Pd(II)- and Pd(0)-cocatalyzed reactions of sulfonamides with MCPs

Article abstract of DOI:10.1021/ol034146p

(Matrix presented) MCPs can efficiently react with sulfonamides in the presence of Pd(0) and Pd(II) catalysts to give the corresponding ring-opened products in high yields.

Full text of DOI:10.1021/ol034146p

ORGANIC
LETTERS
2003
Vol. 5, No. 8
1225-1228
Pd(II)- and Pd(0)-Cocatalyzed Reactions
of Sulfonamides with MCPs
,†
Min Shi,* Yu Chen,‡ and Bo Xu†
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Science, 354 Fenglin Lu, Shanghai 200032, China,
and Department of Chemistry, East China Normal UniVersity,
3663 Zhong Shan Bei Lu, Shanghai 200062, China
mshi@pub.sioc.ac.cn
Received January 26, 2003
ABSTRACT
MCPs can efficiently react with sulfonamides in the presence of Pd(0) and Pd(II) catalysts to give the corresponding ring-opened products in
high yields.
Methylenecyclopropanes (MCPs) 1 are highly strained but
readily accessible molecules that have served as useful
building blocks in organic synthesis. MCPs 1 undergo a
variety of ring-opening reactions because the relief of ring
strain provides a potent thermodynamic driving force.1
Recently, reactions of MCPs with various reactants, catalyzed
by transition metals such as Pd, Rh, Ru, and Pt, have attracted
much attention.2 Among them the Pd(0)- or Pd(II)-catalyzed
reactions hold first place.3 In this paper, we wish to report
an unprecedented Pd(0)- and Pd(II)-cocatalyzed ring-opening
reaction of MCPs 1 with sulfonamides.
During our own investigations on the ring-opening reaction
of MCPs 1 (3.0 equiv) with sulfonamides 2 (1.0 equiv), we
found that either Pd(0) catalyst (5 mol %) [Pd(PPh3)4, Pd2-
(dba)3] with PPh3 (40 mol %) or Pd(II) catalyst (5 mol %)
{Pd(OH)2, Pd(OAc)2, Pd(PPh3)2Cl2, [(η3-allyl)PdCl]2} with
PPh3 (40 mol %) or dppp (12.5 mol %) cannot promote the
reaction of MCP 1a with sulfonamide 2a in toluene or 1,2-
dimethoxyethane (DME) under reflux within 24 h (Table 1,
entries 2-7). A hydropalladation catalytic system [Pd2(dba)3,
HCO2H] developed by Trost for the cycloisomerization of
enynes showed no activity for this reaction (Table 1, entries
8 and 9).4 However, in the coexistence of Pd(0) and Pd(II)
catalyst such as Pd(OH)2/C (5 mol %) and Pd(PPh3)4 (10
mol %) with PPh3 (40 mol %) or Pd(OAc)2 (5 mol %) and
Pd(PPh3)4 (10 mol %) with PPh3 (40 mol %), the reaction
proceeds smoothly to give the corresponding ring-opening
† Chinese Academy of Science.
‡ East China Normal University.
(1) (a) Synthesis of MCPs: Brandi, A.; Goti, A. Chem. ReV. 1998, 98,
598. (b) Carbocyclic Three-Membered Ring Compounds; de Meijere, A.,
Ed.; Houben-Weyl: Thieme, Stuttgart, 1996;
(2) For a recent review, see: Nakamura, I.; Yamamoto, Y. AdV. Synth.
Catal. 2002, 344, 111.
(3) For Pd(0)- or Pd(II)-catalyzed ring-opening reactions, please see: (a)
Nu¨ske, H.; Notlemeyer, M.; de Meijere, A. Angew. Chem., Int. Ed. 2001,
40, 3411. (b) Nakamura, I.; Oh, B.-H.; Saito, S.; Yamamoto, Y. Angew.
Chem., Int. Ed. 2001, 40, 1298. (c) Oh, B.-H.; Nakamura, I.; Saito, S.;
Yamamoto, Y. Tetrahedron Lett. 2001, 42, 6203. (d) Fournet, G.; Balme,
G.; Gore´, J. Tetrahedron 1988, 44, 5809. (e) Bra¨se, S.; de Meijere A. Angew.
