Reductive coupling of carbonyl compounds

As reductions by metals often occur by one-electron transfers, radicals are involved as intermediates. When the reaction conditions are adjusted so that coupling competes favorably with other processes, the formation of a carbon-carbon bond can occur. The reductive coupling of acetone to 2,3-dimethylbutane-2,3-diol (pinacol) is an example of such a reaction. 

Titanium metal is also activated by TMS-C1.242 These conditions were used in a number of dimerizations and cyclizations, including the formation of a 36-membered ring. 

Another process that is widely used involves reduction by Zn-Cu couple. This reagent is especially reliable when prepared from TiCl3 purified as a DME complex,243 and is capable of forming normal, medium, and large rings with comparable efficiency. 

The macrocyclization has proven useful in the formation of a number of natural products.245 These conditions have been used to prepare 36- and 72-membered rings. 

Reduction of Carbon-Carbon Multiple Bonds, Carbonyl Groups, and Other Functional Groups 

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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). 

Catalytic Reductive Coupling of Carbonyl Compounds -The Pinacol Coupling Reaction and Beyond... 

Hirao T (2007) Catalytic Reductive Coupling of Carbonyl Compounds - The Pinacol Coupling Reaction and Beyond. 279 53-75 Hirayama N, see Sakai K (2007) 269 233-271 Hirst AR, Smith DK (2005) Dendritic Gelators. 256 237-273 Holzwarth AR, see Balaban TS (2005) 258 1-38... 

For a review encompassing the transition metal-catalyzed reductive coupling of carbonyl compounds, see Avalos, M. Babiano, R. Gintas, P. ... 

TABLE 5.8. Corey s reductive coupling of carbonyl compounds... 

Benzene hydrocarbons are known to undergo radical coupling reactions and the intramolecular reductive coupling of carbonyl compounds with a benzene ring has been achieved. Best conditions for this process are at a tin cathode with isopropanol solvent and tetaethylammonium tosylate as supporting electrolyte [102, 103], The reaction is performed at constant current in a divided cell. A single stereoiso-... 

Another possibility for creating a new ligand structure is to connect two phos-phaferrocene molecules via their formyl functional groups. The reductive coupling of carbonyl compounds with low-valent Ti reagents - the McMurry reaction - is a technique that has found wide application in organic synthesis [18]. 

The reductive coupling of carbonyl compounds to pinacols (i.e., 1,2-diols) is usually performed in the presence of a low-valent metal such as Li(0), Sm(II) or Ti(III). Under... 

Bolourtchian, M., Zadmard, R. and Saidi, M.R., Microwave promoted reductive coupling of carbonyl compounds to bis(trimethylsilyl) pinacols under solvent-free conditions, Synth. Commun., 1998,28, 2017-2020. 

The magnesium salt of glycol is thus formed. It yields a glycol with the trival name pinacol upon workup with weak acid. Hence, this kind of reductive coupling of carbonyl compounds is called pinacol coupling. 

Reductive coupling of carbonyl compounds to dials. Activated Ti(0) (2, 368-369) effects the reductive coupling of carbonyl compounds to olefins and also converts 1,2-diols to alkenes (7, 368-369). Corey et al. employed this reagent for... 

The reductive coupling of carbonyl compounds with formation of C-C double bonds was developed in the early seventies and is now known as McMurry reaction [38, 39]. The active metal in these reactions is titanium in a low-valent oxidation state. The reactive Ti species is usually generated from Ti(IV) or Ti(III) substrates by reduction with Zn, a Zn-Cu couple, or lithium aluminum hydride. A broad variety of dicarbonyl compounds can be cyclized by means of this reaction, unfunctionalized cycloalkenes can be synthesized from diketones, enolethers from ketone-ester substrates, enamines from ketone-amide substrates [40-42], Cycloalkanones can be synthesized from external keto esters (X = OR ) by subsequent hydrolysis of the primary formed enol ethers (Scheme 9). 

Mukaiyama, T., Sato, T., Hanna, J. Reductive coupling of carbonyl compounds to pinacols and olefins using titanium(IV) chloride and zinc. Chem. Lett. 1973, 1041-1044. 

Fujiwara, Y., Ishikawa, R., Akiyama, F., Teranishi, S. Reductive coupling of carbonyl compounds to olefins by tungsten hexachloride-lithium aluminum hydride and some tungsten and molybdenum carbonyls. J. Org. Chem. 1978,43, 2477-2480. 

The reductive coupling of carbonyl compounds, especially ketones, to give pinacols is an important method for the formation of vicinally functionalized C—C bonds. In addition, the related coupling of carbonyls to give alkenes, the McMurry reaction, provides a complementary route for C=C bond elaboration." ... 

Although the reduction of carbonyls to alcohols or hydrocarbons is well documented, no general method was available for the reductive coupling of carbonyl compounds directly to alkenes prior to the use of low-valent transition metals. The reductive coupling of carbonyl compounds by low-valent transition metals is now an important method for C=C bond formation, and has been widely reviewed." ... 

The most widely used systems are those employing low-valent titanium species. The reductive coupling of carbonyl compounds by titanium reagents was independently discovered in 1973 by Trylik and Mukaiyama, and has since been extensively developed by McMurry and his coworkers." " The McMurry reaction, as it has become known, has proved to be a valuable synthetic tool for the construction of C=C bonds. 

For a detailed discussion of the reductive coupling of carbonyl compounds to alkenes see Section 2.6.7. 

The twofold extrusion of nitrogen and sulfur and selenium and sulfur from 1-thia- and l-selena-3,4-diazolines(77), readily available from the reaction of diazoalkanes with thio- and selenaketones, respectively, as well as from the reductive coupling of carbonyl compounds such as 78, is the preferred method for preparation of olefins of type I and II (98,99). Examples of the extrusion method, developed by Barton (100), and the McMurry reaction (101) are given in Scheme 1. 

Various reactions. The binary salt is a very useful reagent for promoting Barbier reaction, Mukaiyama-aldol reaction, Michael reaction, Mannich reaction, Diels-Alder reaction, as well as the reductive coupling of carbonyl compounds and of imines. 

Z11-AICI3 in MeCN is reported for reductive coupling of carbonyl compounds to form alkenes. ... 

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