Total Synthesis of (±)-Jamtine Using a Thionium/N-Acyliminium Ion Cascade

Abstract

[reaction: see text] The first total synthesis of (+/-)-jamtine (4), a tetrahydroisoquinoline alkaloid reputed for its therapeutic properties, is described. The key step involves a tandem thionium/N-acyliminium ion cyclization from enamido sulfoxide 13. The cascade process takes place with high diastereoselectivity and in excellent yield.

Innovative Catalytic Protocols for the Ring‐Closing Friedel–Crafts‐Type Alkylation and Alkenylation of Arenes

“…Herein, allylic iminium ions are known to be valuable transient electrophilic species for both inter- [80] and intramolecular alkylation of aromatics. [81] In this context, Hiemstra, Rutjes and co-workers very recently reported the use of low loadings of Sn(OTf) 2 (2 %) as a catalyst for the formation of α-vinyl-substituted isoquinolines and β-carbolines in good yields via the allylic Nsulfonyliminium intermediate 100 (Scheme 32). [82] …”

The intermolecular Pictet-Spengler condensation with chiral carbonyl derivatives in the stereoselective syntheses of optically-active isoquinoline and indole alkaloids

“…Among the numerous attractive syntheses described in the recent literature, this work will cover only those approaches in which the carbonyl component is optically active, although not always the only source of chirality. 34 In addition, despite many interesting intramolecular transformations have been carried out employing either vinylogous carbonyls 35 or chiral carbonyls and their synthetic equivalents (not always aldehydes) 36 tethered to the nitrogen atom of the β-arylethylamine precursor, 37 only intermolecular Pictet-Spengler syntheses will be discussed. Synthetic strategies reported in the literature have been divided in those employing carbonyls attached to a removable chiral auxiliary and those in which at least one of the asymmetric centers present in the chiral carbonyl moiety forms part of the desired final product.…”

Facile synthesis of indene and fluorene derivatives through AlCl3‐catalyzed cyclization of in situ formed iminium ions

“…In this context, the iminium ion cyclization reaction has proven to be an extremely useful approach for the rapid and convergent construction of complex structures . One such example is the Pictet‐Spengler reaction, an invaluable method being widely used in both laboratory and industry for the preparation of a diverse array of isoquinoline and indole alkaloids . Despite the cyclization reactions involving iminium ions have led to profound developments in synthetic chemistry, where, very often, they focused on the construction of nitrogen‐containing heterocycles through an endo ‐model .…”

“…One such example is the Pictet‐Spengler reaction, an invaluable method being widely used in both laboratory and industry for the preparation of a diverse array of isoquinoline and indole alkaloids . Despite the cyclization reactions involving iminium ions have led to profound developments in synthetic chemistry, where, very often, they focused on the construction of nitrogen‐containing heterocycles through an endo ‐model . In sharp contrast, the exo ‐model cyclizations leading to the formation of all‐carbon ring skeletons have received considerably less attention (Scheme ), the reports pertaining to this class of reaction remain scarce …”