| A novel and highly selective methodology based on palladium catalyzed cross coupling of either alpha-halo-alpha,beta-unsaturated carbonyl compounds or the corresponding alpha-metallo derivatives was developed. Simple alkyl, homoallyl, homopropargyl, benzyl, aryl, and alkenyl groups could be introduced into the alpha-position of 2-iodocyclohexenone and 2-iodocylopentenone. The yields ranged from good to acceptable. In order to find the optimal conditions, a systematic screening of palladium catalysts as well as generation methods of the organometals were conducted. The synthesis of 3-substituted-2(5H)-furanones through Pd-catalyzed carbonylation of (Z)-3-Iodo-3-substituted-2-propen-1-ol was fully developed. 3-Phenyl-5,6-dihydropyran-2-one was also synthesized through the modified acylpalladium process. The application of this method in the synthesis of hamabiwalactone-B was very successful. The synthetic conditions of 1,5-dienes were optimized. Pd(PPh3)4 was capable to promote the alkenyl-homoallyl and aryl-homoallyl cross-coupling reactions and give good yields in most cases. In more demanding cases, Pd(dppf)Cl 2 would be an optimal catalyst. |
