Zur Synthese. von D-Glucopyrano-(cis-2′, 1′-c)-l,2,3,4-tetrahydro-isochinolinen

By a modified POMERANZ-FRITSCH -reaction substituted D-glucopyrano-1,2,3,4-tetrahydro-isoquinolines have been obtained in high yields from substituted N-benzyl-D-glucosamines. The structure of the products has been confirmed by N.M.R. spectroscopy.     

Reaction of 2,3-Dioxopyrrolo-[2,1-<Emphasis Type="Italic">a</Emphasis>]isoquinolines with Aromatic and Secondary Aliphatic Amines

It has been found that 2,3-dioxopyrrolo[2,1-a]isoquinolines react with aromatic amines in glacial acetic acid and with heteroaromatic and secondary aliphatic amines in the absence of acid with opening of the pyrroledione ring to give 1,2,3,4-tetrahydroisoquinoline enamino ketoamides. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1378–1382, September, 2005.     

A New Approach to Prepare 2-Acetyl-Mono (5,6,7,8)-Nitro-1,2,3,4-Tetrahydroisoquinolines

N-Acetyl-p, m or o-nitro-phenylethylamines and (HCHO)n were treated in 60% H2SO4/HOAc, via α-amidoalkylation to give 2-acetyl-mono(5, 6, 7 or 8)-nitro-1,2,3,4-tetrahydro-isoquinolines.Additionally, some interesting phenomena were observed when the comparison between 2-acetyl-5, 6, 7 or 8-nitro-1,2,3,4-tetrahydroisoquinolines and 2-alkylsulfonyl-5 , 6 or 7- nitro-1,2,3,4-tetrahydroisoquinolines was made.     

Mild and Efficient Syntheses of 1-Aryl-3,4-dihydroisoquinolines and 1-Aryl-3,4-dihydro-β-carbolines via Regiospecific β-Eliminations of the Corresponding N-Tosyl-1,2,3,4-tetrahydroisoquinolines and N-Tosyl-1,2,3,4-tetrahydro-β-carbolines

Treatment of N-tosyl-1-aryl-1,2,3,4-tetrahydro-isoquinolines or N-tosyl-1-aryl-1,2,3,4-tetrahydro-β-carbolines with a strong base such as NaOH or KOH at 70 °C in dimethylsulfoxide (DMSO) produced 1-aryl-3,4-dihydroisoquinolines or 1-aryl-3,4-dihydro-β-carbolines in good yields via mild and regiospecific β-eliminations. A dramatic solvent effect was observed, DMSO was crucial for the reactions. The temperature is also crucial for the reactions and should be kept between 60 and 80 °C.     

A convenient synthesis of 1,1-disubstituted 1,2,3,4-tetrahydroisoquinolines via Pictet-Spengler reaction using titanium(IV) isopropoxide and acetic-formic anhydride

A synthesis of 1,1-disubstituted 1,2,3,4-tetrahydroisoquinolines (6) was achieved in a highly efficient manner via Pictet-Spengler reaction of arylethylamines (1) and acyclic and cyclic ketones (2) using titanium (IV) isopropoxide and acetic-formic anhydride. The cyclization of the in situ formed acyliminium ion (4) to N-formyl 1,2,3,4-tetrahydroisoquinoline (5) was greatly facilitated by using trifluoroacetic acid as an additional reagent. The Pictet-Spengler reaction was carried out by one pot procedure, providing a convenient and effective method for preparing various 1,2,3,4-tetrahydroisoquinolines.     

Alkali metal,alkaline and acidic decomposition of silacyclopentadienes

1,1-Dimethyl-2,5-diphenyl-1-silacyclopentadiene and 1,1-dimethyl-2,3,4,5-tetraphenyl-1-silacyclopentadiene (X) are cleaved by sodium hydroxide as well as by hydrochloric acid to give trans, trans-1,4-diphenylbutadiene and cis, cis-1,2,3,4-tetraphenylbutadiene, respectively. Compound X, hexaphenylsilacyclopentadiene and 1-methyl-1,2,3,4,5-pentaphenyl-1-silacyclopentadiene, on treatment with potassium in 1,2-dimethoxyethane gave intensely red colored dianions which on quenching in moist tetrahydrofuran gave rise to α,α′-dibenzylstilbene. A pathway for the reaction is suggested.     

