Carbonyl compounds coupling

Fig. 11. Priniciple of stereospecific reduction of carbonyl compounds coupled with cofacter regeneration (a) and outline of the stereospecific reduction of ethyl 4-chloroacetoacetate (CAAE) by Sporobolomyces aldehyde reductase (AR) with glucose dehydrogenase (GDH) as a cofactor regenerator in a water-organic solvent two-phasic system (b). CHBE, ethyl 4-chloro-3-hydroxybutanoate...

Abstract The use of organoaluminum-based Lewis acids (A1R X3 R = alkyl, alkynyl, X = halide or pseudohalide) in the period 2000 to mid-2011 is overviewed with a focus on (1) stoichiometric reactions in which one of the organoaluminum substituents is transferred to the substrate (e.g., the opening of epoxides, 1,2-additions to carbonyl compounds, coupling with C-X, and Reissert chemistry) and (2) asymmetric, often catalytic, reactions promoted by Lewis acid catalysts derived from organoaluminum species (e.g., use of auxiliaries with alanes, Diels-Alder, and related cycloaddition reactions, additions to aldehydes and ketones, and skeletal rearrangement reactions). 

Reductive coupling of carbonyl compounds to yield olefins is achieved with titanium (0), which is freshly prepared by reduction of titanium(III) salts with LiAIH4 or with potassium. The removal of two carbonyl oxygen atoms is driven by T1O2 formation- Yields are often excellent even with sensitive or highly hindered olefins. (J.E. McMurry, 1974, 1976A,B). 

Among the appHcations of lower valent titanium, the McMurry reaction, which involves the reductive coupling of carbonyl compounds to produce alkenes, is the most weU known. An excellent review of lower valent titanium reactions is available (195). Titanium(II)-based technology is less well known. A titanium(II)-based complex has been used to mediate a stetio- and regio-specific reduction of isolated conjugated triple bonds to the corresponding polyenes (196). 

Titanium(IV) is a powerful but selective Lewis acid which can promote the coupling of allylsilanes with carbonyl compounds and derivatives In the presence of titanium tetrachlonde, benzalacetone reacts with allyltnmethylsilane by 1,4-addition to give 4-PHENYL-6-HEPTEN-2-ONE. Similarly, the enol silyl ether of cyclopentanone is coupled with f-pentyl chloride using titanium tetrachlonde to give 2-(tert-PENTYL)CYCLOPENTANONE, an example of a-tert-alkylation of ketones. 

Two classes of charged radicals derived from ketones have been well studied. Ketyls are radical anions formed by one-electron reduction of carbonyl compounds. The formation of the benzophenone radical anion by reduction with sodium metal is an example. This radical anion is deep blue in color and is veiy reactive toward both oxygen and protons. Many detailed studies on the structure and spectral properties of this and related radical anions have been carried out. A common chemical reaction of the ketyl radicals is coupling to form a diamagnetic dianion. This occurs reversibly for simple aromatic ketyls. The dimerization is promoted by protonation of one or both of the ketyls because the electrostatic repulsion is then removed. The coupling process leads to reductive dimerization of carbonyl compounds, a reaction that will be discussed in detail in Section 5.5.3 of Part B. 

In similar work, CF3CCI2CO2CH3 yields methyl a-trifluoromethyl-a,(i-un-saturated carboxylates when reacted with a zinc-copper couple, aldehydes, and acetic anhydride [67] (equation 55). This methodology gives (Z)-a-fluoro-a- -un-saturated carboxylates from the reaction of carbonyl compounds with CFCI2CO2CH3 and zinc and acetic anhydride [6 ]. 

Coupling of organic halides with carbonyl compounds promoted by Sml2 in synthesis of heterocycles 99CRV745. 

The intermolecular McMurry reaction is first of all a suitable method for the synthesis of symmetrical alkenes. With a mixture of carbonyl compounds as starting material, the yield is often poor. An exception to this being the coupling of diaryl ketones with other carbonyl compounds, where the mixed coupling product can be obtained in good yield. For example benzophenone and acetone (stoichiometric ratio 1 4) are coupled in 94% yield. ... 

Figure 13,12 Illusti ation of the clean-up method, showing the analysis of an air sample (a) with and (b) without column switching. Details of the analytical conditions are given in the text. Reprinted from Journal of Chromatography, A 697, R R. Kootsti a and H. A. Herbold, Automated solid-phase exti action and coupled-column reversed-phase liquid cltromatogra-phy for the trace-level determination of low-molecular-mass carbonyl compounds in ak , pp. 203-211, copyright 1995, with permission from Elsevier Science.

