Deoxygenation of aldehydes and ketones

The deoxygenation of aldehydes and ketones to the corresponding hydrocarbons via the hydrazones is known as the Wolff-Kishner reduction.28 Various modifications of the original protocols have been suggested. One of the most useful is the Huang-Minlon modification, which substituted hydrazine hydrate as a safer and less expensive replacement of anhydrous hydrazine. In addition, diethylene glycol together with sodium hydroxide was used to increase the reaction... 

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). 

A milder approach for the deoxygenation of aldehydes and ketones involves treatment of the preformed hydrazone with t-BuO K in DMSO at room temperature. Alternatively, conversion of the carbonyl group of aldehydes and ketones into the corresponding tosylhydrazone and reduction of these with NaBH3CN ° or with (RC02)2BH produces the desired methylene compounds in good yields. 

Wolff-Kishner reduction Deoxygenation of aldehydes and ketones under basic conditions to give hydrocarbons via the corresponding hydrazones or semicarbazones. 496... 

Neumann and co-workers reported a catalytic variation of this chemistry. Labile Keggin heteropolymolybdates such as K5PV2M010O40 after activation by H2 catalyze the deoxygenation of aldehydes and ketones. For example, PhCOMe is deoxygenated to PhEt in 100% yield in the presence of K5PV2Moi0O40 supported on A1203.324... 

A very useful variant of the hydrazone reduction is the deoxygenation of aldehydes and ketones via the hydride reduction of tosylhydrazones (Caglioti reaction) The method is mild, convenient and widely applicable. While sodium borohydride was used in the earlier procedures, considerable improvements have been achieved through the uses of sodium cyanoborohydride, catecholborane, diborane, his-benzoyloxy borane and copper borohydride as reducing agents and HMPA, DMF, sulpholane, etc. as solvents. Use of the sterically crowded 2,4,6-triisopropyl tosylhydrazone derivative has greatly facilitated the reduction in some cases (equations 61-64). ... 

Inanaga has studied the use of Smiz deoxygenation of aldehydes and ketones.The reaction proceeds by a two-step mechanism, where Sml2 and CH2I2 react with the carbonyl to form an 0—SmIX species (M), which is converted to a better leaving group and reductively eliminated with Sml2." As the examples depicted in Scheme 20 indicate, no studies of chemoselectivity have been undertaken. ... 

From the following reaction with cyclohexene, it was concluded that the deoxygenation of aldehydes and ketones by Zn/Cu and TMSCI in diethyl ether takes place via a carbenoid intermediate [86a]. 

Solutions of low-valence titanium chloride (titanium dichloride) are prepared in situ by reduction of solutions of titanium trichloride in tetrahydrofuran or 1,2-dimethoxyethane with lithium aluminum hydride [204, 205], with lithium or potassium [206], with magnesium [207, 208] or with a zinc-copper couple [209,210]. Such solutions effect hydrogenolysis of halogens [208], deoxygenation of epoxides [204] and reduction of aldehydes and ketones to alkenes [205,... 

Reduction of aldehydes and ketones usually occurs by the addition of hydrogen across the carbon-oxygen double bond to yield alcohols, but reductive conversion of a carbonyl group to a methylene group requires complete removal of the oxygen, and is called deoxygenation. 

Several other procedures are available for the deoxygenation of the carbonyl groups of aldehydes and ketones to the corresponding methyl and methylene groups, respectively, as outlined below. 

Deoxygenation of the carbonyl group of aldehydes and ketones via the intermediacy of their hydrazone derivatives, known as the Wolff-Kishner reduction,offers an alternative to the thioacetal desulfurization method. The Wolff-Kishner reduction in the presence of hydrazine and NaOH (or KOH) has been replaced largely by the Huang-Minlon method,where the deoxygenation is carried out with hydrazine in refluxing ethylene glycol. 

Kabalka and Chandler now report improved yields (83—98%) in the deoxygenation reaction of aldehydes and ketones, on treatment of their corresponding tosylhydrazones with catecholborane in the presence of tetrabutylammonium acetate as the base. ... 

In the presence of Znl2, dichloromethane or dimethoxyethane solutions of NaBH3CN have been found to deoxygenate aryl aldehydes and ketones as weU as benzylic, allylic and tertiary alcohols in moderate to good yields. In spite of the unfavorably large excess of the reagent, the procedure is simple and the substrates require no previous transformations to halides or tosylates, so that the reagent can also be recommended for the synthesis of... 

The inter- and intramolecular coupling of two carbonyl groups of aldehydes or ketones in the presence of a low-valent titanium species produces a C-C bond with two adjacent stereocenters, a 1,2-diol (a pinacol). These may be further elaborated into ketones by the pinacol rearrangement or be deoxygenated to alkenes (McMurry reaction). 

For the one-step conversion of oxiranes to alkenes a variety of reducing metals have been used, including Li, Ti°, low-valent Nb, Cr , and Sm . ° In the latter case, HMPA and N,N-dimethylami-noethanol facilitate the reaction. Reaction of 2 equiv. of Bu"Li with WCle produces a reagent which effects efficient deoxygenation of oxiranes, as exemplified in equation (8). This reagent is particularly valuable for the deoxygenation of tri- and tetra-substituted oxiranes and is compatible with ethers and esters, although aldehydes and ketones reductively couple with it. 

The combination with ZnClj is capable of deoxygenating a-ferrocenyl carbinols, aldehydes, and ketones. ... 

Reduction of tosylhydrazones. Caglioti (Univ. di Bologna, Italy) introduced a simple method for the deoxygenation of aliphatic aldehydes and ketones under mild and neutral conditions consisting in reaction of the tosylhydrazone with sodium borohydride in methanol.35,36... 

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