Nozaki-Hiyama-Kishi Reaction
The Nozaki-Hiyama-Kishi reaction allows the coupling between halides and aldehydes to generate the corresponding alcohols.
Nozaki-Hiyama-Kishi Reaction
Reaction Mechanism
1. Ni(II) is first reduced to Ni(0) with two equivalents of Cr(II). 2. Oxidative addition of Ni into the halogen-carbon bond. 3. Transmetalation step exchanging Ni with Cr. 4. The generated species reacts with the carbonyl group in a nucleophilic addition. 5. Aqueous work-up results in the final product.
Experimental Procedure
Nickel(II) chloride (0.1 eq) and chromium(II) chloride (8.0 eq) were added in an oven-dry flash in the glovebox. After putting the flask under nitrogen and in a room temperature water bath, the degassed DMF (53.0 mL) was added to the stirring mixture. After 10 minutes, a solution of the vinyl bromide (2.0 eq) and the aldehyde (10.8 mmol, 1.0 eq) in degassed DMF (53.0 mL) was added. Afterwards, the reaction was allowed to warm to 50 ºC and stirred for 1 h. Then the mixture was cooled to room temperature, quenched by water and diluted with Et2O. The layers were separated, and the aqueous layer was extracted with Et2O. The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The resultant residue was purified by FCC to afford the corresponding alcohol (63% yield).
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