Chem., Int, Ed. Engl. 1995, 34, 2545. (f) Lautens, M.; Meyer, C.; Lorenz,
A. J. Am. Chem. Soc. 1996, 118, 10676. (g) Tsukada, N.; Shibuya, A.;
Nakamura, I.; Yamamoto, Y. J. Am. Chem. Soc. 1997, 119, 8123. (h)
Tsukada, N.; Shibuya, A.; Nakamura, I.; Kitahara, H.; Yamamoto, Y.
Tetrahedron 1999, 55, 8833. (i) Nakamura, I.; Saito, S.; Yamamoto, Y. J.
Am. Chem. Soc. 2000, 122, 2661. (j) Nakamura, I.; Itagaki, H.; Yamamoto,
Y. J. Org. Chem. 1998, 63, 6458. (k) Camacho, D. H.; Nakamura, I.; Saito,
S.; Yamamoto, Y. Angew. Chem., Int. Ed. 1999, 38, 3365. (l) Suginome,
M.; Matsuda, T.; Ito, Y. J. Am. Chem. Soc. 2000, 122, 11015. (m) Binger,
P.; B ch, H. M. Top. Curr. Chem. 1987, 135, 77. (n) Ohta, T.; Takaya, H.
In ComprehensiVe Organic Chemistry; Trost, B. M., Fleming, I., Paquette,
L. A., Eds.; Pergamon Press: Oxford, 1991; Vol 5, pp 1185-1205. (o)
Lautens, M.; Klute, W.; Tam, W. Chem. ReV. 1996, 96, 49. (p) Zuber, R.;
Carlens, G.; Haag, R.; de Meijere, A. Synlett 1996, 542.
(4) (a) Trost, B. M.; Lee, D. C.; Rise, F. Tetrahedron Lett. 1989, 30,
651. (b) Trost, B. M.; Li, Y. J. Am. Chem. Soc. 1996, 118, 6625. (c) Trost,
B. M.; Krische, M. J. Synlett 1998, 1.
10.1021/ol034146p CCC: $25.00 © 2003 American Chemical Society
Published on Web 03/28/2003

Table 1. Reaction of MCP 1a with TsNH2 Catalyzed by
Table 2. Reaction of MCPs 1 with TsNH2 Catalyzed by
Various Pd Catalysts (5 mol %) with PPh3 (40 mol %)
Pd(PPh3)4 and Pd(OAc)2 Catalysts
yield (%)f
entry
catalyst
3a
4a
1
2
3
4
5
6
7a
8
9
Pd2(dba)3
Pd(PPh3)4
Pd(PPh3)2Cl2
Pd(OH)2/C
Pd(OAc)2
[(η3-allyl)PdCl]2 (5 mol %) + dppp (12.5 mol %)
Pd2(dba)3 (2.5 mol %) + HCO2H (0.5 eq)
Pd2(dba)3 (2.5 mol %) + HCO2H (0.5 eq) +
PPh3 (5 mol %)
10b
11c
12d
13d
14e
Pd(OH)2/C + Pd(PPh3)4
Pd(OAc)2 + Pd(PPh3)4
Pd(OAc)2 + Pd(PPh3)4
Pd(OH)2/C + Pd(PPh3)4
100
100
100
100
71
a Isolated yields.
Pd(OH)2/C + Pd(PPh3)4
28
ring-opened products 3 and 4 in good yields within short
reaction times (Table 2, entries 1-7). For MCP 1e, the
reaction should be carried out at lower temperature (90 °C)
to get 3 in high yield (Table 2, entries 4 and 5). Except for
1e, N,N-dialkylated product 4 was obtained as major product.
a The reaction was carried out in DME under reflux in the presence of
dppp. b The reaction was carried out for 5 h in toluene under reflux. c The
reaction was carried out for 3 h in toluene under reflux. d 10 mol % of
PPh3 was employed, and the reaction was completed within 6 h. e The
reaction was carried out for 8 h in the absence of PPh3. f Isolated yields.
