Carbon monoxide free aminocarbonylation of aryl and alkenyl iodides using DMF as an amide source

Article abstract of DOI:10.1021/ol026236k

(figure presented) R = aryl or alkenyl Palladium-catalyzed coupling reaction of N,N-dimethylformamide with aryl or alkenyl halides successfully proceeded in the presence of phosphoryl chloride to afford the corresponding tertiary amides in good yields.

Full text of DOI:10.1021/ol026236k

ORGANIC
LETTERS
2002
Vol. 4, No. 17
2849-2851
Carbon Monoxide Free
Aminocarbonylation of Aryl and Alkenyl
Iodides Using DMF as an Amide Source
,†
Kazushi Hosoi,† Kyoko Nozaki,*†,‡,1 and Tamejiro Hiyama*
Department of Material Chemistry, Graduate School of Engineering,
Kyoto UniVersity, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan, and
PRESTO, JST, Honcho, 4-1-8, Kawaguchi, Saitama 332-0012, Japan
nozaki@chembio.t.u-tokyo.ac.jp
Received May 23, 2002
ABSTRACT
Palladium-catalyzed coupling reaction of N,N-dimethylformamide with aryl or alkenyl halides successfully proceeded in the presence of phosphoryl
chloride to afford the corresponding tertiary amides in good yields.
In 1974, Heck reported the synthesis of amides from aryl,
heterocyclic, and alkenyl halides by the reaction with primary
or secondary amines and carbon monoxide catalyzed by Pd
species.2-5 Later, Yamamoto et al. found the double carbon-
ylation of aryl halides afforded R-keto amides and studied
comprehensively the mechanistic aspects of both single- and
double-carbonylative amide formations.6,7 Recently, Indolese
et al. have reported that formamides are employable as the
amine source in the palladium-catalyzed aminocarbonylation
to give primary amides.8 All the precedents utilized carbon
monoxide as the carbonyl source, and the reactions were
carried out under a CO atmosphere. Here, we report the first
example of CO-free aminocarbonylation of aryl and alkenyl
halides. In the presence of Pd catalyst, the coupling reaction
of aryl and alkenyl iodides with N,N-dimethylformamide
(DMF) produces the corresponding aromatic amides in one
step (Scheme 1). The use of phosphoryl chloride (POCl3) as
an additive is the key for the success.
Scheme 1. Aminocarbonylation of Aryl and Alkenyl Iodide
with N,N-Dimethylformamide
† Kyoto University.
‡ JST.
(1) Present Address: Department of Chemistry and Biotechnology,
Graduate School of Engineering, The University of Tokyo, Hongo, Bunkyo-
ku 113-8656 Japan.
(2) Heck, R. F. In Palladium Reagents in Organic Synthesis; Academic
Press: London, 1985; p 352.
(3) Tsuji, J. In Palladium Reagents and Catalysts; John Wiley and Sons
Ltd: Chichester, 1995; p 188.
(4) Schoenberg, A.; Heck, R. F. J. Org. Chem. 1974, 39, 3327.
(5) Aryl chlorides are also applicable to the amide formation: Perry, R.
J.; Wilson, B. D. J. Org. Chem. 1996, 61, 7482.
In the presence of Pd2(dba)3, 4-iodobenzotrifluoride (1a)
was heated with 2 mol of POCl3 in DMF for 24 h to give
N,N-dimethyl-(4-trifluoromethyl)benzamide (2a). In the ab-
sence of POCl3, homocoupling product 3a was obtained in
12% yield, and most of 1a remained unchanged. When aryl
iodide 1a was treated with POCl3 in the absence of Pd
catalyst, no reaction took place. The use of 1 equiv of POCl3
(6) (a) Ozawa, F.; Yamamoto, A. Chem. Lett. 1982, 865. (b) Ozawa, F.;
Soyama, H.; Yamamoto, T.; Yamamoto, A. Tetrahedron Lett. 1982, 23,
3383. (c) Ozawa, F.; Soyama, H.; Yanagihara, I.; Aoyama, H.; Takino, K.;
Izawa, T.; Yamamoto, T.; Yamamoto, A. J. Am. Chem. Soc. 1985, 107,
3235. (d) Yamamoto, A. Bull. Chem. Soc. Jpn. 1995, 68, 433.
(7) Kobayashi, T.; Tanaka, M. J. Organomet. Chem. 1982, 233, C64.
(8) Schnyder, A.; Beller, M.; Mehltretter, G. Nsenda, T.; Studer, M.;
Indolese, A. F. J. Org. Chem. 2001, 66, 4311.
10.1021/ol026236k CCC: $22.00 © 2002 American Chemical Society
Published on Web 07/24/2002

