Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 May 14;23(8):1103-1107.
doi: 10.1055/s-0031-1290765.

The Use of Tertiary Alkylmagnesium Nucleophiles in Ni-Catalyzed Cross-Coupling Reactions

Amruta Joshi-Pangu  1 , Mark R Biscoe
Affiliations

The Use of Tertiary Alkylmagnesium Nucleophiles in Ni-Catalyzed Cross-Coupling Reactions

Amruta Joshi-Pangu et al. Synlett. .

Abstract

Nickel-catalyzed cross-coupling reactions of unactivated tertiary alkyl nucleophiles and aryl bromides have been developed using N-heterocyclic carbene ligands. These processes are reviewed alongside earlier attempts to employ unactivated tertiary alkyl nucleophiles in cross-coupling reactions. Potential mechanisms for the transformations, and future challenges in this field are discussed.

Keywords: Grignard reaction; cross-coupling; homogeneous catalysis; nickel; transition metals.

PubMed Disclaimer

Figures

Figure 1
Figure 1
NHC ligands employed by the Glorius group (5) and by the Biscoe group (6) in Ni-catalyzed cross-coupling reactions of t-BuMgCl and arylbromides
Scheme 1
Scheme 1
Hintermann’s method for the Cu-catalyzed cross-coupling of tertiary alkylmagnesium reagents and polychlorinated aza-aryl electrophiles
Scheme 2
Scheme 2
(a) Lei’s use of t-BuZnCl in a Pd-catalyzed cross-coupling reaction with an aryl iodide. (b) Hu’s stoichiometric treatment of a Ni pincer complex with t-BuMgCl.
Scheme 3
Scheme 3
Possible catalytic cycles for Ni- and Pd-catalyzed cross-coupling reactions of alkyl nucleophiles and aryl halides
Scheme 4
Scheme 4
Side-products resulting from the competing β-hydride elimination pathway
Scheme 5
Scheme 5
Equilibrium between tricoordinate (NHC)2NiCl and its μ-chloronickel dimer
See this image and copyright information in PMC

References

    1. de Meijere A, Diederich F, editors. Metal-Catalyzed Cross-Coupling Reactions. Weinheim: Wiley-VCH; 2004.
    1. Chemler SR, Trauner D, Danishefsky SJ. Angew. Chem. Int. Ed. 2001;40:4544. - PubMed
    2. Netherton MR, Fu GC. In: Topics in Organometallic Chemistry: Palladium in Organic Synthesis. Tsuji J, editor. New York: Springer; 2005. pp. 85–108.
    3. Rudolph A, Lautens M. Angew. Chem. Int. Ed. 2009;48:2656. - PubMed
    4. Jana R, Pathak TP, Sigman MS. Chem. Rev. 2011;111 1417 and references cited therein. - PMC - PubMed

    1. For recent examples of secondary nucleophiles in Pd catalysis: Campos KR, Klapars A, Walsman JH, Dormer PG, Chen C. J. Am. Chem. Soc. 2006;128:3538. Dreher SD, Dormer PG, Sandrock DL, Molander GA. J. Am. Chem. Soc. 2008;130:9257. Han C, Buchwald SL. J. Am. Chem. Soc. 2009;131:7532. Thaler T, Haag B, Gavryushin A, Schober K, Hartman E, Gschwing RM, Zipse H, Mayer P, Knochel P. Nat. Chem. 2010;2:125. Nakao Y, Takeda M, Matsumoto T, Hiyama T. Angew. Chem. Int. Ed. 2010;45:4447. Sandrock DL, Jean-Gerard L, Chen C-Y, Dreher SD, Molander GA. J. Am. Chem. Soc. 2010;132:17108. Thaler T, Guo L-N, Mayer P, Knochel P. Angew. Chem. Int. Ed. 2011;50:2147. Calimsiz S, Organ MG. Chem. Commun. 2011;47:5181. For recent examples of secondary nucleophiles in Ni catalysis: Melzig L, Gavryushin A, Knochel P. Org. Lett. 2007;9:5529. Smith SW, Fu GC. Angew. Chem. Int. Ed. 2008;47:9334. Phapale VB, Guisan-Ceinos M, Bunuel E, Cardenas DJ. Chem. Eur. J. 2009;15:12681. Joshi-Pangu A, Ganesh M, Biscoe MR. Org. Lett. 2011;13:1218.

    1. Hintermann L, Xiao L, Labonne A. Angew. Chem. Int. Ed. 2008;47:8246. - PubMed

    1. For a Cu-catalyzed cross-coupling reaction involving t-BuMgCl and primary alkyl halides see: Terao J, Todo H, Begum SA, Kuniyasu H, Kambe N. Angew. Chem. Int. Ed. 2007;46:2086.

LinkOut - more resources