A Wolff-Kishner reduction

Several methods are available to supplement the phenol alkylations described above. Primary alkylphenols can be produced using the more traditional Friedel-Crafts reaction. Thus an -butylphenol can be synthesized direcdy from a butyl haUde, phenol, and mild Lewis acid catalyst. Alternatively, butyryl chloride can be used to acylate phenol producing a butyrophenone. Reduction with hydrazine (a Wolff-Kishner reduction) generates butylphenol. 

Hydrazones are important intermediates in a Wolff-Kishner reduction, a procedure for reducing a carbonyl group. An example of a Wolff-Kishner reduction appears in Figure 10-27, and the mechanism is in Figure 10-28. 

Stille cross-coupling and reductive N-heteroannulation steps. lodination of 1033, followed by Stille cross-coupling of the corresponding iodo derivative 1034 with the arylstannane 1035, gave the annotation precursor 1036. Reductive N-heteroannula-tion of 1036 afforded the carbazolone 1001, which was previously (99) (see Scheme 5.143) used to prepare clausenalene (90) via a Wolff-Kishner reduction followed by aromatization (659) (Scheme 5.155). 

The synthesis of the right-hand fragment of ziprasidone started with a Wolff-Kishner reduction of isatin 43 to give the oxmdole 44 (Scheme 14). Friedel-Crafts acylation with chloroacetyl chloride afforded aryl ketone 45, which was reduced with triethylsilane in trifluoroacetic acid to the phenethyl chloride 46. The two fragments were joined by alkylation of 40 with 46 in the presence of Nal and Na2CO3 to give ziprasidone (4) in low yield. The yield of the coupling step was improved dramatically when the reaction was conducted in water (Scheme 15). 

The three-step sequence used to convert enone 65 to miltirone (56) is shown in Scheme 5.7 and consists of, first, a Wolff-Kishner reduction to convert the C(5) carbonyl moiety into a methylene, followed by deprotection of the aryl methyl ethers and oxidation to an ortho-quinone using ceric ammonium nitrate. The physical and spectroscopic data of our synthetic miltirone are identical with those reported for the natural material. 

Wolff-Kishner reduction. One step in a study of the absolute configuration of 2 involved a Wolff-Kishner reduction of 1 by the procedure indicated in the formulation. ... 

In their synthesis of fukinone, Marshall and Cohen converted the known ene-ol (340) into (341) by acetylation, allylic oxidation, and conjugate methylation with dimethylcopperlithium. A Wolff-Kishner reduction of (341) followed by oxidation of the resultant alcohol and enol-acetylation yielded (342). The epoxide of (342) was thermolysed to give (343) which, on reaction with iso-propenyl-lithium and selective oxidation, gave the ketol (344) which was converted in two steps into fukinone (335). A number of sesquiterpenoids, e.g. fukinanolide (345), with the rearranged eremophilane skeleton viz. fukinane (346 R = Me) are known. Nay a and Kobayashi have now prepared this parent hydrocarbon by Raney nickel reduction of the thioacetal of fukinan-8-al (346 R = CHO). 

Barton, D. H. R., Ives, D. A. J., Thomas, B. R. A Wolff-Kishner reduction procedure for sterically hindered carbonyl groups. J. Chem. Soc., Abstracts 1955, 2056. 

Brecknell, D. J., Carman, R. M., Schumann, R. C. Kinetic versus thermodynamic effects during a Wolff-Kishner reduction. Aust. J. Chem. 1989, 42, 527-539. 

Thermal decomposition. The usual procedure for cari ying out a Wolff-Kishner reduction is to heat a hydrazone with base to a temperature of 200°. Cram e( ai. reported the striking finding that with dimethyl sulfoxide as solvent and potassium r-butoxide as base the reaction can be conducted at room temperature. For example,... 

Hydrazides (s. a. Carboxylic acid hydrazides) reduction with borane 26,56 Hydrazine (s. a. Wolff-Kishner reduction) 26,15 reaction with dicarboxylic acid anhydrides 8, 482... 

A ketone or aldehyde is reduced to the corresponding hydrocarbon by treatment with zinc amalgam in HCl, in what is known as Clemmensen reduction. A ketone or aldehyde is reduced to the corresponding hydrocarbon by treatment with hydrazine and KOH, in what is known as a Wolff-Kishner reduction. 

We have already seen two other ways to do this kind of transformation (the Clemmensen reduction and desulfurization with Raney Nickel). This is now our third way to reduce a ketone to an alkane, and it is called a Wolff-Kishner reduction. 

The second group of workers (16) obtained 1,2,8,10-tetramethyl-phenanthrene (IX) from the diketone VI-B by the reaction with methyl-lithium followed by a dehydrogenation with selenium. Compound VI-B was prepared from C-3 desoxycassenic acid obtained from a Clemmensen reduction of diketocassenic acid. Further, the acetoxy diketone VI-A was converted to 1,2,8-trimethylphenanthrene by a Wolff-Kishner reduction and mild chromic acid oxidation followed by the Grignard and dehydrogenation sequence. 

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