Carbonyl compounds by -eliminations

All three elimination reactions--E2, El, and ElcB—occur in biological pathways, but the ElcB mechanism is particularly common. The substrate is usually an alcohol, and the H atom removed is usually adjacent to a carbonyl group, just as in laboratory reactions. Thus, 3-hydroxy carbonyl compounds are frequently converted to unsaturated carbonyl compounds by elimination reactions. A typical example occurs during the biosynthesis of fats when a 3-hydroxybutyryl thioester is dehydrated to the corresponding unsaturated (crotonyl) thioester. The base in this reaction is a histidine amino acid in the enzyme, and loss of the OH group is assisted by simultaneous protonation. 

This reaction sequence of conjugate reduction followed by aldol reaction is known as the reductive aldol reaction. In certain instances, reductive elimination from the M-TM-enolate species may occur to furnish M-enolate, which itself may participate in the aldol reaction (Scheme 3). This detour may be described as the background path or stepwise path in one-pot. Indeed, it has been reported that certain cationic Rh complexes such as [Rh(COD)(DPPB)] (COD = 1,5-cyclooctadiene, DPPB = diphenylphosphinobutane) catalyze the aldol reactions of silyl enol ethers and carbonyl compounds by serving as Lewis acids [5-8]. 

Since nucleophilic addition to a metal-coordinated alkene generates a cr-metal species bonded to an -hybridized carbon, facile 3-H elimination may then ensue. An important example of pertinence to this mechanism is the Wacker reaction, in which alkenes are converted into carbonyl compounds by the oxidative addition of water (Equation (108)), typically in the presence of a Pd(n) catalyst and a stoichiometric reoxidant.399 When an alcohol is employed as the nucleophile instead, the reaction produces a vinyl or allylic ether as the product, thus accomplishing an etherification process. 

As peracids react very sluggishly with alcohols, it was apparent that the presence of a nitroxide was playing an important role in the oxidation of the alcohol into a ketone. This seminal serendipitous observation led to the development of the first description of the oxidation of alcohols mediated by catalytic 2,2,6,6-tetramethylpiperidine-l-oxyl (TEMPO) (55), published almost simultaneously by Celia et al and Ganem.3 These authors presented two papers with remarkably similar contents, in which alcohols were oxidized by treatment with MCPBA in CH2CI2 at room temperature in the presence of a catalytic amount of TEMPO (55). In both papers, a plausible mechanism is presented, whereby m-chloroperbenzoic acid oxidizes TEMPO (55) to an oxoammonium salt 56. This oxoammonium salt 56, as detailed in Ganem s paper, can react with the alcohol producing an intermediate 57, which can deliver a carbonyl compound by a Cope-like elimination. 

Cyanohydrin derivatives have also been widely used as acyl anion synthons. They are prepared from carbonyl compounds by addition of hydrogen cyanide. A very useful variant is to use trimethylsilyl cyanide with an aldehyde to produce a trimethylsilyloxy cyanide. The cyano group acidifies the a position (pKA 25) and the a proton can be removed by a strong base. Alkylation of the anion and unmasking of the hydroxy group cause elimination of cyanide and re-formation of the carbonyl group. 

Conversion of a Mannich base hydrochloride into an a,/ -unsaturated carbonyl compound, is illustrated by the formation of phenyl vinyl ketone, which is obtained directly by steam distillation (Expt 6.147). Alternatively the Mannich base may be treated with methyl iodide to form the quaternary salt, which then gives the a,/ -unsaturated carbonyl compound by a base-catalysed elimination reaction. 

Chapter 6. As discussed in Section 4.3.1, imines are formally related to carbonyl compounds by the addition of amine and elimination of water, and we will begin by considering the ways in which metal ions may control this process. 

