Teaching Metathesis “Simple” Stereochemistry

Background Transition metal–catalyzed alkene metathesis has revolutionized organic synthesis during the last two decades, even though the commonly used catalysts do not provide kinetic control over the stereochemistry of the newly formed double bonds. It is of utmost importance to fix this shortcoming, because the olefin geometry not only determines the physical and chemical properties of the alkene products but is also innately linked to any biological activities that the olefins may have. Advances Recent progress in catalyst design led to the development of a first set of metal alkylidene complexes of ruthenium, molybdenum, and tungsten that allow a host of inter- and intramolecular alkene metathesis reactions to be performed with good to excellent levels of Z selectivity (see the figure). This marks a considerable advancement over prior art, even though inherently E -selective catalysts remain elusive. In the case of disubstituted olefins, this gap in coverage can be filled by a sequence of alkyne metathesis followed by stereoselective semi-reduction of the resulting acetylene derivatives, which provides highly selective access to either geometrical series. Because the required alkylidyne catalysts have also been greatly improved in terms of activity, functional group tolerance, and user-friendliness, this method constitutes a valuable preparative complement. Outlook It is expected that the new catalysts will be rapidly embraced by the synthetic community. Because the as-yet limited number of published case studies is very encouraging, it is reasonable to believe that more sophisticated applications to polyfunctionalized and/or industrially relevant targets will follow shortly. Such investigations will allow the selectivity and performance of the stereoselective metathesis catalysts to be scrutinized in great detail. In parallel, growing mechanistic insights into their mode of action will almost certainly be forthcoming that can then be translated into refined ligand design. The resulting feedback loops will likely result in the evolution of ever more selective and practical catalysts, the long-term impact of which on organic synthesis and materials science will surely be profound and lasting.