Van't Hoff Institute for Molecular Sciences , University of Amsterdam , Science Park 904 , 1098 XH Amsterdam , The Netherlands.
J Org Chem. 2018 Dec 21;83(24):15110-15117. doi: 10.1021/acs.joc.8b02378. Epub 2018 Dec 3.
The common para regioselectivity in Pictet-Spengler reactions with dopamine derivatives is redirected to the ortho position by a simple change of solvents. In combination with a chiral auxiliary on nitrogen, this ortho-selective Pictet-Spengler produced the 1-benzyltetrahydroisoquinoline alkaloids ( S)-crassifoline and ( S)-norcrassifoline and the bioactive 1,2-dioxygenated tetrahydroprotoberberine alkaloids ( S)-govaniadine, ( S)-caseamine, and ( S)-clarkeanidine with high enantiopurity. Ortho/para ratios up to 89:19 and diastereomeric ratios up to 85:15 were obtained during formation of the B-ring. The general applicability of this solvent-directed regioselectivity was demonstrated with a second Pictet-Spengler reaction as required for C-ring formation of caseamine (o/p = 14:86 in trifluoroethanol) and clarkeanidine (o/p = 86:14 in toluene).
通过简单地改变溶剂，将多巴胺衍生物的Pictet-Spengler 反应的常见对位区域选择性重新定向到邻位。与氮上的手性辅助剂结合，这种邻选择性的 Pictet-Spengler 产生了 1-苄基四氢异喹啉生物碱（S）-crassifoline 和（S）-norcrassifoline，以及具有高对映纯度的生物活性 1,2-二氧代四氢原小檗碱生物碱（S）-govaniadine、（S）-caseamine 和（S）-clarkeanidine。在 B 环形成过程中，获得了高达 89:19 的邻/对位比值和高达 85:15 的非对映选择性比值。通过第二个 Pictet-Spengler 反应证明了这种溶剂定向区域选择性的通用性，这是 caseamine（在三氟乙醇中为 o/p = 14:86）和 clarkeanidine（在甲苯中为 o/p = 86:14）的 C 环形成所必需的。
