Author Topic: Cross Coupling of Grignards and Halides with NiCl2  (Read 939 times)

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Cross Coupling of Grignards and Halides with NiCl2
« on: March 26, 2003, 01:53:00 AM »
Any opinions on usefulness?  It's an interesting reaction, high yeilding in most cases, including the aromatic gringard they considered (at least with an alkyl bromide!  The tosylate was another matter, although even 56% isn't that horrible).  There were a few pratical details in there that I wasn't aware of (I didn't have the supporting information at the time), but it still looks (at least potentially) really nice and at least somewhat useful.

Nickel-Catalyzed Cross-Coupling Reaction of Grignard Reagents with Alkyl
Halides and Tosylates: Remarkable Effect of 1,3-Butadienes

A new method for the cross-coupling reaction of Grignard reagents with alkyl chlorides, bromides, and tosylates has been developed by the use of a nickel catalyst in the presence of a diene as an additive. This reaction proceeds efficiently at 0-25 C in THF using primary and secondary alkyl and aryl Grignard reagents. Nickel complexes bearing no phosphine ligands, such as NiCl2, Ni(acac)2, and Ni(COD)2, afford the coupling products in good yields, whereas NiCl2(PPh3)2 and NiCl2(dppp) were less effective. 1,3-Butadiene shows the highest activity as an additive for the present coupling reaction. A plausible reaction pathway was proposed.
Reference: Jun Terao, Hideyuki Watanabe, Aki Ikumi, Hitoshi Kuniyasu, and Nobuaki Kambe, J. AM. CHEM. SOC. 2002, 124, 4222-4223

So, what this gives us, is a reasonably simple method (if we can be so impudent as to consider a reaction using Grignards outright simple!) for combining alkyl (and presumably aryl) chlorides  with Grignards.  Imagine: 3,4-methylenedioxy-1-bromobenzene and 3-chloro-1-propene (allyl chloride?), or better yet - 1-chloropropene - plus NiCl and 1,3-butadiene and some magnesium to make safrole or isosafrole, potentially in rather high yeilds.  The dream I'm drooling over is the idea that maybe it would be possible to use 1-chloroacetone, or at least 1-chloroisopropanol...  I'm not to up with it on the specifics of Grignards, so perhaps this is just another flight of fancy...  Anyone else find this interesing, or have I overlooked something criticaland deluded myself?

Edit: Addition by Rhodium

Typical Experimental Procedure

Nickel-Catalyzed Cross-Coupling Reaction of Grignard Reagents with Alkyl Halides and Tosylates:
Remarkable Effect of 1,3-Butadienes


A 50 mL pyrex glass vessel containing a magnetic stirring bar, 1-bromo-4-(2-bromoethyl)benzene (528 mg, 2 mol) and n-BuMgCl (0.9 M in THF, 2.89 mL, 2.6 mmol) was cooled at -78°C. Then 1,3-butadiene (4.48 ml at 20°C under 1 atm) was introduced by a syringe into the vessel. To the mixture was added a catalytic amount of NiCl2 (2.6 mg, 0.02 mmol) and the solution was warmed to 0 °C by an ice-water bath and stirred for 30 min. A saturated aqueous NH4Cl solution (10 mL) was added, and the product was extracted with ether (10 mL), dried over MgSO4, and evaporated to give a colorless product (100% GC yield).


A mixture of cyclopropylmethyl bromide (270 mg, 2 mmol) and n-OctylMgCl (1.0 M in THF, 2.6 mL, 2.6 mmol) was cooled to -78 °C and 1,3-butadiene (4.48 mL at 20 °C under 1 atm) was introduced. After adding NiCl2 (2.6 mg, 0.02 mmol) at -78 °C, the solution was stirring for 30 min at 0 °C. Similar workup as mentioned above afforded a colorless crude product (87% GC yield).


J. Am. Chem. Soc., 124 (16), 4222-4223 (2002)