McMurry reductive coupling

The Ti-mediated McMurry reductive coupling of carbonyl compounds is a valuable and versatile methodology to build C=C double bonds. It is not therefore surprising that it has been utUized, in an intramolecular version, for the constmction of the internal benzene ring of heterohelicene and thia-hehcene scaffolds. One example is the synthesis of thiahehcene 36, obtained in 38% yield from the diketone 37 (Scheme 15) (2004CEJ6531). 

Scheme 10.5 Distal bridging of formyl calixarenes via intramolecular McMurry reductive coupling...

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). 

The McMurry reagent reductively couples trifluoroacetophenones to the eorresponding stilbenes [67] (equation 55), and cross-coupling of ketones is also reported [68] (equation 56). 

The synthetic method leading to Nb-alkylidenes and Nb-alkylidynes was particularly successful, due to a quite remarkable difference in the reaction rate of 29 with ketones or aldehydes, vs the subsequent reaction of the alkylidene with ketones and aldehydes (see Scheme 37). The former reaction takes a few minutes at -40°C, while the latter one occurs in hours at room temperature.88 The reaction between 178 and benzaldehyde led to triphenylethylene and the niobyl derivative 184. Due to the difference in reaction rates between a and b in Scheme 37, it was found that the sequential addition of two different ketones or aldehydes to a THF solution of 29 produced a nonsymmetric olefin in a stepwise McMurry-type reaction.84 This is exemplified in the coupling shown in reaction c (Scheme 37). The proposed reaction pathway does not involve the intermediacy of a pinacolato ligand and therefore differs from the mechanism of the McMurry reaction and related reductive couplings at activated metal sites.89... 

TABLE 5.9. McMurry s reductive coupling of carbonyl compounds... 

McMurry, J. E., and M. P. Fleming. 1974. A new method for the reductive coupling of carbonyls to olefins Synthesis of /3-carotene. J. American Chemical Society 96 4708-9. 

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]. 

Wynberg studied stereochemistry of the McMurry reductive dimerization of camphor in detail (64). In Scheme 37, A and B are homochiral dimerization products derived by the low-valence Ti-promoted reduction, while C and D are achiral heterochiral dimers. The reaction of racemic camphor prefers homochiral dimerization (total 64.9%) over the diastereomeric heterochiral coupling (total 35.1 %). Similarly, as illustrated in Scheme 38, oxidative dimerization of the chiral phenol A can afford the chiral dimers B and C (and the enantiomers) or the meso dimer D. In fact, a significant difference is seen in diastereoselectivity between the enaritiomerically pure and racemic phenol as starting materials. The enantiomerically pure S substrate produces (S,S)-B exclusively, while the dimerization of the racemic substrate is not stereoselective. In the latter case, some indirect enantiomer effect assists the production of C, which is absent in the former reaction. Thus, it appears that, even though the reagents and reaction conditions are identical, the chirality of the substrate profoundly affects the stability of the transition state. 

Accounts of die reductive coupling of two molecules of ketone via the McMurry alkene synthesis have been described66-68 earlier under Miscellaneous Aldols. 

Another class of extended porphycene, containing an extra sp2 hybridized link between 2 and 2 positions of the bipyrrole subunit has been synthesized by hydrogenation of 80 resulting in the formation of 22jt-electron conjugated porphycene homologue 87 (Scheme 38), also synthesized from pyrrole dialdehyde 86 by reductive coupling under McMurry conditions. 

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

Other reports of kinetic studies deal with mechanisms of thermal oxidation of a variety of simple ketones monitored via gas evolution (CO, CO2, H2, etc.), alkaline oxidation of aldehydes with copper and silver tellurates, [M (H2Te06)2] , and oxidation of acetals of simple aldehydes in aqueous acetic acid with (i) N-chlorobenzamide (H2OCI+ is the oxidant inferred) and (ri) W-chlorosaccharin. Accounts of the reductive coupling of two molecules of ketone via the McMurry alkene synthesis have been described earlier under Miscellaneous Aldols. 

Vogel and coworkers have also explored an alternative approach to the synthesis of isocorroles. This more rational approach involves the low-valent titanium-mediated intramolecular reductive coupling of an a,co-formyl-substituted linear tetrapyrrolic species. Specifically, ring closure of the linear species 2.272, carried out under these McMurry-type conditions, afforded the etioisocorrole 2.270 in 10% yield (Scheme 2.2.4). The putative corrologen , thought to occur as an intermediate in this reaction, was not isolated. Rather, oxidation by molecular oxygen or FeCls during workup was presumed to occur spontaneously. 

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