McMurry pinacol coupling

In his recent s5mthesis of 19-hydroxytaxoid 18, an intermediate in the synthesis of the anti-cancer agent 19-hydroxytaxol, Mukaiyama performed an intermolecular McMurry pinacol coupling on diketone 17. Note that the reaction temperature was sufficiently low to allow isolation of the diol intermediate. 

McMurry pinacol couplings can proceed with stereochemical induction from nearby stereogenic carbons. For example, diastereomer 21 was the major heterocoupled stereoisomer observed when aldehyde 19 and ketone 20 were treated under McMurry conditions. A diastereomer of 21 was also produced in 22% yield along with the product of homocoupling of... 

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. 

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]). 

Titanium promotes the pinacol coupling and then deoxygenates the products the McMurry reaction... 

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... 

The first total synthesis of ( )-sarcophytol B (5) from S./i-famesal (92), which was reported by McMurry et al. in 1989, used a low-temperature titanium-induced pinacol coupling reaction of 1,14-dialdehyde as the key step. They concluded that the natural sarcophytol B has the stereochemistry of a trans diol (Scheme 6-5). Li et al. reported on a concise total synthesis of ( )-sarcophytol B (5) from /i./i-famesol (91) by a low-valent titanium-mediated intramolecular McMurry... 

Pinacol Coupling Reactions 2.6.7 McMURRY-TYPE COUPLINGS... 

A variety of natural products have been synthesized via application of reductive pinacolic couplings. An early example is the cyclization of the keto aldehyde (51) to the alkene (52 equation 89) a precursor to the terpene, cuparene (18).A modified McMurry procedure provides a novel route to steroids such as estrone methyl ether, via chemoselective cyclization of the keto aldehyde (53 equation 90). The... 

The mixed coupling of aliphatic compounds is also well established. Through the use of an excess (usually 10-fold) of one of the reactants cross-coupling of aliphatic carbonyls is highly effective. This protocol was first developed by (Torey and then applied to reductive pinacolic couplings by McMurry. Li et al. applied this method to the synthesis of the alkaloid isoharringtonine (83 equation... 

The McMurry coupling (Chapter 6) is closely related to the pinacol coupling. 

Periplanone C. McMurry has reported an enantioselective synthesis of (-)-periplanone C, a sesquiteipene that serves as a sex pheromone for cockroaches, through a route involving a pinacol cyclization of a 1,10-keto aldehyde (Eq. 3.7) [24]. MM2 calculations based on a model for predicting the stereoselection of titanium-mediated pinacol coupling reactions were in qualitative, but not quantitative, agreement with the experimental results. 

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