Intramolecular McMurry coupling

Highly strained cyclic compounds are accessible by an intramolecular variant. An instructive example for the synthetic potential of the McMurry coupling reaction is the synthesis of 3,3-dimethyl-1,2-diphenylcyclopropene 8 ... 

Oda et al. recently reported the synthesis of the highly strained trimeric meta-PAM 139 (Scheme 32) [82]. The required triene 140 was prepared from a,m-dial-dehyde 141 by an intramolecular McMurry coupling reaction. Bromination/dehy-drobromination of 140 furnished 139 as moderately stable, colorless crystals which decomposed above 180°C. The greater degree of strain in 139 compared to... 

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... 

An interesting approach for the synthesis of enantiopure thiophene-based[7]helicene has been described which utilizes an intramolecular McMurry coupling using low-valent titanium as the key step <2004CEJ6531>. It was found that yields of the product varied widely due to the formation of varying quantities of the intermediate diol and desilylated starting material. 

The McMurry coupling can be applied to intramolecular coupling of keto esters. Because the reactivity between ketone and ester groups is so different, the reaction usually requires individualized optimization, especially in the case of large rings. A combination of TiCls and LiAlH4 in the presence of triethylamine in DME is employed for the... 

Macrolactone synthesis 6,51, 71, 72, 94, 124,131,163,187,195 McMurry coupling 43 Medium ring synthesis 43,45,75, 77 Metathesis, Alkene (see Grubbs) Metathesis, Alkyne (see alkyne metathesis) Michael addition Intramolecular 166,166, 167,201 Intermolecular 57,84, 153, 166,204... 

The introduction of the perfluorocyclopentene moiety, as present in the perfluoro-cyclopentenebisthien-3-yl systems 24, has resulted in excellent thermal and chemical stability and often in high fatigue resistance, allowing many switching cycles. The common synthetic route involves double substitution of perfluorocyclopentene with the appropriate aryllithium, but low yields are often encountered. Recently an alternative route, based on an intramolecular McMurry coupling to produce 25, has been developed (Scheme 12 )J381... 

Step 2 Epimerization of C(8) to the more stable C(8)-Hp isomer. Step 3 Intramolecular McMurry coupling. 

The intramolecular McMurry coupling between the C=0 group of an amide and the C=0 double bond of a ketone leads to the formation of a heterocycle with an enamine-like substructure. The most important heterocycle of this type is the indole skeleton ... 

A prototype example is the famous McMurry coupling of carbonyl compounds to alkenes (Scheme 1) [4]. The very high stability of the accumulating titanium oxides constitutes the thermodynamic sink which drives the conversion but demands the use of stoichiometric or excess amounts of the low-valent titanium reagent [Ti]. Only recently has it been possible to elaborate a procedure that for the first time enables us to perform intramolecular carbonyl coupling reactions catalyzed by titanium species [5]. 

The first enantioselective total synthesis of ( )-7,8-epoxycembrene C (33) was achieved via a general approach by employing an intramolecular McMurry coupling and Sharpless asymmetric epoxidation as key steps from readily available starting material. The syntheses presented here verified the absolute stereochemistry assignment of the epoxy configuration of 33 as assumed (1R,8R) (Scheme 6-20). °... 

The McMurry coupling is most useful for the intramolecular reduction of aldehydes and ketones to form cycloalkenes with ring size varying from 3 to 36. The medium and large rings are usually formed with the -configuration . 

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 . 

A one-pot synthesis of phenanthrenes from ortho-alkoxy a re ne aldehydes and ketones has been accomplished using TiCl3-Li-THF [103]. The 2,2 dialkoxystil-benes, resulting from a classical McMurry coupling [80], are subjected to a reductive dealkoxylation and under the reaction conditions applied [103] form the intramolecular CC coupling products in moderate overall yields (25-38%). 

The method for conversion of benzylic bromide to aldehyde with IBX and DMSO has been applied to a molecule containing six such structural units, to deliver a precursor of the belt-shaped [6.8]3cyclacene by a threefold intramolecular McMurry coupling. ... 

Synthesis of 15,16-Diphenyl-l,4,7,10-tetraoxa(10.2)[20]-paracyclophan-15-ene (14, Scheme 9-8) by an Intramolecular McMurry Coupling under Salt Free Conditions [19]... 

Table 13.7. Intramolecular McMurry Coupling of Diketones and Dialdehydes (282)...

The thia[7]helicene 54 is prepared as the pure (f)-(+) enantiomer via an asymmetric Ulhnann coupling of the enantiomerically pure iodo derivative 55 which gives the intermediate 57. Conversion to the dialdehyde 56 is followed by intramolecular McMurry coupling then gives product 54 (Scheme 23) (1997TL457, 1997J04465). 

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). 

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