Development of carbon-carbon bond-forming reactions using γ,γ-dialkoxyallylic zirconium species

Carbon-carbon bond-forming reactions of allylic organometals have been recognized as one of the most fundamental means in organic synthesis, and a number of applications for the synthesis of biologically active molecules have been reported. We have reported the carbon-carbon bond-forming reactions by the use of the allylic and related zirconium species as reactive intermediates. These zirconium species can be generated by treating allylic ethers with zirconocene-butene complex ("Cp2Zr") through the formation of zirconacyclopropane and the following beta-elimination of the alkoxy group. This process was found to be applicable to generate the gamma,gamma-dialkoxyallylic zirconium species 1 from orthoacrylate derivative. Zirconium species 1 possibly has three reactive sites: One is the gamma-position as a typical allyl metal species, the other is the beta-position followed by the alpha-position initiated by nucleophilic character of ketene dialkylacetal moiety and the third one is regioselective coupling reaction at the alpha-position. Thus, gamma,gamma-dialkoxyallylic zirconium species 1 can be conveniently prepared by the reaction of triethyl orthoacrylate with "Cp2Zr". Without an additive, 1 itself reacts with aldelaydes and ketones at the gamma-position to afford the gem-diethoxy homoallylic alcohol derivatives. Under Lewis acid promoted conditions, this zirconium species 1 reacts with a variety of carbonyl compounds selectively at the P-position in the first step, followed by the cyclopropanation or cyclobutanation reaction to afford the corresponding products mainly depending on electronic nature of substrates or reaction conditions. In the presence of CuCN, reaction of 1 with allylic phosphates proceeded at the alpha-position of 1 in a highly S(N)2'-selective manner to give the 5-alkenoates.