A study on the electronic effect of reactions of π-allylpalladiums using 2-arylsulfonyloxy-3-chloropropenes with ethyl malonate and their synthetic utilization

Article abstract of DOI:10.1246/cl.2004.1322

We have studied in detail the electronic effect on the reactions of π-allylpalladium with nucleophiles during the reactions of 2-arylsulfonyloxy-3-chloroprop-1-ene with diethyl malonate. The reaction rates increase increasing with the electron-with-drawing effects. We have also shown some synthetic utilization using these 2-arylsulfonyloxyprop-1-enes.

Full text of DOI:10.1246/cl.2004.1322

1322
Chemistry Letters Vol.33, No.10 (2004)
A Study on the Electronic Effect of Reactions of ꢀ-Allylpalladiums
Using 2-Arylsulfonyloxy-3-chloropropenes with Ethyl Malonate
and Their Synthetic Utilization
Kohei Gotoh, Yasutaka Matsuura, Fuminori Hatanaka, Setsuko Sato, Shinzoh Kagabu, and Mitsuhiro Yoshimatsuꢀ
Department of Chemistry, Faculty of Education, Gifu University, Yanagido 1-1, Gifu 501-1193
(Received June 11, 2004; CL-040670)
We have studied in detail the electronic effect on the reac-
tions of ꢀ-allylpalladium with nucleophiles during the reactions
of 2-arylsulfonyloxy-3-chloroprop-1-ene with diethyl malonate.
The reaction rates increase increasing with the electron-with-
drawing effects. We have also shown some synthetic utilization
using these 2-arylsulfonyloxyprop-1-enes.
OTs
OTs
NaCH(CO2Et)2
Pd(PPh3)4
H
Cl
H
CH(CO2Et)2
H
H
2 (73%)
1
OSO2Ar
Cl
H
Ar=p-MeC6H4,p-MeOC6H4,p-ClC6H4,p-BrC6H4,
p-NO2C6H4
Much attention has been paid to the ꢀ-allylpalladium-medi-
ated functionalization due to the ease of activation of an allylic
system by attack of a nucleophile.1 The regio- and stereoselec-
tivities on the C–C bond formation of the ꢀ-allylpalladium have
been found to be affected by the functions of the nucleophile, the
substitution on the allylic moiety and the nature of the ligands on
the palladium.2 ꢀ-Allylpalladiums bearing various functional
groups have been reported; however, an analysis of the electron-
ic factors does not offer an obvious explanation because it is dif-
ficult to separate the electronic effect from the steric factors. It is
of great significance to clarify the effect of the electronic factors
on the ꢀ-allylpalladiums because of their wide utility in regio-
and stereoselective functionalization.3
Recently, Buchwald et al. used arylsulfonates in the fields of
palladium- or nickel-catalyzed synthetic organic chemistry with
aryl and vinyl tosylates to produce C–C bonds4 and C–N bonds.5
The arylsulfonates are less reactive than the usual triflates;6 how-
ever, they are less expensive, thermally stable and easy to han-
dle. Therefore, they are extensively utilized for the biologically
active compounds such as novobiocin I and 20-deoxyguano-
sines.7–10 We are also very interested in new 2-arylsulfonyloxy-
propenes as a good substrate for either clarifying the electronic
factors on the ꢀ-allylpalladiums or for possible utilization in
the Suzuki-type cross-coupling reactions using the simple
Pd(PPh3)4. Herein, we report the findings regarding the electron-
ic factor of the ꢀ-allylpalladiums and their synthetic utilization
using 2-arylsulfonyloxypropenes and their coupling products.
We first selected 3-chloro-2-tosyloxypropene 1 as the repre-
sentative substrate of the palladium-catalyzed coupling reactions
with diethyl malonate/NaH in THF (Scheme 1). The alkylated
product 2 was obtained in 73% yield, accompanied by a small
amount of the dialkylated product. The reactions without a cat-
alyst did not proceed and the propene 1 was mostly recovered.
Next, we prepared various 2-arylsulfonyloxy-3-chloropropenes
bearing some substituents such as chloro, bromo, methoxy,
and nitro groups on the 4-position of the arylsulfonyl group
and performed the coupling reaction of the 2-arylsulfonyloxy-
prop-1-enes with diethyl malonate in the presence of 5 mol %
of tetrakis(triphenylphosphine)palladium at room temperature.
The yields of the coupled products are plotted in Figure 1 for
reaction times of 1–10 h.
H
Scheme 1. Preliminary study of palladium-catalyzed cross-
coupling reaction of 2-tosyloxypropene 1 with diethyl malonate.
80
70
60
MeO
50
Me
40
Cl
30
20
10
0
Br
NO2
0
2
4
6
8
10
12
time (h)
Figure 1. Rates of palladium-catalyzed cross coupling reac-
tions of 2-arylsulfonyloxypropenes.
In Figure 1, the change in the yield vs time shows plateaus at
about 65% for the compound bearing MeO and Me substituents,
and at about 40% for the Cl and Br substituents. In these regions,
the reactions might have been determined by the activity of the
Pd-catalysts. According to previous investigations, we have
shown the plausible mechanisms and considered the electronic
factors in the palladium-catalyzed cross-coupling reactions of
the 2-arylsulfonyloxypropenes. A reasonable reaction intermedi-
ate might be considered to be the cationic bisphosphine complex
3, which is attacked by a highly acidic carbon nucleophile on the
allylic ligand to give the intermediate 4 (Scheme 2). The rates for
the formations of the products were found to be strongly accera-
lated by the electron-donating ability of the aromatic substituent
X. This is attributed to the assumption that the reductive elimi-
nation of the intermediate 3 having the electron-donating sub-
stituents would be faster than that having the electron-withdraw-
ing groups. Recently, Mayr et al. reported a new methodology
for characterizing the electrophiles by two parameters,11 which
are very useful for predicting the rates of the reactions of nucleo-
philes and electrophiles, the inter- or intramolecular selectivities
Copyright Ó 2004 The Chemical Society of Japan

