Department of Chemistry, Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, United Kingdom.
Department of Chemistry, Rabigh College of Science and Arts, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
J Am Chem Soc. 2021 Jul 28;143(29):10828-10835. doi: 10.1021/jacs.1c04980. Epub 2021 Jul 13.
A new reductive strategy for the stereo- and regioselective synthesis of functionalized isoquinuclidines has been developed. Pivoting on the chemoselective iridium(I)-catalyzed reductive activation of β,γ-unsaturated δ-lactams, the efficiently produced reactive dienamine intermediates readily undergo [4 + 2] cycloaddition reactions with a wide range of dienophiles, resulting in the formation of bridged bicyclic amine products. This new synthetic approach was extended to aliphatic starting materials, resulting in the efficient formation of cyclohexenamine products, and readily applied as the key step in the shortest (five-step) total synthesis of vinca alkaloid catharanthine to date, proceeding via its elusive biosynthetic precursor, dehydrosecodine.
一种新的立体和区域选择性合成功能化异喹啉的还原策略已经被开发出来。该策略以β,γ-不饱和δ-内酰胺的化学选择性铱（I）催化还原活化为基础，有效地生成的反应性烯胺中间体很容易与各种亲双烯体发生[4+2]环加成反应，生成桥联双环胺产物。这种新的合成方法扩展到脂肪族起始原料，有效地形成环己烯胺产物，并容易应用于长春生物碱长春质碱的最短（五步）全合成的关键步骤，通过其难以捉摸的生物合成前体脱氢长春碱进行。
