Published on Brock University (http://www.brocku.ca)
1. Annulated Chiral NHCs:
(a) Benzimidazolylidenes Derived from Phenanthrolines: Our group has developed innovative routes to several chiral imidazoline-type N-hetereocyclic carbenes (NHCs). We have prepared benzimidazolium-based NHCs via reduction of substituted phenanthrolines. In comparison to previous chiral benzimidazolylidenes, the compounds represented by the general structure 4 have several unique features that make them interesting for applications in asymmetric synthesis, both as NHCs and as non-carbenoid reagents: (a) they are amenable to structural diversification because many different substituents (alkyl, aryl) can be regioselectively introduced into the 2- or the 2,9-positions of 1,10-phenanthroline via nucleophilic aromatic substitution (NAS); (b) after reduction, the resulting octahydrophenanthrolines (2) have stereogenic centers locked within rings, the rigidity of which results in well-defined chiral environments for any reagents derived from them (3); (c) they are amenable to electronic modification by electrophilic aromatic substitution (EAS) at the two open positions on the benzene ring, which are activated by the presence of nitrogen atoms para to those sites. Ongoing research in the group is focused on synthetic applications of these reagents.
(b) Stereoselective Synthesis of Pyrroloimidazol(in)ylidenes: Our NHC research has expanded to include a new series of C1-symmetric systems with pyrroloimidazol(in)ylidene (5) frameworks, which retain the annulated chiral structural motif that is a design feature of our reagents. Mono-annulated chiral imidazolium NHC precatalysts 5 superficially resemble much more common triazolium (6) and thiazolium (7) precatalysts, but they have seen limited use despite promising results by Bode demonstrating their divergent reactivity (2009 Org. Lett. 677) when they are employed as nucleophilic catalysts. We have developed a simple two-step stereoselective synthesis of C5-substituted annulated chiral pyrroloimidazol(in)ylidene precatalysts (8 → 10 and 11 → 13) using an approach that borrows from our earlier work with phenanthroline-derived NHCs. This is an important advancement because the previous state-of-the-art to make annulated chiral imidazolylidene precatalysts required 8 synthetic steps, which explains why there are limited catalytic studies of these compounds to date. Refinement of our method will give practical and rapid access to a large number of precatalysts and ligands that until now have been rare. The number of potential applications of these new NHCs is very large and spans nucleophilic organocatalysis, metal-mediated catalysis and emerging fields such as "Frustrated" Lewis Pair (FLP) catalysis. Work in this area is progressing on all fronts.