Hiyama reaction

The intramolecular Hiyama reaction is excellently suited for the construction of carbocyclic and heterocyclic ring systems of different size. In most examples, problems of induced diastereoselectivity are involved (Sections 1.3.3.3.9.2.2. and D.2.3.). In the total synthesis of the antitumor germacranolide ( )-costunolide from ( ,.E)-farnesol, the correctly substituted ( , )-cyclodecadiene moiety was constructed by an intramolecular Hiyama reaction22. 

An intramolecular Hiyama reaction was applied for macrocyclization in the synthesis of the racemic cyclic 14-membered cembranoid antitumor agent asperdiol10. 

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). 

In the context of NHC/metal catalysed cross-coupling reactions, the only example of a Hiyama reaction was reported by Nolan using an in situ protocol by mixing Pd(OAc)j and IPr HCl for the formation of the catalyst. Activated aryl bromides and chlorides, such as 2-chloropyridine, were coupled with phenyl and vinyl-trimethoxysilane in good yields [123] (Scheme 6.39). 

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. 

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

Reactions with Organosilicon Reagents The Hiyama Reaction... 

The coupling of organosilicon compounds with organic electrophiles was not disclosed until 1988 by Hatanaka and Hiyama, when they demonstrated that through the addition of an appropriate silicophilic nucleophile, those desired pentacoordinate species can be generated in situ and transfer an unsaturated group. Nucleophilic fluoride sources were found to be the additive of choice, typically TASK, TBAF, and, in some cases, KF and GsF. These are the fundamental concepts of what is nowadays called the Hiyama reaction. The use of fluoride... 

Cadiot-Chodkiewicz reaction, 11, 19 Hiyama reaction, 11, 23 Kumada-Tamao-Corriu reaction, 11, 20 Migita-Kosugi-Stille reaction, 11, 12 Negishi coupling, 11, 27 overview, 11, 1-37 Suzuki-Miyaura reaction, 11, 2 terminal alkyne reactions, 11, 15 Cu-mediated reactions acetylenes, 10, 551 dienes, 10, 552... 

Cross-coupling reactions 5-alkenylboron boron compounds, 9, 208 with alkenylpalladium(II) complexes, 8, 280 5-alkylboron boron, 9, 206 in alkyne C-H activations, 10, 157 5-alkynylboron compounds, 9, 212 5-allylboron compounds, 9, 212 allystannanes, 3, 840 for aryl and alkenyl ethers via copper catalysts, 10, 650 via palladium catalysts, 10, 654 5-arylboron boron compounds, 9, 208 with bis(alkoxide)titanium alkyne complexes, 4, 276 carbonyls and imines, 11, 66 in catalytic C-F activation, 1, 737, 1, 748 for C-C bond formation Cadiot-Chodkiewicz reaction, 11, 19 Hiyama reaction, 11, 23 Kumada-Tamao-Corriu reaction, 11, 20 via Migita-Kosugi-Stille reaction, 11, 12 Negishi coupling, 11, 27 overview, 11, 1-37 via Suzuki-Miyaura reaction, 11, 2 terminal alkyne reactions, 11, 15 for C-H activation, 10, 116-117 for C-N bonds via amination, 10, 706 diborons, 9, 167... 

Scheme 75 Hiyama reactions with aryl halides...

Usanov and Yamamoto recently found that catalytic amounts of Co(TPP) 367 led to a dramatic rate acceleration of Nozaki-Kishi-Hiyama reactions catalyzed by chromium complex 368 (Fig. 101) [460]. The authors attributed the rate enhancement to initial reduction of 367 to a Co(I) complex. The latter is able to undergo an Sn2 substitution at propargyl bromide 366 giving an allenylCo(ffl) species. It was proposed that its homolysis leads to allenyl radical 366A, which couples to Cr(II) complex 368. The resulting allenyl Cr(III) complex adds in an SN2 process... 

Hiyama reactions. The Hiyama cross-coupling of organosilanes is attractive, as the intermediates are often easy to prepare and the silicon by-products are environmentally benign. A one-pot synthesis of 2-aryl-3-methylpyridines 954 from 2-bromo-3-methylpyridine 953 is illustrative (Scheme 111) <2003JOM(686)58>. 

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

Catalytic Cross Coupling with Organostannanes and Organosilanes, the Stille and Hiyama Reactions... 

Coupling of organosilane derivatives to RX species is known as the Hiyama reaction. This process is seen as more difficult to catalyze than the Stille reaction since a C-Si bond is less reactive than a C-Sn bond. However, addition of additives, such as B114NF or CsF, that form hypervalent silicon intermediates, or the use of more reactive silane precursors, such as Me3SiSiMc3, ArSiMc20H, or Cl2MeSi(vmyl), can overcome this limitation (equation 29). 

Cintas, P. Addition of organochromium compounds to aldehydes the Nozaki-Hiyama reaction. Synthesis 1992, 248-257. 

Wipf, P., Lim, S. Addition of organochromium reagents to aldehydes, ketones and enones a low-temperature version of the Nozaki-Hiyama reaction. J. Chem. Soc., Chem. Common. 1993, 1654-1656. 

Bandini, M., Cozzi, P. G., Melchiorre, P., Umani-Ronchi, A. The first catalytic enantioselective Nozaki-Hiyama reaction. Angew. Chem., Int. Ed. Engl. 1999, 38, 3357-3359. 

Micskei, K., Kiss-Szikszai, A., Gyarmati, J., Hajdu, C. Carbon-carbon bond formation in neutral aqueous medium by modification of the Nozaki-Hiyama reaction. Tetrahedron Lett. 2001,42, 7711-7713. 

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