Palladium-catalyzed coupling reactions of diarylvinylidenecyclopropanes with 2-iodophenol and N-(2-iodophenyl)-4-methylbenzenesulfonamide

Article abstract of DOI:10.1002/ejoc.200800955

A palladium-catalyzed cross-coupling reaction of diarylvinylidenecyclopropanes with 2-iodophenol and N-(2-iodophenyl)-4- methylbenzenesulfonamide provided a variety of cyclopropane-containing 2,2-diaryl-3-tetramethylcyclopropylidene-2,3-dihydrobenzofuran

Full text of DOI:10.1002/ejoc.200800955

FULL PAPER
DOI: 10.1002/ejoc.200800955
Palladium-Catalyzed Coupling Reactions of Diarylvinylidenecyclopropanes with
2-Iodophenol and N-(2-Iodophenyl)-4-methylbenzenesulfonamide
Wei Li[a] and Min Shi*[a]
Keywords: Palladium / Cross-coupling / Annulation / Heterocycles / C–C coupling
A palladium-catalyzed cross-coupling reaction of diarylvinyl- ylcyclopropylidene-1-(toluene-4-sulfonyl)-2,3-dihydro-1H-in-
idenecyclopropanes with 2-iodophenol and N-(2-iodo-
phenyl)-4-methylbenzenesulfonamide provided a variety of
cyclopropane-containing 2,2-diaryl-3-tetramethylcyclopro-
dole derivatives in moderate-to-good yields.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
pylidene-2,3-dihydrobenzofuran and 2,2-diaryl-3-tetrameth- Germany, 2009)
Introduction
Results and Discussion
Cyclopropane subunits are extremely important building
The initial examination was performed by using di-
blocks for organic chemistry and also occur in many natu- phenylvinylidenecyclopropane (1a) and 2-iodophenol (2a;
ral products of secondary metabolism.[1,2] Many cyclopro- 3.0 equiv.) as the substrates upon treatment with Pd(PPh3)2-
pane-containing natural compounds have been isolated Cl2 (5 mol-%) in N,N-dimethylformamide (DMF) at
from plants, fungi, or microorganisms, and they show bio- 100 °C in the presence of potassium carbonate (K2CO3,
logical activity, which may serve as potential drug leads or 3.0 equiv.) or cesium carbonate (Cs2CO3, 3.0 equiv.), and
provide new ideas for the study of enzyme mechanisms. It we found that the reaction proceeded smoothly with 60 or
it also known that cyclopropanes can serve as high-energy 56% conversion, respectively, and coupling product 3a was
intermediates in metabolism (e.g., presqualene), as storage obtained in 41 or 18% yield, respectively, within 64 h
elements to release energy-rich compounds (e.g., ethylene (Table 1, entries 1 and 2). The use of Pd0 such as Pd-
from ACC oxidation), or as trigger components to provide (PPh3)4 or Pd2(dba)3 as the catalyst afforded 3a in trace
a driving force and ensure irreversibility in mechanism- amounts under identical conditions. The examination of
based inhibition (e.g., CC-1065).[3–6] Therefore, the explora- base effects revealed that by utilizing Et3N, (n-C7H15)3N,
tion of a novel synthetic approach for the preparation of or iPr2NEt as the base, 3a could be produced in 67, 56, or
cyclopropane-containing compounds is a very attractive 70% yield, respectively, under otherwise identical condi-
field for organic chemists. Annulation reactions of allenes tions (Table 1, entries 3–5), although other amino bases
and functionalized aryl halides catalyzed by palladium are not positive for the reaction outcomes (Table 1, en-
complexes have been reported by many groups during the tries 6–10). When Pd(OAc)2 was used as the catalyst and
last two decades.[7] In this paper, we wish to report a Pd- 1,4-bis(diphenylphosphanyl)butane (dppb) or 1,3-bis(di-
catalyzed coupling reaction of diarylvinylidenecyclopro- phenylphosphanyl)propane (dppp) was used as a ligand in
panes 1[8] with 2-iodophenols 2 or N-(2-iodophenyl)-4- the presence of Et3N, 3a was obtained in 32 or 37% yield
methylbenzenesulfonamide (4) to provide a variety of cyclo- after 72 h (Table 1, entries 11 and 12). Interestingly, we
propane-containing 2,2-diaryl-3-(tetramethylcyclopropyl- found that the use of Pd(MeCN)2Cl2 and PdCl2 as the
idene)-2,3-(dihydro)benzofuran or 2,2-diaryl-3-(tetrameth- palladium sources afforded 3a in 88 and 76% yields after
ylcyclopropylidene)-1-(toluene-4-sulfonyl)-2,3-dihydro-1H- 72 h, respectively (Table 1, entries 13 and 14). When PdCl2
indole derivatives 3 or 5 in moderate-to-good yields.
