochamigrene derivatives by 1H dynamic nuclear magnetic resonance experiments and molecular-mechanics calculations. An unusually high barrier for the 6-methylenecyclohex-2-en-1-one ring inversion
Abstract
2,10-Dibromo-3-chlorochamigra-7(14),9-dien-8-one (1), isolated from the red alga Laurencia nipponica, is found as an equilibrium mixture of two stable conformational isomers the structure of which has been elucidated by 1H n.m.r. experiments. The ratio of the two stable conformers is 70 : 30 and from this, the Gibbs free energy (ΔG°) has been determined as 2.11 kJ mol–1. A conformational equilibrium of 2-bromo-3-chlorochamigra-7(14),9-dien-8-one (2) has also been observed. The strain-energy difference (ΔH°), calculated using molecular-mechanics calculations, between the two stable conformers of (1) and between those of (2) are 2.35 and 2.81 kJ mol–1, respectively, and the variation in stability of each of the two conformers of (1) and (2) is attributed mainly to the dipole-dipole interaction energy. Using 1H dynamic n.m.r. spectroscopy, the thermodynamical parameters of conformational exchange of (1) have been determined as ΔG313‡= 76 kJ mol–1, ΔH‡= 50 kJ mol–1, and ΔS‡=–84 J mol–1 K–1. The unusually high barrier is caused by the hindered rotation of the C(6)–C(11) axis, and to a large extent, by the non-bonded interaction between the two axial protons, 2-H and 4-Hax, and an exomethylene proton, 14-Hb.