Wolff-Kishner reduction product

Finally, lycorenine and lycorine have been interrelated through their respective Emde bases. Aromatization of XCIII, the Wolff-Kishner reduction product of lycorenine, gave two indoles (XCIV and XCV). The isolation of the phenolic indole (XCV) adds further support for the structure of ring B. Ether cleavage of the Emde base of lycorine (XLII), followed by methylation and dehydrogenation, gave a product identical with XCIV (122). 

The disadvantages associated with the Clemmensen reduction of carbonyl compounds (see 3 above), viz., (a) the production of small amounts of carbinols and unsaturated compounds as by-products, (h) the poor results obtained with many compounds of high molecular weight, (c) the non-appUcability to furan and pyrrole compounds (owing to their sensitivity to acids), and (d) the sensitivity to steric hindrance, are absent in the modified Wolff-Kishner reduction. 

Aryl-4,5-dihydropyridazine-3(2//)-one undergoes ring opening when submitted to Wolff-Kishner reduction, while with lithium aluminum hydride the corresponding 2,3,4,5-tetrahydro product is obtained. 

Both the Wolff-Kishner and Clemmensen reductions of a, -unsaturated ketones give olefins. There has been considerable confusion concerning the exact product composition in the case of A -3-ketones. Wolff-Kishner reduction gives A" -, 5a-A - and 5 -A -olefins, and, depending on the substrate reaction conditions and work-up, any one or more of these may be isolated. (See ref. 287 for a recent review of the Wolff-Kishner reduction.)... 

The stereochemistry of the product resulting from the reaction of a 17-keto steroid with ethylidenetriphenylphosphorane is different from that of the 17-ethylidene steroids obtained by dehydration of 17a-ethyl-17/ -hydroxy compounds, Wolff-Kishner reduction of A -20-keto steroids or by sodium-alcohol or sodium-ammonia " reductions of 17-ethynyl carbinols. These latter products have generally been assumed to possess the trans configuration (C-21 methyl away from the bulk of the ring system) because of anticipated greater stability. The cis configuration for... 

B-norketone (119) by enlarging ring A with diazomethane to give A-homo-B-norketone (120). Wolff-Kishner reduction of (120) gave hydrocarbon (118) identical to the product from ketone (116a). 

The conditions described for the preparation of the semi-carbazone are critical and should be strictly observed. Otherwise, the yield of the product in the subsequent Wolff-Kishner reduction is decreased. 

Wolff-Kishner reduction of ketones bearing other functional groups sometimes gives products other than the expected methylene reduction product. Several examples are given below. Indicate a mechanism for each reaction. 

Wolff-Kishner reduction of ketones that bear other functional groups sometimes give products other than the corresponding methylene compound. Some examples are... 

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). 

Raney nickel reduction of 2-benzyl-5-ethylselenophene (71) yields 1-phenylheptane (72), a conversion analogous to the much used reductive desulfurization of thiophenes (73JGU871). The electrochemical reduction of selenophene-2-carboxylic acid gives a mixture of dimeric products the major product is compound (73). This is in contrast to the 2,5-dihydro derivatives obtained by electrochemical reduction of thiophene and furan carboxylic acids (82CS( 19)95). Wolff-Kishner reduction of 2-selenienyl 2 -thienyl ketone gives, in addition to the expected methylene derivative, 2-(pentenyl)thiophene (72ZOB1780). 

The first microwave-assisted Wolff-Kishner reduction was described by Parquet and Lin in 199763. The transformation of isatin to oxindole was performed on a small scale in a domestic microwave oven in two steps with a total reaction time of 40 s, as compared to 3—4 h if classical heating was utilised (Scheme 4.36). The first step involved the transformation of the carbonyl group into the hydrazone with 55% hydrazine in ethylene glycol and medium power microwave irradiation for 30 s. In the subsequent reduction step, KOH in ethylene glycol was used to substitute the more hazardous sodium ethoxide. The reaction mixture was irradiated for 10 s and the product was obtained in a yield of 32%. 

Indolizines with a saturated six-membered ring may be obtained from pyrrole or furan derivatives.225,226 The reaction of 3,4-dimethylpyrryl-magnesium bromide with y-chlorobutyronitrile followed by dilute acid gave 5,6,7,8-tetrahydro-l,2-dimethyl-5-oxoindolizine. 5,6,7,8-Tetrahy-droindolizine can be obtained by the cyclodehydration of 3-(2-furyl)-propylamine over alumina at 400°C. The same product is obtained by the treatment of 3-(2-pyrryl)propyl cyanide with hydrogen chloride in the presence of boron trifluoride etherate catalyst, followed by Wolff-Kishner reduction of the intermediate ketone. 

The Friedel-Crafts Alkylation may give polyalkylated products, so the Friedel-Crafts Acylation is a valuable alternative. The acylated products may easily be converted to the corresponding alkanes via Clemmensen Reduction or Wolff-Kishner Reduction. 

Mannich reaction of the piperidine derivative (30) with 3-formylfuran gave a mixture of the four stereoisomeric quinolizidin-2-ones, cf. (31). The major product [as (31), but with a /3-furyl group] was isomerized with base to the most stable ftms-quinolizidinone (31), which on Wolff-Kishner reduction afforded a mixture of alkaloids (27) and (21). 

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