Wolff-Kishner cyclization

Friedel-Crafts acylation of dibenzothiophene with succinic anhydride is known to occur in the 2-position, yielding y-oxo-2-dibenzothiophene-but3Tic acid (135a). Subsequent Wolff-Kishner reduction and internal cyclization yields 7-keto-7,8,9,10-tetrahydrobenzo[6]naphtho[2,3-d]thio-phene (136a). - This reaction has been extended to 4-methyldibenzo-... 

Ganter has developed three different approaches to tricyclo[5.2.1.0 ]decane (403), yet another of the nineteen isomeric hydrocarbons of adamantaneland As seen in Scheme XXXIII, the routes involve intramolecular cyclization of keto tosylate 399 followed by Wolff-Kishner reduction of the resulting ketone, thermo-cyclization of 400 and subsequent dechlorination, hydrogenation, and photocycli-zation of aldehydes 401. Majerski s approach involved hypoiodite cleavage of alcohol 402... 

Methyl- 1,3-cyclopentanedione is a key intermediate for the total synthesis of steroids.2 A number of methods have been described for its preparation, among them the condensation of succinic acid with propionyl chloride,3 and that of succinic anhydride with 2-buten-2-ol acetate,4 both in the presence of aluminum chloride. It has also been obtained from 3-methylcyclopentane-1,2,4-trione by catalytic hydrogenation5 and Wolff-Kishner reduction 6 The base-promoted cyclization of 4-oxohexanoic acid ethyl ester and diethyl propionylsuccinate with tertiary alkoxides was first reported by Bucourt.7 The present cyclization process provides an experimentally simple route to 2-methyl-1,3-cyclopentanedione. Using the same procedure, 4-oxoheptanoic acid ethyl ester has been cyclized to give 2-ethyl-l,3-cyclopentanedione in 46% yield... 

An approach to the synthesis of a prostaglandin intermediate began with 2-furanacetonitrile (71JOC3191). Friedel-Crafts acylation with pimelic half-ester acid chloride and Wolff-Kishner reduction of the product with concomitant hydrolysis of the nitrile group to acid yielded the diester (78) on diazomethane treatment. Ring opening of the furan by a standard procedure yielded a diketo diester (79) which on refluxing in aqueous methanolic potassium carbonate underwent hydrolysis and cyclization to the diacid (80 Scheme 19). 

Methyl- or 2-ethyl-benzo[Z> ]thiophenes are conveniently prepared by treatment of 2-benzo[6]thienyllithium with the appropriate alkyl sulfate <70AHC(11)177). Clemmensen or Wolff-Kishner reductions of the 2-acylbenzo[Z>]thiophenes are useful, but since acylation produces a mixture of the 2- and 3-acyl isomers (Section 3.14.2.4), these must be separated. Cyclization of phenyl phenacyl sulfide with hydrofluoric acid leads exclusively to 2-phenyl-benzo[6]thiophene, and 3-phenylbenzo[6]thiophene can be rearranged to the 2-isomer in hydrofluoric acid (Section 3.15.2.3.2). Aromatization of 2-cycIohexenylbenzo[6]thiophene, obtained by condensation of the 2-lithio reagent with cyclohexanone, gives 2-phenyl-benzo[6]thiophene, and the reaction is adaptable to the 2-(l-naphthyl) derivative also. 

For the preparation of 4-(1.2.3.4-tetrahydroquinolino)-phenol 17 three different procedures were worked out [Eqs. (6)-(8)]. 17 was prepared by reacting N-p-methoxyphenyl-anthranilic acid with acetic anhydride and subsequent saponification to l-p-methoxyphenyl-4-hydroxy-2-quinolone, reaction withPOCl3 to form l-p-methoxyphenyl-4-chloro-2-quinolone, hydrogenation to l-(p-methoxy-phenyl)-3.4-dihydro-2-quinolone, splitting the ether with HBr to l-(p-hydroxy-phenyl)3.4-dihydro-2-quinolone, and reduction with LiAlH4 [Eq. (6)J. Another synthetic possibility was the reaction of p-anilinophenol with (3-propiolactone and subsequent cyclization to l-(p-acetoxyphenyl)2.3-dihydro-4-quinolone 18. The next step, the Wolff-Kishner reduction, led directly to the desired product [Eq. (7)]. The third way, the direct amination of p-iodoanisole with 1.2.3.4-tetrahydro-quinoline and the subsequent splitting of 4-(1.2.3.4-tetrahydro-quinolino)-anisol with HBr was the best one [Eq. (8)]. Saponification of l-(p-acetoxyphenyl>2.3-... 

