Palladium-catalyzed carbamoylation of aryl halides by tungsten carbonyl amine complex

Article abstract of DOI:10.1021/jo901486z

(Chemical Equation Presented) In the presence of aminepentacarbonyltungsten, base, and a catalytic amount of palladium(0) complex, carbamoylation of aryl halide proceeds to afford amide. The reaction may involve transmetalation between palladium(II) inter

Full text of DOI:10.1021/jo901486z

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Palladium-Catalyzed Carbamoylation of Aryl Halides by Tungsten
Carbonyl Amine Complex
Wei Ren and Motoki Yamane*
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences,
Nanyang Technological University, 21 Nanyang Link, Singapore 637371, Singapore
yamane@ntu.edu.sg
Received July 27, 2009
In the presence of aminepentacarbonyltungsten, base, and a catalytic amount of palladium(0)
complex, carbamoylation of aryl halide proceeds to afford amide. The reaction may involve
transmetalation between palladium(II) intermediate and carbamoyltungstenate that is generated
in situ. This catalytic cross-coupling reaction provides an alternative method to the conventional
palladium-catalyzed amidation by using gaseous carbon monoxide.
Introduction
To form acylpalladium(II) intermediate B, carbon monoxide is
indispensable, and therefore the reactions are performed under
gaseous carbon monoxide atmosphere. Sometimes a high pres-
sure of carbon monoxide is necessary to realize efficient amide
formation.2e,f,h,j,p-r Recently it was reported that group VI metal
carbonyl complexes could be used as a solid state of the carbon
monoxide sources in the reaction under microwave irradiation.3
Since Heck and his co-worker first reported it,1 the palla-
dium-catalyzed three-component coupling reaction of aryl
halides, carbon monoxide, and amine has been studied en-
ergetically because it is one of the practical catalytic methods
for the preparation of amides.2 By this method amides are
prepared from organic halides and amines with one carbon
elongation. The catalytic cycle is explained as depicted in path
A in Scheme 1. Oxidative addition of aryl halide to palladium-
(0) proceeds to give arylpalladium(II) intermediate A. Migra-
tory insertion of carbon monoxide gives acylpalladium(II)
intermediate B that reacts with amine in the presence of a base
to afford amide with regeneration of palladium(0) catalyst.
SCHEME 1. Reported and Hypothetic Mechanism of Palladium-
Catalyzed Amidation of Aryl Halides
*To whom correspondence should be addressed. Phone: +65 6513 8014.
Fax: +65 6791 1961.
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(c) Schoenberg, A.; Heck, R. F. J. Am. Chem. Soc. 1974, 96, 7761.
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An alternative possible idea for palladium-catalyzed amide
formation is depicted in path B in Scheme 1. This is totally a
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8332 J. Org. Chem. 2009, 74, 8332–8335
Published on Web 10/09/2009
DOI: 10.1021/jo901486z
r
2009 American Chemical Society

Ren and Yamane
JOCArticle
cross-coupling reaction between carbamoylmetal compounds
and organic halides. The key step is the transmetalation
between carbamoylmetal C and palladium(II) intermediate
A to generate carbamoylpalladium(II) intermediate D.
Although there is the advantage that gaseous carbon mon-
oxide is not necessary, this type of catalytic reaction has never
been reported so far. The reason is that useful nucleophilic
carbamoylation reagents C have not been developed.
Only a few nucleophilic carbamoylation reagents have
been found in the literature. For example, there are some
reports on the preparation of carbamoyllithium,4 which is
unstable for use in carbon-carbon bond formation reac-
tions. Especially, carbamoyllithium having a hydrogen on its
nitrogen atom is so unstable that a rearrangement takes place
to form the azaenolate of formamide.4c The carbamoylnickel
complex is known as a rather stable intermediate and is used
for the reaction with carbon electrophiles such as aryl
halides.5 Recently the aluminum azaenolate of carbamoyl-
telluroate was reported as a synthon of carbamoyllithium
and carbamoylation of carbonyl compounds was achieved.6
To the best of our knowledge, these are the only reagents for
nucleophilic carbamoylation reactions.
