McMurry reaction intermolecular

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. ... 

It is difficult to obtain cross-coupling products of two different carbonyl compounds by an intermolecular version of the McMurry reaction. Examples that use excess amounts of one carbonyl component are few. "" When one carbonyl component is replaced by a 1,1-dihalo compound or dithioacetal and the alternative is reduced with a low-valent metal such as low-valent titanium or chromium(ii), cross-coupling products, that is, Wittig-type olefins, are produced in high yields. Because the alternative approach is described elsewhere, we concentrate on only its important features here. 

The dimerization of aromatic aldehydes is used for the synthesis of substituted stilbenes. The intermolecular unsymmetrical McMurry reaction is not very important in organic syntheses because of the formation of a mixture of products. However, the reaction of two aryl ketones 4.80 and 4.81 functionalized by a sulfonyl and a hydroxyl group, respectively,... 

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-... 

McMurry reactions will be presented in the following order intermolecular, intramolecular, mixed (tandem) couplings of aldehydes and ketones, and finally keto ester, oxoamide, and acetal couplings. All the compounds which serve as illustrations are listed in Tables 6.1-6.10, along with the titanium reagents and solvents used for their preparation and the yields of isolated products where not specified, the reactions were performed at solvent reflux temperature. 

Tab. 6.3. Syntheses of alkenes by intermolecular McMurry reactions of aldehydes and ketones with functional heteroatom groups, and of organometallic aldehydes and ketones.

The estrone methyl ether 130 [169], kempene-2 131 [170], and isokhusimone 132 [171] were easily isolated following McMurry reactions of their tricarbonyl precursors as their intermolecular dimerization is much slower than the intramolecular cyclization. 

As reflux temperatures are usually required to effect the deoxygenation step of the McMurry reaction, pinacol intermediates can be isolated if the McMurry reaction is run below room temperature. Though a mixture of diol diastereomers is formed in intermolecular reactions, intramolecular reactions can be highly diastereoselective. ... 

The examples presented illustrate two of the common ways McMurry reactions are run. The first uses the instant method and is intramolecular. The second uses a different order of addition and is intermolecular. 

The intermolecular McMurry carbonyl coupling reaction has been applied to the synthesis of a variety of symmetrically and, in certain cases, unsymmetrically substituted alkenes. 

Cycloalkenes. McMurry and Kees have described an intramolecular coupling of dicarbonyl compounds to cycloalkenes. In the intermolecular version of this reaction titanium(O) powder obtained by reduction with potassium or lithium is used (7, 368). In the intramolecular reaction a superior coupling reagent is prepared by reduction of TiClg with a zinc/copper couple in DME. 

Alkenes can be obtained from aldehydes or ketones on reductive dimerization by treatment with a reagent prepared from titanium(III) chloride and zinc-copper couple (or L1A1H4), or with a species of active titanium metal formed by reduction of titanium(III) chloride with potassium or lithium metal. This McMurry coupling reaction is of wide application, but in intermolecular reactions generally affords a mixture of the E- and Z-alkenes (2.99). 

A different strategy for the formation of the cyclic core of the BFC is based on peptide bond formations O Fig. 45.10). The macrocycle is formed by an intermolecular reaction of an activated disuccinimido ester with a diamine under high-dilution conditions with a yield of >40%. Reduction of the carbonyl groups and alkylation lead to a BFC, which possesses an attachment function for biomolecules on the carbon backbone of the macrocycKc core (McMurry et al. 1992). 

The original Mukaiyama and Tyrhk reagents, TiCl4-Zn and TiCb-Mg in THF, have been modified in order to favor the intermolecular McMurry pinacol reaction and to enhance its diastereoselectivity. The effects of solvent, additives, and/or modified ligands can be illustrated by the reaction of benzaldehyde, and are summarized in Table 6.12. 

In his recent s5mthesis of 19-hydroxytaxoid 18, an intermediate in the synthesis of the anti-cancer agent 19-hydroxytaxol, Mukaiyama performed an intermolecular McMurry pinacol coupling on diketone 17. Note that the reaction temperature was sufficiently low to allow isolation of the diol intermediate. 

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