“We have developed a novel approach to highly enantioselective catalysis, which we have termed asymmetric counteranion-directed catalysis (ACDC). At least in principle, any reaction that proceeds via cationic intermediates can now be conducted in a catalytic asymmetric fashion.”

We describe a new principle for asymmetric catalysis of potentially broad utility. As a first example, we apply our concept within the "hot" area of organocatalysis. Our Angewandte publication has inspired a lot of activities by other groups and we are grateful to our peers for recognizing our contribution and referencing the paper.

We have developed a novel approach to highly enantioselective catalysis, which we have termed asymmetric counteranion-directed catalysis (ACDC). At least in principle, any reaction that proceeds via cationic intermediates can now be conducted in a catalytic asymmetric fashion.

Most chemical reactions proceed via positively or negatively charged intermediates. Previously, reactions involving anions have been successfully catalyzed using chiral cationic catalysts in a highly enantioselective manner, which means that essentially only one of the possible two mirror-image isomers is produced. Surprisingly however, analogous reactions of inverse polarity, that is, those via cationic intermediates—of which there are many important ones—had, despite attempts, not been realized. In our paper we describe the first examples with superb enantioselectivities.

Our studies originated when we observed a strong counteranion effect on the enantioselectivity of a reaction that proceeds via an iminium ion intermediate. Such transformations are normally catalyzed by salts of chiral amines. Our idea was to use a salt consisting of an achiral ammonium ion and a chiral counteranion instead. Although salts are involved, we reasoned that in organic solvent these should be close-contact ion pairs and not solvent-separated ion pairs. A "stereochemical communication" within the ion pair should therefore be feasible. Fortunately, through very recent elegant studies by Takahiko Akiyama and Masahiro Terada, chiral phosphates have been introduced to asymmetric catalysis.

Sonja Mayer, the graduate student involved, carefully made hundreds of ammonium phosphate salts which quickly enabled our idea to work. Finally, she surprised many by obtaining extremely high enantioselectivities. Interestingly, the discovery has been one of those where we initially faced a great deal of skepticism, even within the group. Later everyone was rubbing their eyes, in disbelief that they could have ever questioned such an apparently "obvious" idea!

We currently explore many different reactions that involve cationic intermediates, in organocatalysis, in Lewis acid catalysis, and in transition metal catalysis. Also, there are activities in this area by other groups all over the world and it looks like there are exciting times ahead for ACDC.