McMurry cyclization intramolecular

A third method for the synthesis of cycl[3.2.2]azines, from iV-(aroylmethyl)pyridinium salts via indolizines, involves intramolecular (reductive) McMurry coupling of the latter. For example, 3,5-dibenzoylindolizines, obtained from 2-benzoyl-iV-phenacylpyridinium bromide as shown (Scheme 91), are cyclized using zinc and titanium(iv) chloride to give the 3,4-diphenylcyclazines 352 in high yield (>90%). The reaction cannot be applied, however, to... 

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. 

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 synthesis of the macrocycle 30 with n = 4, pentacyclo[12.2.2.2. 2. 2 ]-tetracosa-1,5,9,13-tetraene, was carried out likewise by McMurry et al. [26]. They used the method cited above to cyclize the diketone 29 in an intramolecular reaction. The macrocycle 30, mp >300 C, was isolated in 90% yield which is extremely high. An X-ray crystal structure showed that the distance between two opposite double bonds is 511 pm, i.e. the metal-carbon distance should be about 250 pm for optimal complexation of a metal cation. For this reason the silver ion was chosen. If the tetraalkene 30 is stirred with silver triflate in THF the expected complex 31, stable against light, heat, and air, precipitates as a colorless solid in 66% yield (mp 145 C). 

Later, p-acetoxy-substituted cyclic enones 87 with various ring sizes were also examined for intramolecular Stetter cyclization. Under the optimized Stetter conditions (1.0 equiv. of thiazolium salt 88 and 1.2 equiv. of EtsN in EtOH under reflux), bicyclic enedione 89 could be synthesized effectively (Scheme 4.27), but the yields mainly depended on the size of the ring in the substrate 87." Increasing the substrate ring size led to improved yields of 89. Cycloheptenone and cyclooctenone derivatives 87c,d afforded the desired enediones 89c,d in 80% yields. To reduce the conjugated C-C double bond, McMurry s procedure" using TiCls as a reductant was employed to give diketones 90 in excellent yields. 

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). 

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. 

Longifolene, one of nature s most interesting and elegantly constructed sesquiterpenes, was first synthesized by Corey etd) using an ingenious intramolecular cyclization reaction of a homodecalin derivative (i—ii). Recently, McMurry and Isser reported a second approach for... 

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