Platinum-catalyzed intermolecular hydroamination of vinyl arenes with carboxamides

Article abstract of DOI:10.1021/ol050745f

(Chemical Equation Presented) Reaction of benzamide with 4-methylstyrene catalyzed by a 1:2 mixture of [PtCl₂(H₂C=CH ₂)]₂ and P(4-C₆H₄CF ₃)₃ (5 mol %) in mesitylene at 140 °C for 24 h led to the isolation of N-(1-p-tolylethyl)benzamide in 85% yield. Electron-rich, electron-poor, and hindered vinyl arenes underwent Markovnikov hydroamination with a range of carboxamides and amide derivatives in moderate to good yield with excellent regioselectivity.

Full text of DOI:10.1021/ol050745f

ORGANIC
LETTERS
2005
Vol. 7, No. 13
2635-2638
Platinum-Catalyzed Intermolecular
Hydroamination of Vinyl Arenes with
Carboxamides
Hua Qian and Ross A. Widenhoefer*
P. M. Gross Chemical Laboratory, Duke UniVersity,
Durham, North Carolina 27708-0346
rwidenho@chem.duke.edu
Received April 6, 2005
ABSTRACT
Reaction of benzamide with 4-methylstyrene catalyzed by a 1:2 mixture of [PtCl2(H2C
C for 24 h led to the isolation of N-(1-p-tolylethyl)benzamide in 85% yield. Electron-rich, electron-poor, and hindered vinyl arenes underwent
Markovnikov hydroamination with a range of carboxamides and amide derivatives in moderate to good yield with excellent regioselectivity.
dCH2)]2 and P(4-C6H4CF3)3 (5 mol %) in mesitylene at 140
°
The importance of amines and amine derivatives in the
synthesis of pharmaceuticals and fine chemicals has stimu-
lated considerable interest in catalytic olefin hydroamination
as a route to nitrogen-containing molecules.1 However,
despite recent advances in this area,3-8 the intermolecular
hydroamination of unactivated olefins remains problematic.
Although lanthanide metallocene,2 bis(phosphine) Rh(I),3 and
bis(2-methylallyl) Ru(II)4 complexes catalyze the anti-
Markovnikov hydroamination of vinyl arenes with alkyl-
amines, these protocols suffer from a number of limitations,
including poor functional group compatibility, poor selectiv-
ity, and/or limited scope. Bis(phosphine) palladium(II)
complexes employed in conjunction with triflic acid catalyze
the Markovnikov hydroamination of vinyl arenes with both
aryl-5 and alkylamines,6 but these protocols are also of limited
scope and are not applicable to the employment of carboxa-
mides and related derivatives as substrates.7,8
As part of a program directed toward the development of
transition metal-catalyzed methods for the addition of carbon-
9,10 and heteroatom-nucleophiles11-13 to unactivated olefins,
we recently reported the Pt(II)-catalyzed intermolecular
hydroamination of ethylene with carboxamides.12 For ex-
