Asymmetric Synthesis of Isoquinoline Derivatives from Amino Acids

Abstract

Reaction of isoquinolines 1 with N-arylsulfonylamino acid fluorides 2 provides a highly stereoselective access to new dihydroimidazo[2,1-a]isoquinolin-3-ones 5 via intermediate N-acylisoquinolinium salts 3. Addition reactions to the enamine double bond, such as hydrogenation or epoxidation with dimethyldioxirane, leads to tetrahydroimidazo[2,1-a]isoquinoline-3-ones 6, 7 and oxiranes 8, respectively. Opening of the oxirane ring of the 8 with nucleophiles allows the synthesis of hydroxytetrahydroimidazo[2,1-a]isoquinolin-3-ones

Stereoselective 1-arylation of isoquinolines via chiral N-acylisoquinolinium salts

“…12,13 In this way, a variety of electron rich aryl and auxiliary in the Reissert reaction (addition of cyanide to position 1) with isoquinolines but in contrast to first assumptions, 16 the reaction was not stereoselective but gave 1:1 mixtures of epimers. 18,20 As an extension of our interest in the application of (R)-menthyl chlorocarbonate and α-amino acid fluorides as auxiliaries in stereoselective 1,2-additions to isoquinolines [16][17][18] we sought their application in the stereoselective introduction of aryl groups into position 1.…”

Asymmetric Synthesis of Imidazo[2,1‐a]isoquinolin‐3‐ones with Dihydroisoquinolines and N‐substituted Amino Acids

“…Beside of substantial researches by Cronin [4] and co‐workers on the synthesis of various dihydro‐imidazo‐phenathridinium derivatives by multi‐step processes, a series of impressive direct methods have been established for the construction of imidazo[2,1‐ a ]isoquinolines [5] . However, there is limited reports on the direct synthesis of enantioenriched imidazo[2,1‐ a ]isoquinoline derivatives [6–8] …”

“…To the best of our knowledge, only three reports have achieved the synthesis of chiral imidazo[2,1‐ a ]isoquinolines (Scheme 1). Liebscher et al have disclosed a highly stereoselective construction of dihydroimidazo[2,1‐ a ]isoquinolin‐3‐ones with isoquinolines and N ‐arylsulfonylamino acid fluorides in 2005 [6] . Taylor and co‐workers have directly coupled dihydroisoquinoline and protected amino acids using propylphosphonic acid anhydride (T3P) and DIPEA.…”

Heterocycles as Key Substrates in Multicomponent Reactions: The Fast Lane towards Molecular Complexity

“…[20] Interesting transformations have been disclosed by the groups of Rudler and Langer, where the addition of silyloxy alkenes to activated azines afforded a variety of highly substituted heterocyclic derivatives (Scheme 10). [21] b-Dicarbonyl Chemistry…”