with 1a retarded the reaction. Both reaction at lower
temperatures and use of other Lewis acids such as BF3‚OEt2,
SnCl4, or TiCl4 were futile. The reaction is specific for DMF,
and no coupling product was obtained with N,N-dimethyl-
acetamide, N-methylformamide, formamide, benzaldehyde,
or butyl formate.
iodide can be converted to an amide group, selectively (entry
6). 1-Iodonaphthalene (1g) and alkenyl iodide 1h also gave
the corresponding amides (entries 7 and 8).
An admixture of DMF and POCl3 is known to produce
imminium salt [Me2N+dCHCl]‚[Cl2P(dO)O-] (Vilsmeier
reagent).10 Also, oxidative addition of aryl halide to Pd(0)
is likely to take place affording arylpalladium halide under
the reaction conditions.11 Thus, we consider the reaction
proceeds via the Heck-type addition of aryl halides to an
imminium species as shown in Scheme 2. Recently, Ishiyama
Various aryl iodides are applicable to the reaction. The
results are summarized in Table 1.9 The aminocarbonylation
Table 1. Aminocarbonylation of Organic Halides in DMF
Using Phosphoryl Chloridea
Scheme 2. Probable Mechanism for the Aminocarbonylation:
Heck-Type Addition of Aryl Halide to C-N Double Bond and
â-Hydride Elimination
and Hartwig reported the Rh-catalyzed Heck-type addition
of aryl halides to N-pyrazylaldimines.12 They describe that
the existence of the neighboring nitrogen atom13 is essential
for the carbon-nitrogen double bond to insert into the aryl-
rhodium bond. Unlike their studies, the Heck-type addition
of aryl-palladium, to an imminium in our case, did not
require the neighboring effect. This may be attributed to the
higher electrophilicity of an imminium than an imine.
Two other possible mechanisms are drawn in Scheme 3.
One is the neucleophilic addition of an arylpalladium halide
to a Lewis acid activated DMF to form a palladium alkoxide
followed by â-hydride elimination.14 Another one is the
oxidative addition of a C-H bond of DMF15 followed by
exchange process yielding Ar-Pd-CONMe2, which pro-
vides the product amide via reductive elimination. Instead
of the exchange, insertion of Ar-X to Ar-Pd-CONMe2 to
afford Pd(IV) might be an alternative precursor for the
a The reactions were performed using 1 (0.3 mmol), Pd2(dba)3 (2.5 mol
%), POCl3 (0.6 mmol), and DMF (3 mL) at 120 °C, unless otherwise stated.
b The reaction was carried out using 0.1 mmol of 1a. c Including 13% of
isomers (determined by GCMS).
proceeded smoothly for iodobenzenes bearing either an
electron-withdrawing or an electron-donating group at the
para position (entries 2-4). The substituent at the ortho
position does not affect the reaction (entry 5). Aryl bromides
are inert against the current aminocarbonylation, and thus,
(10) (a) Vilsmeier, A.; Haack, A. Chem. Ber. 1927, 60, 119. (b) James,
P. N. In Organic Syntheses; Wiley and Sons: New York, 1963; Collect.
Vol. IV, p 539.
(11) Examples of oxidative addition of Ar-I to Pd(0): a) Fitton, B. P.;
Johnson, M. P.; McKeon, J. E. J. Chem. Soc., Chem. Commun. 1968, 6.
See also ref 2.
(12) Ishiyama, T.; Hartwig, J. J. Am. Chem. Soc. 2000, 122, 12043.
(13) Jun, C.-H.; Hong, J.-B. Org. Lett. 1999, 1, 887.
(9) Representative Procedure. A typical procedure for the aminocar-
bonylation is as follows. To a mixture of ethyl 4-iodobenzoate (1b, 82.8
mg, 0.30 mmol) and Pd2(dba)3 (6.9 mg, 15 mmol of Pd) in DMF (3 mL)
was added POCl3 (92.0 mg, 0.60 mmol), and the mixture was heated at
120 °C for 10 h. After aqueous workup, the crude mixture was purified by
silica gel column chromatography (hexane/AcOEt ) 3/1) to obtain N,N-
dimethyl-(4-ethoxycarbonyl)benzamide (2b) in 72% yield.
(14) (a) Quan, L. G.; Lamrani, M.; Yamamoto, Y. J. Am. Chem. Soc.
2000, 122. 4827. (b) Quan, L. G.; Gevorgyan, V.; Yamamoto, Y. J. Am.
Chem. Soc. 1999, 121, 3545. (c) Gevorgyan, V.; Quan, L. G.; Yamamoto,
Y. Tetrahedron Lett. 1999, 40, 4089.
(15) (a) Tatsumi, T.; Tominaga, H.; Hidai, M.; Uchida, Y. J. Organomet.
Chem. 1981, 215, 67. (b) Tsuji, Y.; Yoshii, S.; Ohsumi, T.; Kondo, T.;
Watanabe, Y. J. Organomet. Chem. 1987, 331, 379.
2850
Org. Lett., Vol. 4, No. 17, 2002

