Asymmetric metal-catalyzed [3+2] cycloadditions of azomethine ylides

Cycloadditions of azomethine ylides with olefins provide a short, attractive route to pyrrolidine units with the potential to control the relative and absolute configuration by means of a chiral catalyst. Grigg and co-workers have pioneered the use of chiral transition metal complexes to induce enantioselective cycloadditions of this type. However, stoichiometric amounts of metal complexes were employed in this work. Paying regard to Griggs investigations it was intended to develop a system which gives asymmetric induction using catalytic amounts of chiral transition metal complexes. A first screening of different transition metal sources showed promising results for Cu(I) and Ag(I) species. The application of their complexes with several members of different ligand classes to the 1,3-dipolar cycloaddition reaction directed the interest towards phosphinooxazoline (PHOX) ligands. The catalysts derived from the two different metals and PHOX ligand 39 induced enantioselectivity in both cases. Subsequent investigations demonstrated that also the use of the analogous Au(I) catalyst led to the formation of enantioenriched pyrrolidines. Although the Cu(I)-PHOX catalyst generated the five-membered heterocycle 38a with higher enantiomeric excess than the other two catalysts (Table 28, compare entries 1 with 2 and 3) the focus was directed to the Ag(I) system. Firstly, because a further screening with differently substituted PHOX ligands indicated only for the Ag(I) system the chance of substantial improvement of the enantioselectivity. Secondly, much higher endo:exo selectivity could be observed than for the other two systems. Optimization of the substitution pattern of the PHOX ligand showed that particularly the variation of the substituents at the phosphorous atom and the C5 position of the oxazoline moiety had a positive effect on asymmetric induction. Scheme 47 shows the most selective PHOX ligand (79) found to date which resulted in formation of the pyrrolidine product 38a with 84% enantiomeric excess. Although Ag(I)-PHOX complexes gave only moderate to good asymmetric induction in intermolecular [3+2] cycloadditions, they demonstrated to be efficient catalysts for intramolecular [3+2] cycloadditions of azomethine ylides, giving access to tricylic products with almost complete diastereocontrol and enantiomeric excesses of up to 99%.. Additionally the C5-substituted PHOX ligands, originally synthesized for the [3+2] cycloaddition reaction, were applied to the Ir(I)-catalyzed asymmetric hydrogenation of an imine as well as tri- and tetrasubstituted olefins. They induced similar or superior enantioselectivity than the best PHOX ligand (bis(ortho-tolyl)phosphino-tertbutyloxazoline). This confirmed the preliminary assumption that the steric bulk caused by the substituents at the C5 position of the oxazoline ring might direct the methyl groups of the isopropyl substituent at the C4 position to the coordination center creating a “tertiary butyl substitute“. Thus, this ligand type represents a less expensive substitute of the tert-leucine-derived PHOX ligand

The First Careers Fair Specifically for Chemists in Switzerland

Here we report on the first careers fair for chemists in Switzerland, contactchemists.ch. This event was organized by the Swiss Young Chemists' Committee Basel under the auspices of the SCS. Twelve companies accepted our invitation to take part and present their activities in both poster booths and oral presentations. This was complemented by a workshop that aided applicants in forming a suitable job-finding strategy. An informal exchange of information was possible and made contactchemists.ch a success not only for the participating companies but also for the numerous visitors. Synopses of the oral company presentations are included in this report