Improving Enolate Cross-Coupling

The underappreciated oxidative enolate coupling reaction could become more frequently used in organic synthesis, thanks to Phil S. Baran and Michael P. DeMartino at Scripps Research Institute (Angew. Chem. Int. Ed. 2006, 45, 7083). Until now, the coupling reaction was considered of little practical use because it could reliably put together only two identical enolates; coupling two different enolates would produce more complex structures. But statistically speaking, such a procedure can at best give the cross-coupled product in only 50% yield without requiring a large excess of one of the coupling partners. Now, Baran and DeMartino demonstrate it's possible for intermolecular cross-coupling of different types of enolates, such as a lactam and a ketone (shown, linked by red bond), via enolate oxidation with yields that exceed 50%. The procedure relies on exploiting the natural electronic or steric differences between the coupling partners.