2-Aryl-l-tetralones

A common intermediate in the synthesis of benzo[c]phenanthridines is the 2-aryl-l-tetralone, which provides rings A, B, and D of the alkaloid nucleus. In 1973, two independent research groups reported the synthesis of nitidine via the 3,4-dihydro-2-(3,4-dimethoxyphenyl)-6,7-methylenedioxy-(2/7)-naphthalone 29 (Scheme 2). The synthesis of this intermediate was arrived at by two different routes. Kametani ei al. (73JHC31) reduced 3-(3,4-methylenedioxyphenyl)proprionate 21 to the corresponding alcohol 22 with lithium aluminium hydride, which was then converted to the chloride 23 with thionyl chloride. After production of the nitrile 24 by reaction with sodium cyanide and subsequent hydrolysis to the carboxylic acid 25, Friedel-Crafts cyclization of the acid chloride 26 afforded the tetralone intermediate 27. Reaction with l-bromo-3,4-dimethoxybenzene 28 in the presence of sodium amide yielded the tetralone intermediate 29 in an overall yield of 4%. 

To arrive at the 2-aryl-l-tetralone, Zee-Cheng and Cheng (73JHC85, 73JHC867) used the Claisen-Schmidt aldol condensation of veratral-dehyde 30 and acetopiperone 31 to produce (3, 4 -methylenedioxy)-3,4-dimethoxychalcone 32 quantitatively (Scheme 3). On addition of hydrogen cyanide the cyanoketone 33 was formed, which after basic hydrolysis and... 

A more recent synthesis via the 2-aryl-l-tetralone intermediate developed by Janin and Bisagni (93T10305) provides a route to the benzo[c]phe-nanthrid-6(5//)-ones and 6-chlorobenzo[c]phenanthridines. Synthesis of... 

Alkyl- or aryl-dibenzothiophenes are conveniently prepared from the 2-arylthio-cyclohexanones, which are readily cyclized and dehydrogenated to yield the respective 1-, 2-, 3- or 4-substituted dibenzothiophenes (382 equation 9 Section 3.15.2.3.2). More complex polycyclic systems are available, using suitable aryenethiols, such as naph-thalenethiols, and 2-bromo-l-tetralone to synthesize the appropriate 2-arylthio ketones. Diaryl sulfides can be converted to dibenzothiophene derivatives in satisfactory yields by photolysis in the presence of iodine (equation 10) (75S532). Several alkyldibenzothiophenes with substituents in the 2- and/or 3-positions were prepared in satisfactory yield by the condensation of dichloromethyl methyl ether with substituted allylbenzo[6]thiophenes (equation 11) (74JCS(P1)1744). 

The most widely used route to l-benzazepin-2-ones involves the Beckmann or Schmidt reaction of the easily accessible 1-tetralones. Many biologically active compounds described in this review have been prepared on the basis of these reactions they have been fully reviewed [2], In the Beckmann reaction of 1-tetralone oximes, polyphosphoric acid is used as a catalyst-solvent in most instances. Aryl migration generally takes precedence over alkyl migration under these reaction conditions, and various 1-tetralone oximes substituted on the aromatic and/or aliphatic rings can be converted to the appropriate 2,3,4,5-tetrahydro-l//-l-benzazepin-2-ones (51) [5, 20-23, 36, 59, 65, 80, 107-112]. Both courses of the rearrangement occur in some instances, yielding l-benzazepin-2-ones (51) and the isomeric 2-benzazepine-l-ones, probably due to electronic effects of the substituents [90, 113, 114]. 

Aryl nitriles The most satisfactory route to the naphthalenecarbonitrile 3 is addition of (CH3)3SiCN to the 1-tetralone 1 followed by conversion to the a,(l-unsuturated nitrile 2. Dehydrogenation to the fully aromatic nitrile can be effected with DDQ, but is effected preferably with palladium-on-charcoal in combination with sulfur. 

Relatively stable l,2-dithiole-3-thiones, such as the 5-aryl-substituted compounds, react with 1-acenaphthenone24 or 1-tetra-lone21 in the presence of sodium hydroxide, giving a 2-(l,2-dithiol-3-ylidene)-l-acenaphthenone (or tetralone) (Eq. 7). 

Allylation of simple ketone is not possible under usual conditions, but the reaction can be carried out under selected conditions. Asymmetric allylation of the chiral racemic o -methylcyclohexanone 161 with allyl carbonate proceeded in the presence of LDA as a base with or without MesSnCl as a Lewis acid at room temperature to provide the allylated ketone 162 in very high yield with 82 % ee when (5,5)-Trost L-1 was used. The choice of base is crucial, and it was claimed that no reaction took place when Na or K bases were used in this reaction [57]. Asymmetric allylation of a-aryl and heteroaryl ketones has been carried out. Asymmetric allylation of 2-indolylcyclohexanone 163 took place at 0 C to give the the allyl ketone in 82 % yield with 84 % ee. In this reaction, NaHMDS was used as a base and Trost L-2 as chiral ligand [58]. Asymmetric allylation of the tetralone 164 with allyl acetate was carried out using Trost L-6 in the presence of CS2CO3 to provide the allylated ketone with 91 % ee in 90% yield [59]. 

The intramolecular Buchner reaction of aryl diazoketones has been carried out using both copper(I) and rhodium(II) catalysts. For example, 1-diazo-4-phenylbutan-2-one 27a cyclizes in bromobenzene with copper(I) chloride catalysis, furnishing 3,4-dihydroazulen-l(2//)-one 30 in 50% yield after purification by chromatography over alumina. Trienone 30 is not the primary cyclization product, and the less conjugated isomeric trienone 29a is first produced, but contact with alumina causes isomerization to 30. The yield of this cyclization is further improved when rhodium(II) acetate is used as the catalyst instead of copper(I) chloride. Thus a catalytic amount of rhodium(II) acetate brings about the nearly quantitative conversion of 27a to 29a within minutes in hot dichloromethane. Compound 29a isomerizes to 30 on treatment with triethylamine, and rearranges to 2-tetralone 31a when exposed to silica gel or acid. 

Rhodium(I)-catalyzed reactions of l-(2-bromophenyl)cyclobutanol 47a afforded a 3,3-disubstituted 1-tetralone 48a (Scheme 3.27) [37]. The reaction was proposed to involve oxidative addition of the aryl-Br bond to the alkox-orhodium(I) species, followed by P-carbon elimination. Azetidin-3-ol 47b could be used instead of cyclobutanols to furnish isoquinolinone 48b. 

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