Nozaki–Hiyama–Kishi_reaction
Nozaki–Hiyama–Kishi reaction
Coupling reaction used in organic synthesis
The Nozaki–Hiyama–Kishi reaction is a nickel/chromium coupling reaction forming an alcohol from the reaction of an aldehyde with an allyl or vinyl halide.[1] In their original 1977 publication, Tamejiro Hiyama and Hitoshi Nozaki[2] reported on a chromium(II) salt solution prepared by reduction of chromic chloride by lithium aluminium hydride to which was added benzaldehyde and allyl chloride:
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. Nozaki–Hiyama–Kishi reaction is a useful method for preparing medium-size rings.[3]
In 1983 the scope was extended by the same authors to include vinyl halides or triflates and aryl halides.[4] 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.[5] Since then nickel(II) chloride is used as a co-catalyst.[6]
In the same year Yoshito Kishi et al. independently discovered the beneficial effects of nickel in his quest for palytoxin:[7]
Palladium acetate was also found to be an effective cocatalyst.