Cul/N,N-dimethylglycine-catalyzed coupling of vinyl halides with amides or carbamates

Article abstract of DOI:10.1021/ol049464i

Matrix presented. The Cul-catalyzed coupling reaction of vinyl halides with amides or carbamates proceeds well at room temperature to 80°C in dioxane to give enamides using N,N-dimethylglycine as the promoter and Cs ₂CO₃ as the base.

Full text of DOI:10.1021/ol049464i

ORGANIC
LETTERS
2004
Vol. 6, No. 11
1809-1812
CuI/N,N-Dimethylglycine-Catalyzed
Coupling of Vinyl Halides with Amides
or Carbamates
,‡
Xianhua Pan,† Qian Cai,‡ and Dawei Ma*
Department of Chemistry, Fudan UniVersity, Shanghai 200433, China,
and State Key Laboratory of Bioorganic and Natural Products Chemistry,
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
354 Fenglin Lu, Shanghai 200032, China
madw@pub.sioc.ac.cn
Received March 22, 2004
ABSTRACT
The CuI-catalyzed coupling reaction of vinyl halides with amides or carbamates proceeds well at room temperature to 80 °C in dioxane to give
enamides using N,N-dimethylglycine as the promoter and Cs2CO as the base. The geometry of the C−C double bond is retained during the
3
reaction course.
Enamides are unique functional groups present in many
natural products discovered during the past decades, which
include protease inhibitors TMC-95-A-D,1 sedative and
antiinflammatory peptide frangufoline,2 cytotoxic agents
aspergillamides,3 chondriamides,4 as well as salicylihalamide
A and related compounds.5 In addition, enamides have found
a great deal of usage in the preparation of heterocycles6 and
in asymmetric synthesis of amides and amino acids.7 It is
not surprising then that synthetic interest in this target has
been considerable.6,8-11 Among the emerging methods,
copper-catalyzed coupling reaction of amides with vinyl
halides has received increasing attention and found applica-
tions in the total synthesis of natural products.9-11 Very
recently, two groups have independently observed that this
(5) (a) Yet, L. Chem. ReV. 2003, 103, 4283. (b) Erickson, K. L.; Beutler,
J. A.; Cardellina, J. H., II; Boyd, M. R. J. Org. Chem. 1997, 62, 8188. (c)
Galinis, D. L.; McKee, T. C.; Pannell, L. K.; Cardellina, J. H., II; Boyd,
M. P. J. Org. Chem. 1997, 62, 8968. (d) Kim, J. W.; Shin-ya, K.; Furihata,
K.; Hayakawa, Y.; Seto, H. J. Org. Chem. 1999, 64, 153. (e) Erickson, K.
L.; Beutler, J. A.; Cardellina, J. H., II; Boyd, M. R. J. Org. Chem. 2001,
66, 1532. (f) Dekker, K. A.; Aiello, R. J.; Hirai, H.; Inagaki, T.; Sakakibara,
T.; Suzuki, Y.; Thompson, J. F.; Yamaguchi, Y.; Kojima, N. J. Antibiot.
1998, 51, 14. (g) Kunze, B.; Jansen, R.; Sasse, F.; Hofle, G.; Reichenbach,
H. J. Antibiot. 1998, 51, 1075.
(6) (a) Fu¨rstner, A.; Dierkes, T.; Thiel, O. R.; Blanda, G. Chem. Eur. J.
2001, 7, 5286. (b) Schultz, A. G.; Guzzo, P. R.; Nowak, D. M. J. Org.
Chem. 1995, 60, 8044. (c) Brodney, M. A.; Padwa, A. J. Org. Chem. 1999,
64, 556. (d) Davies, D. T.; Kapur, N.; Parsons, A. F. Tetrahedron 2000,
56, 3941.
(7) For recent reviews, see: (a) Tang, W.; Zhang, X. Chem. ReV. 2003,
103, 3029. (b) Ma, J.-A. Angew. Chem., Int. Ed. 2003, 42, 4290.
(8) (a) Wang X.; Porco, J. A., Jr. J. Org. Chem. 2001, 66, 8215 and
references therein. (b) Snider, B. B.; Song, F. Org. Lett. 2000, 2, 407. (c)
Fu¨rstner, A.; Brehm, C.; Cancho-Grande, Y. Org. Lett. 2001, 3, 3955. (d)
Tanaka, R.; Hirano, S.; Urabe, H.; Sato, F. Org. Lett. 2003, 5, 67. (e)
Kuramochi, K.; Osada, Y.; Kitahara, T. Chem. Lett. 2002, 128. (f)
Kuramochi, K.; Osada, Y.; Kitahara, T. Tetrahedron 2003, 59, 9447. (g)
Lam, P. Y. S.; Vincent, G.; Bonne, D.; Clark, C. G. Tetrahedron Lett. 2003,
44, 4927. (h) Wallace, D. J.; Klauber, D. J.; Chen, C.-Y.; Volante, R. P.
Org. Lett. 2003, 5, 4749.
† Fudan University.
‡ Shanghai Institute of Organic Chemistry.
(1) Kohno, J.; Koguchi, Y.; Nisshio, M.; Nakao, K.; Kuroda, M.; Shimizu,
R.; Ohnuki, T.; Komatsubara, S. J. J. Org. Chem. 2000, 65, 990.
(2) (a) Tschesche, R.; Last, H. Tetrahedron Lett. 1968, 2993. (b)
Tschesche, R.; Wilhelm, H.; Fehlhaber, H.-W. Tetrahedron Lett. 1972, 2609.
(c) Han, Y. N.; Kim, G.-Y.; Han, H. K.; Han, B. H. Arch. Pharm. Res.
1993, 16, 289.
(3) Toske, S. G.; Jensen, P. R.; Kauffman, C. A.; Fenical, W. Tetrahedron
1998, 54, 13459.
(4) (a) Palermo, J. A.; Flower, P. B.; Seldes, A. M. Tetrahedron Lett.
1992, 33, 3097. (b) Davyt, D.; Entz, W.; Fernandez, R.; Mariezcurrena,
R.; Mombru, A. W.; Saldana, J.; Dominguez, L.; Coll, J.; Manta, E. J. Nat.
Prod. 1998, 61, 1560.
(9) (a) Ogawa, T.; Kiji, T.; Hayami, K.; Suzuki, H. Chem. Lett. 1991,
1443. (b) Shen, R.; Porco, J. A., Jr. Org. Lett. 2000, 2, 1333.
10.1021/ol049464i CCC: $27.50 © 2004 American Chemical Society
Published on Web 04/27/2004

