Isoquinolinium salts, synthesis from

In 2008, Jones et cd. disclosed a stoichiometric Rh(III)-mediated reaction of JV-benzylidenemethylamine with dimethyl acetylenedicarboxylate to give the corresponding isoquinolinium salt [52a]. Inspired by this work, in 2012 we developed a Rh(III)-catalyzed one-pot synthesis of isoquinolinium salts 104 from benzaldehydes, primary amines, and internal alkynes by C-H activation and annulation [52b]. This was the first report for the synthesis of isoquinohnium salts by catalytic C-H activation. It is noteworthy that the current procedure was successfully apphed to the total synthesis of isoquinolinone alkaloid oxy-chelerythrine 105 (Eq. (5.99)). In 2013, our group and Huang independently found that various isoquinohnium salts could be synthesized from aryl ketimines, 2-phenyl pyridines, and alkynes under similar reaction conditions, as shown in Eqs. (5.100)-(5.102) [52c-e]. 

Substituted 4-aryl-1 -oxo-1,2-dihydropyrazino[l, 2-i]isoquinolinium salts 402 were obtained when 3-substituted isoquinolines 401 were cleaved from a polymer by treatment 25% TFA (00MIP5). c/i-3,lla-H-3-Phenyl-1,2,3,4,11,11 fl-hexahydropyrazino[l, 2-i]isoquinoline-1,4-dione (404) formed when isoquinoline derivative 403 was cleaved from a resin with 25% TFA during an automated solid-phase synthesis (98BMCL2369). 

Two transformations should be discussed in more detail (1) presence of the amino group in 275 was utilized for the synthesis of the fused isoquinolinium salt 276 bearing the bicyclic heterocycle as an A-substituent <2003JHC1041> (2) selective nucleophilic substitution of 277 with pyrrolidine was reported <2001ZOR604> to yield only substitution on the phenyl substituent without formation of an amide from the ester group 278. 

In the reaction with a less basic amine such as aniline, mixtures of naphthylamines 153 and isoquinolinium salts 152 were obtained (71KGS1437 88UP2). The alternative pathway of formation of naphthylamines 153 from isoquinolinium salts 152 by isomeric recyclization (81T3425) is completely excluded, since model experiments with isoquinolinium salts showed no reaction under the conditions of synthesis of naphthylamines 153. 

Methods of synthesis of bisbenzylisoquinoline alkaloids have been reviewed83 and the use of electrochemical methods for the reduction of the dihydro-isoquinolinium salts that result from Bischler-Napieralsky ring-closures in the synthesis of, for example, espinidine has been studied.84... 

The gross structure, envisaged on the basis of spectral data and biogenetic considerations (32-34), and the relative stereochemistry of alamaridine have been established by synthesis as shown in formula 64. Pakrashi s group (33,34) obtained the tetracycle 141 from the isoquinolinium salt 140 by... 

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