有機催化劑在分子內Michael加成反應之探討

Abstract

藉由分子內不對稱Michael加成反應，發展鏡像選擇性多取代環己酮。本實驗使用起始物(E)-5-硝基-6-芳香基己-5-烯-2-酮117，加入20 mol%的金雞納樹生物鹼雙關能基有機催化劑及20 mol%的4-二甲氨基吡啶，在等比例混合之二甲基亞碸及1,4-二氧陸圜為溶劑及50 oC下，經由氫鍵催化進行反應，得到多取代硝基環己酮衍生物，其有不錯的產率及非常好的立體選擇性(>95:5 dr 和高達96% ee)；將產物120k，進行還原反應，得到多取代環己醇衍生物，加入甲基磺醯氯以及非親核性鹼，製備甲基磺醯酯衍生物，再經過二步簡單的反應，即可合成天然物(-)地棘蛙素85，本實驗室期望能開發更有效合成路徑，製備天然物活性分子，相關合成應用目前仍在進行中。Asymmetric organocatalytic Michael addition has attracted interests due to its environmental friendliness and the generation of multiple stereogenic centers in a single step. In this study‚ treatment of (E)-5-nitro-6-arylhex-5-en-2-one using a catalytic amount of quinine-derived primary amine (20 mol%) and 4-dimethyl aminopyridine (20 mol%) in 1,4-dioxane and DMSO (1:1) at 50 oC to give 3,4-trans- disubstituted cyclohexanones via intramolecular Michael addition process with moderate chemical yields and high-to-excellent stereoselectivities (>95:5 dr and up to 96% ee). We describe a rapid and practical synthetic route involving six-step reaction toward the synthesis of (-)-Epibatidine