3316-80-1

Upstream product

• 67-56-1 methanol 
• 10172-51-7 6,7-dimethoxy-1-phenyl-3,4-dihydroisoquinoline 
• 120-20-7 2-(3,4-dimethoxyphenyl)-ethylamine 
• 579-75-9 2-Methoxybenzoic acid 
• 21615-34-9 2-Methoxybenzoyl chloride 
• 142209-40-3 N-[2-(3,4-Dimethoxy-phenyl)-ethyl]-2-methoxy-benzamide 

Downstream Products

• 3161-11-3 6,7-dimethoxy-1-(2-methoxyphenyl)isoquinoline 
• 1314511-66-4 (+)-6,7-dimethoxy-1-(2-methoxyphenyl)-1,2,3,4-tetrahydroisoquinoline 

Relevant academic research and scientific papers

Josiphos-Type Binaphane Ligands for Iridium-Catalyzed Enantioselective Hydrogenation of 1-Aryl-Substituted Dihydroisoquinolines

Convenient synthesis and useful application of a series of Josiphos-type binaphane ligands were described. The iridium complexes of these chiral diphosphines displayed excellent enantioselectivity and good reactivity in the asymmetric hydrogenation of challenging 1-aryl-substituted dihydroisoquinoline substrates (full conversions, up to >99% ee, 4000 TON). The use of 40% HBr (aqueous solution) as an additive dramatically improved the asymmetric induction of these catalysts. This transformation provided a highly efficient and enantioselective access to chiral 1-aryl-substituted tetrahydroisoquinolines, which were of great importance and common in natural products and biologically active molecules.

Enantioselective Synthesis of 1-Aryl-Substituted Tetrahydroisoquinolines Through Ru-Catalyzed Asymmetric Transfer Hydrogenation

A convenient and general asymmetric transfer hydrogenation of a wide array of 1-aryl-3,4-dihydroisoquinoline derivatives using a [RuIICl(η6-benzene)TsDPEN] complex in combination with a 5:2 HCOOH-Et3N azeotropic mixture as a hydrogen source was developed. Under mild reaction conditions, the described catalytic transformation secured a practical synthetic access to the corresponding valuable chiral 1-aryltetrahydroisoquinoline units with high atom economy, a broad substrate scope, high isolated yields (up to 97%) and good to excellent enantioselectivities (up to 99% ee). It was found that the stereochemical outcome of the reaction was strongly influenced by both the structure of the catalyst and the substituents present on the substrate. The synthetic utility of the present protocol has been demonstrated through the asymmetric synthesis of several biologically important alkaloids including the antiepileptic drug agent 1c, as well as (-)-nor-cryptostyline alkaloids I and II.

Oxidative C-H functionalization: A novel strategy for the acetoxylation/alkoxylation of arenes tethered to 3,4-dihydroisoquinolines

1-Aryl-3,4-dihydroisoquinolines undergo smooth acetoxylation/alkoxylation in the presence of 5 mol % Pd(OAc)2 and a stoichiometric amount of PhI(OAc)2 by means of C-H activation to produce the corresponding acetoxy- and alkoxy-1-aryl-3,4-dihydroisoquinoline derivatives respectively in good yields with high regioselectivity. It is a first example on oxidative functionalization of arenes tethered to dihydroisoquinoline moiety via the C-H activation.

Strategies and synthetic methods directed toward the preparation of libraries of substituted isoquinolines

Strategies for the production of substituted isoquinoline libraries were developed and explored. Routes involving microwave-assisted variants of the Bischler-Napieralski or Pictet-Spengler reaction allowed for cyclization of substituted β-arylethylamine derivatives. The dihydroisoquinolines and tetrahydroisoquinolines thus generated could then be oxidized to their corresponding isoquinoline analogues. An alternate strategy, however, involving the preparation and activation of isoquinolin-1(2H)-ones is demonstrated to be a more practical, rapid, and efficient route to C1- and C4-substituted isoquinoline libraries.

Synthesis and spectral properties of 6,7-dimethoxy-1-[(ortho; and para-R)-phenyl]-3,4-dihydroisoquinoline

The preparation of eleven novel 6,7-dimethoxy-1-[(ortho, and para-R)-phenyl]-3,4-dihydroisoquinolines with possible pharmacological activity is described. The structure of all products was corroborated by ir, 1H nmr, 13C-nmr, and ms.