Dimeric tetrahydroisoquinolines

TERTIARY AMINES Acyclic tertiary amines Pyrrolizidines Phenanthroindolizidines Phenanthroquinolizidines Harringtonine and isoharringtonine Dimeric tetrahydroisoquinolines Dimeric indole alkaloids... 

Ugi five-center three-component reaction of pipecolinic acid and glycol aldehyde dimer with isocyanides gave a 1 1.7-2.1 diastereomeric mixture of l-oxoperhydropyrido[2,Tc][l,4]oxazine-9-carboxamides 397 (Scheme 35) <20010L4149>. Using CF3CH2OH as solvent is critical for the reaction. When 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid was employed, 1,3,4,6,11,11 a-hexahydro-[ l,4]oxazino[4,3+]isoquinoline-4-carboxarnide was formed. 

Two molecules with comparable geometry in an asymmetric unit were found for 3,4-bis(4-fluorophenyl)-l,2,5-oxadiazole 2-oxide. The bond length of the dipolar N-O bond is 1.107 (7) A <2006AXEo4827>. In the molecule of 5-(6,7-dimethoxy-l,2,3,4-tetrahydroisoquinolin-2-yl)-4-phenyl-l,2,5-oxadiazole Ar-oxide, the six-membered heterocyclic ring has a flattened boat form. Intermolecular C-H- O hydrogen bonds link the molecules into dimers, which may be effective in the stabilization of the crystal structure <2006AXEo3130>. 

The initial attack in the anodic oxidation of papaverine73 probably involves a similar attack further oxidation and dimerization leads to the isolated product, 12,12 -bis-(2,3,9,10-tetramethoxyindolo[2,l-a])isoquin61yl. The electrooxidation of a tetramethoxy substituted 2-methyl-l-phenethyl-1,2,3,4-tetrahydroisoquinoline to a dibenzoquinolizinium derivative is analogous.76... 

The initial attack in the anodic oxidation of papaverine [75] probably involves a similar attack further oxidation and dimerization leads to the isolated product, 12,12 -bis-(2,3,9,10-tetramethoxyindolo[2,l-fl]isoquinolyl). An analogous reaction is the electrooxidation of a tetramethoxy-substituted 2-methyl-l-phenethyl-l,2,3,4-tetrahydroisoquinoline to a dibenzoquinolizinium derivative [76] and the oxidation of A,A -triphenyl-( -phenyle-nediamine to 9,10-diphenylphenazine [77]. Intramolecular Michel addition of nitrogen in a tetrahydroquinoline derivative to an o-quinone moity have resulted in the formation of a 5,6-dihydrodibenz[6,d]indolizine derivative [78]. A similar ring closure occurs during the oxidation of various catecholamines [79] and similar compounds [79] to indoles. Cyclic a-carbonylazo compounds, generated by anodic oxidation of the hydrazines, may be trapped by reaction with dienes to the expected heterocycles [80]. 

The Noyori asymmetric transfer hydrogenation was utilized in the synthesis of the chiral 1,2,3,4-tetrahydroisoquinolines by R.A. Sheldon et al. These compounds are important intermediates in the Rice and Beyerman routes to morphine. The "Rice imine" was exposed to a series of chiral Ru " complexes, which was prepared from r -arene-Ru " chloride dimeric complexes and A/-sulfonated 1,2-diphenylethylenediamines along with the azeotropic mixture of HCOOH/NEts. With the best catalyst the desired tetrahydroisoquinoline was isolated in 73% yield and the enantiomeric excess was 99%. 

Electrochemical oxidation of racemic l,2-dimethyl-7-hydroxy-6-methoxy-1,2,3,4-tetrahydroisoquinoline (22) gives a number of dimers (cf. Vols. 2 and 4) but of the three possible racemic C-8—C-8 dimers (cf. Scheme 2) only one, the racemate corresponding to (23), was obtained.Evidently only molecules of (22)... 

The dimerization of the tetrahydroisoquinoline, shown in Table 5, entry 3, yields only one of three possible diastereomers. This outcome is best explained as a result of a surface reaction on the graphite electrode, at which only molecules of identical configuration couple. 

Curare alkaloids are dimers of 1-benzyl-l,2,3,4-tetrahydroisoquinolines linked by one, two, or even three ether bridges positioned in a most varied manner. Discussing them in a... 

Saframycins. An antibiotic complex (to date 22 known components) from cultures of Streptomyces la-vendulae. The S. contain tetrahydroisoquinoline units dimerized via a piperazine structure. They have anti-neoplastic activity and are active against Gram-positive bacteria, e. g., S. B C2gH3,N308, Mr 537.57, orange prisms, mp. 108-109 C, [a]g,°-54.4° (CH3OH). 

Bisbenzyltetrahydroisoquinolines. Biradicalic coupling (C 2.3.1) of two molecules of tetrahydroisoquinolines yields different types of dimeric alkaloids (cf. the formulas for tubocurarine and thalicarpine, Fig. 284). 

Another possible concerted reaction was observed in a study of the dimerization of simple phenolic tetrahydroisoquinolines (6 ), When the anion of N-methyl-6-methoxy-7-hydroxy-l,2,3, -... 

An aq. soln. of 6,7-dimethoxy-2-methyl-l,l-diethyl-l,2,3,4-tetrahydroisoquinoline added to a hot soln. of mercuric acetate and EDTA in 1%-acetic acid, heated 20 min. on a water bath, cooled, and treated with perchloric acid product. Y 80.3%. - Dimeric isoquinoline derivatives of this type have not been reported previously. J. Knabe and H.-P. Herbort, Arch. Pharm. 300, 774 (1967). 

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