Synthesis of 1-Benzyl-, 1-Alkoxyl-, and 1-Aminoisoquinolines via Rhodium(III)-Catalyzed Aryl C–H Activation and Alkyne Annulation

Abstract

One-pot syntheses of 1-benzyl-, 1-alkoxyl-, and 1-alkylamino- isoquinolines through automatic directing group (DGauto)-assisted, rhodium­(III)-catalyzed aryl C–H activation and annulation with internal alkynes were developed. The reactions affording 1-benzylisoquinolines involve a cascade oximation of diarylacetylenes with hydroxylamine, forming aryl benzyl ketone oxime, and oxime-assisted rhodium­(III)-catalyzed aryl C–H activation and followed annulation with another molecule of diarylacetylene in a one-pot manner. The formation of 1-alkoxyl/amino isoquinolines includes the addition of nucleophilic alcohols or amines to aryl nitriles, imine-assisted rhodium-catalyzed aryl C–H activation, and subsequent alkyne annulation.

Transition Metal‐Catalyzed Dual C−H Activation/Annulation Reactions Involving Internal Alkynes

“…[29] A Rh(III)-Rh(I) catalytic cycle was proposed for this reaction, involving the formation of Rh-complex A via the coordination of the N-atom of 41 with Rh(III) and binding of alkyne Hua and Zhou introduced a novel approach for the construction of 1-benzylisoquinolines, 1-alkoxylisoquinolines 44, and 1-aminoisoquinolines 47 through CÀ H activation/ annulation of hydroxyl amine 43 or aryl/heteroaryl nitrile 45 with diaryl/alkyl alkynes 2 (Scheme 24). [30] Annulation of hydroxylamine 43 with diaryl alkynes 2 involved the For the production of 1-alkoxyl/amino isoquinolines 47, the activated nitrile 45 by Cu(II) was added to nucleophile 46 gave benzimide G. In the reaction, the imine group assisted CÀ H activation and insertion of alkyne to furnish 47 (Scheme 25). CÀ H Activation and annulation of 5-aryl pyrazinones 48 with 2.0 equivalents of internal alkynes 2 can be performed in the presence of the Rh(III) catalyst (Scheme 26).…”

“…Hua and Zhou introduced a novel approach for the construction of 1‐benzylisoquinolines, 1‐alkoxylisoquinolines 44 , and 1‐aminoisoquinolines 47 through C−H activation/annulation of hydroxyl amine 43 or aryl/heteroaryl nitrile 45 with diaryl/alkyl alkynes 2 (Scheme 24). [30] Annulation of hydroxylamine 43 with diaryl alkynes 2 involved the formation of the oxime intermediate A , while the reaction of nitrile 45 and a nucleophile 46 , such as amine or alcohol with aryl/alkyl alkynes 2 proceeded via the imine intermediate B . In both reactions, the phenyl moiety acted as a directing group.…”

Diversely functionalized isoquinolines and their core-embedded heterocyclic frameworks: a privileged scaffold for medicinal chemistry

“…Zhou et al reported a one-pot access to 1-benzyl 55 , 1-alkoxyl 58a , and 1-alkylamino 58b isoquinoline through Rh( iii )-catalyzed, automatic directing group-assisted aryl C−H activation and annulation with internal alkynes 52 (Scheme 10). 54 Oximation of diarylacetylenes 52 with hydroxylamine followed by C–H activation generates the intermediate 54 . Successive insertion of the other functionalized alkyne partner 52 following reductive elimination affords bicyclic adduct 55 .…”

“…activation and annulation with internal alkynes 52 (Scheme 10). 54 Oximation of diarylacetylenes 52 with hydroxylamine followed by C-H activation generates the intermediate 54. Successive insertion of the other functionalized alkyne partner 52 following reductive elimination affords bicyclic adduct 55.…”

Ruthenium(II)-Catalyzed Annulation of Oximes with Maleimides: Synthesis of Pyrrolo[3,4-c]isoquinoline-1,3-diones

“…In recent years, many different approaches have been used for the synthesis of isoquinolines. One of the most investigated synthetic methods was the coupling of oximes and alkynes. − Although published articles in this approach showed a broad investigation of coupling of internal or terminal alkynes with oximes in the presence of transition metal catalysts, each of these methods has its own highlights and challenges. Also, as an appropriate alternative, some efforts have been made to replace alkynes with alkenes (Scheme B).…”