Titanium McMurry coupling

Low valent titanium McMurry carbonyl coupling is believed to go through the vic-diol. vic-diols are smoothly converted to the corresponding olefins under these conditions. JOC 1976, 41, 896... 

The formation of the isocorrolecarbaldehyde 5 may be best explained if one invokes 1,2-diol 4 as an intermediate of the McMurry coupling which would then react in a titanium(IV) chloride induced Wagner-Meerwein rearrangement to yield the isocorrole 5 as a minor product during... 

Catalytic turn-over [59,60] in McMurry couplings [61], Nozaki-Hiyama reactions [62,63], and pinacol couplings [64,65] has been reported by Fiirst-ner and by Hirao by in situ silylation of titanium, chromium and vanadium oxo species with McaSiCl. In the epoxide-opening reactions, protonation can be employed for mediating catalytic turn-over instead of silylation because the intermediate radicals are stable toward protic conditions. The amount of Cp2TiCl needed for achieving isolated yields similar to the stoichiometric process can be reduced to 1-10 mol% by using 2,4,6-collidine hydrochloride or 2,6-lutidine hydrochloride as the acid and Zn or Mn dust as the reduc-tant (Scheme 9) [66,67]. 

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... 

Another well-known transformation of carbonyl derivatives is their conversion to pinacols (1,2-diols) via an initial one-electron reduction with highly active metals (such as sodium, magnesium, aluminum, samarium iodide, cerium(III)/ I2, yttrium, low-valent titanium reagents (McMurry coupling), etc.), amines, and electron-rich olefins and aromatics as one-electron donors (D).43 Ketyl formation is rapidly followed by dimerization44 (equation 22). 

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... 

Solutions to similar problems of achieving catalytic turnover [22] in McMurry couplings [23], Nozaki—Hiyama reactions [24], and pinacol couplings [25] have been reported by Fiirstner and by Hirao. The key step in these reactions is the in situ silylation of titanium and vanadium oxo species with Me3SiCl and reduction of the metal halides by suitable metal powders, e. g. zinc and manganese dust, as shown in Scheme 12.13. 

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. 

Fiirstner has discovered that a low-valent titanium generated by pretreatment of titanium powder with Me3SiGl or Et3SiGl is effective for the McMurry coupling vide infra) ... 

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]). 

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 (- -)-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). ... 

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 . 

The mechanism of the McMurry coupling is not entirely clear, but it is composed of two distinct steps 1) pinacol formation and 2) deox genation to the alkene. Extensive research showed that the low-valent titanium is most likely a mixture of Ti " and Ti ° , and the ratio of these species depends on the method of preparation (solvent, temperature, reducing agent, J ecent findings suggest that the reaction possibly involves the formation of a carbene or a metal carbenoid. The nature of the intermediates is strongly dependent on the structure of the carbonyl substrate and the reaction conditions, which is why the reaction is tricky and yields are difficult to reproduce in the laboratory. 

The McMurry coupling route has been utilised by Iwatsuki and co-workers in the synthesis of PDBoxTV 85 (Scheme 1-29) [129]. Dialdehyde 90 is polymerized in the presence of titanium tetrachloride and zinc dust. Molecular weights of 35000 are reported and the polymer is freely soluble in solvents such as chloroform. The reported absorption maximum (605 nm) was close to that observed by the Blohm route [127]. 

Poly(ferrocenylene vinylene) derivatives 68 with values of 3,000-10,000 and polydispersities of ca. 2.2-2.8 (determined by GPG) were synthesized in 1995 in high yields via a titanium-induced McMurry coupling reaction of the corresponding alkylferrocenyl carbaldehyde monomers (Equation (26)). " Gharacterization of these soluble polymers by NMR and IR revealed the presence of trans-Yinylcnc units. The UV-VIS spectra of the polymers are similar to those of the monomers and this indicates a fairly localized electronic structure in the former. The relatively limited electron localization is also reflected in the electrical and optical properties. For example, the values for iodine-doped conductivity a= 10 Scm ) and non-linear third-order optical susceptibility (x = 1-4 x 10 esu) are lower than those of linear conjugated polymers such as poly(l,4-phenylene-vinylene) (a = 2.5x 10 Scm" = 8 X 10 esu). 

McMurry coupling. Pyrroles and indoles are prepared from keto amides. The reaction is suitable for the synthesis of lukianol-A and lamellarin O dimethyl ether. Titanium needs to be present only in substoichiometric quantities, and trimethylsilyl chloride is a useful activator. 

Carbonyl-Coupling Reactions Using Low-Valent Titanium" McMurry, J.E. Chem. Rev., 1989, 89, 1513. 

Alkenes can be obtained from aldehydes or ketones on reductive dimerization by treatment with a reagent prepared from titanium(III) chloride and zinc-copper couple (or L1A1H4), or with a species of active titanium metal formed by reduction of titanium(III) chloride with potassium or lithium metal. This McMurry coupling reaction is of wide application, but in intermolecular reactions generally affords a mixture of the E- and Z-alkenes (2.99). 

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