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. 2009 Jun 10;131(22):7532-3.
doi: 10.1021/ja902046m.

Negishi coupling of secondary alkylzinc halides with aryl bromides and chlorides

Chong Han  1 , Stephen L Buchwald
Affiliations

Negishi coupling of secondary alkylzinc halides with aryl bromides and chlorides

Chong Han et al. J Am Chem Soc. .

Abstract

An efficient palladium-catalyzed process has been developed for Negishi coupling of secondary alkylzinc halides with a wide range of aryl bromides and activated aryl chlorides. A palladium catalyst composed of a new biaryldialkylphosphine ligand, CPhos, effectively promotes the rate of the reductive elimination step relative to the rate of the undesired beta-hydride elimination. The broad substrate scope and excellent ratio of the desired secondary to the undesired primary coupling product make this method a powerful and reliable tool for C(sp(3))-C(sp(2)) bond formation.

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Figures

Figure 1
Figure 1
Ligand effects in the coupling of ortho-substituted aryl bromides with isopropyl zinc bromide.
Scheme 1
Scheme 1
A Simplified Reaction Course for the Coupling of i-PrM with an Aryl Halide.
Scheme 2
Scheme 2
Negishi Cross-Coupling of Secondary Alkylzinc Halides with Aryl or Heteroaryl Bromides and Chlorides.a a Isolated yields; average of two runs. b Reaction conducted in THF. c 2 mol % Pd(OAc)2 and 4 mol % CPhos. d The alkylzinc reagent (1.5 equiv) was slowly added over 30 min. e 23:1 branched: linear.
Scheme 3
Scheme 3
Comparison of Product Distribution for the Coupling of Isopropyl and n-Propyl Zinc Bromide with 2-Bromobenzonitrile.
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References

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