Stereointegrity of Tröger's Base: Gas-Chromatographic Determination of the Enantiomerization Barrier

Abstract

Tröger's base 1 (2,8-dimethyl-6H,12H-5,11-methanodibenzo[b,f][1,5]diazocine) undergoes enantiomerization in the gas and liquid phases. By enantioselective stopped-flow multidimensional gas chromatography, Eyring activation parameters of the enantiomerization barrier have been determined in the inert mobile gas phase (helium): ΔG⧧gas(298.15 K) = 112.8 ± 0.5 kJ mol-1; ΔH⧧gas = 62.7 ± 0.3 kJ mol-1; ΔS⧧gas = −168 ± 6 J (K mol)-1. An enantiomerization pathway proceeding via a degenerated retro-hetero-Diels−Alder ring opening or formation of a zwitterionic structure of 1 is proposed. By enantioselective dynamic gas chromatography, Eyring activation parameters have also been determined via computer-aided simulation of experimental interconversion peak profiles in the chiral stationary liquid phase: ΔG⧧liq(298.15 K) = 117.8 ± 0.5 kJ mol-1; ΔH⧧liq = 48.9 kJ mol-1; ΔS⧧liq = −231 ± 8 J (K mol)-1. Surprisingly, in the presence of the chiral stationary phase (CSP) Chirasil-β-Dex, required for enantiomer separation of 1, the enantiomerization barrier is higher than in the gas phase. The concept of the retention increment R' has been applied to distinguish the enantiomerization barrier of 1 in the dissolved and complexed state of the stationary phase.