Room temperature nickel(0)-catalyzed Suzuki-Miyaura cross-couplings of activated alkenyl tosylates: Efficient synthesis of 4-substituted coumarins and 4-substituted 2(5H)-furanones

Article abstract of DOI:10.1002/adsc.200404150

Room temperature nickel(0)/tricyclohexylphosphine [Ni(0)/PCy ₃]-catalyzed Suzuki-Miyaura cross-couplings of 4-(p- toluenesulfonyloxy)coumarins and 4-(p-toluenesulfonyloxy)-2(5H)-furanone with arylboronic acids are described in this communcation

Full text of DOI:10.1002/adsc.200404150

COMMUNICATIONS
Room Temperature Nickel(0)-Catalyzed Suzuki--Miyaura
Cross-Couplings of Activated Alkenyl Tosylates:Efficient
Synthesis of 4-Substituted Coumarins and 4-Substituted 2(5H)-
Furanones
Zhen-Yu Tang, Qiao-Sheng Hu*
Department of Chemistry, College of Staten Island and the Graduate Center of the City University of New York, Staten
Island, NY 10314, USA
Fax: (þ1)-718-982-3910, e-mail: qiaohu@mail.csi.cuny.edu
Received: June 1, 2004; Accepted: August 8, 2004
Abstract: Room temperature nickel(0)/tricyclohexyl-
phosphine [Ni(0)/PCy3]-catalyzed Suzuki–Miyaura
cross-couplings of 4-(p-toluenesulfonyloxy)coumar-
ins and 4-(p-toluenesulfonyloxy)-2(5H)-furanone
with arylboronic acids are described in this commun-
cation. Our study shows that activated alkenyl tosy-
lates possess higher activities than aryl tosylates in
the Suzuki–Miyaura cross-couplings. The mild reac-
tion conditions and the high efficiency of the Ni(0)/
PCy3 catalyst make it very useful in the synthesis of
4-substituted coumarins and 4-substituted 2(5H)-fur-
anones, two families of biologically important mole-
cules.
ladium loading (5%). The search for more efficient
methods for the synthesis of these biologically promis-
ing compounds continues.
In our laboratory, we have initiated a project to ex-
plore the synthetic utilization of less studied aryl/alkenyl
arenesulfonates, which are readily accessible from phe-
nols or enols and arenesulfonyl chlorides. Recently, we
have demonstrated the room temperature Ni(0)/PCy3-
catalyzed cross-coupling reactions of aryl p-toluenesul-
fonates with arylboronic acids.[8] The mild conditions
(room temperature, THF as solvent and K3PO4 as
base) of the Ni(0)/PCy3 catalyst system, which might
be more compatible with a,b-unsaturated ester func-
tional groups, led us to undertake Ni(0)/PCy3-catalyzed
cross-coupling reactions of activated alkenyl tosylates,
particularly the readily accessible 4-(p-toluenesulfonyl-
oxy)coumarin and 4-(p-toluenesulfonyloxy)-2(5H)-fur-
anone, with arylboronic acids. In this communication,
our results are reported.
Keywords: arylboronic acids; cross-coupling; nickel;
phosphane ligand; tosylates
Our study began with the cross-coupling of 4-(p-tolu-
4-Substituted coumarins and 4-substituted 2(5H)-fura- enesulfonyloxy)coumarin with phenylboronic acid. We
nones are two families of biologically important mole- found that under our catalyst protocol {3% of bis(1,5-cy-
cules with interesting biological properties, including clopentadiene)nickel(0) [Ni(COD)2]/12% PCy3,
3
anti-HIVand antibiotic activities.[1,2] A number of meth- equivs. of potassium phosphate (K3PO4) as base, tetra-
ods have been developed for their synthesis in the past hydrofuran (THF) as solvent}, the reaction went to com-
years. Among the various methods reported, transition pletion within 4 h at room temperature and the desired
metal-catalyzed cross-couplings of 4-(p-toluenesulfonyl- product was isolated in 94% yield. This result not only
oxy)coumarin and 4-(p-toluenesulfonyloxy)-2(5H)-fur- established the feasibility of employing Ni(0)/PCy3 as
anone with arylboronic acids are especially attractive an efficient catalyst for the cross-coupling of 4-(p-tolu-
approaches due to the readily accessibility of 4-(p-tolu- enesulfonyloxy)coumarin with arylboronic acids under
enesulfonyloxy)coumarin and 4-(p-toluenesulfony- mild conditions, but also suggested that 4-(p-toluenesul-
loxy)-2(5H)-furanone, and the air-stable, non-toxic na- fonyloxy)coumarin was more reactive than aryl tosy-
ture of arylboronic acids.[3–7] In this context, Yang and lates, which required 8 h to go to completion under oth-
