Nozaki-Hiyama

In a recent synthesis of (-i-)-discodermolide, Nozaki-Hiyama reaction of the aldehyde 1617 with the unsaturated Peterson reagent 1618 then treatment with KH in THE gave the diene 1619 in 74% yield [19] (Scheme 10.8). 

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]. 

The multi-component procedure is also effective for the chromium-catalyzed addition of organic halides to aldehydes (the Nozaki-Hiyama-Kishi reaction) [73]. The active Cr(II) species is recycled by redox interaction with Mn powder as the stoichiometric co-reductant in the presence of MesSiCl (Scheme 34), which mainly liberates the chromium catalyst from the alkoxide adduct. The chemo- and diastereo-selective addition reaction is performed with a variety of organic halides and alkenyl triflates. In the case of crotyl bromide, the addition is highly stereoconvergent, i.e., the respective anti-... 

Grigg and coworkers developed bimetallic domino reactions such as the electro-chemically driven Pd/Cr Nozaki-Hiyama-Kishi reaction [69], the Pd/In Barbier-type allylation [70], Heck/Tsuji-Trost reaction/1,3 dipolar cycloaddition [71], the Heck reaction/metathesis [72], and several other processes [73-75]. A first example for an anion capture approach, which was performed on solid phase, is the reaction of 6/1-134 and 6/1-135 in the presence of CO and piperidine to give 6/1-136. Liberation from solid phase was achieved with HF, leading to 6/1-137 (Scheme 6/1.30) [76]. 

Nozaki-Hiyama-Kishi (NHK) reactions215,216 are well known and often employed as a useful method for the synthesis of natural products by coupling of allyl, alkenyl, alkynyl, and aryl halides or triflates with aldehydes. The organochromium reagents are prepared from the corresponding halides or triflates and chromium(ll) chloride, and are employed in polar aprotic solvents (THF, DMF, DMSO, etc.). Subsequently, it was found that nickel salts exhibited a significant catalytic effect on the formation of the C-Cr bond217,218 (Equation (19)). 

For a review encompassing the Nozaki-Hiyama-Kishi reaction, see Marshall, J. A. McNulty, L. M. Chemtracts 1997, 10, 50-52. 

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. 

Scheme 12.14. Cozzi s catalytic enantio-selective Nozaki—Hiyama reaction.

For recent reviews of catalytic Nozaki-Hiyama coupling, see [258-261]. 

Nozaki-Hiyama-Kishi-type reactions to construct a fluoroolefin... 

G. Dutheuil, X. Lei, X. Pannecoucke, J.C. Quirion, A novel diastereoselective synthesis of (Z)-fluoroalkenes via a Nozaki-Hiyama-Kishi-Type reaction, J. Org. Chem. 70 (2005) 1911-1914. 

Threc-carbon ring expansion was carried out in two stages. First, two-carbon homologation of the exo methylene ketone 8 followed by trapping of the intermediate enolate as the triflate led to 9. Nozaki-Hiyama-Kishi coupling followed by acetylation smoothly converted 9 into 10. 

A chiral bis-oxazoline catalyses asymmetric Nozaki-Hiyama allenylation of aldehydes.179 For example, benzaldehyde is converted to silylated allene (62) using a bromoalkynylsilane, BrCH2-C = C-SiR R2 the product is readily desilylated quantitatively without loss of ee. 

The Nozaki-Hiyama Kishi reaction has been successfully utilized in the total synthesis of palytoxin (355) [170] brefeldin (356) [172], halichondrin B [173], brevetoxin [174], pinnatoxin A [174a] and others. The coupling of alkynyl iodides with aldehydes can be carried out smoothly using CrCl2 and 0.01% of NiCk... 

For a review on the Nozaki-Hiyama reaction, see P. Cintas, Synthesis, 1992, 248. 

Chromium. Similar chlorosilane-mediated catalytic processes can be envisaged with many other early transition metals. The development of the first Nozaki-Hiyama-Kishi reactions catalyzed by chromium species [13] illustrates how to avoid the use of an excess of a physiologically suspect and rather expensive salt without compromising the efficiency, practicality and scope of the reaction. The tentative catalytic cycle is depicted in Scheme 3. 

Scheme 3. Proposed catalytic cycle for the first Nozaki-Hiyama-Kishi reactions catalyzed by chromium species.

Scheme 5. An electrochemically driven Nozaki-Hiyama-Kishi reaction.

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