was the first choice for this transformation because N-
monosubstituted amino acids showed a poor ability to
promote this reaction (entries 6-8) and only moderate yield
was observed in case of N,N-dibenzylglycine as the additive
(entry 9). Thus, we concluded that the optimized combination
for this reaction was to use dioxane as the solvent, Cs2CO3
as the base, and N,N-dimethylglycine as the additive. Further
exploration indicated that, employing this combination, the
reaction still worked well at 60 °C or even at room
temperature by using stoichiomertic amounts of CuI and
additive (entries 10 and 11).
With the optimized condition in hand, we then explored
the scope of this reaction by varying vinyl halides, amides,
and carbamates. As displayed in Table 2, using the coupling
with 1-iodocyclohexene as a model reaction, both cyclic and
acyclic amides were found suitable substrates (entries 1-3).
Carbamates also worked to give the corresponding vinylation
products 5 and 14 (entries 4 and 17). When cis-type acyclic
vinyl iodides were used, only cis-vinylation products were
isolated (entries 5 and 6), which indicated that the geometry
of the C-C double bond was retained during the reaction
course. Interestingly, coupling of 3-iodo-2-cyclohexenone
with benzamide furnished enamide 8 in 82% yield (entry
7), which implied that this process could be used for
synthesizing a class of potential anticonvulsants.13
Table 1. Coupling Reaction of 1-Iodocyclohexenene with
2-Pyrrolidinone under the Catalysis of CuI and Amino Acidsa
entry
amino acid
base
solvent
yield (%)b
1
2
3
4
5
6
7
8
9
Me2NCH2CO2H‚HCl
Me2NCH2CO2H‚HCl
Me2NCH2CO2H‚HCl
Me2NCH2CO2H‚HCl
Me2NCH2CO2H‚HCl
L-proline
MeHNCH2CO2H
BnHNCH2CO2H
Bn2NCH2CO2H
Me2NCH2CO2H‚HCl
Me2NCH2CO2H‚HCl
Cs2CO3
Cs2CO3
Cs2CO3
K2CO3
KOH
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
toluene
dioxane
DMSO
35
85
50
61
<10
20
21
25
50
85c
78d
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
10
11
a Reaction conditions: CuI (0.1 mmol), amino acid (0.2 mmol),
1-iodocyclohexenene (1 mmol), 2-pyrrolidinone (1.2 mmol), base (2 mmol),
solvent (1 mL), 80 °C, 12 h. b Isolated yield. c Reaction was carried out at
60 °C. d Reaction was carried at rt for 30 h, and CuI (1 mmol) and N,N-
dimethylglycine hydrochloride salt (1 mmol) were used.
To develop an efficient protocol to prepare N-acyl viny-
logous carbamic acids and derivatives, Porco and co-workers
have investigated systematically copper-mediated coupling
reaction of amides with â-iodoacrylates.10c They found that
the reaction yields could be improved by using some
substituted 1,10-phenanthrolines as the additives, while the
diamine ligands were less effective for this reaction. On the
basis of these studies, a mild condition was discovered to
obtain the desired coupling products in moderate to good
yields; however, a drawback is that 3 equiv of amides should
be used to ensure satisfactory yields. Thus, this transforma-
tion became an ideal model to test our catalytic system. To
our delight, heating a mixture of (E)-allyl 3-iodoacrylate (1
mmol) and sorbic amide (1 mmol), CuI (0.1 mmol), N,N-