An effective method for the preparation of mono N-alkyl derivatives of 1,1′-bis(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline)

The condensation of 1,1′-bis(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline) with alkyl, aralkyl and aryl aldehydes, but not ketones, in ethanol or chloroform provides useful cyclic aminal [8-substituted 5,6,10,11,15b,15c-hexahydro-2,3,13,14-tetramethoxy-8H-imidazo[5,1-a:4,3-a′]diisoquinoline] intermediates that when subsequently treated with sodium cyanoborohydride in ethanol, followed by the addition of 2 M hydrochloric acid, gave monosubstituted N-alkyl 1,1′-bis(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline) derivatives in very high yields. The rates of the initial condensation with four different aldehydes were measured, and the entire sequence was successfully applied in one example to a ‘one-pot’ process; this signals a versatile route to differentially N-substituted 1,1′-bis(1,2,3,4-tetrahydroisoquinoline) derivatives.     

Short synthesis of tryptophane and β-carboline derivatives by reaction of indoles with N-(diphenylmethylene)-α,β-didehydroamino acid esters

The ethylaluminum dichloride catalyzed Michael-type addition of indoles 1a-h to the N-(diphenylmethylene)-α,β-didehydroamino acid esters 2a-c allows a new synthesis of β-methyltryptophanes 41,m and a new route for 1,1-diphenyl-3-carbalkoxy-1,2,3,4-tetrahydro-β-carbolines 5a-m.     

Synthesis of isoquinoline. Synthesis of 7-hydroxy-6-methoxy-2methyl-(4-hydroxy-3,5-dimethoxyphenethyl)-1,2,3,4-tetrahydro-isoquinoline, an intermediate in the synthesis of homapomorphine alkaloids

Polymethoxylated 1-phenethyl-3, 4-dihydro- and -1, 2, 3, 4-tetrahydro-isoquinolines were selectively demethylated by varying the mineral acid treatment. Under these conditions, the 6-methoxyl was the most stable, while the 4′-methoxyl was the most labile. Based on this study and by employing an unprotected phenolic intermediate in the Bischler-Napieralski cyclization, an efficient, simple and technically feasible synthesis of the diphenol 1 , an important intermediate in the synthesis of homoapomorphine alkaloids, was achieved.     

Synthesis of substituted bis(3,3-dialkyl-3,4-dihydro-1-isoquinolyl)methanes

Symmetrical and non-symmetrical substituted bis(3,4-dihydro-1-isoquinolyl)methanes were synthesized by fusion of substituted 1-methylthio-3,4-dihydroisoquinolines with 1-methyl-3,4-dihydroisoquinolines and by the Ritter reaction of 1,1-dialkyl-2-arylethanols with 1-cyanomethylidene-1,2,3,4-tetrahydroisoquinoline or malononitrile.     

(3 + 3)-Cyclodimerization of donor-acceptor cyclopropanes. Three routes to six-membered rings

The ability of donor-acceptor cyclopropanes to (3 + 3)-cyclodimerize is disclosed. It has been found that Lewis acid-induced transformations of 2-(hetero)arylcyclopropane-1,1-dicarboxylates containing electron-abundant aromatic substituents led to the construction of six-membered cyclic systems. Depending on the substrate properties and the Lewis acid applied, three types of products can be obtained: (1) 1,4-diarylcyclohexanes, (2) 1-aryl-1,2,3,4-tetrahydronaphthalenes, and (3) 9,10-dihydroanthracenes.     

PS-PEG resin-supported palladium-MOP complexes. Application in asymmetric π-allylic reduction

Homochiral palladium complexes of polymeric 2′-, 6-, and 6′-anchored 2-diphenylphosphino-1,1′-binaphthyl (MOP) ligands were prepared on polystyrene-poly(ethylene glycol) (PS-PEG) resin. The PS-PEG resin-supported palladium-MOP complexes exhibited high catalytic activity, stereoselectivity (up to 80% ee), and recyclability (six times) in the asymmetric allylic reduction of 1-vinyl-1,2,3,4-tetrahydronaphth-1-yl benzoate to give 1-vinyl-1,2,3,4-tetrahydronaphthalene.     

A novel synthesis of 1H-pyrrole-2,3,4,5-tetracarboxylates

A novel and convenient synthesis of 1H -pyrrole-2,3,4,5-tetracarboxylates is described. Photocyclization of 1,1′-bis(methoxycarbonyl)divinylamine with acetylenedicarboxylates gave 7-azabicyclo[2.2.1]hept-2-ene-1,2,3,4-tetracarboxylates 2a-i , which on melting split ethylene off to yield 1H-pyrrole-2,3,4,5-tetracarboxylates 3a-i quantitatively.     

Palladium-catalyzed denitrogenation reaction of 1,2,3-benzotriazin-4(3H)-ones incorporating isocyanides

1,2,3-Benzotriazin-4(3H)-ones and 1,2,3,4-benzothiatriazine 1,1(2H)-dioxide reacted with isocyanides in the presence of a palladium catalyst to give 3-(imino)isoindolin-1-ones and 3-(imino)thiaisoindoline 1,1-dioxides, respectively, in high yield. An intermediate azapalladacycle was generated through denitrogenation of the triazine moiety, and an isocyanide was incorporated therein.     