was used as a palladium source and dppp was employed
as a ligand, to our delight, we found that coupling product
3a was obtained in 94% yield along with 100% conversion
of 1a after 72 h, whereas the phosphane ligand dppb was
totally ineffective and Et3N was not as good a base as
iPr2NEt under identical conditions (Table 1, entries 15–
17). The structure of 3a was further confirmed by X-ray
diffraction.[9]
[a] State Key Laboratory of Organometallic Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences,
354 Fenglin Lu, Shanghai 200032, China
Fax: 86-21-64166128
E-mail: Mshi@mail.sioc.ac.cn
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
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Palladium-Catalyzed Coupling Reactions of Diarylvinylidenecyclopropanes
Table 1. Optimization of the coupling reaction conditions catalyzed
by palladium complexes.
Table 2. PdCl2-catalyzed coupling reactions of 1 with 2a under the
optimal conditions.
zene ring, the corresponding dihydrobenzofuran derivatives
3i–n were also obtained in moderate-to-good yields under
the standard conditions (Table 3, entries 1–6). It should be
noted that 2-iodobenzoic acid is totally inactive in this reac-
tion.
Table 3. PdCl2-catalyzed coupling reactions of 1 with 2b and 2c
under optimal conditions.
With these optimal conditions being identified, we next
examined the scope of this interesting coupling reaction.
Vinylidene substrates
1 bearing electron-withdrawing
groups on their benzene rings underwent the coupling reac-
tions smoothly to provide the corresponding 2,2-diaryl-3-
(tetramethylcyclopropylidene)-2,3-(dihydro)benzofuran de-
rivatives 3b–g in moderate-to-good yields within 4–5 d
(Table 2, entries 1–6). As for vinylidene 1e having a chlorine
atom on the benzene ring, PdCl2 (10 mol-%) and dppp
(20 mol-%) are required to give 3e in 50% yield (Table 2,
entry 4). However, as for vinylidene 1h bearing a moderately
electron-donating methyl group on the benzene ring, the
reaction was sluggish to afford the corresponding coupling
product in low yield. After a series of trial-and-error experi-
ments, we found that the addition of [Et3NH][BF4] (20 mol-
%) as a coadditive could improve the situation to some ex-
tent:[10] dihydrobenzofuran derivative 3h was obtained in
36% yield (Table 2, entry 7).
Next, on the basis of the above results, we attempted to
As for 2-iodophenols 2b and 2c bearing a moderately utilize N-(2-iodophenyl)-4-methylbenzenesulfonamide (4)
electron-donating methyl group and a moderately electron- as a coupling reagent to react with 1a under similar condi-
withdrawing chloro group at the para position of the ben- tions. However, it was found that corresponding dihydro-
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W. Li, M. Shi
FULL PAPER
Table 4. Optimization of the conditions for the reaction of 1a with 4 catalyzed by palladium complexes.
indole 5a was obtained in low yield (9–18%) under the moderate yields (30–64%) whether electron-donating or
above standard conditions (Table 4, entries 1–3). The ad- -withdrawing groups were introduced in the benzene ring
dition of nBu4NI (3.0 equiv.) as a phase-transfer catalyst of 1 (Table 5, entries 1–7).
