McMurry reaction intramolecular

The proposed catalytic mechanism for intramolecular McMurry reaction begins with the reduction of TiCl3 by zinc metal to generate the activated titanium species A-19. Reductive cyclization of the dicarbonyl substrate forms the McMurry coupling product, along with titanium oxide complex B-15. To close the catalytic cycle, the oxide complex B-15 is converted to TiCl3 by Me3SiCl (Scheme 63).8d,8e... 

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 McMurry reaction involving low-valent titanium species accomplishes coupling of two carbonyl groups to furnish aUcenes. The low-valent titanium species is generated either from TiCls/LAH , TiCls/Mg or TiCU/Zn-Cu. When one or both carbonyl substrates carry one or more additional double bonds, dienes or polyenes result from this reaction (equation 109) . The McMurry coupling reaction is remarkably selective and a wide variety of functionalities are tolerated. This reaction can be carried out in both inter- and intramolecular modes to furnish a variety of dienes and polyenes. Synthesis of dienes and polyenes where McMurry coupling has been a key reaction is given in Table 21 . 

Intramolecular free radical cyclization of dicarboxylic esters leads to a-hydroxy ketones (acyloins). Reductive coupling of dicarbonyl compounds provides 1,2-diols ipinacols) and further reaction of these yields cycloalkenes (McMurry reaction). These cyclization reactions are especially valuable for the preparation of medium and large rings that are not readily accessible by other methods. 

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). 

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... 

This process is similar to the Mcmurry reaction [167] the reductive dimerization of aldehydes and ketones by [Ti] forming oleftnic C=C bonds. The mechanism of the Furstner synthesis presumably involves single-electron transfer to the carbonyl groups (78 -> 80) and intramolecular radical combination in 80 (supported by Ti-chelation) to... 

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. 6.6. Syntheses of phenanthrenes, helicenes, circulenes, and heterocyclic alkenes by intramolecular McMurry reactions.

Pyrrolo[2,1,5-cd]indolizines and porphyrins It has recently been found that McMurry coupling opens an efficient route for the preparation of pyrrolo[2,l,5-cdjindolizines 101 and other substituted derivatives, by intramolecular reductive condensation of 3,5-diacylindolizines [139] (Figure 6.18). Another application of the McMurry reaction in nitrogen heterocyclic chemistry is in the synthesis of porphyrinoids octaethylisocorrole 102 and corphycene 103 have been synthesized by intramolecular cyclization of the corresponding tetrapyrrolic a,porphyrin derivatives have been obtained by tandem reactions (Section 6.2.3). 

It is primarily in its crucial and elegant use as a key step of numerous syntheses of natural products that the McMurry reaction has proved so successful. Indeed, intramolecular carbonyl coupling has proved to be one of the best methods for... 

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