C O MMU N I C A T I O N S
Scheme 1. Catalytic Cycle for the Hydroamination of Vinylarenes
Catalyzed by Palladium-diphosphine Complexes
and free 2-vinylnaphthalene. If 1a-c deinserted vinylarene to form
the active catalyst, then the catalyst generated in this manner would
react with the free vinylarene present in the highest concentration,
which is the unsubstituted 2-vinylnaphthalene in this case. Control
experiments catalyzed by [(R)-Tol-BINAP]Pd(OTf)2 and employing
2-vinylnaphthalene and 6-methoxy-2-vinylnaphthalene as well as
a 1:1 mixture as substrates showed that the two olefins were
comparable in reactivity. Reactions of 1c in the presence of 2 equiv
of free 2-vinylnaphthalene were conducted with 100 equiv of aniline
to ensure that reaction with aniline occurred faster than generation
of other isomers or diastereomers of 1a. 1H NMR spectra obtained
at the early stages of the reaction showed that N-1-(6-methoxy-2-
naphthyl)ethylaniline formed prior to the unsubstituted naphthethyl-
amine. These data strongly support the intermediacy of the isolated
complexes in the catalytic process.
Additional support for formation of the amine product directly
from the η3-arylethylpalladium complexes was obtained from
reactions of the analogous η3-benzyl complex {[(R)-Tol-BINAP]-
(benzyl)Pd}(OTf) (2), which cannot extrude olefin. Complex 2 was
prepared as a single isomer by oxidative addition of benzyl bromide
to [(R)-Tol-BINAP)]2, followed by addition of silver triflate.12
Reaction of 2 with aniline at 75 °C for 2 h formed N-benzylaniline
in 87% yield.
The C-N bond-forming process could occur by external attack
on the η3-benzyl complex in analogy to attack on an η3-allyl, or it
could occur by coordination of amine and C-N bond-forming
reductive elimination with or without prior deprotonation of the
N-H bond of the coordinated amine. The first path would lead to
inversion of configuration and the second path to retention of
configuration. With crystalline samples of enantio- and diastereo-
merically pure 1a, we could distinguish between these mechanisms.
Reaction of 1a bearing the (S) configuration at C1 with excess
aniline occurred by inversion of configuration and gave (R)-N-1-
(2-naphthyl)ethylaniline in 84% yield and 71% e.e. Thus, external
nucleophilic attack at carbon forms the C-N bond in the predomi-
nant benzylic amine product.
naphthalene in the presence of either 1c or [(R)-Tol-BINAP]Pd-
(OTf)2 as catalyst precursor.
In summary, we have uncovered the major pathway for hy-
droamination of vinylarenes using aniline substrates catalyzed by
phosphine-ligated palladium triflates. This mechanism, summarized
in Scheme 1, involves insertion of styrene into a palladium hydride
and external, nucleophilic attack of amine on an η3-benzyl complex.
Further studies on the relationship between intermediate structure,
reaction rates, and enantioselectivity for other substrate combina-
tions are in progress.
Acknowledgment. We gratefully acknowledge financial support
from the NIH (R01-GM55382). U.N. thanks FWF Austria for a
Schro¨dinger postdoctoral fellowship.
Supporting Information Available: Synthetic procedures, char-
acterization data for compounds 1a-c, 2, 3, and details of crystal
structure analysis of 1a and 3 (PDF). This material is available free of
References
(1) Mu¨ller, T. E.; Beller, M. Chem. ReV. 1998, 98, 675-703.
(2) Benson, S. W. Thermochemical Kinetics: Methods for the Estimation of
Thermochemical Data and Rate Parameters, 2nd ed.; John Wiley and
Sons: New York, 1976.
(3) See for example: (a) Seligson, A. L.; Trogler, W. C. Organometallics
1993, 12, 744-751. (b) Lo¨ber, O.; Kawatsura, M.; Hartwig, J. F. J. Am.
Chem. Soc. 2001, 123, 4366-4367. (c) Cheng, X.; Hii, K. K. M.
Tetrahedron 2001, 57, 5445-5450. (d) Kawatsura, M.; Hartwig, J. F.
