Wolff-Kishner type reduction

Low-valent nitrogen and phosphorus compounds are used to remove hetero atoms from organic compounds. Important examples are the Wolff-Kishner type reduction of ketones to hydrocarbons (R.L. Augustine, 1968 D. Todd, 1948 R.O. Hutchins, 1973B) and Barton s olefin synthesis (p. 35) both using hydrazine derivatives. 

Synthetic strategy Multi-component one-pot protocol for the Wolff-Kishner type reductive deoxygenation of acyl phosphonates... 

Keywords Carboxylic acids, acyl chlorides, dichloromethane, room temperature, Arbuzov reaction, acyl phosphonates, Wolff-Kishner type reductive deoxygenation, alkyl phosphonates... 

Kedrowski and Dougherty developed a one-pot, four-step room temperature protocol for the synthesis of allylphosphonates (6) from acyl chlorides/carboxylic acids (5) via a Wolff-Kishner-type reductive deoxygenation (Scheme 3). This method offers a low-temperature alternative to the Arbuzov reaction that works well for a variety of aliphatic acids and shows a functional group tolerance similar to that of other hydrazone-forming reactions. The investigators also proposed a mechanism for this transformation (Scheme 4). 

Scheme 3 Synthesis of alkylphosphonates from acyl chlorides/carboxylic acids via a Wolff-Kishner-type reductive deoxygenation.

A third type of reduction of a-substituted ketones is typified by the expulsion of the substituent and the reduction of the keto function to form an olefin. Wolff-Kishner reductions of a-hydroxy, a-acetoxy, " a-halo, °° and a-epoxy (see below) ketones are the most frequently encountered steroid examples of this general class. ... 

Also other reaction types have been dealt with in CHEC(1984) and CHEC-II(19%) like reduction to alcohols (e.g., sodium borohydride), Wolff Kishner reduction, nucleophilic addition via reaction with Grignard reagents or organo-lithium compounds, and formation of imine type functional groups (e.g., hydrazones). New examples are the reaction of... 

Since its introduction early in this century, the deoxygenation of aldehydes and ketones to methyl or methylene derivatives, respectively, via base treatment of hydrazone intermediates (equation 1) has proven to be one of the most convenient and synthetically useful processes available for this important type of transformation. The reaction is termed the Wolff-Kishner reduction in recognition of the two original independent discoverers.However, the initial recipes introduced proved tedious and unreliable with many structural, especially hindered, examples. This led to substantial efforts devoted over the years to developing more convenient and successful experimental procedures, resulting in a number of improved and more reliable modifications which are most often utilized at present. More recently, modified procedures have been provided which utilize hydride reductions of p-toluenesulfonylhydrazone (to-sylhydrazone) derivatives and subsequent decomposition to release the hydrocarbon products under much milder and less basic conditions than those normally required for Wolff-Kishner reductions (equation 2). 

The above mentioned isomerization of CCCLI to CCCLII constitutes a route from the 9/3,19-cyclosteroids to a new skeletal type which is characteristic of a small group of Buxus alkaloids and will be dealt with in the subsequent text. Another reaction applied to an analogous structural type and leading to cleavage of the cyclopropane ring was reported by Kupchan and Abushanab 219) who had subjected 9, 19-cyclo-5a-pregnane-3,l 1,20-trione-3,2()-diethylene ketal to Wolff-Kishner reduction and obtained a mixture of 10-epimeric ketals CCCLX and CCCLXI. 

This type of compound is called a hydrazone, and is the first intermediate in a very important reaction called the Wolff-Kishner reduction. This reaction, along with the Clemmensen reduction (which we will discuss in more detail in the chapter on redox reactions), is one of the principal methods for reducing a carbonyl compound to the corresponding alkane, i.e. R2C=0 to R2CH2. In... 

These types are particularly involved whose one of the leaving groups is part of the chain. Thus, in the abnormal Wolff-Kishner reduction 4,5-dihydro-lH-pyrazoles are formed (e.g. 311), whose pyrolysis leads to [2,3,(4)I,(2)3(4)]-eliminations of nitrogen with-cyclopropane formation. In this way 311 forms 312 (75%)163). The three assistant figures are necessary in order to fix which chain-bonds migrate and where the second leaving group is located. Even the eliminations of carbenes (formally)... 

Pyridinium salts of type (57) are smoothly converted into iV-substituted pyridones (58) on reaction with pentyl nitrite and sodium methoxide, in an average yield of 64% (Scheme 24). 3-Phenacylpyridinium salts, e.g. (59), react with hydrazine and potassium hydroxide to give 4-alkyl-6-phenylpyridazines, e.g. (60), by a process involving ring-opening, ring-closure, and Wolff-Kishner reduction (Scheme 25). ... 

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