coworkers reported the palladium(0)-catalyzed Suzu- erwise identical conditions. A number of arylboronic
ki–Miyaura cross-couplings of 4-(p-toluenesulfonylox- acids have thus been employed for the cross-couplings
y)coumarin and 4-(p-toluenesulfonyloxy)-2(5H)-furan- and our results are listed in Table 1. As shown in Table 1,
one.[4a–c,7a] However, their reaction protocol requires complete conversions, as well as excellent isolated
heating in basic aqueous solution, which may be detri- yields, were observed for all the boronic acids employed
mental to the a,b-unsaturated ester functional groups, although an extended reaction time was needed for ster-
and lengthy reaction time as well as relatively high pal- ically hindered boronic acids (Table 1, entries 7 and 8).
Adv. Synth. Catal. 2004, 346, 1635–1637
DOI:10.1002/adsc.200404150
ꢀ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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Zhen-Yu Tang, Qiao-Sheng Hu
COMMUNICATIONS
Table 1. Room temperature Ni(0)-catalyzed Suzuki cross-
coupling reactions of 4-(p-toluenesulfonyloxy)coumarins.[a]
Table 2. Room temperature Ni(0)-catalyzed Suzuki cross-
coupling reactions of 4-(p-toluenesulfonyloxy)-2(5H)-fura-
none.[a]
[a]
Reaction conditions: tosylate (1.0 equiv.), arylboronic
acids (1.5 equivs.), Ni(COD)2/PCy3 (3 mol %/12 mol %),
K3PO4 (3 equivs.), THF (2 mL), room temperature.
[b]
Isolated yields (average of two runs).
Refs.[7a]
[c]
[d]
[a]
Reaction time: 8 h (not minimized).
3% Ni(PCy3)2Cl2/n-BuLi was used as catalyst.
Reaction conditions: tosylate (1.0 equiv.), arylboronic
[e]
acids (1.5 equivs.), Ni(COD)2/PCy3 (3 mol %/12 mol %),
K3PO4 (3 equivs.), THF (2 mL), room temperature.
[b]
Isolated yields (average of two runs).
Refs.[4a, b]
[c]
reactions of 4-(p-toluenesulfonyloxy)-2(5H)-furanone
with arylboronic acids. It was found that 4-(p-toluenesul-
fonyloxy)-2(5H)-furanoneindeedcoupledsmoothlywith
arylboronic acids under our reaction condition (Table 2).
The Ni(0)/PCy3 catalyst generated from Ni(PCy3)2Cl2/n-
[d]
Reaction time: 8 h (not minimized).
3 mol % Ni(PCy3)2Cl2/n-BuLi was used as catalyst.
[e]
We have also sought to use the air-stable bis(tricyclohex- BuLi has also been tested and it also showed a similar ef-
ylphosphine)nickel(II) chloride [Ni(PCy3)2Cl2][9] as cat- ficiency as that of Ni(COD)2/PCy3 (Table 2, entry 2).
alyst precursor to substitute the air-sensitive Ni(COD)2.
We have also carried out a reactivity study for 4-(p-tol-
We found that although Ni(PCy3)2Cl2 and Ni(PCy3)2Cl2/ uenesulfonyloxy)coumarin, 4-(p-toluenesulfonyloxy)-
2 PCy3 were ineffective for the cross-coupling of 4-(p- 2(5H)-furanone and p-tolyl tosylate. We found that
toluenesulfonyloxy)coumarin with phenylboronic acid, when the mixture of 4-(p-toluenesulfonyloxy)coumarin
likely due to their inability to generate the catalytically (1 equiv.) and 4-(p-toluenesulfonyloxy)-2(5H)-fura-
active Ni(0) species under the reaction conditions, the none (1 equiv.) reacted with phenylboronic acid
catalyst generated from Ni(PCy3)2Cl2/n-BuLi was as ef- (1 equiv.), almost a 1:1 ratio of the corresponding prod-
ficient as that of Ni(COD)2/PCy3 (Table 1, entry 2).
ucts were formed. This suggests that the reactivities of 4-
Our success in Ni(0)/PCy3-catalyzed Suzuki–Miyaura (p-toluenesulfonyloxy)coumarin and 4-(p-toluenesulfo-
cross-couplings of 4-(p-toluenesulfonyloxy)coumarins nyloxy)-2(5H)-furanone are similar to each other. On
suggested that the Ni(0)/PCy3 catalyst system should the other hand, reaction of p-tolyl tosylate (1 equiv.)
also be effective for the cross-couplings ofother activated and 4-(p-toluenesulfonyloxy)coumarin (1 equiv.) with
alkenyl tosylates with arylboronic acids. We have thus phenylboronic acid (1 equiv.) yielded the corresponding
also carried out the Ni(0)/PCy3-catalyzed cross-coupling cross-coupling products in a 1:9 ratio. These results im-
Scheme 1. Ni(0)-catalyzed cross-couplings of p-tolyl tosylate, 4-(p-toluenesulfonyloxy)coumarin, 4-(p-toluenesulfonyloxy)-
2(5H)-furanone with phenylboronic acid.
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Adv. Synth. Catal. 2004, 346, 1635–1637

