Tandem McMurry reaction

The tandem McMurry reaction of dicarbonyl compounds consists of an initial in-termolecular coupling followed by an intramolecular cydization (Scheme 6.3). 

The tandem McMurry reaction has been successfully used for the synthesis of cyclophanes (Figure 6.22 Table 6.8) such as 133 and 134 [114, 115, 173], and is a classical route to expanded porphyrin systems. 

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. 

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). 

Fiirstner reported the first McMurry-type reactions working with 5-10 mol% of titanium trichloride and stoichiometric amounts of zinc powder in the presence of chlorotrimethylsilane. The amount of TiCl3 could be reduced to 2 mol% when (ClMe2SiCH2)2 was used as a reagent [125, 131]. At the same time, Burton and coworkers reported atom transfer radical additions of perfluoroalkyl iodides 39 to alkenes 40 catalyzed by 20 mol% of a low-valent titanium compound generated from TiCLt and zinc powder affording 41 in 10-85% yield (Fig. 13). A tandem radical addition/5-exo cyclization/iodine transfer reaction with diallyl ether proceeded in 66% yield [132]. 

In the laboratory of T. Nakai, the asymmetric tandem Claisen-rearrangement-ene reaction sequence followed by a modified McMurry coupling was used to access (+)-9(11)-dehydroestrone methyl ether. The Claisen-ene product was subjected to ozonolysis and epimerization to the 8,14-anf/ configuration. The C-ring was constructed by treating the tricyclic diketo aldehyde with TiCl3-Zn(Ag) in DME to afford the desired final product in 56% yield. 

An ingenious approach to racemic estrone has used two reactions in a combined tandem Cope-Claisen rearrangement (ref. 130). 1-Bromomethyi-3,4-dihydro-6-methoxynaphthalene is used to alkylate 1-methoxycarbonyl-2-methylcyclopent-2-ene and the ester group in the product converted to a vinyloxymethyl substituent. Thermolysis afforded a mixture of diastereoisomeric aldehydes (2 1) containing a majority of the trans compound. Ozonolysis and epimerisation at the 8-position succeeded by McMurry coupling gave the required tetracyclic structure from which racemic estrone methyl ether was obtained. 

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