Studies Towards the Synthesis of Functionalized Medium‐Sized Carbocyclic and Fused Bicyclic Systems by Alkoxy Radical Fragmentation (ARF)

Abstract

AbstractThe stereoselective construction of polyfunctionalized medium‐sized carbocyclic and fused bicyclic systems from substituted bicyclo[3.n.1]alkanones has been studied; the strategy employed involved Suarez’s alkoxy radical fragmentation reaction (ARF) as the key step. The scope of the reaction was examined and this methodology was found to be especially useful for stereo‐ and regioselective construction of eight‐membered carbocycles including bicyclo[6.4.0]dodecane systems, a framework that is present in a variety of biologically active natural products. This reaction was also used successfully in the synthesis of seven‐membered carbocycles but with low selectivity. It was found that the presence of a hemiketal functionality in the molecule is essential for the ARF reaction to occur; hence nine‐ and ten‐membered ring analogs could not be attained since the precursor bicyclic ketones do not form the required hemiketals. This is borne out by MM calculations. Finally, a diquinane was also synthesized. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)