Olefin metathesis: a versatile synthetic tool for use in preparation of Active Pharmaceutical Ingredients
TOMASZ K. OLSZEWSKI1*, MAREK FIGLUS2, MICHAL BIENIEK2
*Corresponding author
1. Wroclaw University of Technology, Faculty of Chemistry, Department of Organic Chemistry, Wybrzeze St. Wyspianskiego 27, 50-370 Wroclaw, Poland
2. Apeiron Catalysts Sp. z o. o., Dunska 9, 54-427 Wroclaw, Poland
Abstract
Olefin metathesis is a powerful transformation based on catalytic reaction between alkenes. It allows a formation of a variety of structurally diverse molecules that cannot be easily prepared by alternative routes. Recently developed methods require relatively low catalyst loading and enable easy removal of residual ruthenium from the reaction product. These developments have attracted the attention of process chemists who add metathesis reaction to a toolbox of reliable methods for production of pharmaceuticals. This review presents selected examples of successful application of olefin metathesis in the synthesis of active pharmaceutical ingredients from laboratories within the pharmaceutical industry.
INTRODUCTION
Olefin metathesis is a powerful transformation that has gained a real significance in advanced organic synthesis for the formation of C = C double bonds (1). The development of well-defined and stable catalysts along with the understanding of the reaction mechanism has revolutionized retro-synthetic planning (2). The importance of olefin metathesis was recognized in 2005, with the award of the Nobel Prize in Chemistry to Yves Chauvin, Richard R. Schrock, and Robert H. Grubbs (3).
The success of this transformation was fully associated with the development of efficient and durable catalysts (Figure 1). Among them: the first generation Grubbs catalyst G-I, Hoveyda-Grubbs catalyst H-I and the indenylidene bearing complex Ind-II (4), are characterized with high activity, selectivity, and functional group tolerance. The replacement of the electron-rich phosphine group with N-heterocyclic carbene (NHC) ligand resulted in the formation of second-generation catalysts G-II, G-II’ and H-II, H-II’. These catalysts are chara ...
