McMurry coupling synthesis

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 ... 

This rational approach for the synthesis of isocorroles is complemented by observations discovered in investigations on porphycencs. Firstly as minor side products of the McMurry coupling of 2,2 -bipyrroles-5,5 -dicarbaldehydes, e.g. 3, isocorroles arc formed, e.g. 5.2... 

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... 

Covalent attachment of adamantane molecules is a key strategy to string them together and construct molecular rods. The McMurry coupling reaction was employed to obtain polyadamantane molecular rods (see Fig. 35) [170]. As another example, synthesis of tetrameric 1,3-adamantane and its butyl derivative has been reported [171] (see Fig. 36). 

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... 

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. 

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... 

Accounts of die reductive coupling of two molecules of ketone via the McMurry alkene synthesis have been described66-68 earlier under Miscellaneous Aldols. 

Another improved synthesis of unsubstituted porphycene 38 (R=H) using ferf-butyl substituents as temporary stabilizing groups, as outlined in Scheme 22, has been described (07JPP596). Thus, deprotection of the N-tosyl-protected bipyrrole 46, followed by formylation yields diformyl intermediate 36, which readily undergoes McMurry coupling to produce 38 (R=H, f-Bu). 

Titanium compounds are used very frequently in organic synthesis, however, often stoichiometrically [8]. [Cp2TiCl]2 is the most frequently applied titanium reagent to mediate radical reactions (reviews [123, 124]). Radicals are also often invoked in McMurry couplings mediated by low-valent titanium species (reviews [125-127]) and in the related pinacol coupling (reviews [128-130]). 

Stereoselective McMurry coupling. Clive and co-workers1 report that a modified McMurry reagent prepared in DME with C8K and TiCl3 ( 2 1) can effect highly stereoselective coupling of keto aldehydes. Thus the key step in a synthesis... 

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 first enantioselective total synthesis of (- -)-l 1,12-epoxycembrene C (28) has been accomplished via a macro-olefination strategy by employing titanium-mediated McMurry coupling as a key step and the Sharpless asymmetric epoxidation for the introduction of chiral epoxide. Based on the enantioselective Sharpless asymmetric epoxidation, Li et al. assumed the configuration of natural 28 to be (115,125) (Scheme 6-21). ... 

Stuhr-Hansen has reported on a microwave-induced high yielding synthesis of alkenes by McMurry coupling of aldehydes and ketones. With microwave heating, the corresponding alkenes have been produced much faster with higher yields (>80%) as compared to conventional heating. 

Both X-ray crystallographic studies and theoretical predictions have been done to show that these sexithiophenes take a helical conformation. Internal torsional forces between rings have been used to drive the molecule to take a solid state helical conformation. Synthesis of tetrathia-[7]-helicene (TH[7]) 85 has been carried out by McMurry coupling of 2-formyl-benzo[l,2-i 4,3-... 

Other reports of kinetic studies deal with mechanisms of thermal oxidation of a variety of simple ketones monitored via gas evolution (CO, CO2, H2, etc.), alkaline oxidation of aldehydes with copper and silver tellurates, [M (H2Te06)2] , and oxidation of acetals of simple aldehydes in aqueous acetic acid with (i) N-chlorobenzamide (H2OCI+ is the oxidant inferred) and (ri) W-chlorosaccharin. Accounts of the reductive coupling of two molecules of ketone via the McMurry alkene synthesis have been described earlier under Miscellaneous Aldols. 

In 1994 Cava and coworkers reported the synthesis of the tetrathiophene-containing systems 4.183 and 4.184. The first of these was the non-conjugated tetrathiaporphyrinogen-(2.1.2.1) 4.183. This species was isolated in remarkably high yield (78%) from the reductive McMurry coupling of dialdehyde 4.182 (Scheme 4.5.5). Dehydrogenation of this macrocycle was effected by treatment with DDQ, followed by hydrazine. This afforded the neutral aromatic tetrathia[22]porphyrin-(2.1.2.1) systems 4.184 in 82% yield. 

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 . 

Since, for secrecy reasons, information on new processes and the state of their development is not always published, or only after long delays, the classification applied or recent developments may be misleading. For example, the potential of phase-transfer catalyzed processes may already be more important than the present literature indicates. The same statement could apply for areas such as amidocarbonylation, the synthesis of fine chemicals by means of metallocenes, the reductive/oxidative carbonylation of aromatic amines or nitro derivatives, Heck coupling using palladacycles and heterocyclic carbene complexes, catalytic McMurry coupling, or other proposed methods. Recent developments must therefore leave open the stage of development reached, perhaps signaling that at the time of publication no commercialized, licensable process is yet known to the scientific community. 

---