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-H_ax, and an exomethylene proton, 14-H_b.