afforded 5a in 38% yield (Table 4, entry 4). The use of di-
Table 5. PdCl2-catalyzed coupling reactions of 1 with 4 under the
optimal conditions.
phenylphosphanylferrocene (dppf) and tris(2-furyl)phos-
phane (TFP) as the phosphane ligands to replace dppp did
not improve the yield of 5a (Table 4, entries 5 and 6). After
several experiments, we were pleased to find that the use of
Ag2CO3 (2.0 equiv.)[11] and [Et3NH][BF4] (2.0 equiv.) as the
additives under otherwise identical conditions produced 5a
in 58% yield (Table 4, entry 7). The use of PdCl2 and
Ag2CO3 is crucial for this coupling reaction, because if
PdBr2 is used as a catalyst or AgNO3 (2.0 equiv.) as the
coadditive rather than PdCl2 or Ag2CO3, 5a was formed
in 15 or 11% yield, respectively (Table 4, entries 8 and 9).
However, when Ag2CO3 or [Et3NH][BF4] was used sepa-
rately in this reaction, the achieved yields of 5a were much
lower than that using them together (Table 4, entries 10 and
11). The positive effect of Ag2CO3 is presumably due to the
abstraction of a halide from the arylpalladium complex and
the formation of a cationic arylpalladium intermediate sta-
bilized by BF4– from [Et3NH][BF4], which is assumed to be
more reactive toward addition to the C=C=C bond.[12]
The generality of this coupling reaction was also exam-
ined by using a variety of vinylidenes 1 under the optimal
conditions. The results are summarized in Table 5. The cor-
responding dihydroindole derivatives 5b–h were obtained in
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Palladium-Catalyzed Coupling Reactions of Diarylvinylidenecyclopropanes
The solvent was removed in vacuo, and the residue was purified by
a flash column chromatography on silica gel (petroleum ether/
EtOAc, 80:1).
When methyl (2-iodophenyl)carbamate (6) was used as
the coupling reagent, we found that the corresponding dihy-
droindole derivative 7 was formed in 60% yield by using
Pd(OAc)2 as a catalyst and Na2CO3 (2.0 equiv.) as a base
2,2-Diphenyl-3-(2,2,3,3-tetramethylcyclopropylidene)-2,3-dihydro-
in DMF at 100 °C (Scheme 1). Its structure was unambigu- benzofuran (3a): A white solid. M.p. 132–134 °C. 1H NMR
ously determined by X-ray diffraction.[13]
(300 MHz, CDCl3, TMS): δ = 0.70 (s, 6 H, 2CH3), 1.28 (s, 6 H,
2CH3), 6.89 (d, J = 7.8 Hz, 1 H, Ar), 6.94 (d, J = 7.8 Hz, 1 H, Ar),
7.13–7.19 (m, 1 H, Ar), 7.26–7.33 (m, 7 H, Ar), 7.36–7.39 (m, 4 H,
Ar) ppm. 13C NMR (75 MHz, CDCl3, TMS): δ = 20.2, 20.4, 21.2,
23.0, 94.7, 110.3, 121.1, 122.2, 126.6, 127.7, 127.8, 128.1, 129.1,
131.4, 139.2, 142.8, 160.0 ppm. IR (CH Cl ): ν = 3061, 3034, 2989,
˜
2
2
2916, 2863, 1591, 1507, 1490, 1475, 1461, 1447, 1372, 1316, 1288,
1242, 1120, 1033, 1005, 952, 893, 745, 698, 627, 614 cm–1. MS: m/z
(%) = 366 (15) [M]+, 351 (55), 323 (15), 270 (100), 247 (9), 232 (10),
215 (9), 165 (12), 91 (14). C27H26O (366.50): calcd. C 88.48, H 7.15;
found C 88.44, H 7.09.
Scheme 1. Pd(OAc)2-catalyzed coupling reaction of 1 with 6.
