McMurry reaction alkenes

Carbonyl compounds the McMurry reaction Alkenes olefin metathesis Stereoselective Methods for E-Alkenes... 

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). 

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. ... 

Metal alkylidene complexes find application in the metathesis of alkenes, the cvclopropanation of alkenes (Grubbs, Schrock), Wittig type reactions, and the McMurry reaction. In suitable complexes a-elimination can occur twice yielding alkylidync complexes. See Figure 2.21 for an example with tungsten. 

Fig. 17.55. Reductive coupling of a dicarbonyl compound to afford diastereomeric glycols or diastereomeric alkenes (McMurry reaction).

Fig. 17.56. Mechanistically relevant observations on the McMurry reaction. At higher temperatures, the diastereomeric dititanium glycolates rac-B and meso-B are reduced to cis,trans-mixtures of the alkene C. The stereoselectivity of the alkene formation is low, but different for each of the dititanium glycolates. This proves that the reduction of rac-B and meso-B to the alkene does not proceed via the same intermediate. The mechanistic implications of these findings are shown in Figure 17.58.

Fig. 17.58. The mechanism of the McMurry reaction. A mixture of diastereomers of the dititanium(III) glycolate C is either directly generated via the initially formed Ti(in) ketyl B (variant 1) or in multiple steps (variant 2). At sufficiently high temperatures, C is then reduced to a mixture of diastereomers of the corresponding dititanium(III) glycolate G. The latter decomposes via homolytic cleavage of one of its C—0 bonds to furnish the radical intermediate H. If the only C—0 bond left in this radical also breaks homolytically—which partly occurs without ( ) prior rotation around the C-C(OTiCl) bond—the alkene is formed as an F,Z-mixture. Its composition may (somewhat) depend on the configuration of the dititanium(II) glycolate precursor G (cf. Figure 17.56).

Fig. 14.49. Mechanism of the McMurry reaction. The heterocyclic monotitanium glycolates A and B or analogous dititanium glycolates decompose at higher temperatures via heterolytic cleavage of one of their C—O bonds and form the radical intermediate C. The alkene is formed by cleavage of the second C—O bond. This alkene is not obtained as a single stereoisomer because of the free rotation about the C—C(O) bond in the radical intermediate C. Note that the alkene is formed with a cis, fraraj-selectivity that is independent of the configuration of the titanium glycolate precursor(s).

The main advantage of this reaction over the McMurry reaction (see section on McMurry alkenation ) is the notion that the reaction can take place with two different ketones. In this regard the diazo-thioketone coupling is a cross-coupling rather than a homocoupling. 

Even the ease of retrieval or possible photocatalytic uses or such in alkene synthesis from the carbonyl compounds principal in biochemistry (McMurry reaction) apparently cannot compensate for this as Ti is unable to bind the primary substrate. Eor Al, Zr or Ti abundance cannot replace catalytic versatility with respect to various functions, that is... 

Titanium can be used as the metal source of electrons in the pinacol reaction and, provided the reaction is kept cold and not left for too long, diols can be isolated from the reaction (see the example at the end of the previous section). However, unlike magnesium or aluminium, titanium reacts further with these diol products to give alkenes in a reaction known as the McMurry reaction, after its inventor. 

McMurry reactions also work very well intramolecularly, and turn out to be quite a good way of making cyclic alkenes, especially when the ring involved is medium or large (over about eight members). For example, the natural product flexibilene, with a 15-membered ring, can be made by cycliz-inga 15-keto-aldehyde. 

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). 

Welzel, P. McMurry reaction for alkene syntheses. Nachrichten aus Chemie, Technik und Laboratorium 1983, 31,814-816. 

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." ... 

The intermolecular McMurry reaction has proven a particularly valuable route to alkenic hydrocarbons. This is especially true for polyenes and sterically hindered kenes. For example, -carotene (37 equation 78) can be prepared in 85% yield by reductive dimerization of retinal. Isorenieratene (38 equation 78) is similarly synthesized in 96% yield, and the aldehyde (39 equation 79) has been ela-... 

Strained and sterically hindered alkenes are of special interest in physical organic chemistry. By their very nature these structures are difficult to synthesize and the McMurry reaction represents the only viable route to many such compounds (see Table 2). Torsionally distorted alkenes, capable of exhibiting optical activity without a chiral center, have also been prepared. If the reaction is carried out in a chiral solvent the ( ) isomer is formed selectively (equation 82). 

A wide range of alkenic compounds exhibiting interesting properties associated with their ir-systems have been elaborated via the reductive coupling carbonyls. For example, Marshall and coworkers have studied the intramolecular McMurry reaction as a route to betweenanenes, a class of conformationally... 

We now turn to two reactions, the McMurry and metathesis, that have the same disconnection but both reagents have identical functional groups carbonyls for the McMurry and alkenes for metathesis. These methods have the advantage of simplicity but there are obvious problems of selectivity. 

There are many sigmatropic rearrangements and all are -selective in open chain compounds but can give Z-alkenes if the structure of the compound demands it. In this way they resemble the McMurry reaction and olefin metathesis. Many such reactions are used to transmit three-dimensional stereochemistry rather than for E/Z control in alkenes. 

McMurry olefin synthesis. Lenoir has published a variation of the McMurry reaction for reductive coupling of ketones (6, 589). The actual reagent presumably is also TiCl2, but is produced by reduction of TiCU in THF or dioxane with zinc. This reagent in the presence of pyridine converts ketones into tetrasubstituted alkenes. The reaction is most satisfactory with symmetrical ketones mixtures of (E)- and (Z)-isomers obtain from unsymmetrical ketones, with the latter predominating. Strongly hindered ketones are reduced by the reagent to the secondary alcohol. 

The McMurry reaction (see Section 2.9) can allow the formation of alkenes from dicarbonyl compounds. This reaction generates an intermediate 1,2-diol (pinacol), which is converted on the surface of the titanium to the alkene. The two carbon-oxygen bonds do not break simultaneously and the reaction is not stereospecific. Thus, both anti and syn acycUc 1,2-diols give mixtures of Z- and -alkenes. With cyclic 1,2-diols, the two oxygen atoms must be able to bond to a common titanium surface. Thus, the cis-diol 45 eUnunates to the alkene 46, whereas the trans-dio 47 is inert under these reaction conditions (2.43). ... 

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