Isoquinoline derivatives, formation

Most annulation procedures, which produce nitrogen heterocycles start from a tert-butvlimine, where the sacrificial organic moiety is released in the course of the process as isobutene. Ring closure of the 2-iodoveratraldehyde derivative shown in 4.34. and ethyl phenylpropiolate, for example, led to the formation of the appropriate isoquinoline derivative in excellent yield. Formation of the isomeric 4-phenylisoquinoline compound was also observed (5%).42... 

The intramolecular palladium catalyzed ring closure of the tetrahydro-isoquinoline derivative depicted in 8.41. led to the formation of the aporphine derivative in good yield, which was then converted into racemic aporphine in three steps. In the ring closing step 20 mol% palladium acetate and 40 mol% tricyclohexylphosphine were used as catalyst. The removal of the hydroxyl group was also achieved by palladium catalysis through its conversion to triflate and the subsequent reduction with ammonium formate in the presence of palladium acetate and dppf.53... 

Nickel(O) complexes catalyse [2+2+2] cycloaddition. Catalytic asymmetric synthesis of isoquinoline derivative 134 is possible based on enantiotopic group-selective formation of the nickelacyclopentadiene 133 from 132 using the Ni(0) complex coordinated by a chiral ligand under acetylene atmosphere [56]. 

Roydhouse, M.D. and Walton, J.C. (2007) Formation of a tetracyclic isoquinoline derivative by rearrangement of a [(bromophenyl)butyryl]oxazolidinone. European Journal of Organic Chemistry, 1059-1063. 

Perllissier H (2003) Dynamic kinetic resolution. Tetrahedron 59 8291-8327 Pictet A, Spengler T (1911) Formation of isoquinoline derivatives by the action of methylal on phenylethylamine, phenylalanine and tyrosine. Ber Dtsch Chem Ges 44 2030-2036... 

The diazonium salt 453, derived from aminoisoquinoline 452, undergoes thermal cyclization to afford 6-thiaellip-ticine 454 and 37/-pyrazolo[3,4-, ]isoquinoline 455. Formation of 454 may involve the cyclization of an aryl radical intermediate (Scheme 74) <1996CC2711>. Isomerically pure 4,6-dimethyldibenzothiophene 457 <1996T3953> and benzothiophene 459 <2005T8711> can be synthesized from the diazonium salts 456 and 458, respectively. 

In Section III,C it was shown that various 1-substituted 1,2-dihydroiso-quinolines can be cyclized intramolecularly to give pavinanes, isopavinanes, homopavinanes, and homoisopavinanes. Section III,D deals with the formation of 3-substituted isoquinoline derivatives from 1-allyl-, 1-benzyl-1,2-dihydroisoquinolines, and related compounds. In this section some synthetic reactions of 1,2-dihydroisoquinolines are reported. 

Pictet, A., Spengler, T. Formation of Isoquinoline Derivatives by the Action of Methylal on Phenylethylamine, Phenylalanine and Tyrosine. Ber. 1911,44,2030-2036. 

Gabriel-Colman rearrangement. Formation of isoquinoline derivatives by the action of sodium ethoxide on phthalimidoacetic esters. 

The dihydroisoquinoline derivative 11, which was formed as an intermediate upon reaction of benzophenone imine (9) with methyl 2-chloro-2-cyclopropylideneacetate (10) in carbon tetrachloride, can be regarded as an acceptor-substituted spirocyclopropane derivative. Under the conditions of its formation, it rearranges with attack of chloride ion on the spirocyclopropane group to give the ) -chloroethyl-substituted isoquinoline derivative 12. ... 

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>. 

Isoquinoline derivatives are an important family of natural products. They have diverse biological activities and are used, for example, as bronchodi-lators, skeletal muscle relaxants, and antiseptics. The solid-phase synthesis of a 43,000-compound tetrahydroisoquinoline 2 combinatorial library has been reported by Griffith et al. [32]. The library was synthesized by a three-step procedure. An imine was formed by reacting a substituted benzaldehyde with a methylbenzhydrylamine (MB HA) resin-bound amino acid. Imine formation was driven to completion using trimethylorthoformate as a dehydrating reagent. Treatment of the imine with homophthalic anhydride provided the desired tetrahydroisoquinoline (Fig. 3a). 

Isoindolines and isoquinolines a,co-Diynes in which the connecting chains contain a nitrogen atom undergo [2+2+2]-cycloaddition with ketene equivalents derived from the carbene complexes. After the formation of a benzene ring, the products are isoindoline or isoquinoline derivatives. 

