Pd-Catalyzed Cyclization to Form Benzo-pyranones from Enediynes

Significance

This paper describes the synthesis of substituted dibenzo[b,d]pyran-6-ones by a Pd-catalyzed, one-step, tandem cyclization reaction from enediynes. For the 14 cases studied, yields vary from poor to modest; furthermore, interesting chlorinated and minor byproducts are formed in a few cases. A mechanism involving the formation of a vinyl palladium intermediate which undergoes 6-endo cyclization to yield the product is proposed. A 5-exo cyclization to the observed chlorinated product is observed when the terminal alkene substituent is a sterically hindered alkyl group or an electron-rich aryl ring. The starting methyl 2-[6-substituted-3(Z)-hexen-1,5-diynyl]benzo­ates were prepared in moderate to excellent yield by the well-established Sonogashira methodology.

Comment

The synthesis of functionalized dibenzo[b,d]pyran-6-ones has attracted considerable attention due to their pharmaceutically important properties (X. Wang et al. J. Med. Chem. 2006, 49, 5631). Substantial solvent screening was carried out and control experiments (absence of PdCl₂) resulted in the formation of different products. Alternative and very competitive routes to similar dibenzopyrones via directed ortho metalation-Suzuki cross-coupling sequences are available (C. A. James, V. Snieckus Tetrahedron Lett. 1997, 38, 8149).