Heterocyclization of 1,1-dicyano-2-(trifluoromethyl)ethylenes with 1,3,3-trimethyl-3,4-dihydroisoquinoline and its derivatives

1,3,3-Trimethyl-3,4-dihydroisoquinolines react with 1,1-dicyano-2,2-bis(trifluoromethyl)ethylene to give 4-amino-6,6-dimethyl-2,2-bis(trifluoromethyl)-3-cyano-6,7-dihydro-2H-benzo[a]quinolizines. The reaction of 3,3-dimethyl-1-cyanomethylidene-1,2,3,4-tetrahydroisoquinoline and the methyl ester of 3,3-dicyano-2-(trifluoromethyl)acrylic acid leads to 5,5-dimethyl-3-oxo-2-(trifluoromethyl)-2-(dicyanomethyl)-2,3,5,6-tetrahydropyrrolo[2,1-a]isoquinoline.A. N. Nesmeyanov Institute of Heteroorganic Compounds, Russian Academy of Sciences, 117813 Moscow. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 8, pp. 1888–1892, August, 1992.     

Synthesis, structure, and biological activity of ferrocenyl carbohydrate conjugates

Seven ferrocenyl carbohydrate conjugates were synthesized. Coupling reactions of monosaccharide derivatives with ferrocene carbonyl chloride produced {6-N-(methyl 2,3,4-tri-O-acetyl-6-amino-6-deoxy-alpha-D-glucopyranoside)}-1-ferrocene carboxamide (3), {1-O-(2,3,4,6-tetra-O-benzyl-D-glucopyranose)}-1-ferrocene carboxylate (4), and {6-O-(1,2,3,4-tetra-O-acetyl-beta-D-glucopyranose)}-1-ferrocene carboxylate (5). Similarly, 1,1'-bis(carbonyl chloride)ferrocene was coupled with the appropriate sugars to produce the disubstituted analogues bis{6-N-(methyl 2,3,4-tri-O-acetyl-6-amino-6-deoxy-alpha-D-glucopyranoside)}-1,1'-ferrocene carboxamide (8), bis{1-O-(2,3,4,6-tetra-O-benzyl-D-glucopyranose)}-1,1'-ferrocene carboxylate (9), and bis{6-O-(1,2,3,4-tetra-O-acetyl-beta-D-glucopyranose)}-1,1'-ferrocene carboxylate (10). {6-N-(Methyl-6-amino-6-deoxy-alpha-D-glucopyranoside)}-1-ferrocene carboxamide monohydrate (12) was synthesized via amide coupling of an activated ferrocenyl ester with the corresponding carbohydrate. All compounds were characterized by elemental analysis, 1H NMR spectroscopy, and mass spectrometry. X-ray crystallography confirmed the solid-state structure of three ferrocenyl carbohydrate conjugates: 2-N-(1,3,4,6-tetra-O-acetyl-2-amino-2-deoxy-D-glucopyranose)-1-ferrocene carboxamide (1), 1-S-(2,3,4,6-tetra-O-acetyl-1-deoxy-1-thio-D-glucopyranose)-1-ferrocene carboxylate (2), and 12. The above compounds, along with bis{2-N-(1,3,4,6-tetra-O-acetyl-2-amino-2-deoxy-D-glucopyranose)}-1,1'-ferrocene carboxamide (6), bis{1-S-(2,3,4,6-tetra-O-acetyl-1-deoxy-1-thio-D-glucopyranose)}-1,1'-ferrocene carboxylate (7), and 2-N-(2-amino-2-deoxy-D-glucopyranose)-1-ferrocene carboxamide (11) were examined for cytotoxicity in cell lines (L1210 and HTB-129) and for antimalarial activity in Plasmodium falciparum strains (D10, 3D7, and K1, a chloroquine-resistant strain). In general, the compounds were nontoxic in the human cell line tested (HTB-129), and compounds 4, 7, and 9 showed moderate antimalarial activity in one or more of the P. falciparum strains.     

Practical synthesis of an open geodesic polyarene with a fullerene-type 6:6-double bond at the center: diindeno[1,2,3,4-defg;1',2',3',4'-mnop]chrysene

Diindeno[1,2,3,4-defg;1',2',3',4'-mnop]chrysene (1), the smallest possible alkene-centered C60 substructure with a curved pi-system, is obtained in 25-35% yield by flash vacuum pyrolysis of the twisted 1,1'-dibromobifluorenylidene (2) on a 100 mg scale at 1050 degrees C. At 1200 degrees C, the bowl-shaped hydrocarbon 1 rearranges to the planar isomer diindeno[5,6,7,1-defg;5',6',7',1'-lmnop]chrysene (14) by a double 5/6 ring-expansion/ring-contraction. X-ray crystallography establishes that the central carbon atoms of 1 are nearly 80% as pyramidalized as the carbon atoms of C60 (POAV angles = 9.0 degrees and 11.6 degrees for 1 and C60, respectively). A four-step synthesis has been developed to prepare the pyrolysis precursor (2) as a mixture of (E)- and (Z)-isomers in 39% overall yield from commercially available 9-fluorenone-1-carboxylic acid (10).     

