Reduction of tetralone

A modified oxazaborolidine 2 catalyzing the enantioselective reduction of acetophenone or tetralone with borane proved to give ttn values in the same order of magnitude [10, 11]. Using a special hydroxyproUne-based polymer-enlarged oxazaborolidine 3, a ttn of 1400 for the reduction of tetralone was achieved (Fig. 3.1.3, 3) [5, 12]. 

Scheme 13 Reduction of tetralone (127) with sodium borohydride afforded alcohol, which was benzylated to obtain the derivative (132), which on treatment with boron tribromide in dichloromethane yielded this diol (134) in major proportion. It was converted to compound (136) by treatment with triethyl orthoformate and then catalytic hydrogenation. Oxidation of (136 and on subjection of the resulting ketone with methylmagnesium bromide followed by heating with p-toluensulfonic acid in toluene produced compound (129).

Figures Conversion and enantiomeric excess overtime in the reduction of tetralone with borane in a continuously operated Chemzyme membrane reactor.

A number of products in which one of the naphthalene rings has been reduced have interesting pharmacological properties. Reaction of tetralone 30 with dimethylamine under TiCl catalysis produces the corresponding enamine (31). Reaction with formic acid at room temperature effects reduction of the... 

Johnson has developed two linear approaches to synthesize the C-nor-D-homosteroid skeleton (Scheme 2.2). In his first approach [21], tetralone 19, obtained from reduction of 2,5-dimethoxynaphthalene, was used as the source of the C,D-rings. The B- and A-rings were constructed by sequential Robinson annulations (19 —> 20 —> 21). The Cl 1,12 olefin was then introduced to provide 22. Ozonolysis of 22 followed by an aldol reaction of the resulting dialdehyde gave 23. Subsequent deformylation and deoxygenation afforded the cyclopamine skeleton 24. 

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. 

Partial reduction of naphthols was accomplished by sodium in liquid ammonia. In the absence of alcohols small amounts of 5,8-dihydro-a-naphthol or 5,8-dihydro- -naphthol were isolated. In the presence of tert-amyl alcohol, a-naphthol gave 65-85% yield of 5,8-dihydro-a-naphthol while -naphthol afforded 55-65% of -tetralone [399] Procedure 26, p. 211). Lith-... 

Tetralone has been prepared by a variety of methods, but the only practical procedures are relatively recent ones involving reduction of /9-naphthyl methyl ether with sodium and alcohol2 or with sodium and liquid ammonia,3 high-pressure catalytic hydrogenation of /9-naphthol,4 or catalytic oxidation of 2-tetralol by hydrogen transfer with ethylene.6... 

Tetralone 31 could also be synthesized much more efficiently by employing a chemoselective ketone reduction of 32 to give the lactone 33. A double Friedel-Crafts alkylation/acylation sequence employing a variety of Lewis or protic acids and benzene gave the tetralone 31 directly. Triflic acid and HF produced the highest yields of tetralone, presumably through the intermediacy of the diaryl acid 34 (Scheme 6)... 

Quallich and Woodall described the first asymmetric synthesis utilizing a catalytic enantioselective reduction of the ketoester 35 with (S)-terahydro-l-methyl-3,3-diphenyl-lH,3W-pyrrolo[l,2-c][l,3.2]oxazaborole (CBS) to give the desired hydroxyester 36 (90% ee). After mesylation, Sn2 displacement with a higher-order cuprate derived from copper cyanide gave the diaryl r-butyl ester 37 with good chirality transfer. Intramolecular Friedel-Crafts cyclization gave the tetralone 31 in 90% ee (Scheme 7). ... 

Sertraline is the active pharmaceutical ingredient (API) in Pfizer s antidepressant Zoloft [25]. The developed commercial process employs an SMB chromatographic resolution of tetralone (Scheme 13.10) in >99% ee followed by diastereoselective reductive amination to give 95% sertraline (cis-isomer) and 5% trans-isomer the (4R)-tetralone can be racemized with an alkoxide base [8]. Asymmetric processes to sertraline have been described [26]. Our studies started with the original patented process involving palladium-catalyzed reductive amination of a tetralone to give a mixture of 80% racemic-cis and 20% racemic-trans diastereomers [27]. The cis-diastereomer can be purified by selective crystallization from toluene followed by diastereomeric crystallization of the (lS,4S)-enantiomer using (R)-... 

The iV-aminopyrrole - benzene ring methodology has been applied to a synthesis of the 9,10-dihydrophenanthrene juncusol (218) (81TL1775). Condensation of the tetralone (213) with pyrrolidine and reaction of the enamine with ethyl 3-methoxycarbonylazo-2-butenoate gave pyrrole (214). Diels-Alder reaction of (214) with methyl propiolate produced a 3 1 mixture of (215) and its isomer in 70% yield. Pure (215) was reduced selectively with DIBAL to the alcohol, reoxidized to aldehyde, and then treated with MCPBA to generate formate (216). Saponification to the phenol followed by O-methylation and lithium aluminum hydride reduction of the hindered ester afforded (217), an intermediate which had been converted previously to juncusol (Scheme 46). 

A cyclic ketone, 1-tetralone, was reduced with diphenylsilane in the presence of the Rh/(S,R)-2 complex (substrate Rh ligand=50 l 2) in toluene at room temperature followed by hydrolysis to give the S alcohol in 92% optical yield (Scheme 2) [8]. Use of the Rh/4 complex (substrate Rh ligand=100 l 1.2) at 0 °C yielded the S product in 80% optical yield [17]. The reduction of 4-chromanone with the same complex gave an optical yield of 87%. 

Consequently, Dehmlow and coworkers modified the cinchona alkaloid structure to elucidate the role of each ofthe structural motifs of cinchona alkaloid-derived chiral phase-transfer catalysts in asymmetric reactions. Thus, the quinoline nucleus of cinchona alkaloid was replaced with various simple or sterically bulky substituents, and the resulting catalysts were screened in asymmetric reactions (Scheme 7.2). The initial results using catalysts 8-11 in the asymmetric borohydride reduction of pivalophenone, the hydroxylation of 2-ethyl-l-tetralone and the alkylation of SchifF s base each exhibited lower enantiomeric excesses than the corresponding cinchona alkaloid-derived chiral phase-transfer catalysts [14]. 

Kagan and Schiffers carefully studied the effect of the lithium salts of BINOL (17) and related axially chiral binaphthols on the reduction of a variety of ketones with trialkoxysilanes [24]. They found that diethyl ether, with TMEDA as an additive, was the best solvent for asymmetric reduction of ketones. In the presence of 5 mol% of the monolithium salt of BINOL (17), acetophenone (1) could be reduced with trimethoxysilane in 80% yield and with 61% ee. Enantiomeric excesses > 90% were achieved under the same conditions with 2, 4, 6 -trimethyl-acetophenone (18) or a-tetralone (19) as substrates. Aliphatic ketones such as... 

A total synthesis of dihydrolycorine (85), y-lycorane (87) and 8-lyco-rane (92), has been achieved starting from the indanone carboxylic acid 77. This, in turn, was obtained, like the tetralone ester 76, from the known anhydride (75) via Friedel-Crafts cyclization of the monomethyl esters obtained from 75 by treatment with 1 mole of methanol. Reduction of the methyl ester of 77 (LiAlH4), followed by Mn02 oxidation,... 

The reduction of alkoxynaphthalenes 398) was used by Hoechst for the synthesis of P-tetralones ... 

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