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. 2011 Mar 4;13(5):1218-21.
doi: 10.1021/ol200098d. Epub 2011 Feb 10.

Nickel-catalyzed Negishi cross-coupling reactions of secondary alkylzinc halides and aryl iodides

Amruta Joshi-Pangu  1 , Madhu Ganesh, Mark R Biscoe
Affiliations

Nickel-catalyzed Negishi cross-coupling reactions of secondary alkylzinc halides and aryl iodides

Amruta Joshi-Pangu et al. Org Lett. .

Abstract

A general Ni-catalyzed process for the cross-coupling of secondary alkylzinc halides and aryl/heteroaryl iodides has been developed. This is the first process to overcome the isomerization and β-hydride elimination problems that are associated with the use of secondary nucleophiles, and that have limited the analogous Pd-catalyzed systems. The impact of salt additives was also investigated. It was found that the presence of LiBF(4) dramatically improves both isomeric retention and yield for challenging substrates.

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Figures

Figure 1.
Figure 1.
Proposed catalytic cycle for the Ni-catalyzed cross-coupling of secondary alkyl nucleophiles and aryl halides.
Figure 2.
Figure 2.
Ligand screen for the Ni-catalyzed cross-coupling of iodobenzene and s-BuZnI.
Scheme 1.
Scheme 1.
Ni-Catalyzed Cross-Coupling Reactions of i-PrZnI and s-BuZnI with Aryl and Heteroaryl Iodides a ArI (1 mmol), RZnI (1.5–2.5 mmol); average isolated yield of 2 runs; all products are formed with > 100:1 branched to linear ratio. b With LiBF4 (1 equiv) as additive. c 70:1 s-Bu to n-Bu; see ref 11. dVolatile products: GC yields are 80% (i-Pr) and 82% (s-Bu).
Scheme 2.
Scheme 2.
Ni-Catalyzed Cross-Coupling Reactions of 1-Iodo-3,5-Dimethylbenzene with Different Secondary Alkylzinc Iodidesa a ArI (1 mmol), RZnI (1.3–1.5 mmol); average isolated yield of 2 runs.
Scheme 3.
Scheme 3.
Effect of Exogenous Salts on Yield and Isomerization (14:15)a a Yields and selectivities determined by GC with dodecane as an internal standard. b 3 equiv added.
See this image and copyright information in PMC

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