Nozaki-Hiyama-Kishi Nickel/Chromium Coupling reaction

The Nozaki-Hiyama-Kishi reaction is a nickel/chromium coupling reaction forming an alcohol from reaction of an aldehyde with a allyl or vinyl halide. In their original 1977 publication, Tamejiro Hiyama and Hitosi Nozaki ["Grignard-type carbonyl addition of allyl halides by means of chromous salt. A chemospecific synthesis of homoallyl alcohols" Yoshitaka Okude, Shigeo Hirano, Tamejiro Hiyama, Hitosi Nozaki J. Am. Chem. Soc. 1977; 99(9); 3179-3181. DOI|10.1021/ja00451a061 ] reported on a chromium(II) salt solution prepared by reduction of chromic chloride by lithium aluminum hydride to which was added benzaldehyde and allyl chloride:

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Compared to Grignard reactions, this reaction is very selective towards aldehydes with large tolerance towards a range of functional groups such as ketones, esters, amides and nitriles. Enals give exclusively 1,2-addition. Solvents of choice are DMF and DMSO, one solvent requirement is solubility of the chromium salts.

In 1983 the scope was extended by the same authors to include vinyl halides or triflates and aryl halides ["Selective grignard-type carbonyl addition of alkenyl halides mediated by chromium(II) chloride" Kazuhiko Takai, Keizo Kimura, Tooru Kuroda, Tamejiro Hiyama, and Hitosi Nozaki Tetrahedron Letters Volume 24, Issue 47, 1983, Pages 5281-5284 DOI|10.1016/S0040-4039(00)88417-8] . It was observed that the success of the reaction depended on the source of chromium(II) chloride and in 1986 it was found that this is due to nickel impurities ["Reactions of alkenylchromium reagents prepared from alkenyl trifluoromethanesulfonates (triflates) with chromium(II) chloride under nickel catalysis" K. Takai, M. Tagashira, T. Kuroda, K. Oshima, K. Utimoto, H. Nozaki J. Am. Chem. Soc.; 1986; 108(19); 6048-6050. DOI|10.1021/ja00279a068] . Since then nickel(II) chloride is used as a co-catalyst.

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In the same year Yoshito Kishi et al. independently discovered the beneficial effects of nickel in his quest for palytoxin ["Catalytic effect of nickel(II) chloride and palladium(II) acetate on chromium(II)-mediated coupling reaction of iodo olefins with aldehydes" Haolun Jin, Junichi Uenishi, William J. Christ, Yoshito Kishi J. Am. Chem. Soc.; 1986; 108(18); 5644-5646. DOI|10.1021/ja00278a057] :

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Palladium acetate was also found to be an effective cocatalyst.

Reaction mechanism

Nickel is the actual catalyst when small amounts of a nickel salt is added in the reaction. Nickel(II) chloride is first reduced to nickel(0) with 2 equivalents of chromium(II) chloride (as sacrificial catalyst) leaving Chromium(III) chloride. The next step is oxidative addition of nickel into the carbon to halide bond forming a alkenylnickel R-Ni(II)-X intermediate followed by a transmetallation step exchanging NiX with a Cr(III) group to an alkenylchromium R-Cr(III)-X intermediate and regenerating Ni(II). This species reacts with the carbonyl group in a nucleophilic addition.

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The amount of nickel used should be low as a direct alkene coupling to a diene is a side reaction [Organic Syntheses, Coll. Vol. 9, p.472 (1998); Vol. 72, p.180 (1995). http://orgsynth.org/orgsyn/pdfs/CV9P0472.pdf] .

Related reactions are the Grignard reaction (Magnesium), the Barbier reaction (zinc) and addition reactions involving organolithium reagents.

References