9546
J. Am. Chem. Soc. 2000, 122, 9546-9547
Table 1. Effect of Catalyst Components and Acid on the
Palladium-Catalyzed Intermolecular Hydroamination
of Vinylarenes Using Arylamines
Hydroamination of Styrene with Anilinea
entry
catalyst
yield, %b
Motoi Kawatsura and John F. Hartwig*
1
2
3
4
5
6
7
8
2% [Pd(PPh3)4]
0
28
Department of Chemistry, Yale UniVersity
P.O. Box 208107, New HaVen, Connecticut 06520-8107
ReceiVed June 26, 2000
2% Pd(OC(O)CF3)2/8% PPh3
2% [Pd(PPh3)4]/20% TFA
2% [Pd(PPh3)4]/20% TfOH
2% Pd(OC(O)CF3)2/8% PPh3/20% TFA
2% [Pd(OC(O)CF3)2]/3% DPPF
2% [Pd(OC(O)CF3)2]/3% DPPF/20% TfOH
2% [(DPPF)Pd(OTf)2]
67
83
68
The catalytic, intermolecular hydroamination of olefins is a
highly desired, but difficult process.1-5 Efficient, intramolecular,
lanthanide-catalyzed hydroaminations of alkenes have been devel-
oped by Marks,6,7 but intermolecular reactions are generally slow.8
Late metal-catalysts would be more desirable for this reaction
because they are generally less sensitive to air and more tolerant
of polar functionality. However, intermolecular hydroaminations
of olefins that are catalyzed by late metals have shown slow rates
and limited scope. RhCl3 catalyzes the addition of secondary
amines to ethylene at high temperature, but other olefins are unre-
active.9 Phosphine complexes of iridium(I) catalyze the addition
of aniline to norbornene,10,11 but other substrates are unreactive.
Phosphine-ligated Rh(I) catalyzes the addition of piperidine to
vinylpyridine,12 and in one case to addition of morpholine to
styrene in low yield,13 but reaction of piperidine or aniline with
styrene gives enamine by oxidative amination14 or product mix-
tures.13,15-17 We report an efficient, palladium-catalyzed hydro-
amination of vinylarenes using aromatic amines to give sec-phen-
ethylamine products in the presence of acid cocatalyst (eq 1).
78
>99
96
a Reactions were run for 6 h in toluene solvent at 100 °C. Reactions
with lower yields did not show complete conversion. b Yields are for
isolated material and are an average of two runs.
We investigated several acids for this process and found that
reactions conducted in the presence of acids weaker than TFA
did not occur, but reactions in the presence of triflic acid were
faster than those conducted with TFA. Counterion effects, not
acid strength, must account for this difference in rates because
anilinium is the actual acid when either TFA or HOTf is used as
cocatalyst.
The role of the acid is complex and under investigation, but
several conclusions may be drawn at this time. One might propose
that this reaction occurs by an uncatalyzed addition of acid to
the olefin,19 and a metal-catalyzed conversion of the acid adduct
to the final amine. However, the leveling effect of aniline prevents
addition reactions by the strong acid, and two experiments suggest
that the anilinium acid does not react in an uncatalyzed fashion
with free olefin: no reaction occurred between aniline and styrene
in the presence of TFA without palladium catalyst, and reactions
of the sec-phenethyl trifluoroacetate with aniline catalyzed by (R)-
BINAP/Pd(trifluoroacetate)2 gave racemic product instead of the
nonracemic product formed in the overall hydroamination (see
below). Moreover, preliminary experiments indicate that the
benzylic trifluoroacetate of >92% ee reacts with aniline when
catalyzed by [((R)-BINAP)Pd(OSO2CF3)2] to give product that
is lower in ee than that formed from the overall catalytic process.
Thus, the catalytic cycle is unlikely to involve a product formed
from addition of acid to the vinylarene.
High-throughput screening studies in our laboratory recently
showed that [Pd(PPh3)4] was an efficient catalyst for the addition
of aniline to dienes in the presence of acetic acid.18 This result
served as a lead for systems that would catalyze the addition of
arylamines to vinylarenes. After varying several reaction param-
eters, we found that the reaction of aniline with styrene occurred
to give the Markovnikov addition product in high yields after 12
h at 100 °C when catalyzed by a mixture of [Pd(PPh3)4] and TFA
or triflic acid cocatalyst.