Under similar conditions, even benzylic C-H bonds of some hydrocarbons (xanthene and fluorene) are converted to the ketones (e.g., fluoren-9-one). Notwithstanding the parallel activities of the two catalysts, different mechanisms were tentatively proposed (277-279). Thus, for R.UC0AI-LDH-CO3, it was postulated that the presence of Co in the structure facilitated the formation of high-valent Ru(V)=0 species. In contrast, for the Ru-HAP catalyst, it was proposed that after coordination of the reactant to Ru as an alcoholate, the carbonyl compound was eliminated, leaving a Ru-H compound, which in a next step is reoxidized by O2. The basic nature of the HAP (or LDH) support may actually favor the latter route, with formation of an alcoholate. Filtration tests and elemental analyses confirm the stability of the supported species in both catalysts. 

Alkenes may be prepared by elimination reactions with a regio-chemistry (Hofmann or SaytzefO that depends on the structure of the substrate and the reaction conditions. Alkenes may also be obtained from carbonyl compounds by the Witlig reaction and by the hydrogenation of alkynes. 

Cyanohydrins can be reconverted to carbonyl compounds by treatment with base. This process is just the reverse of the addition of HCN deprotonation followed by elimination of CN. 

Oxidation. Oxidation of alkyl halides by DMSO requires high temperatures (100-150°), and yields are relatively low except for primary iodides (1, 303). Epstein and Ollinger11 find that halides can be oxidized to carbonyl compounds by DMSO at room temperature (4-48 hours) in the presence of silver perchlorate as assisting agent. Chlorides are relatively unreactive, but bromides and iodides are oxidized relatively easily. Yields are higher with primary halides than with secondary halides. Cyclohexyl halides are oxidized to only a slight extent to cyclohexanone, the main product being cyclohexene, formed by elimination. 

Preparation ofa, -Unsaturated Carbonyl Compounds by Decarboxylation-Elimination (B)... 

General Preparations.—Alkenes. Dehalogenation of vicinal dihalides is easily carried out using sodium in liquid ammonia, e.g. 1,2-dichlorocyclo-octane gave ds-cyclo-octene in 95% yield.The scope of the synthesis of ap-unsaturated carbonyl compounds by syn-elimination from 2-phenylselenoxides has been studied only low yields of the desired ketone were obtained from 2-phenylseleno-cycloheptanone and cyclo-octanone because of the competing Pummerer rearrangements, but improved yields could be obtained by prior conversion of the ketones into ketals. The reaction worked well for 2-methoxycarbonyl cyclic ketones, e.g. 2-methoxycarbonylcyclo-oct-2-en-l-one was prepared in 93% yield. ... 

The radical addition of sulfinates to unsaturated compounds via the iodosulfonylation-dehydroiodination reaction sequence constitutes a general method for the preparation of vinyl sulfones the latter may be rearranged to aUyUc sulfones by treatment with base. The radical addition may be carried out on a, -unsaturated carbonyl compounds as well as alkenes. In the case of unsaturated carbonyl compounds the elimination process can be quite stereoselective, ( )-alkenes being normally formed. For the addition to nonconjugated alkenes, conditions have been described for the preparation of either ( )- or (. -alkenes. ... 

We have seen numerous examples of acid-catalyzed dehydration of alcohols, so it may seem strange that aldols can dehydrate in basic solution. This is another example of how the acidity of the a hydrogens affects the reactivity of carbonyl compounds. Here, elimination occurs by initial formation of an enolate, which then loses hydroxide to form the a,(3-unsaturated aldehyde. 

Petasis and co-workers extended the above methylenation procedure to the alkylidenation of carbonyl compounds by using dialkyltitanocenes [lie, 62]. Like methylidenation with dimethyltitanocene, the Petasis alkylidenation is believed to proceed via the formation of titanocene-alkylidenes through a-elimination of dialkyltitanocenes. This assumption is supported by the isolation of the cy-clometalated product 32, which is indicative of the intermediary formation of titanocene-benzylidene 34 by thermolysis of dibenzyltitanocene 33 bearing a tert-butyl group on the Cp ring (Scheme 4.30) [83]. 

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