ample, reaction of benzamide and ethylene (50 psi) catalyzed
(1) (a) Mu¨ller, T. E.; Beller, M. Chem. ReV. 1998, 98, 675. (b) Bytschkov,
I.; Doye, S. Chem. Eur. J. 2003, 935.
(2) Ryu, J-. S.; Li, G. Y.; Marks, T. J. J. Am. Chem. Soc. 2003, 125,
12584.
(3) (a) Beller, M.; Trauthwein, H.; Eichberger, M.; Breindl, C.; Herwig,
J.; Mu¨ller, T. E.; Thiel, O. R. Chem. Eur. J. 1999, 5, 1306. (b) Utsunomiya,
M.; Kuwano, R.; Kawatsura, M.; Hartwig, J. F. J. Am. Chem. Soc. 2003,
125, 5608.
(4) Utsunomiya, M.; Hartwig, J. F. J. Am. Chem. Soc. 2004, 126, 2702.
(5) Kawatsura, M.; Hartwig, J. F. J. Am. Chem. Soc. 2000, 122, 9546.
(6) Utsunomiya, M.; Hartwig, J. F. J. Am. Chem. Soc. 2003, 125, 14286.
(7) Transition metal-catalyzed intermolecular hydroamination of ethylene,7a,b
strained olefins,7c 1,3-dienes,7d,e and Michael acceptors7f,g is also known.
(a) Coulson, D. R. Tetrahedron Lett. 1971, 12, 429. (b) Brunet, J.-J.; Cadena,
M.; Chu, N. C.; Diallo, O.; Jacob, K.; Mothes, E. Organometallics 2004,
23, 1264. (c) Casalnuovo, A. L.; Calabrese, J. C.; Milstein, D. J. Am. Chem.
Soc. 1988, 110, 6738. (d) Baker, R.; Onions, A.; Popplestone, R. J.; Smith,
T. N. J. Chem. Soc., Perkin Trans. 2 1975, 1133. (e) Lober, O.; Kawatsura,
M.; Hartwig, J. F. J. Am. Chem. Soc. 2001, 123, 4366. (f) Seligson, A. L.;
Trogler, W. C. Organometallics 1993, 12, 744. (g) Gaunt, M. J.; Spencer,
J. B. Org. Lett. 2001, 3, 25.
(9) Indoles: (a) Liu, C.; Han, X.; Wang, X.; Widenhoefer, R. A. J. Am.
Chem. Soc. 2004, 126, 3700. (b) Liu, C.; Widenhoefer, R. A. J. Am. Chem.
Soc. 2004, 126, 10250.
(10) Activated methylene compounds: (a) Widenhoefer, R. A. Pure Appl.
Chem. 2004, 76, 671 and references therein. (b) Liu, C.; Wang, X.; Pei, T.;
Widenhoefer, R. A. Chem. Eur. J. 2004, 10, 6343. (c) Han, X.; Wang, X.;
Pei, T.; Widenhoefer, R. A. Chem. Eur. J. 2004, 10, 6333. (d) Wang, X.;
Widenhoefer, R. A. Chem. Commun. 2004, 660. (e) Qian, H.; Pei, T.;
Widenhoefer, R. A. Organometallics 2005, 24, 287. (f) Liu, C.; Widen-
hoefer, R. A. Tetrahedron Lett. 2005, 46, 285.
(11) Alkylamines: Bender, C. F.; Widenhoefer, R. A. J. Am. Chem. Soc.
2005, 127, 1070.
(12) Carboxamides: Wang, X.; Widenhoefer, R. A. Organometallics
2004, 23, 1649.
(8) Stahl has recently reported the catalytic intermolecular oxidative
amination of aromatic8a and aliphatic8b R-olefins with amides. (a) Timokhin,
V. I.; Anastasi, N. R.; Stahl, S. S. J. Am. Chem. Soc. 2003, 125, 12996. (b)
Brice, J. L.; Harang, J. E.; Timokhin, V. I.; Anastasi, N. R.; Stahl, S. S. J.
Am. Chem. Soc. 2005, 127, 2868.
10.1021/ol050745f CCC: $30.25
© 2005 American Chemical Society
Published on Web 05/20/2005

