Catalytic McMurry reaction

With the catalytic McMurry reaction a few mole percent of DME-free TiCl3 are sufficient to run the reaction to completion. The trick is that stoichiometrically added zinc continuously provides low-valent titanium and the oxygen that is released is bound by a supersto-ichiometric amount of chlorosilane as a disilyl ether ( disiloxane ). This procedure has been utilized for many indole syntheses based on the McMurry reaction (Side Note 17.6). 

Side Note 17.6. Fiirstner Indole Synthesis - Catalytic McMurry Reaction... 

As already discussed, low-valent titanium can be generated in situ from catalytic amounts of TiCls, by use of excess Zn powder and TCS 14 in acetonitrile, to cy-clize reductively 2-benzoylaminoacetophenone 2091 to the indole 2092, in 80% yield, in an elegant version of the McMurry reaction [23, 64]. Replacement of the Zn metal powder by Ti powder and TCS 14 is very effective - 2092 is obtained in 97% yield [64]. In these reactions the intermediate Ti(0)Cl is apparently recycled by MesSiCl 14 into TiCh [64]. In these Fiirstner versions of the McMurry reaction... 

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... 

Scheme 12.13. Filrstner s McMurry reaction that is catalytic in titanium.

It was clear at the outset that the basic principle of this catalytic scenario may apply to other transformations as well. An obvious extension concerns the pinacol coupling since any McMurry reaction probably passes through the 1,2-diolate stage (c/. Scheme 1) [4]. In fact, several titanium-catalyzed procedures have been reported which rely on chlorosilane additives for the liberation of the product and the simultaneous regeneration of the TiClj salt. They involve either [CpjTiClj] cat., Zn, chlorosilane [8], or... 

Even the ease of retrieval or possible photocatalytic uses or such in alkene synthesis from the carbonyl compounds principal in biochemistry (McMurry reaction) apparently cannot compensate for this as Ti is unable to bind the primary substrate. Eor Al, Zr or Ti abundance cannot replace catalytic versatility with respect to various functions, that is... 

Importantly, this method was shown to be effective for many conventional McMurry reactions as well, and a catalytic variant, using commercially-available titanium powder, followed one year later." The catalytic reaction relied on an admixed chlorosilane, which both activated the commercial titanium powder by destroying the tightly bound oxide layer and regenerated, via ligand exchange, the active titanium chloride from the inactive titanium oxychloride product. 

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]. 

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. 

McMurry coupling, Tebbe reagent, Petasis reagent and Takeda reagent) and catalytic alke-nation of aldehydes and ketones plus the related reactions in each case. 

Only a small minority of organometallic reactions have cleared the hurdle to become catalytic reality in other words, catalyst reactivation under process conditions is a relatively rare case. As a matter of fact, the famous Wacker/Hoechst ethylene oxidation achieved verification as an industrial process only because the problem of palladium reactivation, Pd° Pd", could be solved (cf. Section 2.4.1). Academic research has payed relatively little attention to this pivotal aspect of catalysis. However, a number of useful metal-mediated reactions wind up in thermodynamically stable bonding situations which are difficult to reactivate. Examples are the early transition metals when they extrude oxygen from ketones to form C-C-coupled products and stable metal oxides cf. the McMurry (Ti) and the Kagan (Sm) coupling reactions. Only co-reactants of similar oxophilicity (and price ) are suitable to establish catalytic cycles (cf. Section 3.2.12). In difficult cases, electrochemical procedures should receive more attention because expensive chemicals could thus be avoided. Without going into details here, it is the basic, often inorganic, chemistry of a catalytic metal, its redox and coordination chemistry, that warrant detailed study to help achieve catalytic versions. 

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