dimethylglycine hydrochloride salt (0.2 mmol), and Cs2CO3
(2 mmol) in dioxane at 45 °C for 12 h produced the cross-
coupling product 9 in 56% yield (entry 8). By using
stoichiomertic amounts of CuI and N,N-dimethylglycine
hydrochloride salt this reaction even worked at room
temperature to give 9 in 43% yield (entry 9). Similarly, a
coupling reaction using equal molar amounts of (E)-allyl
3-iodoacrylate and 2-pyrrolidinone at the above two condi-
tions afforded enamide 10 in good yields (entries 10 and
11). These yields are almost identical with those obtained
by using a 3-fold excess of amides.10c Furthermore, our
catalytic system was found compatible with the coupling
of methyl cis-3-iodoacrylate with several amides or
carbamides to give the corresponding enamides 11-14 in
good yields at either 60 °C or room temperature (entries 11-
17). Thus, the combination of CuI as the catalyst, N,N-
reaction could be carried out under relatively mild conditions
with the assistance of either N,N′-dimethyl ethylenediamine
or substituted 1,10-phenanthrolines.10 A similar strategy was
used by Colleman and Liu to develop a facile route to the
enamide side chains of salicylihalamide A and related
compounds.11 Herein we wish to describe a new catalytic
system for this transformation, which showed advantage in
some aspects over the existing two systems.
Our previous studies have demonstrated that some amino
acids are excellent promoters for copper-catalyzed Ullmann-
type coupling reactions.12 In Buchwald’s report,10b N,N-
dimethylglycine was reported to be much less active than
N,N′-dimethyl ethylenediamine as an additive for CuI-
catalyzed coupling of 2-pyrrolidinone and 2-methyl-1-
bromopropene. We reasoned that this problem might result
from the solvent they used, and therefore controlled experi-
ments were undertaken. As shown in Table 1, heating a
mixture of 1-iodocyclohexene, 2-pyrrolidinone, Cs2CO3, CuI,
and N,N-dimethylglycine hydrochloride salt in toluene at 80
°C for 12 h gave coupling product 1 in only 35% yield (entry
1). However, it was observed that the yield jumped to 85%
if the solvent was switched to dioxane (entry 2). Changing
the solvent to DMSO or base to K2CO3 and KOH all gave
considerably lower yields (entries 3-5). We next tested other
amino acid additives and found that N,N-dimethyl glycine
(10) (a) Shen, R.; Lin, C. T.; Bowman, E. J.; Bowman, B. J.; Porco, J.
A., Jr. J. Am. Chem. Soc. 2003, 125, 7889. (b) Jiang, L.; Job. G. E.; Klapars,
A.; Buchwald, S. L. Org. Lett. 2003, 5, 3667. (c) Han, C.; Shen, R.; Su, S.;
Porco, J. A., Jr. Org. Lett. 2004, 6, 27.
(11) Coleman, R. S.; Liu, P.-H. Org. Lett. 2004, 6, 577.
(12) (a) Ma, D.; Cai, Q.; Zhang, H. Org. Lett. 2003, 5, 2453. (b) Ma, D.
Cai, Q. Org. Lett. 2003, 5, 3799. (c) Ma, D.; Cai, Q. Synlett 2004, 128. (d)
Zhu, W.; Ma, D. Chem. Commun. 2004, 888. For a related work, see: (e)
Deng, W.; Wang, Y.; Zou, W.; Liu, L.; Guo, Q. Tetrahedron Lett. 2004,
45, 2311.
(13) Foster, J. E.; Nicholson, J. M.; Butcher, R.; Stables, J. P.; Edafiogho,
I. O.; Goodwin, A. M.; Henson, M. C.; Smith, C. A.; Scott, K. R. Bioorg.
Med. Chem. 1999, 7, 2415.
1810
Org. Lett., Vol. 6, No. 11, 2004

