Different Metal, Different Isomer
Simply choosing a ruthenium or a palladium catalyst
provides a novel means of diastereocontrol when making
complex bicyclic compounds
Stephen K. Ritter
Exquisite control over the stereoselective synthesis of bicyclic compounds is possible
simply by choosing one catalyst metal over another, report Barry M. Trost, Eric M.
Ferreira, and Alicia C. Gutierrez of Stanford University (J. Am. Chem. Soc., DOI:
10.1021/ja8078835). Trost's group introduced the metal-catalyzed enyne
cycloisomerization reaction in 1985 as a strategy for synthesizing complex organic
molecules. Follow-up studies have expanded the scope of the reaction and provided insight
into the mechanism. In the latest rendition of the reaction, Trost and coworkers converted
an alkyne-substituted cyclohexene into a bicyclic compound. The trans stereoisomer forms
when a ruthenium catalyst is used, and the cis version forms when a palladium catalyst is
used (shown). The difference plays out in one of the proposed intermediates: Both metals
form a cyclic complex via coordination to the alkene and alkyne bonds of the substrate, but
ruthenium uses the carbonyl oxygen of one methyl ester group to temporarily steady itself,
whereas palladium does not. The result is that the carbonyl directs formation of the trans
isomer, providing a novel means of diastereocontrol.