Stereochemistry in the gas phase

Asymmetric synthesis is a key theme of organic chemistry. Nevertheless, the search for new or more efficient enantioselective reactions is often still guided by the principle of trial and error. Accordingly, the contributions of the research team to this topic are aimed towards the development of a fundamental understanding of the requirements for asymmetric induction in chemical reactions. Instead of searching for new protocols for applied synthesis, we therefore try to design sufficiently small model systems in the idealized gas phase, in which the stereoelectronic effects can be understood (and if possible quantified) at a molecular level [Topics in Current Chemistry 225: 133-152 (2003)].

As one example for such research, it is referred to an investigation of stereoselectivity in the time-honored McLafferty reaction. To this end, diastereospecifically deuterated 2-methylvaleramides were prepared by preparative synthesis and investigated by photoionization studies using synchrotron radiation [International Journal of Mass Spectrometry 240: 121-137 (2005)]).

The spectra shown at the right-hand side reveal the occurrence of a distinct diastereoselectivity in this reaction in that the proportion of the McLafferty fragments significantly differs for the two diastereomers investigated (syn- and anti-deuteration relative to the methyl substituent).

While the above example deals with pure organic ions, the major research in this subproject is related with organometallic complexes. In the case of the gas-phase reactions of 2-pentanol with bare Fe+ ions, for example, we could find a small, but yet significant enantioselective effect in the association reaction of the primary bond activation product (structures R-24 and S-24a in the Scheme below) with additional 2-pentanol.

Recently, we extended the range of possible chiral ligands to the aza[6]helicences (structures 1 and 2 on left) available in the research group of Ivo Starý. The particularly attractive aspect of the azahelicenes is that their chirality arises from the relatively stiff backbone of a polycyclic aromatic skeleton, which renders these compounds as promising candidates for the understanding of stereochemical effects in the gas phase, because the rigidity allows to perform high-level ab initio studies in reasonable time. In first experiments with 1 and 2, we could already note a significant chiral induction in the reactions of the protonated azahelicenes with chiral substrates in the gas phase. Presently, we are working on the reactions of transition-metal complexes of 1 and 2 with chiral compounds.