Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA.
Nat Protoc. 2014 Aug;9(8):1860-6. doi: 10.1038/nprot.2014.125. Epub 2014 Jul 10.
This protocol describes a method for the laboratory synthesis of enantiomerically enriched, chiral tetrahydroisoquinolines through the application of a chiral sulfinamido urea catalyst for the Povarov reaction. Tetrahydroisoquinolines are bicyclic organic frameworks present in a wide assortment of natural and synthetic biologically important compounds including martinelline, scoulerine and tubocurarine. The methodology involves the [4+2] cycloaddition of a N-arylimines with electron-rich olefins such as vinyl lactams and dihydropyrroles in the presence of a two-catalyst system consisting of an achiral strong Brønsted acid (o-nitrobenzenesulfonic acid), together with the chiral sulfinamido urea derivative 1. The anion-binding properties of the urea lead to the association of the ion pair that results from protonation of the imine substrate. Cycloaddition is followed by spontaneous proton loss with re-aromatization to provide the tetrahydroisoquinoline products in highly enantio-enriched form.
本方案描述了通过应用手性磺酰胺脲催化剂来进行 Povarov 反应，从而在实验室中合成对映体富集的手性四氢异喹啉的方法。四氢异喹啉是一类存在于多种天然和合成生物重要化合物中的双环有机骨架，包括马丁宁、斯卡灵和筒箭毒碱。该方法包括在双催化剂体系（由非手性强布朗斯台德酸（对硝基苯磺酸）和手性磺酰胺脲衍生物 1 组成）存在下，使 N-芳基亚胺与富电子烯烃（如乙烯基内酰胺和二氢吡啶）进行[4+2]环加成反应。脲的阴离子结合特性导致与质子化亚胺底物形成的离子对的缔合。环加成后，通过自发质子缺失并重新芳构化，以高对映体富集形式提供四氢异喹啉产物。