Scheme 1
Table 1. Effect of Solvent, Phosphine, and Temperature on the
Pt(II)-Catalyzed Reaction of Benzamide (2 M) with
4-Methylstyrene (4 Equiv)
entry
PR3
temp (°C)
solvent
yield (%)a
for 24 h led to isolation of 2 in 85% yield relative to
benzamide as a single regioisomer (Table 1, entry 7).15,16
Electron-rich, electron-poor, and hindered vinyl arenes
underwent platinum-catalyzed hydroamination with a range
of aryl carboxamides, including p-methoxy-, p-bromo-,
p-trifluoromethyl-, p-carbomethoxy-, o-methyl-, and p-OT-
BDMS-substituted benzamides, 2-naphthylcarboxamide, and
benzo[1,3]dioxole-5-carboxamide to form the corresponding
N-(1-arylethyl)carboxamides in moderate to good yield with
excellent regioselectivity (Table 2, entries 1-14). In addition
to arylamides, valeramide, 2-oxazolidone, and p-toluene-
sulfonamide also reacted with vinyl arenes under platinum
catalysis to form the corresponding N-(1-arylethyl) amide
derivatives in moderate to good yield with excellent regio-
selectivity (Table 2, entries 15-18). Despite the rather
forcing conditions required to effect the catalytic intermo-
lecular hydroamination of vinyl arenes, the protocol tolerated
a number of polar functional groups, including aryl halides,
carboxylic esters, acetals, and silyl ethers (Table 2, entries
4, 6, 10, and 13).
1
2
3
4
5
6
7
PPh3
none
120
120
120
140
140
140
140
dioxane
dioxane
dioxane
dioxane
toluene
xylene
24
71
72
77
81
79
85
P(4-C6H4CF3)3
P(4-C6H4CF3)3
P(4-C6H4CF3)3
P(4-C6H4CF3)3
P(4-C6H4CF3)3
mesitylene
a Isolated yield relative to benzamide of >95% pure material.
by a 1:2 mixture of [PtCl2(H2CdCH2)]2 (1) and PPh3 at 120
°C for 24 h led to isolation of N-ethylbenzamide in 97%
yield (eq 1). Although the platinum-catalyzed hydroamination
of ethylene tolerated a range of amide derivatives, this
procedure proved to be largely ineffective for the hydroami-
nation of R-olefins.14 We have continued our efforts in this
area, and here we report the platinum-catalyzed Markovnikov
hydroamination of vinyl arenes with carboxamides and
related compounds.
On the basis of heats of formation data,17 we estimate an
enthalpy of reaction for the hydroamination of a vinyl arene
with a carboxamide of ∆H ≈ -14 kcal mol-1.18 In addition,
the entropy of reaction for the hydroamination of ethylene
Reaction of benzamide and 4-methylstyrene (4 equiv)
employing conditions optimized for the hydroamination of
ethylene with carboxamides12 led to isolation of N-(1-p-
tolylethyl)benzamide (2) in only 24% yield (Table 1, entry
1). We noted with interest that 1 was a significantly more
effective catalyst for the hydroamination of 4-methylstyrene
with benzamide than was a mixture of 1 and PPh3 (Table 1,
entry 2). This observation suggested that an electron-deficient
phosphine might be more suitable as a supporting ligand for
the Pt(II)-catalyzed hydroamination of vinyl arenes than was
PPh3. Indeed, further experimentation validated this hypoth-
esis (Table 1, entries 3-7). In an optimized procedure,
reaction of a concentrated mesitylene solution of benzamide
(2 M) and 4-methylstyrene (4 equiv) catalyzed by a mixture
of 1 (2.5 mol %) and P(4-C6H4CF3)3 (5 mol %) at 140 °C
(15) In addition to 2, reaction of benzamide (2 M) and 4-methylstyrene
(4 equiv) catalyzed by 1 (2.5 mol %)/P(4-C6H4CF3)3 (5 mol %) at 140 °C
for 24 h led to the isolation of (E)-1,3-bis(p-tolyl)-1-butene in ∼15% yield
based on 4-methylstyrene. Dimerization of the vinyl arene necessitated the
use of an excess of vinyl arene. For example, reaction of benzamide (2 M)
and 4-methylstyrene (1 equiv) catalyzed by 1 (2.5 mol %)/P(4-C6H4CF3)3
(5 mol %) at 140 °C for 24 h led to the isolation of 2 in only 43% yield.
(16) (a) Although strong acids such as HOTf catalyze the intramolecular
hydroamination of olefins with carboxamides at elevated temperatures,16b
the presence of a significant acid-catalyzed background reaction in the Pt-
catalyzed hydroamination of vinyl arenes was ruled out, as reaction of
benzamide, 4-methylstyrene, and a catalytic amount of HCl (5 mol %) in
mesitylene at 140 °C for 24 h formed no significant amounts (<10%) of 2
as determined by GC analysis. (b) Schlummer, B.; Hartwig, J. F. Org. Lett.
2002, 4, 1471.
(17) Pedley, J. B.; Rylance, J. Sussex N. P. L. Computer Analyzed
Thermochemical Data: Organic and Organometallic Compounds; Univer-
sity of Sussex: Brighton, UK, 1977.
0
(18) ∆Hf values for 1-butene, acetamide, and n-butylacetamide in the
gas phase are -0.1, -56.9, and -72.9 kcal mol-1, respectively. From these
values, we calculate an enthalpy of reaction for the conversion of 1-butene
and acetamide to n-butylacetamide of ∆H ) -15.9 kcal mol-1. ∆Hf 0 values
for n-butane, styrene, and ethylbenzene in the gas phase are -30.1, 35.3,
and 7.0 kcal mol-1, respectively. These values combined with that for
1-butene indicate that the CdC bond of styrene is 1.7 kcal mol-1 more
stable than the CdC bond of 1-butene. From these values, we estimate an
enthalpy of reaction for the hydroamination of styrene with acetamide of
(13) Hydroxyl groups: (a) Qian, H.; Han, X.; Widenhoefer, R. A. J.
Am. Chem. Soc. 2004, 126, 9536. (b) Han, X.; Widenhoefer, R. A. J. Org.
Chem. 2004, 68, 1738.
(14) In a single example, reaction of valeramide with propylene (100
psi) and a catalytic 2:1 mixture of PPh3 and 1 at 120 °C for 80 h formed
N-isopropylvaleramide in 73% isolated yield.12
∆H ) -14.2 kcal mol-1
.
2636
Org. Lett., Vol. 7, No. 13, 2005