1
The structures of 3 and 4 were established by by the H
and 13C NMR spectroscopic data (Supporting Information)
and X-ray analysis. The X-ray crystal structure of 4a is
shown in Figure 1.6
product 4a quantitatively within 3 or 5 h (Table 1, entries
10 and 11). Considering the fact that a combination of Pd-
(OAc)2 and PPh3 is routinely used to generate a PPh3-
modified Pd(0) species for synthetic reactions, it is not clear
that Pd(OAc)2 remains as it is in the reaction mixture. Thus,
we checked the amount of PPh3 on this reaction. In this
reaction system, the addition of PPh3 is required in order to
get 4a in high yields within a shorter reaction time.5
However, the amount of PPh3 can be reduced to 10 mol %
and give results similar to those with 40 mol % of PPh3
(Table 1, entries 12 and 13). In the absence of PPh3, 3a and
4a were obtained in 28% and 71%, respectively, after 8 h
under the same conditions (Table 1, entry 14). In addition,
there is no report to clarify that the combination of Pd(OH)2
with PPh3 can give a Pd(0) species. It was found that the
ring-opening reaction of MCP 1a with sulfonamide 2a
cocatalyzed by Pd(OH)2/C and Pd(PPh3)4 with PPh3 gave
results the same as those of Pd(OAc)2 and Pd(PPh3)4 with
PPh3 (Table 1, entries 10 and 11; entries 12 and 13). On the
basis of the above investigations, the catalytic ability of this
mixed valence of the Pd catalytic system might be related
with the Pd(II) catalyst [Pd(OAc)2 or Pd(OH)2].
Figure 1. X-ray crystal structure of 4a.
The product ratio of 3 and 4 cannot be adjusted by the
reactant ratio because in the reaction of 1a (1.0 equiv) with
2a (1.0 equiv) under the same conditions, 4a was obtained
as a major product as well, whereas 3a can be produced as
the major product if the reaction time is shortened (Scheme
1).
By means of this Pd(0)- and Pd(II)-cocatalyzed reaction
system, it was found that the other MCPs 1b-g (3.0 equiv)
also can react with 2a (1.0 equiv) to afford the corresponding
(5) In the absence of PPh3, the precipitation of black Pd metal was
observed during reaction.
1226
Org. Lett., Vol. 5, No. 8, 2003

previously existed in the reaction system. This in situ formed
Pd(II) species is more active and reacts quickly with MCPs
1 activated by weak Lewis acid Pd(II) [Pd(OAc)2 or Pd-
(OH)2] catalyst to give the corresponding ring-opened
products.
Scheme 1. Pd(0)- and Pd(II)-Cocatalyzed Ring-Opening
Reaction of 1a with 2a at 90 °C
Scheme 2 Plausible Reaction Mechanism for Pd(II)- and
We further confirmed that in the combination of Pd-
(OH)2/C and Pd(PPh3)4 with PPh3 for other substrates, similar
results were obtained (Table 3, entries 1-4).
Pd(0)-Cocatalyzed Reactions
Table 3. Reaction of MCPs 1 with TsNH2 Catalyzed by
Pd(PPh3)4 and Pd(OH)2/C Catalyst
The concept of using transition metal and Lewis acid
cocatalysts has been reported before.9 In this reaction system,
we tried the Pd(PPh3)4 (10 mol %) and Sn(OTf)2 or Sc(OTf)3
(5 mol %) cocatalytic system,10 but no reaction occurred in
the presence of these bimetallic systems.
a Isolated yields.