P. R. Kootstr-a and H. A. Herbold, Automated solid-phase extraction and coupled-column reversed-phase liquid cliromatogr aphy for the trace-level determination of low-molecular-mass carbonyl compounds in ak , 7. Chromatogr. 697 203-211 (1995). 

Muzart et al. described the coupling of aryl iodides and bromides with allylic alcohols to give the corresponding (3-arylated carbonyl compounds [87]. Calo et al... 

Although carbonyl compounds, such as formaldehyde (27,28], can couple with Ce(IV) ion to initiate acrylonitrile (AN) or methyl methacrylate (MMA) polymerization, the remarkable activity of aliphatic aldehyde had not been noticed until the paper of Sun et al. [29] was published. They found that aliphatic aldehydes always... 

One of the most gentle methods for the generation of reactive allylmetallic reagents was introduced in 1977 by Hiyama and Nozaki1,2,3,33. By the action of two equivalents of chromi-um(II) chloride on allylic halides in tetrahydrofuran at 0°C in the presence of a carbonyl compound, reductive coupling with the formation of a homoallylic alcohol takes place. 

C-coupling is of outstanding importance in the azo coupling reaction for the synthesis of azo dyes and pigments. An aromatic or heteroaromatic diazonium ion reacts with the so-called coupling component, which can be an aromatic primary, secondary, or tertiary amine, a phenol, an enol of an open-chain, aromatic, or heteroaromatic carbonyl compound, or an activated methylene compound. These reactions at an sp2-hybridized carbon atom will be discussed in Chapter 12. In the... 

In azo couplings with carbonyl compounds, three tautomeric products are possible, compared with only two for phenols and aromatic amines (discussed in Section 12.1). The ketohydrazone 12.75 is most often dominant, but for easily enolizable 1,3-dicarbonyl compounds (X=CO-R and similar structures) the azoenol 12.76 is the major product. The azoketone 12.77 is often postulated as primary product, but has rarely been identified in an unambiguous fashion using modern methods. The CH2 group should be easily detectable in the lH NMR spectrum. 

Metal-induced reductive dimerization of carbonyl compounds is a useful synthetic method for the formation of vicinally functionalized carbon-carbon bonds. For stoichiometric reductive dimerizations, low-valent metals such as aluminum amalgam, titanium, vanadium, zinc, and samarium have been employed. Alternatively, ternary systems consisting of catalytic amounts of a metal salt or metal complex, a chlorosilane, and a stoichiometric co-reductant provide a catalytic method for the formation of pinacols based on reversible redox couples.2 The homocoupling of aldehydes is effected by vanadium or titanium catalysts in the presence of Me3SiCl and Zn or A1 to give the 1,2-diol derivatives high selectivity for the /-isomer is observed in the case of secondary aliphatic or aromatic aldehydes. 

The direct preparation of arylboronic esters from aryl halides or triflates now allows a one-pot, two-step procedure for the synthesis of unsymmetrical biaryls (Scheme 1-41) [147]. The synthesis of biaryls is readily carried out in the same flask when the first coupling of the triflate with diboron 82 is followed by the next reaction with another triflate. The synthesis of naturally occurring biflavanoids and the couphng of N-(phenylfluorenyl)amino carbonyl compounds to polymeric supports are reported [154]. 

The identification and quantification of potentially cytotoxic carbonyl compounds (e.g. aldehydes such as pentanal, hexanal, traw-2-octenal and 4-hydroxy-/mAW-2-nonenal, and ketones such as propan- and hexan-2-ones) also serves as a useful marker of the oxidative deterioration of PUFAs in isolated biological samples and chemical model systems. One method developed utilizes HPLC coupled with spectrophotometric detection and involves precolumn derivatization of peroxidized PUFA-derived aldehydes and alternative carbonyl compounds with 2,4-DNPH followed by separation of the resulting chromophoric 2,4-dinitrophenylhydrazones on a reversed-phase column and spectrophotometric detection at a wavelength of378 nm. This method has a relatively high level of sensitivity, and has been successfully applied to the analysis of such products in rat hepatocytes and rat liver microsomal suspensions stimulated with carbon tetrachloride or ADP-iron complexes (Poli etui., 1985). 

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