In this paper are present an investigation of in situ-
generation of carbamoylmetalate as a nucleophilic carbamo-
ylation reagent and its application to palladium-catalyzed
carbamoylation of aryl halides.
Results and Discussion
As shown in Scheme 2, we expected that group VI carba-
moyl complexes C0 would be generated by the combined use
of bases and aminepentacarbonylmetal complexes that were
known to be easily prepared as air-stable crystalline com-
plexes in most cases.12
SCHEME 2. Generation of Carbamoyl Metalate
Actually, group VI metal benzylamine pentacarbonyl
complexes 2 [(OC)5MNH2CH2Ph; M = Cr, Mo, W] were
prepared as air-stable solids in 2 steps from the correspond-
ing hexacarbonyl complexes according to the reported pro-
cedure13,14 with some modifications (Scheme 3).
Acyl transition metal complexes are known to be used as
nucleophilic acylation reagents.7 Especially, group VI metal
carbonyl complexes, such as chromium, molybdenum, and
tungsten complexes, are used for this purpose and a variety
of nucleophilic acylation reactions are reported.8 Moreover,
it is known that transmetalation between these acylmetalates
and palladium(II) intermediates proceeds to generate
acylpalladium(II) complexes.8c,d Therefore, it was expected
that group VI carbamoyl metal complexes could be used as
nucleophilic carbamoylation reagents. So far carbamoyl
complexes of group VI metals were mostly used as inter-
mediates for the synthesis of alkoxy(amino)carbene metal
complexes9 and the preparation of ureas10 or formamides,11
while never being used for C-C bond formation reactions.
SCHEME 3. Preparation of Group VI Metal Carbonyl Amine
Complexes
With the amine complexes in hand, we tried to investigate
the palladium-catalyzed carbamoylation of aryl halides.
First, iodobenzene was selected as the substrate. To a
mixture of tungsten benzylamine complex 2a (1 mmol) and
base (1.1 mmol) in THF were added iodobenzene (1.5 mmol),
Pd(OAc)2 (0.05 mmol), and P(o-Tol)3 (0.1 mmol) and the
reaction mixture was heated to reflux (Scheme 4). When
LiHMDS was used as the base, the reaction was completed in
2 h and benzamide 3a was obtained in 70% yield. It was
found that the use of K2CO3 gave an excellent yield (95%)
although it required longer reaction time. In both cases a
small amount of biphenyl (<3%) was obtained as the side
product. When a control reaction was performed without
Pd(OAc)2 and P(o-Tol)3, amide 3a was obtained in <4% as a
mixture of undefined compounds and benzylamine complex
2a was recovered in 42%.15 Carbamoylation of iodobenzene
ꢀ
€
(4) (a) Banhidai, B.; Schollkopf, U. Angew. Chem. 1973, 85, 861.
(b) Rautenstrauch, V.; Joyeux, M. Angew. Chem., Int. Ed. Engl. 1979, 18,
83. (c) Rautenstrauch, V.; Joyeux, M. Angew. Chem., Int. Ed. Engl. 1979, 18,
ꢀ
85. (d) Ramon, D. J.; Yus, M. Tetrahedron 1996, 52, 13739.
(5) (a) Corey, E. J.; Hegedus, L. S. J. Am. Chem. Soc. 1969, 91, 1233.
(b) Fukuoka, S.; Ryang, M.; Tsutsumi, S. J. Org. Chem. 1971, 36, 2721.
(6) Kambe, N.; Inoue, T.; Takeda, T.; Fujiwara, S.-I.; Sonoda, N. J. Am.
Chem. Soc. 2006, 128, 12650.
(7) (a) Seebach, D. Angew. Chem., Int. Ed. 1969, 8, 639. For acyl nickel
complexes, see: (b) Ryang, M.; Kwang-Myeong, S.; Sawa, Y.; Tsutsumi, S. J.