Scheme 2
Table 2. Reaction of Amides (2 M) with Vinyl Arenes (4
Equiv) Catalyzed by a Mixture of [PtCl2(H2CdCH2)]2 (1) (2.5
Mol %) and P(4-C6H4CF3)3 (5 Mol %) in Mesitylene at 140 °Ca
formed a ∼2:2:1:1 mixture of p-toluamide, 2, benzamide,
and N-(1-p-tolylethyl)p-toluamide (3) (Scheme 1).
The outer-sphere attack of indoles,9a alkoxides,20 and
amines21 on platinum-olefin complexes has been established.
On the basis of these precedents, we propose a mechanism
for the platinum-catalyzed hydroamination of vinyl arenes
involving outer-sphere attack of the amide on the platinum-
complexed olefin of I to form zwitterionic complex II
(Scheme 2). Thermodynamic,22 NMR,23 and X-ray crystal-
lographic analyses24 of Pd(II) and Pt(II) styrene complexes
point to the zwitterionic character of the M-olefin interaction
that places significant positive charge on the benzylic carbon
atom. Significant contribution of this resonance structure (I-
σ) to the Pt-olefin interaction of I would account for the
high Markovnikov selectivity of the platinum-catalyzed hy-
droamination of vinyl arenes. Loss of HCl from II followed
by protonolysis of the Pt-C bond of the resulting platinum
â-aminoalkyl complex III would release the N-(1-arylethyl)-
carboxamide with regeneration of the PtCl2 catalyst.25
In summary, we have developed an effective protocol for
the Markovnikov hydroamination of vinyl arenes with
carboxamides and related derivatives to form N-(1-arylethyl)
amide derivatives in good yield with high regioselectivity.
Our efforts are currently directed toward expanding the scope
(19) Steinborn, D.; Taube, R. Z. Chem. 1986, 26, 349.
(20) (a) Stille, J. K.; Morgan, R. A.; Whitehurst, D. D.; Doyle, J. R. J.
Am. Chem. Soc. 1965, 87, 3282. (b) Whitla, W. A.; Powell, H. M.; Venanzi,
L. M. Chem. Commun. 1966, 310.
(21) Panunzi, A.; De Renzi, A.; Paiaro, G. J. Am. Chem. Soc. 1970, 92,
3488.
(22) Cooper, D. W.; Powell, J. Inorg. Chem. 1976, 15, 1959.
(23) (a) Kurosawa, H.; Majima, T.; Asada, N. J. Am. Chem. Soc. 1980,
102, 6996. (b) Kurosawa, H.; Urabe, A.; Emoto, M. J. Chem. Soc., Dalton
Trans. 1986, 891.
(24) (a) Miki, K.; Shiotani, O.; Kai, Y.; Kasai, N.; Kanatani, H.;
Kurosawa, H. Organometallics 1983, 2, 585. (b) Van der Poel, H.; Van
Koten, G. Inorg. Chem. 1981, 20, 2941.
a See Supporting Information for reaction times. b Isolated yield relative
to benzamide of >95% pure material. c Catalyst loading: 1 (5 mol %) and
P(4-C6H4CF3)3 (10 mol %). d Reaction temperature ) 120 °C. e 4-Vinyl-
anisole (1.1 equiv) was added slowly to the reaction mixture.
(25) Protonolysis of Pt(II) alkyl complexes with HCl and other acids
has been studied in detail. These studies have established a mechanism
involving protonation at platinum followed by reductive elimination from
the resulting platinum(IV) hydride complex. (a) Stahl, S. S.; Labinger, J.
A.; Bercaw, J. E. J. Am. Chem. Soc. 1996, 118, 5961. (b) Johansson, L.;
Tilset, M. J. Am. Chem. Soc. 2001, 123, 739. (c) Prokopchuk, E. M.;
Puddephatt, R. J. Organometallics 2003, 22, 787. (d) Crumpton-Bregel, D.
M.; Goldberg, K. I. J. Am. Chem. Soc. 2003, 125, 9442. (e) Reinartz, S.;
White, P. S.; Brookhart, M.; Templeton, J. L. Organometallics 2000, 19,
3854.
with ammonia was determined to be ∆S ≈ -30 e.u.19 Using
these values, we estimate a free energy of reaction for the
hydroamination of a vinyl arene with a carboxamide of ∆G
≈ -1.5 kcal mol-1 at 140 °C,18 which suggests that
hydroamination is reversible under these conditions. Indeed,
heating a 1:1 mixture of p-toluamide and 2 with a catalytic
1:2 mixture of 1 and P(4-C6H4CF3)3 at 140 °C for 24 h
Org. Lett., Vol. 7, No. 13, 2005
2637

and elucidating the mechanisms of the platinum-catalyzed
hydroamination of unactivated olefins with carboxamides.
Supporting Information Available: Experimental pro-
cedures and spectroscopic data for new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
Acknowledgment. Acknowledgment is made to the NSF
(CHE-03-04994) for support of this research. R.W. thanks
the Camille and Henry Dreyfus Foundation and GlaxoSmith-
Kline for unrestricted financial assistance.
OL050745F
2638
Org. Lett., Vol. 7, No. 13, 2005