Phenacylpyridinium methiodide, when treated with hydrazine under WolfF-Kishner reduction conditions, is transformed into 6-phenyl-4-propylpyridazine. Some related pyridazines were prepared in a similar manner, but 3-benzoylpyridinium methiodide failed to react [80JCS(P1)72]. 2-Dimethylamino-5-phenyl-l, 3,4-thiadiazin-6-one reacts with the electron-rich 1-diethylaminopropyne to give two pyridazines, 49 and 50, in 72% and 2% yield, respectively. The formation of both compounds is explained by the initial addition of ynamine, ring opening, and cyclization in two ways (82CC1003). 

Ishwarane (371) has been isolated from the petals of Cymbopetalum penduli-forum (Dunal) Baill. Last year, Kelly et al. reported the synthesis of isoish-warane (372) which they have now extendedto the synthesis of ishwarane itself. The enone (373) was converted in five steps into the ketol (374). Treatment of the tosylate of (374) with dimsyl sodium afforded the cyclized ketone (375) which gave ishwarane on Wolff-Kishner reduction. The complete details of the elegant synthesis of hinesol (376) by Marshall and Bradyhave now been published. 

The synthesis of sparteine, following the hypothesis of Schopf, can be accomplished from acetone, formaldehyde, and piperidine (57). The resulting Mannich base is dehydrogenated with mercuric acetate and the resultant intermediate spontaneously cyclizes to 8-ketosparteine (LIT), from which Wolff-Kishner reduction generates d -sparteine (II). 

The shortest synthesis of papaverine was achieved in the laboratory of R. Hirsenkom starting from racemic stilbene oxide and using a modified Pomeranz-Fritsch reaction The aminolysis of the stilbene oxide led to the formation of the cyclization precursor, which upon treatment with excess benzoyl chloride, underwent cyclization to give the N-benzoyl 1,2-dihydroisoquinoline derivative. Reduction under Wolff-Kishner conditions afforded papaverine. 

Haworth phenanthrene synthesis. Acylation of aromatic compounds with aliphatic dibasic acid anhydrides to (i-aroylpropionic acids, reduction of the carbonyl group according to Clemmensen or Wolff-Kishner procedures, cyclization of the y-arylbutyric acid with 85% sulfuric acid, and conversion of the cyclic ketone to polycyclic hydroaromatic and subsequently to aromatic compounds. 

Reduction of luteidine (29) by sodium borohydride or hydrogenation in the presence of Raney nickel gave tetrahydroluteidine (44), whereas Wolff-Kishner reduction of 28 gave the cyclopropane 45. Cyclization of 28 in acetic acid containing hydrogen chloride gas gave the acetal 46 16). 

Yamamoto et al. have been trying to synthesize limonene by a biomimetic cyclization of nerol (37) derivatives. The principle is to use the chiral derivative 523 and an alkylaluminum. After much experimentation,the best conditions were with the reagent 524 in CCI3F, when 77% ee of (-I-)-limonene (285) was obtained.It is widely believed still that the Wolff-Kishner reduction of optically active carvone (281) will yield optically active limonene (e.g., see Ref. 16, p. 152), a reaction reported by Friedman and Miller." This was already doubtful (Friedman and Miller gave no experimental evidence), since Jeger et al. had shown in 1950 that the Wolff-Kishner reaction with a,p-unsaturated ketones displaces the double bond, but Akhila and Banthorpe have now shown conclusively that (-)-carvone (281) yields ( )-limonene [( -285] by the Wolff-Kishner reaction. ... 

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