Chemistry Letters Vol.33, No.10 (2004)
1323
and the reaction mechanisms. However, there are few examples
of ꢀ-allylpalladiums bearing different substituents. We could
use the novel allylic palladium intermediates, which are good
candidates to compare the electrophilicities of the allylic cations
without the any steric factors.
formed some transformations into more useful compounds.
The palladium-catalyzed Sonogashira and Stille coupling reac-
tions12 of the 2-p-methoxyphenylsulfonyloxypropene 2 pro-
duced the enyne 7a and diene 7b in good yields, respectively.
The intramolecular cyclization-coupling reactions of the 2-tosyl-
oxy-1,6-enynes prepared from 2 were examined. The yields and
stereoselectivities of the dienes 9b, 9c are excellent and no other
isomers were observed; however, 9a was contaminated with the
Z-isomer (10%).
OSO C H X
2
6
4
OSO C H X
2
6 4
oxidative addition
-
Cl
Cl
Pd
Ph P
PPh
3
3
This work was supported in part by a Grant-in-Aid for
Pharmaceutical Research (# 14572000) from the Ministry of
Education, Culture, Science, Sports, and Technology, Japan.
3
OSO C H X
2
6
4
OSO C H X
nucleophile
2
6
4
Nu
Nu
References and Notes
Pd(PPh )
3 2
1
S. A. Godleski, ‘‘Comprehensive Organic Synthesis,’’ ed. by
B. M. Trost, I. Fleming, and L. A. Paquette, Pergamon, New
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5
4
Scheme 2.
2
alkyl: E. Keinan and M. Sahai, J. Chem. Soc., Chem.
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and A. Virgili, J. Org. Chem., 53, 5328 (1988); ester: D. J.
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Timms, Aust. J. Chem., 30, 2167 (1977); D. A. Hunt, J. M.
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J. Chem., 30, 553 (1977); W. R. Jackson and J. U. G. Strauss,
Tetrahedron Lett., 16, 2591 (1975); nitrile: J. Tsuji, H. Ueno,
Y. Kobayashi, and H. Okumoto, Tetrahedron Lett., 22, 2573
(1981); sulfanyl: S. A. Godleski and E. B. Villhauer, J. Org.
Chem., 49, 2246 (1984); S. A. Godleski and E. B. Villhauer,
J. Org. Chem., 51, 486 (1986); P(O)R2: Z. Zhu and X. Lu,
Tetrahedron Lett., 28, 1897 (1987).
Ar CO2Et
Ph
H
R
H
i
H
CO2Et
CO2Et
6a (Ar=Ph)(98%)
ii
ArSO3
H
6b (Ar=4-ClC6H4)
(95%)
H
CO2Et
7a (58%)
R=CO2Et
H
R
Ar=p-MeC6H4
2
iii
iv
H
OTs
R=SO2Ph
Ar=p-MeOC6H4
H
H
CO2Et
EtO2C
CO2Et
3
4
D. P. Grant, N. W. Murral, and A. S. Welch, J. Organomet.
Chem., 333, 403 (1987).
v
8 (94%)
H
SO2Ph
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Ar
H
H
7b (48%)
H
9a (Ar=Ph) (71%)
9b (Ar=2-MeOC6H4) (92%)
9c (Ar=4-MeOC6H4) (90%)
EtO2C CO2Et
5
6
Scheme 3. Synthetic utilizations of 2-arylsulfonyloxypropenes,
Reagents: (i) ArB(OH)2/5 mol % Pd(PPh3)4/EtOH–benzene;
(ii) phenylacetylene/Pd(PPh3)4/Cul/benzene/rt; (iii) vinyltri-
butyltin/Pd(PPh3)4/LiBr; (iv) proparyl bromide/NaH/DMF/
0 ꢁC; v, ArB(OH)2/5 mol % PdCl2/PPh3/Na2CO3aq/EtOH–
toluene (1:1)/reflux/30 min.
7
8
Next, our attention focused on the synthetic utility based on
the cross-coupling reaction at the enol carbon of 3-chloro-2-p-
toluenesulfonyloxyprop-1-ene 2 with various nucleophiles in
the presence of tetrakis(triphenylphosphine)palladium. First,
we showed the reactions with arylboronic acids as described
in Scheme 3. The reactions cleanly occurred and afforded the
arylated products 6a, 6b in excellent yields. These results
indicate that the 3-chloro-2-tosyloxyprop-1-ene is a good tool
for the three component coupling reactions. Therefore, we fur-
ther investigated the one-pot alkylation–arylation reaction of
the selected 2-tosylate 1 with CH2(CO2Et)2/NaH/PhB(OH)2/
Na2CO3aq. The reaction conditions were investigated in detail
and the product 6a was obtained in 80% yield. We further per-
9
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(2003).
12 W. Scott and J. K. Stille, J. Am. Chem. Soc., 108, 3033
(1986).
Published on the web (Advance View) September 11, 2004; DOI 10.1246/cl.2004.1322