“I believe that, in the future, new cascade sequences will be designed to access intricate structural motifs directly applicable to natural product synthesis.”

Our publication details the discovery of a new chemical strategy using organocatalysis, for the rapid construction of molecular complexity, based on the biochemical blueprints of cascade catalysis. This research has inspired the development of more complex enantioselective cascade sequences. I believe that, in the future, new cascade sequences will be designed to access intricate structural motifs directly applicable to natural product synthesis.

Certainly, organo-cascade catalysis is a new strategy for the chemical sciences and will be of great benefit to practitioners of synthesis, both within the pharmaceutical industry and academia, which require rapid access to chemical diversity with predictable control of stereoselectivity.

Organo-cascade catalysis, as we have introduced it, represents a new paradigm for the field of target-oriented synthesis as it is a powerful strategy that provides rapid access to structural complexity from simple starting materials and commercially available amine organocatalysts. Importantly, our organo-cascade catalysis protocols have led to the invention of enantioselective transformations that were previously unknown within the realms of asymmetric catalysis.

Inspired by nature’s synthetic proficiency in its use of continuous enzymatic cascade sequences for the rapid construction of complex natural products, I became interested in developing a practical laboratory approach to cascade catalysis. The main challenge was to identify synthetic catalyst systems that displayed the characteristics of enzymes in their capacity to coexist in the same reaction medium, without suffering destructive catalyst-catalyst interactions detrimental to catalyst turnover.

Over the past eight years, my laboratory has been involved in the development of the field of organocatalysis, a research area that relies upon the use of small organic molecules as catalysts for enantioselective transformations. By combining orthogonal modes of substrate activation in the forms of iminium (LUMO-lowering) and enamine (HOMO-raising) catalysis, using imidazolidinone organocatalysts previously developed in my group, we have developed the first examples of enantioselective organocatalytic cascade sequences.