Organomet. Chem. 1966, 5, 305. (c) Sawa, Y.; Hashimoto, I.; Ryang, M.;
Tsutsumi, S. J. Org. Chem. 1968, 33, 2159. (d) Corey, E. J.; Hegedus, L. S. J.
Am. Chem. Soc. 1969, 91, 4926. For acylstannanes, see: (e) Kosugi, M.; Naka, H.;
Migita, T. Chem. Lett. 1987, 1371. For acyl iron complexes, see: (f) Koga, T.;
Makinouchi, S.; Okukado, N. Chem. Lett. 1988, 1141. For acyl zirconium
complexes, see: (g) Hanzawa, Y.; Tabuchi, N.; Taguchi, T. Tetrahedron Lett.
1998, 39, 6249. (h) Hanzawa, Y.; Tabuchi, N.; Saito, K.; Noguchi, S.; Taguchi, T.
Angew. Chem., Int. Ed. 1999, 38, 2395. (i) Hanzawa, Y.; Taguchi, T. J. Synth.
Org. Chem. Jpn. 2004, 62, 314. For acylsilanes, see: (j) Obora, Y.; Ogawa, Y.;
Imai, Y.; Kawamura, T.; Tsuji, Y. J. Am. Chem. Soc. 2001, 123, 10489.
(k) Yamane, M.; Amemiya, T.; Narasaka, K. Chem. Lett. 2001, 1210.
(8) (a) Sangu, K.; Watanabe, T.; Takaya, J.; Iwasawa, N. Synlett 2007, 6,
929. (b) Sakurai, H.; Tanabe, K.; Narasaka, K. Chem. Lett. 1999, 28, 309.
(c) Yamane, M.; Ishibashi, Y.; Sakurai, H.; Narasaka, K. Chem. Lett. 2000,
29, 174. (d) Sakurai, H.; Tanabe, K.; Narasaka, K. Chem. Lett. 2000, 29, 168.
(9) (a) Fischer, E. O.; Kollmeier, H. J. Angew. Chem., Int. Ed. 1970, 9, 309.
(b) Fischer, E. O.; Winkler, E. Angew. Chem., Int. Ed. 1971, 10, 922.
(10) (a) Diaz, D. J.; Darko, A. K.; McElwee-White, L. Eur. J. Org. Chem.
2007, 4453. (b) Diaz, D. J.; Hylton, K. G.; McElwee-White, L. J. Org. Chem.
2006, 71, 734. (c) Hylton, K.-G.; Main, A. D.; McElwee-White, L. J. Org.
Chem. 2003, 68, 1615. (d) McCusker, J. E.; Grasso, C. A.; Main, A. D.;
McElwee-White, L. Org. Lett. 1999, 1, 961.
(12) For the generation of carbamoyl metal complexes, we used metal
pentacarbonyl amine complexes but not a combination of metal hexacarbo-
nyl complexes and amine because metal pentacarbonyl complexes are known
as a better electrophile in the reaction with carbon nucleophiles such as
organozinc reagents to form acylmetal complexes. For an efficient synthesis
of carbene complexes via acyl metalate in the reaction of pentacarbonyl-
€
chromium complexes and organozinc reagents, see: Stadtmuller, H.; Kno-
chel, P. Organometallics 1995, 14, 3163.
(13) Abel, E. W.; Butler, I. S.; Reid, J. G. J. Chem. Soc. 1963, 2068.
(14) Schenk, W. A. J. Organomet. Chem. 1979, 179, 253.
(15) The carbamoylation product 3a was obtained in a small amount
(<4%) even in the absence of palladium catalyst. This suggests that phenyl
iodide could oxidatively added to tungstenate(0) complex although it was not
efficient. Further study on the possibility of carbamoylation without using
palladium catalyst is still under investigation. For oxidative addition of aryl
halides to group VI metal(0) complexes, see: (a) Pan, Y. H.; Ridge, D. P. J.
Am. Chem. Soc. 1992, 114, 2773. (b) Looman, S. D.; Richmond, T. G. lnorg.