A New Class of Tunable Dendritic Diphosphine Ligands: Synthesis and Applications in the Ru‐Catalyzed Asymmetric Hydrogenation of Functionalized Ketones

A series of tunable G₀–G₃ dendritic 2,2′‐bis(diphenylphosphino)‐1,1′‐binaphthyl (BINAP) ligands was prepared by attaching polyaryl ether dendrons onto the four phenyl rings on the P atoms. Their ruthenium complexes were employed in the asymmetric hydrogenation of β‐ketoesters, α‐ketoesters, and α‐ketoamides to reveal the effects of dendron size on the catalytic properties. The second‐ and third‐generation catalysts exhibited excellent enantioselectivities, which are remarkably higher than those obtained from the small molecular catalysts and the first‐generation catalyst. Molecular modeling indicates that the incorporation of bulky dendritic wedges can influence the steric environments around the metal center. In addition, the ruthenium catalyst bearing a second‐generation dendritic ligand could be recycled and reused seven times without any obvious decrease in enantioselectivity.     

Darstellung einiger perfluorbenzol-di-, tri- und tetrasulfonsäuren

1,2,3,4-Tetrafluorbenzenesulfonic acid, 1,2,4,5-tetrafluorobenzenesulfonic acid, 1,2,3,5-tetrafluorobenzenedisulfonic acid, 1,3,5-trifluorobenzene-2,4-disulfonic acid and 1,3,5-trifluorobenzenetrisulfonic acid are obtained by sulfonation of the three isomeric tetrafluorobenzenes, and of 1,3,5-trifluorobenzene, with stabilized SO₃ at normal pressure. Starting from dilithium 1,2,3,4-tetrafluorobenzenedisulphinate 1,2,3,4-tetrafluorobenzenedisulfonic acid can be prepared via oxidation with hydrogen peroxide. Fluorine displacement reactions lead to 1-thiol-2,3,5-trifluorobenzenedisulfonic acid, 1-thiol-2,3,6-trifluorobenzenedisulfonic acid, 1-thiol-2,4,5-trifluorobenzenedisulfonic acid, 1-thiol-2,5-difluorobenzenetrisulfonic acid and 1-thiol-3,5-difluorobenzenetrisulfonic acid, which can be converted into 1,2,4-trifluorobenzenetrisulfonic acid, 1,3-difluorobenzenetetrasulfonic acid and 1,4-difluorobenzenetetrasulfonic acid by oxidation procedures. N.m.r. parameters of the new compounds are described.     

New tetracyclic compounds containing the β-carboline moiety

Oxidation of 1-methyl-3-methoxycarbonyl-β-carboline with selenium dioxide gave 1-formyl-3-methoxycarbonyl-β-carboline II . Compound II reacted with acetic or propionic anhydride to give easily the 2-methoxycarbonyl-6H-indolo[3,2,1-d,e][1,5]naphthyridin-6-ones III ; reaction of II with some primary amines led to the formation of the Schiff bases IV , which were reduced to the 1-aminomethyl-3-methoxycarbonyl-β-carbolines V with sodium borohydride. Cyclization of V with aqueous formaldehyde led to the pyrimido[3,4,5-lm]pyrido[3,4-b]indoles VI . Analogously, cyclization with formaldehyde, acetone or 1,1′-carbonyldiimidazole of the 3-aminomethyl- 1,2,3,4-tetrahydro-β-carbolines VIII , obtained by reaction of 3-methoxycarbonyl-1,2,3,4-tetrahydro-β-carboline VII with amines followed by lithium aluminium hydride reduction of the resulting amides, gave the imidazo[1′,5′-1,6]pyrido[3,4-b]indoles IX and X . Dieckmann cyclization of 3-methoxycarbonyl-2-[(3-ethoxycarbonyl)-1-propyl]-1,2,3,4-tetrahydro-β-carboline XI led to a 1:1 mixture of the β-ketoesters XII and XIII , which underwent deethoxycarbonylation to 5,6,8,9,10,11,11a,12-octahydroindolo[3,2-b]quinolizin-11-one XIV . Finally, the polyphosphoric acid (or esters) catalyzed cyclization of the N-acyl derivatives XVI of 3-hydrazinocarbonyl-β-carboline XV led smoothly to the 3-(1,3,4-oxadiazol-2-yl)-β-carbolines XVII .