2- Tetralones synthesis

Tetralone synthesis. Murphy and Wattanasin7 have devised a simple tctralone synthesis involving cyclization of aryl aroyl cyclopropanes. A ehaleonc (2) is cyclo-propanated by 1 to give a 1 1 mixture of 3 and 4, which can be separated. This step is not necessary since 4 is readily cpimerized to 3 under the conditions for... 

A benzomorphan analog of pethidine, bearing a 6-ethoxycarbonyl group (155) was prepared by May et al.(95) by a modified 1-tetralone synthesis. It... 

Functionalization of the bridgehead 2-position in benzomorphans by standard synthetic approaches is not easy. This led Portoghese and Ramakrishnan(117) to devise a new 2-tetralone synthesis from a conventional benzomorphan Hofmann elimination product (185). Demethylation of 185 was effected by trichloroethylchloroformate to 186, which, in turn, was oxidized to the 2-tetralone (187). Removal of the trichloroethyl carbamate protecting group gave 189, presumably via 188. Treatment of 189 with KCN in weak... 

The substitution pattern in the benzene ring of 1 controls the regioselectivity of this 3-tetralone synthesis. 7-Substituted-2-tetralones arc obtained from precursors substituted in the p-position (CH, OCH, OAc). An -methyl substituent in 1 results in 5-methyl-2-tetralone (86%), whereas a j-methoxyl substituent in 1 results in a one-step direct conversion to 6-methoxy-2-tetralone (86%). 

The association of the xanthate-based tetralone synthesis with the alkyla-tive Birch reduction and other reactions allowing the modification of the aromatic core constitutes a particularly potent combination. This is illustrated by the expedient synthesis of tricyclic system 65 pictured in the top part of Scheme 36 (Cordero-Vargas et al, personal communication). Routes to highly complex architectures can be conceived through modification of the olefinic partner, the substitution pattern of the aromatic moiety, or the nature of the alkylating agent associated with the Birch reduction. 

To extend this powerful new dihydrofuran synthesis to more complex systems, related reactions with branched /1-dicarbonyl systems were investigated [20]. hi a similar fashion, the cfs-fused furanoids 40 and 41 were prepared from hexane-2,4-dione (37), ethyl isobutyryl acetate (38), and 2. These targets are important chiral synthons, since there are many natural products bearing ethyl and isopropyl residues on furanoid rings. The flexibility of this method was also tested with the aromatic /3-diketone 39 yielding furanoid 42, which is an important system for tetralone synthesis (Scheme 8). 

A further example is given below illustrating the use of a dibasic anhydride (succinic anhydride) the succinoylation reaction is a valuable one since it leads to aroyl carboxylic acids and ultimately to polynuclear hydrocarbons. This general scheme of synthesis of substituted hydrocarbons through the use of succinic anhydride is sometimes called the Haworth reaction. Thus a-tetralone (see below) may be reduced by the Clemmensen method to tetralin (tetrahydronaphthalene) and the latter converted into naphthalene either catal3d.ically or by means of sulphur or selenium (compare Section, VI,33). 

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). 

Similarly, the method has been applied to the synthesis of five- (244) and seven- (245,246) membered-ring ketone analogs of (0-tetralone. 

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. 

The. synthesis starts with the Stobbe condensation of diethylsuccinate and 3,4-dichloroben-zophenone (13). The product (14) is hydrolyzed and decarboxylated to a cis-trans mixture of olefins (15). This last is reduced using a Pd/C catalyst and then undergoes unidirectional Friedel-Crafts intramolecular acylation into the more reactive ring to produce substituted tetralone 16. 

Suggest a synthesis for 5-Meo tetralone (1) used for a tetracycline synthesis (see p 431 ). 

The difficult disconnection is (a) so we make it the first disconnection as it will then be a cycllsatlon in the synthesis. Further/disconnections can follow the pattern of the synthesis of 7-MeO tetralone in Chapter T 24. 

The problem with this synthesis is that essentially only para product (2) is formed in the initial Fricdel-Crafts reaction. A solution is to block the para position with a chlorine atom which can be removed by hydrogenolysis. This tetralone (1) is now a commercial product. 

Azines have been prepared by initial condensation of diethoxyphosphinyIhydrazine anions with aldehydes or ketones (Scheme 9). Phosphoryl azides undergo 1,3-dipolar cycloaddition to 2-tetralone enamines to give triazolines, possibly en route to amidines. A full paper on the addition of diethyl dibromophosphoramidate to alkenes(leading to the synthesis of 2-bromoalkylamines) has appeared. ... 

Phenylnaphthalene has been prepared by the reaction of a-halonaphthalenes with mercury diphenyl3 6 or with benzene in the presence of aluminum chloride,6 and by means of the Gri-gnard synthesis, starting with either bromobenzene, cyclohexyl chloride, and a-tetralone 7 or with a-bromonaphthalene and cyclohexanone.6 8 9 Dehydrogenation of the reduced naphthalene has been accomplished by the use of sulfur,6 bromine,8 platinum black, or selenium.7 The formation of the hydrocar-... 

Tab. 5.31 Synthesis of diaryl-a-tetralones from isophorone and chalcone under MW + PTC conditions.

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