13C NMR studies of a 1:1 mixture of 1a and Pd(OAc)2 in
[d6]benzene at room temperature were carried out. In the
absence of Pd(OAc)2, the olefinic carbon signals of 1a
appeared at δ 124.486 and 130.531, while the downfield shift
of olefinic carbon within the cyclopropane at δ 124.509 and
upfield shift of olefinic carbon connecting to the phenyl
groups at δ 130.523 in 1a were observed in the presence of
Pd(OAc)2. Because of the poor solubility of Pd(OAc)2 in
[d6]benzene at room temperature, we also carried out the
13C NMR studies of a 1:1 mixture of 1a and Pd(OAc)2 in
[d6]benzene at 70 °C. In the absence of Pd(OAc)2, the olefinic
carbon of 1a appeared at δ 124.356 and 130.689, whereas
the upfield shift of olefinic carbon connecting to cyclopro-
pane at δ 124.195 and downfield shift of olefinic carbon
connecting to phenyl group at δ 130.906 in 1a were observed
in the presence of Pd(OAc)2. Using CDCl3, which can easily
This is a very unusual phenomenon in Pd chemistry. To
the best of our knowledge, no such mixed valence Pd-
cocatalyzed system has been disclosed before. Recently
Yamamoto’s group revealed that a Pd(II) catalyst exhibits
dual roles: it can act simultaneously as a Lewis acid and as
a transition metal catalyst in the synthesis of cyclic alkenyl
ethers from acetylenic aldehydes.7 On the basis of this new
concept, we can conclude that in this novel catalytic system,
the Pd(II) complex acted as a Lewis acid and the Pd(0)
complex as a transition metal catalyst. A conceivable
mechanism of the present reaction is elucidated in Scheme
2. This is a simple Pd(0)-catalyzed reaction that has been
disclosed in previous papers.3i,j Pd(II) [Pd(OAc)2 or Pd(OH)2]
acted as a weak Lewis acid to help the ring opening of
cyclopropane and subsequently accelerate the reaction.8 We
believe that Pd(II) species from Pd(0) with sulfonamides is
different from Pd(II) catalyst [Pd(OAc)2 or Pd(OH)2] that
(8) Lewis acid catalyzed ring-opening reaction of MCPs has been
disclosed by our group: (a) Shi, M.; Xu, B. Org. Lett. 2002, 4, 2145. (b)
Shi, M.; Chen, Y.; Xu, B.; Tang, J. Tetrahedron Lett. 2002, 43, 8019. On
the other hand, Kilburn reported Lewis acid mediated cascade reactions of
silyl-substituted methylenecyclopropane with ketones and aldehydes: (c)
Peron, G. L. N.; Kitteringham, J.; Kilburn, J. D. Tetrahedron Lett. 2000,
41, 1615. (d) Peron, G. L. N.; Norton, D.; Kitteringham, J.; Kilburn, J. D.
Tetrahedron Lett. 2001, 42, 347. (e) Patient, L.; Berry, M. B.; Kilburn, J.
D. Tetrahedron Lett. 2003, 44, 1015.
(9) (a) Sawamura, M.; Sudoh, M.; Ito, Y. J. Am. Chem. Soc. 1996, 118,
3309. (b) Kamijo, S.; Yamamoto, Y. Angew. Chem., Int, Ed. 2002, 41,
3230. (c) Ikeda, S.-i.; Mori, N.; Sato, Y. J. Am. Chem. Soc. 1997, 119,
4779.
(6) The crystal data of 4a has been deposited in CCDC with number
178988. Empirical formula: C39H37NO2S. Formula weight: 583.76. Crystal
color, habit: colorless, prismatic. Crystal dimensions: 1.368 × 0.288 ×
0.151 mm3. Crystal system: monoclinic; lattice type: primitive. Lattice
parameters: a ) 9.4257(8) Å, b ) 23.866(2) Å, c ) 14.1584(12) Å, R )
90°, â ) 91.312(2)°, γ ) 90°, V ) 3184.1(5) Å3. Space group: P2(1)/c;
Z ) 4; Dcalc ) 1.218 g/cm3; F000 ) 1240. Diffractometer: Rigaku AFC7R.
Residuals: R, Rw: 0.0464, 0.0481.
(7) Asao, N.; Nogami, T.; Takahashi, K.; Yamamoto, Y. J. Am. Chem.
Soc. 2002, 124, 764.
