Isoquinoline derivatives via

Tetrahydroisoquinolines were also prepared by an electrophilic aromatic substitution reaction of 2-amidoacroleins. Exposure of IV-aryl-substituted 3-amido-1,3-dioxins 82 to Lewis acids results in retrocycloadditions to afford 2-amidoacroleins 83 and concomitant electrophilic aromatic substitution to afford tetrahydroisoquinolines 84 <01OL3349>. The synthesis of isoquinoline derivatives via cyclization reactions received attention as well. Some examples include the preparation of isoquinolines by a photocyclization of l-methoxy-2-azabuta-l,3-dienes <01TL3575>. The photochemically induced preparation of 1-methyl-1,2,3,4-tetrahydronaphtho[2,l-/ isoquinolines was also reported <01T1981>. 

Alkyl arylacetates react with Tf20 to give a cation which in the presence of a nitrile affords isoquinoline derivatives via cychza-tion of the intermediate nitrilium cation (eq 27). ... 

Sdnchez-Sancho, F., Mann, E. and Herradon, B. (2001) Efficient synthesis of chiral isoquinoline and pyrido[l,2-6]-isoquinoline derivatives via intramolecular Heck reactions. Adv. Synth. Catal., 343, 360-8. 

S. Monsal, A. Maity, R. Paira, M. Banerjee, YP. Bharitkar, A. Hazra, S. Banerjee, N.B. Mondals, Efficient synthesis of novel tetrahydropyr-rolo[3, 4 3.4]pyrrolo[2.1-fl] isoquinoline derivatives via simple and convenient MCR in aqueous micellar system. Tetrahedron Lett. 53 (2012) 1288-1291. 

The Delft synthesis makes use of an acid-catalyzed ring closure - in fact an intramolecular aromatic alkylation - of a l-(3,5-dihydroxy-4-methoxybenzyl) isoquinoline derivative that is prepared starting from (natural) gallic acid. One of the hydroxyl groups is removed via a Pd/ C hydrogenation of the benzyl ether. Other catalytic steps play an important role some steps were improved recently [27]. The crucial step in the Rice synthesis makes use of a l-(2-bromo-5-hydroxy-4-methoxybenzyl)isoquinoline derivative that is also cyclized in an acid-catalyzed ring closure to the morphinan skeleton, followed by catalytic removal of the bromo substituent (Scheme 5.8). 

The synthesis of compound 135 (Scheme 12) includes the production of isoquinoline 132 via a Bischler-Napieralski reaction, its reduction and alkylation on the nitrogen atom followed by cyclization of N-alkyl derivatives 134 in the presence of acids (83JHC1477 Scheme 36). 

Primary amines reacted via a palladium-catalysed allene insertion-nucleophilic incorporation-Michael addition cascade to give isoquinoline derivatives. The yields were good and fifteen examples are reported <03TL7445>. 

One of the most powerful methods for the construction of tetrahydroisoquinoline systems is the Pictet-Spengler cyclisation. The reaction consists of the condensation of a b-phenylethylamine derivative with a carbonyl compound, generating an imine (Schiffs base), which undergoes cyclisation via an intramolecular electrophilic aromatic substitution yielding the isoquinoline derivative. The Pictet-Spengler reaction is traditionally carried out in a protic solvent with acid catalysts, usually acetic acid or trifluoroacetic acid. 

The synthesis of Amaryllidaceae alkaloids siculine, oxocrinine and peicrinine was reported using a key phenyliodine(III) bis(trifluoroacetate)-mediated intramolecular p-p diphenol coupling reaction of norbelladine derivatives followed by an intramolecular Michael addition <04T4901>. An alternative approach to isoquinoline derivatives was reported by Chang and coworkers. In this report the benzene nucleus is installed via an intramolecular electrophilic cyclization of 3,4-disubstituted lactams 87 to provide 3,4-dihydrobenzo[g]isoquinoline-l(27/)-one 88 and 3,4-dihydroisoquinoline-l(2/7)-one 89 derivatives in good yields <04TL10637>. 

In a study on the activation of macrocyclic enediynes by transannular cyclization it was found that the deprotection of the sulfonamide group of ketone 91 triggered the formation of aminol 92 which readily provided the isoquinoline derivative 93 via a Bergman cyclization reaction <04AG(E)132>. 

Dichloromethylenebenzamide could also be reacted with 2-aminoisoquinoline to give the angularly fused 2-phenyl-4-oxotriazino[2,l-a]isoquinoline derivative in poor yield <76CB118>. Ethoxy-carbonyl isocyanate with 2-(substituted amino)pyridines (131) gave 1-substituted betaines (133) via allophanates (132) (Scheme 9) <76CB366I>. 

The arylation of sodium cyanide can be achieved in moderate yields with electron-withdrawing iodonium salts [87]. The synthesis of esters was achieved by palladium-catalyzed carbonylative reaction of alcohols with diaiyliodonium salts under a CO atmosphere [262]. More recently, a base-mediated arylation of qui-nones with electron-donating iodonium salts in refluxing DCE was reported in moderate to good yields [263]. Quinoline anilides could be arylated at the P-carbon by a Pd- or Ni-catalyzed reaction proceeding via activation of sp C-H bonds (Scheme 22a) [264, 265]. Vinyl isocyanides were arylated at room temperature in a photoredox-catalyzed system with an iridium catalyst and visible light, followed by cyclizatimi to give isoquinoline derivatives [266]. 

Several typical synthetic methodologies for the preparation of fluorinated isoquinoline derivatives emeiged in the 1950s and 1960s. Fundamental reactivities and properties of such compounds were also concomitantly reported. In 1951, Roe and Teague reported the first synthesis of monofluorinated isoquinolines (Scheme 1) [9]. They successfully prepared 1-, 3-, 4-, and 5-fluoroisoquinolines via heating diazonium intermediates... 

In contrast to nucleophilic fluorination, fluoroisoquinoline syntheses via direct electrophilic fluorination were reported relatively recoitly. In 2007, Price developed direct electrophilic C-H bond fluorination of an isoquinoline derivative with Selectfluor (l-(chloromethyl)-4-fluoro-l,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate), F-TEDA), [39] which is known as an efficient electrophilic fluorine source [40-42]. 

Guimond N, Fagnou K (2009) Isoquinoline synthesis via rhodium-catalyzed oxidative cross-coupling/cyclization of aryl aldimines and alkynes. J Am Chem Soc 131 12050-12051 Booth BL, CoUis A (1989) One-step synthesis of A -(l-benzylisoquinohn-3-yl)phenylacet-amidinium trifluoromethanesulphonate derivatives from phenylacetonitiiles and trifluoro-methanesulphonic Acid. J Chem Res Synop 304-305... 

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