Silver/Rhodium Relay Catalysis Enables C−H Functionalization of In Situ Generated Isoquinolines with Sulfoxonium Ylides: Construction of Hexahydrodibenzo[a,g]quinolizine Scaffolds

Abstract

Employing silver/rhodium relay catalysis strategy, an intramolecular electrophilic cyclization and CÀ H activation followed by cascade hydrogenation and reductive amination has been developed. The acylmethylated isoquinoline derivatives could be afforded with broad substrate scope in 23-88% yields, which could be further transformed to the core skeleton of hexahydrodibenzo[a,g] quinolizine as drug-candidates. Moreover, this reaction was achieved in a gram-scale. A reasonable reaction mechanism has been proposed based on a series of control and KIE experiments.

Facile synthesis of isoquinolines and isoquinolineN-oxidesviaa copper-catalyzed intramolecular cyclization in water

“…Based on the above results and the previous work, 14,17,18 a possible reaction pathway is proposed for the formation of isoquinolines 2 and isoquinoline N -oxides 4 (Scheme 4). Initially, ortho -alkynylaryl oxime derivatives 1 or 3 were easily converted to intermediates A by a Cu( i )-catalyzed intramolecular cyclization.…”

“…In 2009, Zhang and co-workers reported an interesting work involving the product selectivity control reactions to afford isoquinolines and isoquinolin-1(2 H )-ones by simple subtle structure modification of ortho -alkynylaryl aldehyde oxime derivatives. 14 Subsequently, Li, 15 Harrity, 16 Shi 17 and others 18 disclosed a rhodium( iii ), platinum(0), silver( i ) and gold( i )-catalyzed intramolecular cyclization reaction using the same or analogous starting materials for the synthesis of isoquinolines and their derivatives, respectively. However, despite these significant advances made in accessibility of isoquinolines and their derivatives, some challenging issues still remain in terms of the use of toxic organic solvents, precious metal catalysts, harsh reaction conditions, which lead to poor atom economy and are inconsistent with the principles of green chemistry.…”

Recent Advances in Metal‐Catalyzed C−H Bond Functionalization Reactions of Sulfoxonium Ylides

“…[41c] Shi et al discussed a Ag/Rh(III) relay catalyzed methodology of an intra-molecular electrophilic cyclization of o-alkyl benzaldoxime derivative and CÀ H activation with sulfoxonium ylide followed by cascade hydrogenation and reductive amination to produce hexahydrodibenzo[a,g]quinolizine scaffolds (Scheme 38). [42] Ruthenium-Catalyzed Reactions Among the Ru complexes, the [Ru(p-cymene)Cl 2 ] 2 was used widely for the functionalize reaction of the sulfoxonium ylides. In these Ru-catalyzed CÀ H functionalization reactions, the sulfoxonium ylides were used for direct functionalization with diazo compounds and cyclopropanol (Scheme 39).…”

“…discussed a Ag/Rh(III) relay catalyzed methodology of an intra‐molecular electrophilic cyclization of o ‐alkyl benzaldoxime derivative and C−H activation with sulfoxonium ylide followed by cascade hydrogenation and reductive amination to produce hexahydrodibenzo[a,g]quinolizine scaffolds (Scheme 38). [42] …”

Copper-Catalyzed Domino Three-Component Benzannulation: Access to Isoquinolines

“…Particularly, isoquinoline motifs possess various bioactivities such as cardiovascular, antitumor, anti-inflammatory, or anti-malaria properties. In order to improve the chemical toolbox for the synthesis of biologically relevant molecules, great effort has been devoted to developing efficient methodologies for the preparation of isoquinolines, which include transition-metal-catalyzed annulation reactions of 2-alkynylbenzyl azides or 2-alkylnyl aromatic imines and oximes, C–H functionalization, dehydrogenation of N -heterocycles, the tandem reduction/radical cyclization protocol, and tandem reduction/rearrangement of cyclic imides . Most of these procedures require multistep synthesis or prefunctionalized substrates or give limited substrate scope.…”