CCDC-666660 (for 3a) and -682315 (for 7) contain the supplemen-
tary crystallographic data for this paper. These data can be ob-
tained free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
Conclusion
We developed efficient methods for the coupling reac-
tions of diarylvinylidenecyclopropanes 1 with 2-iodophen-
ols 2 and N-(2-iodophenyl)-4-methylbenzenesulfonamide
(4) to provide a variety of cyclopropane-containing 2,2-
diaryl-3-(tetramethylcyclopropylidene)-2,3-(dihydro)benzo-
furan and 2,2-diaryl-3-(tetramethylcyclopropylidene)-1-(tol-
uene-4-sulfonyl)-2,3-dihydro-1H-indole derivatives 3 and 5
or 7 in moderate-to-good yields catalyzed by various palla-
dium complexes in the presence of bases and other coaddi-
tives. A variety of vinylidenes 1 and 2-iodophenols 2 as well
as N-(2-iodophenyl)-4-methylbenzenesulfonamide and
methyl (2-iodophenyl)carbamate are suitable for this coup-
ling reaction to provide the corresponding cyclopropane-
containing five-membered heterocycles in a one-step reac-
tion. Efforts are in progress to elucidate further mechanistic
details of these reactions and to understand their scope and
limitations.
Supporting Information (see footnote on the first page of this arti-
cle): Detailed description of the experimental procedures; full char-
acterization of 3a–n, 5a–h, and 7; X-ray crystal structure and struc-
ture refinement details of 3a and 7.
Acknowledgments
We thank the Shanghai Municipal Committee of Science and Tech-
nology (06XD14005, 08dj1400100–2), National Basic Research
Program of China [(973)-2009CB825300], and the National Natu-
ral Science Foundation of China (20872162, 20672127, and
20732008) for financial support.
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phenol: Under an argon atmosphere, vinylidene 1 (0.18 mmol), 2-
iodophenol (119 mg, 0.54 mmol, 3.0 equiv.), PdCl2 (2 mg,
0.01mmol, 5 mol-%), dppp (7 mg, 0.18mmol, 10 mol-%), and
iPr2NEt (97 mg, 0.54 mmol, 3.0 equiv.) were dissolved in DMF
(3 mL), and the mixture was stirred for 72 h at 100 °C. To the re-
sulting mixture was added H2O (5 mL), and the solution was ex-
tracted with Et2O (3ϫ10 mL). The combined organic phase was
washed with brine (1ϫ10 mL) and dried with anhydrous MgSO4.
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W. Li, M. Shi
clinic; lattice type: primitive; lattice parameters:
10.1236(15) Å, b = 16.644(3) Å, c = 12.9345(19) Å, α = 90°, β
= 103.075(3)°, γ = 90°, V = 2122.9(5) Å3; space group: P21/n;
Z = 4; Dcalcd. = 1.147 gcm–3; F000 = 784; diffractometer: Rigaku
AFC7R; residuals: R; Rw: 0.0832, 0.2052.
FULL PAPER
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[10]
[11]
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[13] Crystal data for 7: Empirical formula: C29H29O2N; formula
weight: 423.53; crystal color, habit: colorless, prismatic; crystal
dimensions: 0.456ϫ0.407ϫ0.311 mm; crystal system: triclinic;
lattice type: primitive; lattice parameters: a = 9.2549(9) Å, b =
9.6975(9) Å, c = 14.4465(14) Å, α = 77.841(2)°, β = 78.066(2)°,
3
¯
γ = 67.680(2)°, V = 1160.93(19) Å ; space group: P1; Z = 2;
Dcalcd. = 1.212 gcm–3; F000 = 452; diffractometer: Rigaku
AFC7R; residuals: R, Rw: 0.0588, 0.1546.
Received: September 30, 2008
[9] Crystal data for 3a: Empirical formula: C27H26O; formula
weight: 366.48; crystal color, habit: colorless, prismatic; crystal
dimensions: 0.437ϫ0.421ϫ0.311 mm; crystal system: mono-
Published Online: November 25, 2008
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