Nozaki-Hiyama reagent

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). 

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)). 

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. 

Nozaki-Hiyama-Kishi Reaction (Organochromium Reagents)... 

The one-pot Barbier-type addition of alkenyl, aryl, allyl, vinyl, propargyl, alkynyl, or allenylchromium compounds to aldehydes or ketones is known as the Nozaki-Hiyama-Kishi (NHK) reaction. An excellent review by Furstner published in 1999 detailed the exhaustive literature on the carbon-carbon bond formations involving organochromium(III) reagents. This chapter will present major developments and examples of recent carbon-carbon bond formation methodology and improvements as well as their use in natural products synthesis since 1999. 

The Nozaki-Hiyama-Kishi (NHK) reaction, first reported in the late 1970s, has become an important and versatile carbon-carbon, bond-forming process, involving the nucleophilic addition of organochromium(III) reagents to carbonyl compounds (Scheme 12.1). ... 

A valuable feature of the Nin/Crn-mediated Nozaki-Takai-Hiyama-Kishi coupling of vinyl iodides and aldehydes is that the stereochemistry of the vinyl iodide partner is reflected in the allylic alcohol coupling product, at least when disubstituted or trans tri-substituted vinyl iodides are employed.68 It is, therefore, imperative that the trans vinyl iodide stereochemistry in 159 be rigorously defined. Of the various ways in which this objective could be achieved, a regioselective syn addition of the Zr-H bond of Schwartz s reagent (Cp2ZrHCl) to the alkyne function in 165, followed by exposure of the resulting vinylzirconium species to iodine, seemed to constitute a distinctly direct solution to this important problem. Alkyne 165 could conceivably be derived in short order from compound 166, the projected product of an asymmetric crotylboration of achiral aldehyde 168. 

Cahiez, G. Figadere, B. Tetrahedron Lett. 1986,27,4445. For other organometaUic reagents with high selectivity towards aldehyde functions, see Kauffmann, T. Hamsen, A. Beirich, C. Angew. Chem. Int Ed. 1982, 21, 144 Takai, K. Kimura, K. Kuroda, T. Hiyama, T. Nozaki, H. Tetrahedron Lett. 1983, 24, 5281 Soai, K. Watanabe, M. Koyano, M. Bull. Chem. Soc. Jpn. 1989, 62, 2124. 

Okude, Y., Hiyama, T., Nozaki, H. Reduction of organic halides by means of chromium(lll) chloride-lithium aluminum hydride reagent in anhydrous media. Tetrahedron Lett. 1977, 3829-3830. 

Hiyama, T., Okude, Y., Kimura, K., Nozaki, H. Highly selective carbon-carbon bond forming reactions mediated by chromium(ll) reagents. Bull. Chem. Soc. Jpn. 1982, 55, 561-568. 

Nozaki, H., Hiyama, T., Oshima, K., Takai, K. Highly selective synthesis with novel metallic reagents. ACS Symp. Ser. 1982, 185, 99-108. 

Besides the alkyllithium compounds numerous other reagents have been used to initiate the dehalogenation, including such systems as CrClj/LiAIH, (Okuda Y, Hiyama T, Nozaki H... 

Lewis acid breaks up the closed transition state normally found in thermal reactions. Contrary to the Hiyama-Nozaki reaction the induced stereoselections for allylstannanes-i-Lewis acids are extremely high, due to chelate-Cram controlled mechanisms [reaction (91), Scheme 30] [76]. Reagent controlled diastereoselec-tivity may be exerted in terms of 1,3- [reaction (92)] [77] and 1,5-inductions [reaction (93)] [78]. 

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