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
. 2009 Aug 19;131(32):11625-33.
doi: 10.1021/ja904654j.

Stereogenic-at-metal Zn- and Al-based N-heterocyclic carbene (NHC) complexes as bifunctional catalysts in Cu-free enantioselective allylic alkylations

Yunmi Lee  1 , Bo Li, Amir H Hoveyda
Affiliations

Stereogenic-at-metal Zn- and Al-based N-heterocyclic carbene (NHC) complexes as bifunctional catalysts in Cu-free enantioselective allylic alkylations

Yunmi Lee et al. J Am Chem Soc. .

Abstract

Investigations detailed herein demonstrate the ability of chiral bidentate N-heterocyclic carbenes to promote directly-without the need for a Cu salt-site- and enantioselective C-C bond forming reactions. Within this context, catalytic allylic alkylations of various allylic phosphates with dialkylzinc and trialkylaluminum reagents, performed with chiral bidentate imidazolinium salts and in the absence of a Cu salt, are described. The Cu-free transformations deliver products bearing tertiary or (all-carbon) quaternary stereogenic centers with exceptional site- (>98:<2 S(N)2':S(N)2) and high enantioselectivity [up to 97.5:2.5 enantiomer ratio (er)]. A chiral Zn-based N-heterocyclic carbene (NHC) complex, which serves as the catalyst for the enantioselective allylic alkylation reactions, is isolated and fully characterized. Spectroscopic and X-ray crystallographic studies indicate that the sulfonate group within the stereogenic-at-Zn bidentate complexes coordinates syn to the proximal phenyl substituent of the NHC backbone (vs the initially expected anti). Investigations regarding a related NHC-Al complex reveal similar structural attributes. The studies outlined provide a plausible rationale regarding the mechanism of Cu-free allylic alkylation reactions that involve dialkylzinc or trialkylaluminum reagents as well as the previously reported alkylmagnesium halides. On the basis of the research disclosed, it is proposed that bidentate metal-carbene complexes can serve as effective bifunctional catalysts, a critical attribute that differentiates such NHC-based complexes from the corresponding monodentate variants.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Chiral Bidentate NHC–Metal Complex as a Bifunctional Catalyst.
Scheme 1
Scheme 1
Lewis Base Activation in Cu-Based and Cu-Free Pathways to Catalytic Allylic Alkylation
Scheme 2
Scheme 2
Synthesis and Structure of NHC–Zn(II) Complex 25a aAll NMR data were measured in THF-d8. Mes = 2,4,6-Me3-C6H2.
Scheme 3
Scheme 3
Catalytic EAA with NHC–Zn Complex 25 and a Proposed Mechanism
Scheme 4
Scheme 4
Synthesis and Catalytic Activity of NHC–Zn(II) Complex 27a aAll NMR data were measured in THF-d8.
Scheme 5
Scheme 5
Effect of Structure on the Ability of Bidentate NHC Complexes to Serve as Catalysts
Scheme 6
Scheme 6
Synthesis and Structure of NHC–Al(III) Complex 29
See this image and copyright information in PMC

References

    1. For reviews on N-heterocyclic carbenes as ligands in metal-catalyzed processes, see: Kantchev EAB, O'Brien CJ, Organ MG. Angew Chem, Int Ed. 2007;46:2768–2813.Gade LH, Bellemin-Laponnaz S. Top Organomet Chem. 2007;21:117–157.Tekavec TN, Louie J. Top Organomet Chem. 2007;21:159–192.Glorius F, editor. N-Heterocyclic Carbenes in Transition Metal Catalysis. Springer-Verlag; Berlin, Heidelberg: 2007.

    1. For Cu-free (non-enantioselective) conjugate addition and/or intramolecular allylic alkylation processes involving organozinc reagents, see: Komanduri V, Pedraza F, Krische MJ. Adv Synth Catal. 2008;350:1569–1576.Kobayashi K, Ueno M, Naka H, Kondo Y. Chem Commun. 2008:3780–3782.

    1. For a report regarding Cu-free enantioselective allylic alkylation reactions promoted by Mg-based chiral bidentate NHC complexes and involving alkylmagnesium halides, see: Lee Y, Hoveyda AH. J Am Chem Soc. 2006;128:15604–15605.

    1. For Cu-free catalytic enantioselective conjugate addition reactions involving dialkylzinc reagents, see: Bräse S, Höfener S. Angew Chem, Int Ed. 2005;44:7879–7881.

    1. For overviews regarding stereogenic-at-metal complexes, see: Brunner H. Angew Chem, Int Ed. 1999;38:1194–1208.Fontecave M, Hamelin O, Ménage S. Top Organomet Chem. 2005;15:271–288.For a recent example, see: Malcolmson SJ, Meek SJ, Sattely ES, Schrock RR, Hoveyda AH. Nature. 2008;456:933–937.

Publication types