Stereoselective Organocatalytic Addition of Nucleophiles to Isoquinolinium and 3,4-dihydroisoquinolinium Ions: A Simple Approach for the Synthesis of Isoquinoline Alkaloids

Abstract

The frequent occurrence of chiral 1-substituted-1,2,3,4-tetrahydroisoquinoline ring systems in a large number of alkaloids, possessing a broad spectrum of biological and pharmaceutical properties, has prompted out a considerable interest in their synthesis. Economical and valuable stereoselective processes based on organocatalytic transformations represent a new avenue for approaching isoquinoline alkaloids with efficiency and creativity.

Experimental and Computational Studies Unraveling the Peculiarity of Enolizable Oxoesters in the Organocatalyzed Mannich-Type Addition to Cyclic N-Acyl Iminium Ions

“…Dearomative Mannich-type reactions have recently been reported by us and other groups using activated quinolinium ions as the electrophilic acceptor, both using synergistic cooperative catalysis starting from N,O-acetals [19][20][21][22], or directly from quinolines [23]. Moreover, the frequent occurrence of 1-substituted-1,2,3,4-tetrahydroisoquinoline ring systems has stimulated considerable interest in their asymmetric synthesis by the use of metal-and organocatalysis [24]. Major advances using an organocatalytic approach have been developed by Cozzi et al, by enantioselective addition of aldehydes to isoquinolinium carbamates [25], and by Liu et al, using a cross-dehydrogenative coupling of carbamoyl isoquinolines with aldehydes [26].…”

Organocatalytic Enantioselective Oxidative CH Alkenylation and Arylation of N‐Carbamoyl Tetrahydropyridines and Tetrahydro‐β‐carbolines

“…To the best of our knowledge, there have been no reports on a catalytic enantioselective CH functionalization of tetrahydropyridines or THCs to date. Moreover, the synthetic utility of the existing methods is limited because removal of the N ‐aryl group in the presence of other functional groups proved to be difficult 2g. 10 Herein, we report the first organocatalytic asymmetric CH alkenylation and arylation reactions of N ‐carbamoyl tetrahydropyridines and THCs with excellent enantiocontrol.…”

Organocatalysis: A Tool of Choice for the Enantioselective Nucleophilic Dearomatization of Electron-Deficient Six-Membered Ring Azaarenium Salts

“…Whereas enantioselective hydride addition requires the use of pre-functionalized azaarenes (introduction of Nu prior to the addition of the hydride) and leads to tetrahydro products (and therefore will not be discussed herein) [7][8][9], nucleophilic dearomatization (Nu = H) offers the advantage of introducing chemical diversity Taking into account the above-mentioned challenges, enantioselective nucleophilic dearomatization of azaarenium salts has attracted a great deal of attention mostly by using metal catalysts with chiral ligands [11][12][13][14][15][16][17][18][19][20]. Nevertheless, in the last fifteen years and due to the advent of organocatalysis [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36], which was recently highlighted through the Taking into account the above-mentioned challenges, enantioselective nucleophilic dearomatization of azaarenium salts has attracted a great deal of attention mostly by using metal catalysts with chiral ligands [11][12][13][14][15][16][17][18][19][20]. Nevertheless, in the last fifteen years and due to the advent of organocatalysis [21][22]…”

“…Nevertheless, in the last fifteen years and due to the advent of organocatalysis [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36], which was recently highlighted through the Nobel Prize of Prof. B. List and Prof. D. MacMillan, several enantioselective organocatalytic dearomatization reactions of azaarenium salts have been reported [11,[13][14][15][16]18,19,37,38]. Organocatalysts can be classified following the mode of activation of either the electrophilic and/or nucleophilic partners involved in a given reaction [24,25].…”