95(P-24) 多成分反応による実用的シクロブタン合成法の開発と天然物合成への応用(ポスター発表の部)

抄録

Four-membered carbocycles, such as cyclobutanes and cyclobutenes, have been attracted as a unique building block for natural and medicinal compounds, because their cyclic skeletons and their substituents can offer a unique conformation based on the characteristic angular and torsional effects. We report here development of catalytic reactions to prepare four-membered carbocycles in efficiency, and its application to the synthesis of a marine sesquiterpene, paesslerin A. At first, we have found Tf_2NH efficiently catalyzes (2+2)-cycloaddition of silyl enol ethers. The catalyst allows the synthesis of multi-substituted four-membered carbocycles in high yield with high selectivity. Furthermore, we have demonstrated the reactions proceed under ecological and practical conditions (high TON, high TOF, non-halogenated solvent, and multi-gram synthesis). Next, we have developed novel multi-component cascade (4+2)-(2+2) cycloaddition to afford bicyclo[4.1.0]octane skeletons from siloxydiene and 2 equivalent of acrylate (or plopiolate) with high diastereoselectivity. It is noteworthy that the MCR process is accompanied by formation of 4 carbon-carbon bonds and 4 stereogenic centers in a single operation. Finally, we report stereoselective synthesis of proposed structure of paesslerin A using the above reactions. Total synthesis was completed in 8 steps from a known compound (34% overall yield). However, comparison of the spectral data of our synthetic compound with those reported for natural paesslerin A revealed they were not identical. X-ray crystallographic analysis of the synthetic compound concluded the reported structure was incorrect. Further studies toward synthesis of correct structure of paesslerin A are in progress.