Nozaki-Hiyama reaction

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]. 

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

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. 

The catalytic asymmetric allylation of aldehydes is another reaction that has received a great deal of attention. Both allylstannes and the less reactive allylsilanes undergo addition to aldehydes with high ee in the presence of enantiomerically pure Lewis acids and Lewis bases and asymmetric versions of the chromium-catalysed Kishi-Nozaki-Hiyama reaction utilising allyl halides have recently been developed. 

The Nozaki-Hiyama reactions are able to proceed by the coupling reaction of carbonyl compounds such as ketone and aldehyde with unsaturated halides to afford selectively an aldehyde carbonyl coupling reaction product as shown in eq. (13.53) [83]. 

The Nozaki-Hiyama reactions are applied mainly to coupling reactions between aldehydes and unsaturated halides. For example, an intermediate of antibiotics rifamycin S synthesis is shown in eq. (13.54) [86,86a]. 

Halogenated alkenols are versatile synthetic intermediates as well as critical structural units in a variety of biologically active natural products. Previous preparations of these structures are often hampered by multistep synthesis and by poor stereoselectivity. The Nozaki-Hiyama reaction has provided good synthetic entry to these structures. For example, a highly... 

Inoue M, Nakada M. Structure elucidation and enantiose-lective total synthesis of the potent HMG-CoA reductase inhibitor FR901512 via catalytic asymmetric Nozaki Hiyama reactions. J. Am. Chem. Soc. 2007 129 4164— 4165. 

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