13, y-disubstituted (x-alkylidene-y-butyrolactones with cis or trans relative configurations were synthesized in both optically active forms from readily available homochiral allylic 2-alkynoates by Pd(II) catalysis in the presence of CuX2 and LiX Synthesis of homochiral compounds as candidates for drug screening is becoming a key issue in the pharmaceutical industry.l Chiral, non-racemic 7-1actones are important synthetic intermediates in the syntheses of many natural products. 2 They are also key moieties in a wide range of natural products and biologically active compounds 3 The physiological activity of these 7-1actones often depends on the absolute configuration.4 Thus, a variety of synthetic methods for these compounds continues to be reported.l3' 5 Transition metal catalyzed reactions, especially those that construct cyclic structures from easily available acyclic precursors, have received much attention owing to the template action of the transition metals. 6 Recently, we have developed some efficient methods for the construction of c~-alkylidene-ybutyrolactone ring from acyclic allylic 2-alkynoates under the catalysis of palladium(II). 7' 8 Our recent research revealed that when a stereogenic center was introduced into the l'-position of the 2'-alkenyl group in the starting material, the reaction showed unusually high diastereoselectivity. In this communication, we wish to report this unusual stereochemistry and its application in the synthesis of enantiopure [3, y-disubstituted c~alkylidene-y-butyrolactone derivatives
We began our research with (R)-I '-pentylallyl 2-butynoate((R)-la) under PdC12(PhCN)2 catalysis in the presence of CuCl2 and LiCI in acetonitrile. The reaction went on cleanly, only cis-product (referring to the relative stereochemistry of 4, 5-substituents), (4R, 5R)-2aA was obtained in high yield (95%)(entry 1 in Table )
The exocyclic C-C double bond in (4R, 5R)-2aA was assigned as the Z configuration by comparing the