Zheng et al.
SCHEME 2. Immobilization of Pd-NHC Complexes onto
SCHEME 1. Schematic Representation of Magnetic
Nanoparticle Facilitated Solid-Phase Suzuki Cross-Coupling
Reactions
the Surface of Iron Oxide Nanoparticles
immobilized reagents buried inside the beads; and because of
the maghemite (γ-Fe2O3) core magnetism, nanoparticles with
their immobilized Pd catalyst can be magnetically separated
from resins via applying an external magnetic field after
reaction.10
mixture. This will circumvent time-consuming and laborious
purification steps and allow solid-phase organic synthesis
amenable to automation.
Results and Discussion
However, despite tremendous progress on solid-phase organic
synthesis, to the best of our knowledge, no orthogonal supports
assisting solid-phase reactions have yet been reported. The
design of matrixes orthogonal to solid-phase resins still remains
a scientifically intriguing challenge. This is partially be-
cause most (>99%) of the sites of attachment of solid-phase
resins are not on the surface of a bead, but are actually buried
inside the interiors of the polymeric resins instead.6 A chemi-
cal reagent and its carrier (orthogonal support) need to pene-
trate the interpolymeric chain spaces of a bead swollen in an
organic medium to react. As a consequence, the pore-like
structures and topography of a swollen solid-phase bead present
three-dimensional steric restrictions to incoming orthogonal
matrixes.6
In this paper, we would like to report the use of magnetic
nanoparticles (∼4 nm) as the first example of an orthogonal
support of the solid-phase resins (Scheme 1). In our study, the
Pd catalyst was immobilized on the surface of magnetic
nanoparticles7 for catalyzing the solid-phase Suzuki cross-
coupling of an aryl halogen on resins and an arylboronic acid
in the solvent phase.8,9 Due to their small dimensions (∼4 nm),
magnetic nanoparticles can penetrate the pores of resins and
bring the attached catalytic groups to close proximity of the
The maghemite nanoparticle-supported Pd catalyst Iron
Oxide-Pd, used for promoting solid-phase Suzuki reactions
(Scheme 1), was synthesized via multiple steps from nonfunc-
tionalized 4 nm iron oxide nanocrystals (Scheme 2).11a Organic
silane groups were utilized for immobilization of Pd-NHC
complexes to the surface of maghemite nanoparticles because
silanes were known to have a large affinity for under-coordinated
surface sites of metal oxide particles.12 Elemental analysis
determined the Pd loading capacity of Iron Oxide-Pd (4 nm)
to be about 0.29 mmol/g. Aryl halogens were also immobilized
onto the 1% divinylbenzene-cross-linked polystyrene resins
(Acros Organics, 200-400 mesh). The loading capacity of the
resins was found to be 0.87 mmol/g via elemental analysis. A
typical Suzuki cross-coupling reaction involved an aryl halogen
(1 mmol) on resins (1.22 g), an arylboronic acid (2 mmol), and
(8) For selected publications on Pd-mediated cross-coupling reactions
see: (a) Miyaura, N.; Yamada, K.; Suzuki, A. Tetrahedron Lett. 1979, 20,
3437. (b) Zapf, A.; Ehrentraut, A.; Beller, M. Angew. Chem., Int. Ed. 2000,
39, 4153. (c) Walker, S. D.; Barder, T. E.; Martinelli, J. R.; Buchwald, S.
L. Angew. Chem., Int. Ed. 2004, 43, 1871. (d) Littke, A. F.; Fu, G. C.
Angew. Chem., Int. Ed. Engl. 1978, 17, 3387. (e) Herrmann, W. A. Angew.
Chem., Int. Ed. 2002, 41, 1290. (f) Miura, M. Angew. Chem., Int. Ed. 2004,
43, 2201. (g) Lebel, H.; Janes, M. K.; Charette, A. B.; Nolan, S. P. J. Am.
Chem. Soc. 2004, 126, 5046. (h) Altenhoff, G.; Goddard, R.; Lehmann, C.;
Glorius, F. J. Am. Chem. Soc. 2004, 126, 15196. (i) Batey, R. A.; Shen,
M.; Lough, A. J. Org. Lett. 2002, 4, 1411. (j) Hadei, N.; Kantchev, E. A.
B.; O’Brien, C. J.; Organ, M. G. Org. Lett. 2005, 7, 1991.
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reactions include: (a) Byun, J.-W.; Lee, Y.-S. Tetrahedron Lett. 2004, 1837.
(b) Berteina, S.; Wendeborn, S.; Brill, W. K.-D.; De Mesmaeker, A. Synlett
1998, 6, 676. (c) Wang, Y.; Sauer, D. R. Org. Lett. 2004, 6, 2793. (d)
Yamada, Y. M. A.; Takeda, K.; Takahashi, H.; Ikegami, S. Org. Lett. 2002,
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(10) Usually about 83% of Iron Oxide-Pd (based on the weights) could
be separated from resins via a magnetic concentration step. However,
repeated magnetic separation steps were needed to ensure complete removal
of Iron Oxide-Pd out of resins. A picture of magnetic concentration using
a permanent magnet is included in the Supporting Information. During
magnetic separation, the mixture was then vigorously shaken followed by
applying an external permanent magnet. Iron Oxide-Pd was accumulated
on the sidewall of a cuvette. Excessive borate and suspended resins in
solution were transferred out of the cuvette by using a pipet.
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538 J. Org. Chem., Vol. 71, No. 2, 2006