Beijing National Laboratory for Molecular Sciences (BNLMS), Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry, Peking University , Beijing 100871, China.
J Org Chem. 2016 Nov 4;81(21):10165-10171. doi: 10.1021/acs.joc.6b01908.
A concise total synthesis of mesembrine (four steps from known compound) was achieved both racemically and asymmetrically. Two key reactions were used here. One is the Rh(I)-catalyzed [5 + 1] cycloaddition of vinylcyclopropane 3c and CO. The other one is Buchwald's Pd-catalyzed coupling reaction that coupled β,γ-cyclohexenone 2c with aryl bromide 5 (using dppe ligand for racemic or (S)-Antphos ligand for asymmetric synthesis) to give γ,γ-disubstituted α,β-cyclohexenone 1c. Finally, aza-Michael addition converted 1c to mesembrine.
实现了 mesembrine（从已知化合物四步合成）的简洁对映选择性全合成。这里使用了两个关键反应。一个是 Rh(I)催化的乙烯基环丙烷 3c 和 CO 的[5+1]环加成。另一个是 Buchwald 的 Pd 催化偶联反应，该反应将β,γ-环己烯酮 2c 与芳基溴化物 5（使用 dppe 配体进行外消旋合成或 (S)-Antphos 配体进行不对称合成）偶联，得到γ,γ-二取代的α,β-环己烯酮 1c。最后，氮杂迈克尔加成将 1c 转化为 mesembrine。
