C O M M U N I C A T I O N S
Table 2. Ruthenium-Catalyzed Hydroamination of Vinylarenes
morpholino group. With 10% catalyst and conversion of the styrene
and piperidine to 94% of the hydroamination product, half the added
enamine remained, and no enamine from piperidine accumulated
(eq 4).
with Alkylaminesa
The precise mechanism of the ruthenium-catalyzed hydroami-
nation has not yet been revealed, but it is likely to be distinct from
that of the rhodium-catalyzed process. The rhodium catalysts for
hydroamination and oxidative amination induced isomerization of
N-deuteriomorpholine to form 2-deuteriomorpholine.21,22 This
exchange did not occur in the presence of the ruthenium catalysts.
Studies to increase catalyst activity by determining the detailed
mechanism of this reaction are in progress.
a Amine/vinylarene/Ru/DPPPent/TfOH ) 1:2:0.05:0.07:0.10 (1 mmol of
amine) in 0.50 mL of dioxane. b Isolated yield. c 4 mmol of vinylarene was
used. d 80 °C. e 48 h. f 0.25 mL of dioxane. g 110 °C. h DiPPF was used as
ligand. i 1.5 mmol of vinylarene was used. j 72 h.
hydroamination,14 the exchange of benzyl groups between amines20
was not observed. Thus, the lower yields of product from addition
of these less reactive amines reflects 67 and 53% conversions. More
hindered acyclic, aliphatic amines, such as dibutylamine, generated
only trace product at 100 °C.
Acknowledgment. We thank the NIH-NIGMS (GM55382) for
support. M.U. thanks Mitsubishi Chemical Corporation for support.
Supporting Information Available: Experimental procedures for
catalytic reactions (PDF). This material is available free of charge via
The hydroamination of vinylarenes with morpholine in the
presence of Ru(cod)(2-methylallyl)2 and DPPPent encompassed
electron-poor to electron-neutral styrenes (entries 9-11). Further,
the first transition metal-catalyzed hydroamination of R-methyl
styrene was observed (entry 14). Conversions of R-methyl styrene
were modest, but a single-addition product was observed.
The combination of Ru(cod)(2-methylallyl)2 and di-isopropyl-
phosphinoferrocene (DiPPF) was more active for hydroaminations
of vinylarenes containing electron-withdrawing groups. For ex-
ample, the reactions of vinylarenes containing 3- and 4-CF3 groups
in the presence of 5% Ru(cod)(2-methylallyl)2 and 7% DiPPF gave
the addition products in good to moderate yields (entries 12-13),
while the same reactions in the presence of the catalyst with
DPPPent occurred in less than 20% yield.
References
(1) Halpern, J.; Harrod, J. F.; James, B. R. J. Am. Chem. Soc. 1961, 83, 753.
(2) Noyori, R. AdV. Synth. Catal. 2003, 345, 15.
(3) Marciniec, B.; Gulinski, J. J. Mol. Catal. 1981, 10, 123.
(4) Glaser, P. B.; Tilley, T. D. J. Am. Chem. Soc. 2003, 125, 13640.
(5) Tokunaga, M.; Eckert, M.; Wakatsuki, Y. Angew. Chem., Int. Ed. 1999,
38, 3222.
(6) Tokunaga, M.; Wakatsuki, Y. Angew. Chem., Int. Ed. 1998, 37, 2867.
(7) For stoichiometric examples with Ru, see ref 8.
(8) (a) Schaffrath, H.; Keim, W. J. Mol. Catal. A: Chem. 2001, 168, 9. (b)
Ovchinnikov, M. V.; LeBlanc, E.; Guzei, I. A.; Angelici, R. J. J. Am.
Chem. Soc. 2001, 123, 11494.
(9) Mu¨ller, T. E.; Beller, M. Chem. ReV. 1998, 98, 675.
(10) Roesky, P. W.; Mu¨ller, T. E. Angew. Chem., Int. Ed. 2003, 42, 2708.
(11) Nobis, M.; Driessen-Ho¨lscher, B. Angew. Chem., Int. Ed. 2001, 40, 3983.
(12) For anti-Markovnikov lanthanide-catalyzed reactions of primary amines
with vinylarenes, see: Ryu, J. S.; Li, G. Y.; Marks, J. T. J. Am. Chem.
Soc. 2003, 125, 12584.
One might propose that isomerization of the Markovnikov
product to the terminal amine or hydrogenation of an enamine
formed by oxidative amination accounts for the anti-Markovnikov
hydroamination products. Three results show that the amines are
formed by direct, irreversible, anti-Markovnikov hydroamination.
First, the reaction of 2,5-dimethylstyrene with morpholine was
conducted in the presence of the isolated, branched amine. No
isomerization of the branched to the terminal amine occurred (eq
2). Second, the reaction of morpholine with 2,5-dimethylstyrene
was conducted in the presence of the amine containing an N-Boc
piperazinyl group. The reaction generated neither free styrene nor
the product from exchange of morpholine with the N-Boc piper-
azinyl group (eq 3). Third, the reaction of styrene with piperidine
was conducted in the presence of 10% enamine containing the
(13) Kawatsura, M.; Hartwig, J. F. J. Am. Chem. Soc. 2000, 122, 9546.
(14) Utsunomiya, M.; Hartwig, J. F. J. Am. Chem. Soc. 2003, 125, 14286.
(15) Casalnuovo, A. L.; Calabrese, J. C.; Milstein, D. J. Am. Chem. Soc. 1988,
110, 6738.
(16) Dorta, R.; Egli, P.; Zuercher, F.; Togni, A. J. Am. Chem. Soc. 1997, 119,
10857.
(17) Utsunomiya, M.; Kuwano, R.; Kawatsura, M.; Hartwig, J. F. J. Am. Chem.
Soc. 2003, 125, 5608.
(18) Beller, M.; Eichberger, M.; Trauthwein, H. Angew. Chem., Int. Ed. Engl.
1997, 36, 2225.
(19) Triphos ) Bis(2-diphenylphosphinoethyl)phenylphosphine, Xantphos )
9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene.
(20) Murahashi, S.-I.; Yoshimura, N.; Tsumiyama, T.; Kojima, T. J. Am. Chem.
Soc. 1983, 105, 5002.
(21) Beller, M.; Trauthwein, H.; Eichberger, M.; Breindl, C.; Herwig, J.; Mu¨ller,
T. E.; Thiel, O. R. Chem. Eur. J. 1999, 5, 1306.
(22) Rh complexes of DPEphos also induced migration of morpholine-d1, M.
Utsunomiya and J. F. Hartwig, unpublished results.
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