Strategies to bypass the taxol problem. Enantioselective cascade catalysis, a new approach for the efficient construction of molecular complexity

Millions of years of evolution have allowed Nature to develop ingenious synthetic strategies and reaction pathways for the construction of architectural complexity. In contrast, the field of chemical synthesis is young with its beginnings dating back to the early 1800's. Remarkably, however, the field of chemical synthesis appears capable of building almost any known natural isolate in small quantities, yet we appear to be many years away from operational strategies or technologies that will allow access to complexity on a scale suitable for society's consumption. This essay attempts to define some of the issues that currently hamper our ability to efficiently produce complex molecules via large-scale total synthesis. In particular, issues such as 'regime of scale' and 'stop-and-go synthesis' are discussed in terms of a specific example (the taxol problem) and more broadly as they apply to the large-scale production of complex targets. As part of this essay we discuss the use of enantioselective cascade catalysis as a modem conceptual strategy to bypass many of the underlying features that generally prevent total synthesis being utilized on a manufacturing scale. Last we provide a brief review of the state of the art with respect to complex molecule production via enantioselective cascade catalysis.