7-Methoxy-l-tetralone

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). 

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. 

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. 

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. 

Starting with this hypothesis, several 6-sila-steroids were prepared127-129. As an example, the syntheses of 6,6-dimethyl-6-sila-oestradiol (197) and 6,6-dimethyl-6-sila-mestranol (198) are described in Scheme 25. Not only the synthesis of the key intermediate 4,4-dimethyl-4-sila-6-methoxy-l-tetralone (7 96) but also the well known organic reactions, leading from 196 to 197 and 198, are strongly influenced by the specific properties of the silicon atom. Although known reactions of steroid chemistry could be used for further transformations from 196 to 197 and 198, conditions were not directly transferable because of the chemical behaviour of the Si-Calkyi and Si-Qryl bond. Important differences in the pH- and solvent profile were neces-... 

Arylacetic acids. A new synthesis of phenylacetic acids from aromatic ketones is illustrated for conversion of 6-methoxy-l-tetralone (1) into 6-methoxy-l,2,3,4-tetrahydronaphthalene-1-carboxylic acid (3). 

Vilsmeier fom lation of 6-methoxy-l-tetralone yields the 1-chloronaphthalene-2-aldehyde which on treatment with aniline and subsequent thermolysis affords the 5,6-dihydrobenz[c]acridine. The presence of electron... 

Methoxy-l-tetralone (7) is converted into 6-methoxy-l-naphthol (8) in 80% yield by bromination followed by dehydrohalogenation." The bromination was... 

The structure and absolute stereochemistry of hinesol (282) has now been firmly established by an unequivocal synthesis which involved the tricyclic dienone (329) prepared from 6-methoxy-l-tetralone. Treatment of the dienone with lithium dimethylcopper gave a mixture of syn and anti enones (330). By a series of stereoselective reactions this compound was converted to the diol (331) whose mono-mesylate underwent a base-induced cleavage to give the spiro[4,5]-ketone (332). Elaboration of this ketone to hinesol was accomplished along... 

Surprisingly, the TiCl4-catalyzed conversion of 1 -tetralone results only in the formation of a dimer [84 c], while 6-methoxy-l -tetralone can be converted to the 3,9,15-trimethoxy-5,6,11,12,17,18-hexahydrobenzo [c] naphtho [2,1 -p] -chrysene (114) in moderate yields [152a]. 

Besides the aforementioned A-ring aromatic steroids and contraceptive agents, partial synthesis from steroid raw materials has also accounted for the vast majority of industrial-scale steroid synthesis. One notable exception, however, was the first industrial-scale synthesis of optically active steroids performed by workers at Roussel-UCLAF. The linear synthesis began with a suitable B—C-ring synfhon, 6-methoxy-l-tetralone (186). In a series of steps, tetralone (186) was converted to 2-methyl-2-cyanotetralone (270). Condensation of (270) with dimethyl succinate followed by carbonyl reduction, saponification, and resolution produced the optically active tricyclic acid (271). A series of reductions, a decarboxylation, and a hydrolysis produced (272). Appendage of the A-ring functionality by alkylation produced intermediate (273). Compound (273) was used as a common intermediate for the synthesis of 19-norsteroids, estrogens, and corticosteroids (230). 

Diethylaluminum cyanide is an efficient reagent for use in cyanohydrin synthesis 6-methoxy-l-tetralone can be converted into its cyanohydrin.only by use of that compound.168... 

Among seven tetralones known to Aristolochia so far, four tetralones, aristelegone A (547), B (548), C (549) and D (550) have been described in A. elegans collected in Taiwan [168,252], The other three, 4-hydroxy-4,7-dimethyl-l-tetralone (551), 4,7-dimethyl-6-methoxy-l-tetralone (553) and aristolindiquinone (552) were reported from A. brevipes [273], A. tagala [384], and A. indica [92,385], respectively. All the tetralones except aristolindiquinone possess a keto function at C-l. Aristolindiquinone (552) is a fully aromatic tetralone with ap-quinone unit. 

Posner has devised a novel one-pot (but low yield) synthesis of ( )-9(ll)-dehydro-8-epiestrone methyl ether 210 by a coupled sequence of two Michael reactions and a Wittig reaction (tandem Michael-Michael ring closure) (Scheme 26), 6-Methoxy-l-tetralone 205 was converted, via trimethylsilyl enol ether... 

Reaction of 6-methoxy-l-tetralone (30) with methylmagnesium iodide gave the dihydronaphthalene (31) in high yield (Scheme 4). However, the transformation of 31 to the tetralone 33, via perbenzoic acid epoxidation followed by acid workup, was capricious and resulted in low yields. A better route was developed, involving hydroboration (hydrogen peroxide oxidation) to the alcohol 32, followed by Pfitzner-Moffatt oxidation to the tetralone 33 in an overall yield of 61%. Other oxidation methods were tried but with varied and poor results. Alkylation of the tetralone 33 with 3-bromopropyne yielded 34, which underwent hydration [mercury (II) acetate in acetic acid-formic acid] to the diketone (35). The enone (36) obtained by base catalyzed cyclization was ster-eospecifically reduced with lithium aluminum hydride to the allylic alcohol... 

Starting material of the synthesis is 6-methoxy-l-tetralone, which is first reacted with vinylmagnesium chloride to give the corresponding vinyl alcohol. Condensation with 2-ethylcyclopentane- 1,3-dione imder basic or acidic catalysis (p-TsOH, benzene, 82 %) [54] leads, accordingtoTorgov [55], to aseco-dione, which is then reduced with Saccharomyces uvarum to the yS-hydroxy-ketone. [56]... 

Two methods of synthesis of the acid (5) from 6-methoxy-l-tetralone (8), formed in two stages from nerolin (7) [139-142], have also been proposed. One of them [143, 144], like that just described above, is based on the introduction of the and 0 2 atoms by the Reformatskii reaction of the ketone (8). The ester formed (10) is converted into the bromide (11) and the 0 3 and 0 4 atoms are introduced by the condensation of the latter with sodiomalonic ester and decarboxylation. Dehydrogenation of the resulting acid (12) gives the acid (5). According to the other method for synthesizing this acid [140], the acids are introduced in one stage... 

The unsaturated ketone (85) has also been obtained by two methods. Dieckmann cyclization of the diester (80) and hydrolysis of the reaction product to (85) [209] is the first method of synthesis. The other method [140, 212, 213] starts from the dienic ester (9), the preparation of which from 6-methoxy-l-tetralone is described in Scheme 1. Selective hydrogenation leads to the monounsaturated acid (86), which cyclizes to (85) under the action of zinc chloride.t... 

Syntheses via BCD Intermediates with a Five-Mem-bered Ring D. These syntheses generally start from 6-methoxy-l-tetralone or its 5-methyl derivative, which are used as the BC fragments. All the methods used in Chapter II for the synthesis of estrogenic hormones from 14-oxa compounds are employed for the construction of ring D. It must be mentioned that some of the intermediates illustrated in Schemes 70 and 71 have also been obtained by syntheses of the BD - C type (cf. Section 3 of this chapter). 

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