A Combined Experimental and Theoretical Study on the Stereodynamics of Monoaza[5]helicenes: Solvent-Induced Increase of the Enantiomerization Barrier in 1-Aza-[5]helicene.

Helicenes and heterohelicenes are attractive compounds with great potential in materials sciences to be used in optoelectronics as ligand backbones in enantioselective catalysis and as chiral sensors. The properties of these materials are related to the stereodynamics of these helical chiral compounds. However, little is known about features controlling stereodynamics in helicenes; in particular, for heterohelicenes the position of the heteroatom could be relevant in this respect. Herein the complete stereodynamic characterization of monoaza[5]helicenes is shown by enantioselective dynamic HPLC and DFT calculations. At variance with previous theoretical calculations, 1-aza[5]helicene shows a surprisingly high enantiomerization barrier, which is triggered by specific solvent interactions.

Chiral 1,2-dialkenyl diaziridines: synthesis, enantioselective separation, and nitrogen inversion barriers.

trans-1,2-Disubstituted diaziridines form stable enantiomers at ambient conditions because of the two stereogenic pyramidal nitrogen atoms. Functionalized trans-1,2-disubstituted diaziridines can be utilized as a chiral switching moiety between two enantiomeric states in more complex molecular structures. However, the synthesis of functionalized diaziridines is quite challenging, because of the limited tolerance of reaction conditions that can be applied. Here we present a strategy to make trans-1,2-disubstituted diaziridines accessible as versatile building blocks in C-C-bond formations, i.e., the Heck reaction, and therefore introducing aryl substituents. The synthesis of trans-1,2-dialkenyl diaziridines with terminal alkenyl substituents and their stereodynamic properties are described.

Stereodynamics of small 1,2-dialkyldiaziridines.

Diaziridines are very interesting representatives of organic compounds containing stereogenic nitrogen atoms. In particular, 1,2-dialkyldiaziridines show extraordinarily high stereointegrity. The lone electron pairs of the nitrogen atoms are in trans configuration, avoiding a four-electron repulsive interaction. Furthermore, the trans configuration of the substituents at the nitrogen atoms is energetically favored because of reduced steric interactions. Therefore only two stereoisomers (enantiomers) are observed. At elevated temperatures the enantiomers are interconverting because of the limited stereointegrity of the chirotopic nitrogen atoms. The enantiomerization rate constants and the activation parameters of interconversion are of great interest. Here, we investigated the stereodynamics of a set of small 1,2-dialkyldiaziridines bearing short substituents (Me, Et, iPr, tBu), using enantioselective dynamic gas chromatography (DGC). Separation of enantiomers of all compounds, including the highly volatile 1,2-dimethyldiaziridine, was achieved using heptakis(2,3-di-O-ethyl-6-O-tert-butyldimethylsilyl)-ß-cyclodextrin in 50% PS086 (w/w) as chiral stationary phase in fused silica capillaries with a length of up to 50 m. Measurements at variable temperatures were performed and reaction rate constants were determined using the unified equation of chromatography implemented in the software DCXplorer. The activation barriers at room temperature for 1-(tert-butyl)-2-ethyldiaziridine, ΔG(╪)(298K) = 123.8 kJ mol(-1) (ΔH(╪) = 115.5±2.9 kJ mol(-1), ΔS(╪) = -28±1 J mol(-1) K(-1)), and 1-ethyl-2-isopropyldiaziridine, ΔG(╪)(298K) = 124.2 kJ mol(-1) (ΔH(╪) = 113.1±2.4 kJ mol(-1), ΔS(╪) = -37±2 J mol(-1) K(-1)), were determined, representing some of the highest values observed for nitrogen inversion in diaziridines.

Stereodynamics of tetramezine.

The antidepressant drug tetramezine [1,2-bis-(3,3-dimethyldiaziridin-1-yl)ethane] consists of two bridged diaziridine moieties with four stereogenic nitrogen centers, which are stereolabile and, therefore, are prone to interconversion. The adjacent substituents at the nitrogen atoms of the diaziridines moieties exist only in an antiperiplanar conformation, which results in a coupled interconversion. Therefore, three stereoisomers exist (meso form and two enantiomeric forms), which epimerize when the diaziridine moieties are regarded as stereogenic units due to the coupled interconversion. Here, we have investigated the epimerization between the meso and enantiomeric forms by dynamic gas chromatography. Temperature-dependent measurements were performed, and reaction rate constants were determined using the unified equation of chromatography implemented in the software DCXplorer. The activation barriers of the epimerization were found to be ΔG(≠) = 100.7 kJ mol(-1) at 25°C and ΔG(≠) = 104.5 kJ mol(-1) at 37°C, respectively. The activation enthalpy and entropy were determined to be ΔH(≠) = 70.3 ± 0.4 kJ mol(-1) and ΔS(≠) = -102 ± 2 J mol(-1) K(-1) .