A facile access to spiro furanone skeleton based on Pd(II)-mediated cyclization-carbonylation of propargylic esters

The oxidative cyclization-carborylation of propargylic esters mediated by Pd(II) afforded cyclic orthoesters, which were hydrolyzed into gamma-acetoxy-beta-ketoesters. Based on the NMR experiments, it was presumed that the cyclization reaction was initiated by a nucleophilic attack of carbonyl oxygen to the alkyne carbon coordinated to palladium(II). When the gamma-acetoxy-beta-ketoesters were treated with a basic condition, Knoevenagel-Claisen type condensation took place, and spiro furanone derivatives were obtained in good yields. We applied these reactions to steroid derivatives, and steroid derivatives having a spiro furanone fragment were synthesized. Among them, the spiro furanone 4j had vasorelaxant and bradycardiac activities. Compounds 2i-4k had inhibitory effect on CYP3A. (c) 2005 Elsevier Ltd. All rights reserved.