L-Tetralones

Substantial amounts of 3,3,6,8-tetramethyl-l-tetralone [5409-55-2] are also formed, most notably ia the vapor-phase process (216). This tetralone has been synthesized from isophorone and mesityl oxide and it can thus be assumed to be a product of these two materials ia the isophorone process (217,218). 

The most recent, and probably most elegant, process for the asymmetric synthesis of (+)-estrone appHes a tandem Claisen rearrangement and intramolecular ene-reaction (Eig. 23). StereochemicaHy pure (185) is synthesized from (2R)-l,2-0-isopropyhdene-3-butanone in an overall yield of 86% in four chemical steps. Heating a toluene solution of (185), enol ether (187), and 2,6-dimethylphenol to 180°C in a sealed tube for 60 h produces (190) in 76% yield after purification. Ozonolysis of (190) followed by base-catalyzed epimerization of the C8a-hydrogen to a C8P-hydrogen (again similar to conversion of (175) to (176)) produces (184) in 46% yield from (190). Aldehyde (184) was converted to 9,11-dehydroestrone methyl ether (177) as discussed above. The overall yield of 9,11-dehydroestrone methyl ether (177) was 17% in five steps from 6-methoxy-l-tetralone (186) and (185) (201). 

When the 1-monoximes or dioximes of 4-acetyl-l-tetralones are hydrogenated in the presence of palladium, mixtures of diastereoisomeric 1-aminotetralones are formed. The m-aminoketone isomers readily form dehydrobenzoisoquinuclideines (3,4-disubstituted-1,4-dihydro-1,4-ethano-isoquinolines). Quaternary immonium salts prepared from these bicyclic imines are then converted by bases to bicyclic enamines [2,4-disubstituted-3-alkylidene-1,4-ethano-1,2,3,4-tetrahydroisoquinolines (25)]. 

In the first of these sequences, often called the Torgov-Smith synthesis, the initial step consists in condensation of a 2-alkyl-cyclopentane-l,3-dione with the allyl alcohol obtained from 6-methoxy-l-tetralone and vinylmagnesium chloride. Although this reaction at first sight resembles a classic SN displacement, the reaction is actually carried out with only a trace of base. 

Hydrogenolysis of aromatic carbonyls occurs mainly by conversion to the benzyl alcohol and its subsequent loss. If hydrogenolysis is desired, the usual catalyst is palladium 38). Hydrogenolysis is facilitated by polar solvent and by acid (55). For instance, hydrogenation of 3,3-dicarbethoxy-5,8-dimethoxy-l-tetralone (5) over 5% Pd-on-C gave 6 quantitatively 54) when hydrogen absorption ceased spontaneously. 

The use of such an oxazaborolidine system in a continuously operated membrane reactor was demonstrated by Kragl et /. 58] Various oxazaborolidine catalysts were prepared with polystyrene-based soluble supports. The catalysts were tested in a deadend setup (paragraph 4.2.1) for the reduction of ketones. These experiments showed higher ee s than batch experiments in which the ketone was added in one portion. The ee s vary from 84% for the reduction of propiophenone to up to >99% for the reduction of L-tetralone. The catalyst showed only a slight deactivation under the reaction conditions. The TTON could be increased from 10 for the monomeric system to 560 for the polymer-bound catalyst. 

The reaction was monitored by TLC (eluent //-hexane diethyl ether, 8 2). 2-Isobutylidene-l-tetralone (UV active) stained light purple with p-anisalde-hyde dip, R 0.66 and the epoxide (UV active) dark purple, R 0.30. 

The first promising asymmetric aldol reactions through phase transfer mode will be the coupling of silyl enol ethers with aldehydes utilizing chiral non-racemic quaternary ammonium fluorides,1371 a chiral version of tetra-n-butylammonium fluoride (TBAF). Various ammonium and phosphonium catalysts were tried138391 in the reaction of the silyl enol ether 41 of 2-methyl-l-tetralone with benzaldehyde, and the best result was obtained by use of the ammonium fluoride 7 (R=H, X=F) derived from cinchonine,1371 as shown in Scheme 14. 

Streptomyces griseus NRRL 8090 catalyzes a series of biotransformations of naphthalene and 2-methyl-1,4-naphthaquinone to their corresponding racemic and diastereomeric 4-hydroxy-1-tetralones (Figure 12.1). The yields of 4-hydroxy-l-tetralone obtained with S. griseus are much higher than those produced by various fungi that oxidize naphthalene. ... 

Methoxy-l-tetralone will be available from K K Laboratories, New York, although the submitters have used a material, m.p. 77-80°, produced by Osaka Yuki Gosei K. K., Nishinomiya-shi, Japan. 

Crystals of 6-methoxy-l-tetralone may separate from the solution on cooling, but redissolve upon addition of the cooled diethylaluminum cyanide solution. 

Phe residue, obtained as a pale yellow oil, weighs approximately 7.4 g. and consists of l-cyano-l-hydroxy-6-methoxytetra-lin and a small amount of unchanged 6-methoxy-l-tetralone. Phe oil is transferred to a lO-rnl. Glai.sen flask, a small... 

The cyanohydrin initially formed is unstable and readily reconverted to the starting 6-methoxy-l-tetralone on evaporation of the extracts unless slight acidity of the solution is maintained by addition of a trace amount of p-toluenesulfonic acid monohydrate. As this acid is relatively insoluble in methylene chloride, it should be added directly to the flask used for evaporation of the solvent. 

The present method developed by the submitters is the only practical process for preparation of l-cyano-6-methoxy-3,4-dihydronaphthalene. Birch and Robinson have reported that 6-methoxy-l-tetralone did not react with hydrogen cyanide or sodium acetylide. 

As noted earlier, most classical antidepressant agents consist of propylamine derivatives of tricyclic aromatic compounds. The antidepressant molecule tametraline is thus notable in that it is built on a bicyclic nucleus that directly carries the amine substituent. Reaction of 4-phenyl-l-tetralone (18) (obtainable by Friedel-Crafts cyclization of 4,4-diphenyl butyric acid) with methyl amine in the presence of titanium chloride gives the corresponding Schiff base. Reduction by means of sodium borohydride affords the secondary amine as a mixture of cis (21) and trans (20) isomers. The latter is separated to afford the more active antidepressant of the pair, tametraline (20). 

New chiral auxiliaries for nucleophilic reactions have been prepared from 5-hydroxy-l-tetralone <2001TA2605> and myrtenal <2001TA3095> and their use in diastereoselective reactions has been evaluated. It was found that both the tetralone- <2003EJ0337, 2003JOC6619> and the myrtenal- <2003TA3225, 2005TA1837> derived 2-acyl-l,3-oxathianes reacted diastereoselectively with nucleophiles (Equations 60 and 61). 

Dihydroxy-l-tetralone Diisoprene 2,3-Dimethoxy-5,6-dimethyl-l,4-benzoquinone Isosclerone ( )-Limonene Aurantiogliocladin... 

Anm. wahrend d. Korr. 6-Methoxy-l-tetralon, in dem dor clcktronische Eliekt des Aromaten dem in (7) vergleichbar ist, liefert jedoch iibcrvvicgend das Laktam mit CO am Bcnzolring [analog (14)] Evans, D. u. I. M. Lockhart, The Schmidt reaction with aromatic ketones. J. Cheni. Soc. [London] 1965, 4806. 

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