C O MMU N I C A T I O N S
Table 2. Variation of Nitrogen Nucleophiles in the Aerobic
On the basis of the reactivity described herein, we envision many
new opportunities for the intermolecular oxidative functionalization
of alkenes with molecular oxygen. Studies directed toward this end
are ongoing.
Oxidative Amination of Styrenea
Acknowledgment. We thank I. Guzei for crystallographic
characterization of 4, and J. L. Brice for helpful discussions. This
work was supported by the Dreyfus Foundation (New Faculty
Award), NSF (CAREER, CHE-0094344), NIH (RO1 GM67173-
01), and the Sloan Foundation (Research Fellowship).
Supporting Information Available: Experimental procedures,
product characterization, and crystallographic data (PDF, CIF). This
References
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a Reaction conditions: styrene (3 mmol), nucleophile (0.5 mmol),
(CH3CN)2PdCl2 (0.025 mmol), CuCl2 (0.025 mmol), base (0.05 mmol), 1
atm of O2, 2 mL of DME, 60 °C, 24 h. b Isolated yield, based on nucleophile.
c Base ) NEt3. d Base ) [NBu4]OAc. e Base ) NaOAc.
coordinated olefin (eq 4).12,13 Further studies will be necessary to
identify mechanistic details of the catalytic reactions, in particular
to determine the origin of base-induced rate enhancement and the
unusual switch in product regioselectivity. Nucleophilic attack on
a coordinated olefin represents one reasonable mechanism, but the
data cannot exclude a pathway involving N-H activation followed
by olefin insertion into the palladium-nitrogen bond.14
(3) (a) Hosokawa, T.; Takano, M.; Kuroki, Y.; Murahashi, S.-I. Tetrahedron
Lett. 1992, 33, 6643-6646. (b) Ragaini, F.; Longo, T.; Cenini, S. J. Mol.
Catal. A-Chem. 1996, 110, L171-L175.
(4) Recent examples of rhodium-catalyzed oxidative amination have been
reported in which styrene serves a dual role as a substrate and a sacrificial
oxidant. For leading references, see: (a) Brunet, J. J.; Neibecker, D.;
Philippot, K. Tetrahedron Lett. 1993, 34, 3877-3880. (b) Beller, M.;
Trauthwein, H.; Eichberger, M.; Breindl, C.; Herwig, J.; Muller, T. E.;
Thiel, O. R. Chem.-Eur. J. 1999, 5, 1306-1319.
(5) Protonation of palladium(0) could promote the novel palladium(II)-hydride-
mediated hydroamination reaction described recently by Hartwig and co-
workers. (a) Kawatsura, M.; Hartwig, J. F. J. Am. Chem. Soc. 2000, 122,
9546-9547. (b) Nettekoven, U.; Hartwig, J. F. J. Am. Chem. Soc. 2002,
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(6) Catalyst/additive loadings and product yields are reported relative to
oxazolidinone, which is usually the limiting reagent.
(7) For numerous examples of triethylamine used as a base in palladium-
catalyzed cross-coupling reactions, see: Metal-Catalyzed Cross-Coupling
Reactions; Diederich, F., Stang, P. J., Eds.; Wiley-VCH: New York, 1998.
The beneficial effect of base in the catalytic reaction permits
several other nitrogen nucleophiles to be used (Table 2). Successful
examples include chiral oxazolidinones, a cyclic imide and amide,
and p-toluenesulfonamide. With the primary sulfonamide, an
initially formed enamide product presumably tautomerizes under
the reaction conditions to form the imine. Further exploration of
the substrate scope is ongoing, but we note that each of the
successful nucleophiles possesses a relatively acidic N-H group.
Less acidic nucleophiles, including morpholine, piperidine, and
anilines, were unsuccessful under the present conditions. The
ineffectiveness of the latter class of substrates probably reflects their
coordinating ability and is related to the observation that catalytic
(8) Direct amination of the benzylic C-H bond cannot be excluded, but we
consider this less likely. For recent characterization of palladium migration
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1
turnover is inhibited at elevated [NEt3] (>15 mol %). H NMR
2527.
spectroscopic studies (THF-d8) reveal that triethylamine readily
displaces olefins coordinated to palladium(II).15
(10) Previous studies reveal that steric properties of secondary amine and olefin
substrates influence the regiochemistry of palladium-mediated olefin
amination. See ref 1a.
In each of the reactions above, the copper cocatalyst is required
for efficient catalytic turnover. Nevertheless, preliminary observa-
tions suggest it will be possible to identify alternative catalytic
conditions compatible with direct dioxygen-coupled turnover.16
Palladium acetate (8) is less effective than 3 under standard reaction
conditions. The combination of 8 with catalytic quantities of NEt3
(5 mol %), however, promotes efficient catalytic turnover in the
absence of copper cocatalyst under otherwise identical conditions
(eq 5). This catalyst system bears significant resemblance to recently
reported methods for alcohol oxidation13,16b-d and intramolecular
oxidative amination of olefins.2d The versatility demonstrated by
such a simple catalyst composition holds significant promise for
the development of new dioxygen-coupled oxidation reactions.
(11) Preliminary studies indicate that with 4 as the catalyst, one equivalent of
NEt3 remains coordinated throughout the reaction, and the other serves
as a Brønsted base. The first equivalent of NEt3 can be successfully
replaced by other donor ligands, such as the N-heterocyclic carbene, 1,3-
bis-(2,6-diisopropylphenyl)-imidazol-2-ylidene) (IPr).
(12) Hegedus, L. S.; Åkermark, B.; Zetterberg, K.; Olsson, L. F. J. Am. Chem.
Soc. 1984, 106, 7122-7126.
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J. Am. Chem. Soc. 2002, 124, 8202-8203. (b) Schultz, M. J.; Park, C.
C.; Sigman, M. S. Chem. Commun. 2002, 3034-3035. (c) Bagdanoff, J.
T.; Ferreira, E. M.; Stoltz, B. M. Org. Lett. 2003, 5, 835-837. (d)
Steinhoff, B. A.; Stahl, S. S. Org. Lett. 2002, 4, 4179-4181.
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(b) Seul, J. M.; Park, S. J. Chem. Soc., Dalton Trans. 2002, 1153-1158.
(15) Anastasi, N. R., Stahl, S. S., unpublished results.
(16) For leading references on direct dioxygen-coupled palladium oxidation
catalysis, see the following and references therein: (a) refs 2 and 13. (b)
Sheldon, R. A.; Arends, I.; Ten Brink, G. J.; Dijksman, A. Acc. Chem.
Res. 2002, 35, 774-781. (c) Nishimura, T.; Onoue, T.; Ohe, K.; Uemura,
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Nelson, R. C.; Kozee, M. A. J. Am. Chem. Soc. 2001, 123, 7188-7189.
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