Table 2. Coupling Reaction of Vinyl Halides with Amides or Carbamates under the Catalysis of CuI and N,N-Dimethylglycinea
a Reaction conditions: CuI (0.1 mmol), N,N-dimethylglycine HCl salt (0.2 mmol), vinyl halide (1 mmol), amide or carbamate (1 mmol), Cs2CO3 (2
mmol), dioxane (1 mL). b Isolated yield. c Amide (1 mmol) was used. d CuI (1 mmol) and N,N-dimethylglycine hydrochloride salt (1 mmol) were used.
e Product Z/E ) 4/1 corresponding to the starting vinyl bromide Z/E ) 4/1.
dimethylglycine as the additive, Cs2CO3 as the base, and
dioxane as the solvent provided a more practical condition
for preparation of N-acyl vinylogous carbamic acids and
derivatives.
Org. Lett., Vol. 6, No. 11, 2004
1811

When substrates were switched from vinyl iodides to vinyl
bromides, higher reaction temperature was needed to com-
plete the coupling reaction (entries 18-21). When a mixture
of 2-bromo-cis-2-butene and 2-bromo-trans-2-butene was
used, both cis- and trans-products were detected by 1H NMR
in the same ratio (4:1) as the starting material (entry 19).
This result indicated that the geometry of the C-C double
bond was retained in this condition, which was further proved
since only cis-enamide was determined in the coupling of
cis-â-bromostyene (entry 20). More importantly, we observed
that cis-â-bromocinnamic acid methyl ester reacted with a
carbamide to deliver a stereochemically retained product 18
in 63% yield (entry 21), which may be a potential precursor
for asymmetric synthesis of amino acids.7,8h
groups were found to tolerate to this condition, which would
allow the preparation of a variety of enamides. In addition,
the present catalytic system can be easily removed from the
reaction system by simple washing, which makes separation
more convenient. Thus, it should find applications in the
synthesis of biologically and synthetically important enam-
ides.
Acknowledgment. The authors are grateful to the Chinese
Academy of Sciences, National Natural Science Foundation
of China (grants 20321202 and 20132030), and Science and
Technology Commission of Shanghai Municipality (grants
02JC14032 and 03XD14001) for their financial support.
Supporting Information Available: Experimental pro-
cedures and characterization for compounds 1-18. This
material is available free of charge via the Internet at
http://pubs.acs.org.
In summary, we have demonstrated that N,N-dimethyl-
glycine is a powerful promoter for CuI-catalyzed coupling
reactions of vinyl halides with amides or carbamides using
dioxane as the solvent and Cs2CO3 as the base. A wide range
of functional groups such as ketone, ester, and dienoic amide
OL049464I
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Org. Lett., Vol. 6, No. 11, 2004