The palladium catalyst is more likely to be modified by the
acid cocatalyst. Experiments in Table 1 suggest that the acid
oxidizes [Pd(PPh3)4] to a Pd(II) species and that it plays a second,
yet undefined, role in accelerating reaction rates. The yields in
Table 1 reflect reaction rates; in general the reactions showed
little byproduct other than unreacted starting materials. The oxi-
dative role of the acid is demonstrated by the absence of reaction
when using [Pd(PPh3)4] alone as catalyst, but the formation of
addition product when using 2% Pd(OC(O)CF3)2/8% PPh3 (entry
2) or 2% [Pd(OC(O)CF3)2]/3% DPPF (entry 6). A second cocata-
lytic role for the acid was demonstrated by the accelerated rates
when using 2% Pd(OC(O)CF3)2 and either PPh3 or DPPF in the
presence of 20% TFA or HOTf (entries 5 and 7 vs 2 and 6) as
catalyst. The importance of counterion was shown by the reaction
in entry 8, which occurred in the absence of acid. This reaction
occurred more rapidly than the reaction in entry 6, which con-
tained trifluoroacetate as counterion and no added acid.
The scope of catalyst is relatively broad, and results using
several reaction conditions are provided in Table 1. Reactions
employing precatalysts in oxidation state Pd(0) or Pd(II) ligated
by either mono- or bisphosphine ligands were effective catalysts.
However, catalysts bearing either sterically hindered or unhindered
alkylphosphines have not been effective, and nickel and platinum
complexes of mono- or bis-arylphosphines have provided no
reaction. For studies on reaction scope, we selected the conditions
in entries 4 and 7, which involve commercially available catalyst
components.
(1) Muller, T. E.; Beller, M. Chem. ReV. 1998, 98, 675-703.
(2) For early stoichiometric additions of amines to olefins and catalytic
oxidative amination see this and the following three references. Panunzi, A.;
DeRenzi, A.; Palumbo, R.; Paiaro, G. J. Am. Chem. Soc. 1969, 91, 3879-
3883.
(3) A° ckermark, B.; Ba¨ckvall, J. E.; Hegedus, L. S.; Siirala-Hansen, K.;
Sjoberg, K.; Zetterberg, K. J. Organomet. Chem. 1974, 72, 127-138.
(4) Hegedus, L. S.; Allen, G. F.; Bozell, J. J.; Waterman, E. L. J. Am.
Chem. Soc. 1978, 100, 5800-5807.
(5) Ambuehl, J.; Pregosin, P. S.; Venanzi, L. M.; Ughetto, G.; Zambonelli,
L. J. Organomet. Chem. 1978, 160, 329.
(6) Tian, S.; Arredondo, V. M.; Stern, C. L.; Marks, T. J. Organometallics
1999, 18, 2568-2570.
(7) Gagne´, M. R.; Nolan, S. P.; Marks, T. J. Organometallics 1990, 9,
1716-1718.
(8) Li, Y.; Marks, T. J. Organometallics 1996, 15, 3770-3772.
(9) Coulson, D. R. Tetrahedron Lett. 1971, 429-430.
(10) Casalnuovo, A. L.; Calabrese, J. C.; Milstein, D. J. Am. Chem. Soc.
1988, 110, 6738-6744.
(11) Dorta, R.; Egli, P.; Zurcher, F.; Togni, A. J. Am. Chem. Soc. 1997,
119, 10857-10858.
(12) Beller, M.; Trauthwein, H.; Eichberger, M.; Breindl, C.; Mu¨ller, T.
E. Eur. J. Inorg. Chem. 1999, 1121-1132.
(13) Beller, M.; Trauthwein, H.; Eichberger, M.; Breindl, C.; Herwig, J.;
Muller, T. E.; Thiel, O. R. Chem. Eur. J. 1999, 5, 1306-1319.
(14) Beller, M.; Eichberger, M.; Trauthwein, H. Angew. Chem., Int. Ed.
Engl. 1997, 36, 2225-2227.
(15) Brunet, J.-J. Gazz. Chim. Ital. 1997, 127, 111-118.
(16) Brunet, J.; Commenges, G.; Neibecker, D.; Philippot, K. J. Organomet.
Chem. 1994, 469, 221.
(17) Beller, M.; Thiel, O. R.; Trauthwein, H. Synlett 1999, 243.
(18) Kawatsura, M.; Hartwig, J. F. 2000, unpublished results.
(19) Allen, A. D.; Resenbaum, M.; Seto, N. O. L.; Tidwell, T. T. J. Org.
Chem. 1982, 47, 4234.
10.1021/ja002284t CCC: $19.00 © 2000 American Chemical Society
Published on Web 09/15/2000