Heterobiaryl synthesis by contractive C–C coupling via P(V) intermediates

Abstract

Heterocycles meet and marry on phosphorus Metals such as palladium are routinely used to link together carbon rings in pharmaceutical synthesis. However, the presence of nitrogen in both rings can trip up this process. Hilton et al. report a versatile alternative process in which phosphorus takes the place of the metal. The phosphorus binds successively to both rings at the sites opposite the nitrogen, and treatment with acidic ethanol then pushes them off, bound to each other. Theory implicates a five-coordinate phosphorus intermediate that kinetically favors coupling of the two nitrogen-bearing rings over reactions of the other all-carbon substituents. Science , this issue p. 799