Organometallics 2001, 20, 1960-1964. (e) Beller, M.; Trauthwein, H.;
Eichberger, M.; Breindl, C.; Mu¨ller, T. E. Eur. J. Inorg. Chem. 1999,
1121-1132.
This stereochemistry for stoichiometric C-N bond formation was
surprising because the reaction catalyzed by {[(R)-Tol-BINAP]Pd-
(OTf)2} produced predominantly the (S)-amine. We propose that
the major isolated diastereomer produces the minor enantiomer in
the catalytic system, as has been commonly observed in asymmetric
hydrogenation.13 31P NMR spectroscopy of the catalytic reaction
(vide supra) showed that 17-20% of the total amount of palladium
complexes were three isomers present in a ratio of 8:5:4. Due to
the low concentrations of these isomers, complete structural
assignment was not possible. However, ROESY and heteronuclear
correlation experiments revealed a syn-anti arrangement of the
phenethyl moiety for one of them.
(4) Åkermark, B.; Ba¨ckvall, J. E.; Hegedus, L. S.; Zetterberg, K. J. Organomet.
Chem. 1974, 72, 127-138.
(5) Gagne´, M. R.; Stern, C. L.; Marks, T. J. J. Am. Chem. Soc. 1992, 114,
275-294.
(6) (a) Casalnuovo, A. L.; Calabrese, J. C.; Milstein, D. J. Am. Chem. Soc.
1988, 110, 6738-6744. (b) Dorta, R.; Egli, P.; Zuercher, F.; Togni, A. J.
Am. Chem. Soc. 1997, 119, 10857-10858.
(7) Kawatsura, M.; Hartwig, J. F. J. Am. Chem. Soc. 2000, 122, 9546-9547.
(8) The formation of related η3-benzyl or 1-phenylethyl palladium complexes
bearing diphosphine, phosphine-phosphite, or R-diimine donors has been
observed in different catalytic reactions: (a) Lin, Y.-S.; Yamamoto, A.
Organometallics 1998, 17, 3466-3478. (b) Nozaki, K.; Komaki, H.;
Kawashima, Y.; Hiyama, T.; Matsubara, T. J. Am. Chem. Soc. 2001, 123,
534-544. (c) LaPointe, A. M.; Rix, F. C.; Brookhart, M. J. Am. Chem.
Soc. 1997, 1119, 906-917. For structurally characterized examples of
η3-(1-aryl)alkyl palladium complexes see: (d) Gatti, G.; Lo´pez, J. A.;
Mealli, C.; Muso, A. J. Organomet. Chem. 1994, 483, 77-89. (e) Rix, F.
C.; Brookhart, M.; White P. S. J. Am. Chem. Soc. 1996, 118, 2436-
2448.
(9) Shortest nonbonding interactions between the phosphine and the
naphthethyl ligand were C9-C19 (2.8166 Å), C8-C19 (3.0367 Å), and
C11-C15 (3.3568 Å).
Comparison of the rate constants for the stoichiometric reaction
between 1c and aniline with those for the reaction of aniline with
6-methoxy-2-vinylnaphthalene catalyzed by 1c confirmed that the
major diastereomer reacts more slowly than the ensemble of minor
ones. The stoichiometric reaction at 40 °C occurred with a rate
constant (2.3(2) × 10-5 M-1 s-1) that was about 3.5 times slower
than that for the overall catalytic reaction (7.7(2) × 10-5 M-1 s-1).
These ratios of rate constants are in rough agreement with the 60%
e.e. observed in the reaction of aniline with 6-methoxy-2-vinyl-
(10) Jira, R. In Applied Homogeneous Catalysis with Organometallic Com-
pounds; Cornils, B., Herrmann, W. A., Eds.; VCH: Weinheim, 1996; pp
374-393.
(11) For example, crystals of 1a that were dissolved in THF at room temperature
showed two isomers in a ratio of 96:4. In CD2Cl2 the ratio was 84:16,
decreasing to 80:20 at 50 °C.
(12) The intermediate [(R)-Tol-BINAP]Pd(benzyl)(bromide) complex 3 was
also characterized by crystal structure analysis; see Supporting Information.
(13) Landis, C.; Halpern, J. J. Am. Chem. Soc. 1987, 109, 1746-1754.
JA017521M
9
J. AM. CHEM. SOC. VOL. 124, NO. 7, 2002 1167