(10) Sn(OTf)2 is the best Lewis acid for ring-opening reactions of MCPs
1 with alcoholic and aromatic amino nucleophiles.8a,b
Org. Lett., Vol. 5, No. 8, 2003
1227

dissolve Pd(OAc)2 at room temperature, as a solvent, a
relatively obvious chemical shift was observed from δ
124.376 to 124.338 and δ 129.902 to 129.833. All the 13C
NMR charts have been elucidated in Supporting Information.
These results may indicate that Pd(II) such as Pd(OAc)2 can
be potentially coordinated by olefinic moiety in MCPs,
although the observed chemical shift differences are small.
To confirm the mechanism shown in Scheme 2, the ring-
opening reaction of MCP 1a with deuterated p-toluene-
sulfonamide TsND2 (D content 75%) was performed.11 The
reaction of 1a with TsND2 under the same conditions as
above afforded 4a-d in 100% yield in which the deuterium
content at the C-1 position was 51% yield (Scheme 3).
Scheme 4 Synthesis of Allylic Amines
Scheme 3 Reaction of TsND2 with 1a
via denitrobenzenesulfonylation using thiophenol under basic
conditions (Scheme 4).13 Thus, this novel catalytic reaction
provides an alternative synthetic method for the preparation
of allylic amines under mild conditions.
In conclusion, during our investigation on the ring-opening
reactions of MCPs 1, we found that Pd(0) and Pd(II) can
efficiently cocatalyze the reaction of MCPs 1 with sulfona-
mides 2 to give high yields of the corresponding ring-opened
products 3 and 4. Perhaps the catalytic system presented here
may be applicable to a wide range of Pd-catalyzed trans-
formations. Efforts are underway to elucidate the mechanistic
details of this catalytic system and to identify systems
enabling the acceleration of reaction rate under the same
conditions and subsequent transformation thereof.
Deuterium incorporation did not occur at the other carbon
of 4a. The result supports the Markovnikov hydropalladation
mechanism elucidated in Scheme 2.
In this catalytic system, these other sulfonamides 2b-d
also smoothly reacted with MCPs 1 to give the ring-opened
products in very high yields (Table 4).
Acknowledgment. We thank the State Key Project of
Basic Research (Project 973) (no. G2000048007), Shanghai
Municipal Committee of Science and Technology, and the
National Natural Science Foundation of China for financial
support (20025206 and 20272069).
Table 4. The Reaction of MCP 1a with RSO2NH2 Catalyzed
by Pd(0) and Pd(II) Catalyst
Supporting Information Available: Spectroscopic data
(1H and 13C NMR) of the compounds in Tables 1-4 and
Scheme 4 and detailed descriptions of experimental proce-
dures. This material is available free of charge via the Internet
at http://pubs.acs.org.
yield (%)a
entry
RSO2NH2
temp (°C)
5
6
OL034146P
1
2
3
CH3SO2NH2 2b
p-NO2C6H4SO2NH2 2c
m-NO2C6H4SO2NH2 2b
110
120
120b
5b (91)
6c (100)
(11) TsND2 was prepared according to the literature: (a) Smith, J. K.;
Bergbreiter, D. E.; Newcomb, M. J. Org. Chem. 1985, 50, 4549. (b) Inbar,
S.; Linschitz, H.; Cohen, S. G. J. Am. Chem. Soc. 1981, 103, 1048. Please
also see ref 3j.
5d (60)
a Isolated yields. b The reaction time is 48 h.
(12) (a) Prashad, M. J. Med. Chem. 1993, 36, 631. (b) Stutz, A. Angew.
Chem., Int. Ed. Engl. 1987, 26, 320. (c) Vedejs, E.; Gingras, M. J. Am.
Chem. Soc. 1994, 116, 579. (d) Kadota, I.; Kawada, M.; Muramatsu, Y.;
Yamamoto, Y. Tetrahedron: Asymmetry 1997, 8, 3887.
(13) Fukuyama, T.; Jow, C.-K.; Cheung, M. Tetrahedron Lett. 1995, 36,
6373.
By means of this ring-opening reaction, various allylic
amines, which are useful as intermediates and have signifi-
cant physiological properties,12 can be exclusively produced
1228
Org. Lett., Vol. 5, No. 8, 2003