Chim. Acta 1995, 240, 479. (c) Lucht, B.; Poss, M. J.; Richmond, T. G.
J. Chem. Educ. 1991, 68, 786 and ref 8a).
(11) Doxsee, K. M.; Grubbs, R. H. J. Am. Chem. Soc. 1981, 103, 7696.
J. Org. Chem. Vol. 74, No. 21, 2009 8333

Ren and Yamane
JOCArticle
was also performed by using other group VI metal benzyl-
amine complexes 2b and 2c. Molybdenum complex 2b gave
good yield of 3a; however, chromium complex 2c gave only
39% yield.
TABLE 1. Palladium-Catalyzed Carbamoylation of Aryl Halidesa
SCHEME 4. Palladium-Catalyzed Carbamoylation of Phenyl
Iodide
Palladium-catalyzed carbamoylation of a variety of aryl
halides was performed and the results are summarized in
Table 1. It was found that not only aryl iodides but bromides
could be used as the coupling partners although it requires
longer reaction time and larger amounts of the catalyst
loading (10 mol %). This higher reactivity of the iodide
was applied for the chemoselective carbamoylation of
1-bromo-4-iodobenzene and 4-bromobenzamide 3e was ob-
tained selectively in good yield (entry 7). Functional group
tolerance was tested by using 4-substituted phenyl halides
and it was found that vinyl, acyl, ethoxycarbonyl, and
methoxy groups were not affected under the reaction condi-
tions (entries 8-10). This reaction was also applicable for the
catalytic carbamoylation of heteroaromatic halides. 3-Thio-
phenecarboxamide 3i was obtained from 3-bromothiophene
in 63% yield (entry 11).
We applied this palladium-catalyzed carbamoylation re-
action for a lactam synthesis. Tungsten amine complexes 2d
and 2e having a 2-iodoaryl moiety were prepared and sub-
jected to the palladium-catalyzed reaction conditions
(Scheme 5). Intramolecular carbamoylation proceeded to
give 5- and 6-membered ring lactams 3j and 3k.
SCHEME 5. Palladium-Catalyzed Intramolecular Carbamoy-
lation
aReaction conditions: 2a (1 mmol), Ar-X (1.5 mmol), K2CO3 (1.1
mmol), Pd(OAc)2 (5 mol % for aryl iodide, 10 mol % for aryl bromide),
P(o-Tol)3 (10 mol % for aryl iodide, 20 mol % for aryl bromide).
bWithout Pd(OAc)2 and P(o-Tol)3. c2a was recovered in 42%. d3b and
3b0 were obtained in 63% and 11% yields, respectively.
temperature or higher pressure of carbon monoxide is
necessary to accomplish amide formation via path A
(Scheme 1). On the contrary, tungsten benzylamine carbonyl
complex gave the amide in 84% yield. Although we cannot
completely exclude the possibility of path A, these results
suggest the reaction proceeds via path B, transmetalation of
carbamoylmetalate.
The main difference between path A and B is whether the
reaction proceeds via acylpalladium intermediate (path A)
or carbamoylpalladium intermediate (path B). Then we
performed the palladium-catalyzed reaction in the pre-
sence of reactive alkene to trap the palladium inter-
mediates (Scheme 7). When norbornene was added to the
As stated in the Introduction, there are two possible
mechanisms for the palladium-catalyzed amide formation.
If amine and carbon monoxide are released from the tung-
sten center in the reaction conditions, the two mechanisms
cannot be distinguished. To have some insight into the
mechanism of this palladium-catalyzed carbamoylation,
the following reactions were performed. The palladium-
catalyzed reaction was performed with the combination of
benzylamine and carbon monoxide (1 atm) instead of using
tungsten amine carbonyl complex (Scheme 6). When
2-bromonaphthalene was subjected to the reaction, the
corresponding amide 3c was not obtained at all in spite
of refluxing 36 h. It seems to be required that a higher
8334 J. Org. Chem. Vol. 74, No. 21, 2009

Ren and Yamane
JOCArticle
SCHEME 6. Mechanistic Investigation
Conclusions
In conclusion, palladium-catalyzed carbamoylation of
aryl halides was accomplished by using aminepenta-
carbonyltungsten(0). The reaction may involve transmetala-
tion between carbamoylmetalate and palladium(II) inter-
mediate although the mechanism is not clear yet. This
reaction can be performed without using gaseous carbon
monoxide and may provide an alternative method of con-
ventional palladium-catalyzed three-component coupling
reaction of aryl halide, carbon monoxide, and amine.