In support of the hypothetical phytochemical formation of tetrahydro-isoquinoline derivatives from phenethylamine derivatives and aldehydes, Schopf and Bayerle (118) examined the condensation of acetaldehyde with... 

Oxyberberine (XVIII) is the first product of the oxidation of berberine. It may be reduced to tetrahydroberberiiie at a lead cathode in alcoholic sulfuric acid (215). Its synthesis is therefore a synthesis of berberine. The general procedure for the synthesis of this type of compound is described in connection with the synthesis of cryptopine, and oxyberberine itself was prepared by this procedure. Another synthesis of oxyberberine was achieved by Perkin, Ray, and Robinson (216). The 8-piperonyl-ethylimide of meconinecarboxylic acid (XX) was heated with phosphoryl chloride to yield an uncharacterized isoquinoline derivative, presumably XXI, which when reduced with zinc in acetic acid suffered reduction of the doubl bond, opening of the lactone ring, lactam formation, and dehydration to yield oxyberberine. This ready elimination of water was later observed in ophiocarpine (6). 

Reactions with aikynes may aiso result in the formation of cyclized products. Thus a ruthenium-catalysed reaction with aromatic amides has been used to give isoquinoline derivatives. On the basis of values of the kinetic isotope effect, A h/ d> proposed that the rate-determining step is a concerted acetate-assisted metalation-deprotonation process to yield the intermediate (30), followed by aikyne insertion and ring closure. The reaction of arylketones with alkynes may yield indenols when catalysed by rhodium cyclopentadienyl in the presence of silver and copper salts. The reaction proceeds regioselectively, so that reaction of acetophenone with 1-phenyl-1-propene... 

Formation of isoquinoline derivatives or substituted benzothiazines by the action of alkoxides on phthalimidoacetic or saccharin esters or ketones ... 

In 1967, the formation of diethyl 4,5,6,7-tetrafluoro-benzo[h]thiophen-2,3-dicarboxylate 259 in 49 % yield, by the reaction of lithium pentafluorobenzenethiolate with diethyl acetylenedicarboxylate in THF under reflux, was reported [ 124], Later, the cyclization reaction was shown to occur under very mild conditions (-70 to -58 °C) in 74 % yield [125], A similar reaction of lithium l,3,4,5,6,7,8-heptafluoro-2-naphthalenethiolate and its isoquinoline derivative with dimethyl acetylenedicarboxylate was reported to give polyfluorinated condensed products 261 and 262 [126],... 

Ring-fluorinated isoquinoline derivatives thus synthesized exhibit a wide range of bioactivities that rival or surpass those of the original fluorine-free compounds, hi addition to such remarkable potentials in the field of pharmaceutical sciences, the formation of supramolecular structures and the use of ligands of light-emitting metal complexes have also attracted considerable attention as possible functions of fluoroisoquinolines. This section describes conaete examples of the properties and applications of fluoroisoquinoline derivatives. 

When the reaction of Ai-sulfonyl aryl aldimines and alkynes was carried out in the presence of 5 mol% of [RuCl2(p-cymene)]2, 20 mol% of AgSbFg, 10 mol% TsNH2 and 4 equiv. of AcOH in dioxane at 95°C, after 20 h, no isoquinoline derivative was obtained as for ketimines (Scheme 20), but indenamine derivatives were obtained instead resulting from C-H bond activation, insertion of alkyne, and C-C bond formation [(Eq. 104)] [196]. 

An interesting smooth ring opening of o-diazides to form 1,4-dicyanobutadiene has been discovered A selective cleavage of the Ci-N-bond of certain isoquinoline derivatives can be effectively performed with ethyl chloroformate. This little known cleavage was discovered approximately 40 years ago and used recently again with success Photolysis of solutions of 1,2,3-triazolines results in loss of nitrogen and clean formation of aziridines... 

Using a dipole precursor as the amine component in imine formation, the iso-quinolinium intermediate undergoes [3 + 2] cycloaddition to form fused isoquinoline derivatives. Su and Porco found that treatment of alkynylimines 175 with AgOTf (10 mol %) affords azomethine ylides 178, which undergo dipolar cycloaddition in the presence of appropriate alkynes to give pyrrole-fused isoquinolines 176 (Scheme 19.44) [80]. 

Jensen KB, Roberson M, J0rgensen KA (2000) Catalytic enantioselective 1,3-dipolar cycloaddition reaction of cyclic nitrones a simple approach for the formation of optically active isoquinoline derivatives. J Org Chem 65 9080-9084... 

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