CP2TiCl in natural product synthesis

The synthesis of complex natural products constitutes one of the most exigent tests to prove the usefulness of a new reagent or catalyst. During the past 10 years, methods based on the Cp2TiCl-promoted and/or -catalyzed radical epoxide opening have been used by several authors as the key step for the synthesis of more than 50 natural products and advanced synthons. At first, owing to its selectivity and the extremely mild experimental conditions employed, stoichiometric Cp2TiCl was chosen for deoxygenation and reductive epoxide opening on densely functionalized substrates, but during the last 5 years catalytic Cp2TiCl has been increasingly employed to achieve radical cyclizations of different epoxyalkenes and epoxyalkynes, affording straightforward strategies for the synthesis of complex natural products. In these fields Cp2TiCl-based methods have already largely proved their synthetic usefulness but other Cp2TiCl-mediated reactions have as yet been scarcely applied. This review focuses on the increasing scope of applications that employ the Cp2TiCl-mediated procedures in the synthesis of natural products. We also present the basic concepts of these methods to facilitate and encourage further synthetic applications.