Experimental Section
SCHEME 7. Attempt To Trap the Palladium Intermediate
General Procedure for Pd-Catalyzed Carbamoylation of Aryl
Halides. A mixture of tungsten amine complex 2a (0.44 g,
1.0 mmol), aryl halide (1.5 mmol), Pd(OAc)2 (5 mol % in the
case of aryl iodide, 10 mol % in the case of aryl bromide),
P(o-Tol)3 (10 mol % in the case of aryl iodide, 20 mol % in the
case of aryl bromide), and K2CO3 (0.152 g, 1.1 mmol) in THF
(10 mL) was heated to reflux. The reaction was monitored
by thin-layer chromatography. The volatile materials were
removed under reduced pressure and the residue was purified
by flash column chromatography (SiO2, hexane:ethyl acetate =
8: 1) to afford the pure products 3a-i.
N-Benzyl-4-vinylbenzamide (3f). Amide 3f (0.15 g, 0.63 mmol)
was synthesized following the general procedure. White solid;
mp 116-117 °C; IR (KBr) 3280, 3261, 3082, 3030, 2922, 1641,
palladium-catalyzed reaction of iodobenzene, phenylcarba-
moylation products 4 were obtained in 46% yield as a
mixture of syn and anti stereoisomers along with benzamide
3a and a small amount of 2-carbamoylnorbornane 5.16 The
fact that not benzoyl- but carbamoylnorbornane was ob-
tained suggests that the reaction proceeds via carbamoylpal-
ladium intermediate (path B in Scheme 1) although there is
still a possibility to form product 4 via CO insertion to the
norbornanylpalladium intermediate.
1564, 1502, 1454, 1427, 1357, 1323, 1246, 1078, 856, 700 cm-1
;
1H NMR (CDCl3, 500 MHz) δ 4.62 (d, J = 6.0 Hz, 2H), 5.35 (d,
J = 11.0 Hz, 1H), 5.82 (d, J = 17.5 Hz, 1H), 6.62 (br s, 1H), 6.73
(dd, J = 11.0, 17.5 Hz, 1H), 7.27-7.35 (m, 5H), 7.43 (d, J = 8.5
Hz, 2H), 7.76 (d, J = 8.0 Hz, 2H); 13C NMR (CDCl3, 125 MHz)
δ (ppm) 44.0, 116.0, 126.2, 127.3, 127.5, 127.8, 128.7, 133.3,
135.9, 138.2, 140.6, 167.0; ESI-HRMS found m/z 238.1221,
calcd for C16H16NO (M þ H)þ 238.1232.
Acknowledgment. We thank Nanyang Technological
University for generous financial support.
(16) If the reaction proceeds via phenylpalladation of norbornene fol-
lowed by reductive elimination, cis-exo stereoisomer should be obtained. For
cis-exo addition in palladium-catalyzed arylacylation of norbornene, see:
Yamane, M.; Kubota, Y.; Narasaka, K. Bull. Chem. Soc. Jpn. 2005, 78, 331.
The mechanism of the formation of the trans-stereoisomer of 4 and 2-
carbamoylnorbornane 5 is not clear at this stage. Further experimental
investigations are necessary to make it clear.
Supporting Information Available: General experimental
procedures for the synthesis of compounds 3 and spectral data
for all compounds. This material is available free of charge via
the Internet at http://pubs.acs.org.
J. Org. Chem. Vol. 74, No. 21, 2009 8335