key reaction, butyl formate, which has similar formyl group,
would have given the product. The fact that no reaction was
observed either with benzaldehyde or butyl formate may
suggest that the formation of highly electrophilic species,
the Vilsmeier reagent in this case, is essential for the reaction
to take place. It should be noted that, in all the three
mechanisms mentioned above, conventional examples require
the existence of base to regenerate Pd(0) species from
H-Pd-X, although the conditions we employed do not
contain any base.
Scheme 3. Two Other Possible Mechanisms: (i) Nucleophilic
Addition of Arylpalladium to a Carbonyl Activated by a Lewis
Acid and (ii) Oxidative Addition of Formyl C-H Followed by
an Exchange Process
In conclusion, here we have reported the efficient single-
step synthesis of arylcarboxamides from aryl halides and
DMF. The reaction proceeds in the absence of carbon
monoxide unlike the precedent aminocarbonylation reactions.
Acknowledgment. We acknowledge financial support
from the Ministry of Education, Science, Sports and Culture,
Japan. T.H. is thankful for a Grant-in-Aid for COE Research
on Elements Science, No. 12CE2005.
reductive elimination of amide.16,17 Here, if the reaction
involved a nucleophilic addition of arylpalladium, the more
electrophilic aldehyde would be more reactive. Meanwhile,
if the C-H activation of the formyl group of DMF were the
Supporting Information Available: Experimental pro-
cedures and characterization of products. This material is
available free of charge via the Internet at http://pubs.acs.org.
(16) (a) Meegalla, S. K.; Taylor, N. J.; Rodrigo, R. J. Org. Chem. 1992,
57, 2422. (b) Larock, R. C.; Doty, M. J. J. Org. Chem. 1993, 58, 4579.
(17) Satoh, T.; Itaya, T.; Miura, M.; Nomura, M. Chem. Lett. 1996, 823.
OL026236K
Org. Lett., Vol. 4, No. 17, 2002
2851