RT Ni (0)-Catalyzed Suzuki–Miyaura Cross-Couplings of Alkenyl Tosylates
COMMUNICATIONS
Congress-CUNY Research Award Programs is also gratefully
acknowledged.
ply that 4-(p-toluenesulfonyloxy)coumarin and 4-(p-tol-
uenesulfonyloxy)-2(5H)-furanone are more reactive
than p-tolyl tosylate (Scheme 1).
In summary, we have demonstrated that Ni(0)/PCy3 is a
highly active catalyst system for the room temperature Su-
zuki–Miyaura coupling of the readily accessible 4-(p-tol-
uenesulfonyloxy)coumarin and 4-(p-toluenesulfonyl-
oxy)-2(5H)-furanone with arylboronic acids. Our study
showed that the electron-withdrawing group-substituted
alkenyl tosylates possess higher activities than aryl tosy-
lates. The mild reaction conditions, the high efficiency
and the easy availability of the Ni(0)/PCy3 catalyst make
this catalyst system very useful in the synthesis of biologi-
cally important 4-substituted coumarins and 4-substituted
2(5H)-furanones. It is believed that the Ni(0)/PCy3 catalyst
system could be extended for the cross-couplings of other
alkenyl sulfonates. Work along this line is underway.
References and Notes
[1] Selected recent reports on coumarins: a) L. Xie, Y. Take-
uchi, L. M. Cosentino, A. T. McPhail, K.-H. Lee, J. Med.
Chem. 2001, 44, 664–671; b) A. Murakami, G. Gao, M.
Omura, M. Yano, C. Ito, H. Furukawa, D. Takahashi, K.
Koshimizu, H. Ohigashi, Bioorg. Med. Chem. Lett. 2000,
10, 59–62; c) Y. Fall, C. Teran, M. Teijeira, L. Santana,
E. Uriarte, Synthesis 2000, 643–645; d) A. J. Vlietinck,
T. De Bruyne, S. Apers, L. A. Pieters. Planta Med. 1998,
64, 97–109.
[2] Selected recent reports on 2(5H)-furanones and deriva-
tives: a) F. Bellina, C. Anselmi, S. Viel, L. Mannia, R. Ros-
si, Tetrahedron, 2001, 57, 9997–10007 and references cited
˜
therein; b) M. J. Ortega, E. Zubía, J. M. Ocana, S. Naran-
´
jo, J. Salva Tetrahedron, 2000, 56, 3963–3967; c) T. Honda,
Experimental Section
H. Mizutani, K. Kanai, J. Org. Chem. 1996, 61, 9374–9378;
d) S. L. Midland, N. T. Keen, J. J. Sims, J. Org. Chem. 1995,
60, 1118–1119.
General Procedure for the Ni(0)/PCy3-Catalyzed
Suzuki–Miraura Couplings of 4-(p-
Toluenesulfonyloxy)coumarin and 4-(p-
Toluenesulfonyloxy)-2(5H)-furanone
[3] For recent examples: a) D. V. Kadnikov, R. C. Larock,
Org. Lett. 2000, 2, 3643–3646; b) M.-L.Yao, M.-Z. Deng,
Heteroatom Chem. 2000, 11, 380–382.
[4] For recent examples of Pd(0)- or Ni(0)-catalyzed cross-
couplings of 4-(p-toluenesulfonyl)- or 4-halocoumarins:
a) J. Wu, L.Wang, R. Fathi, Z. Yang, Tetrahedron Lett.
2002, 43, 4395–4397; b) J. Wu, Z.Yang, J. Org. Chem.
2001, 66, 7875–7878; c) J. Wu, Y. Liao, Z.Yang, J. Org.
Chem. 2001, 66, 3642–3645; d) L. Schio, F. Chatreaux,
M. Klich, Tetrahedron Lett. 2000, 41, 1543–1545;
e) G. M. Boland, D. M. X. Donnelly, J.-P. Finet, M. D.
Rea, J. Chem. Soc. Perkin Trans. 1 1996, 2591–2597.
[5] For a report on Suzuki–Miyaura coupling reactions in-
volving other vinyl tosylates: M. A. Huffman, N. Yasuda,
Synlett 1999, 471–473.
[6] For recent examples: a) P. Forgione, D. Wilson, A. G. Fal-
lis Tetrahedron Lett. 2000, 41, 17–20; b) R. Maon,
A. M. E. Richecoeur, J. B. Sweeney, J. Org. Chem. 1999,
64, 328–329; c) S. Ma, Z. Shi J. Org. Chem. 1998, 63,
6387–6389; d) W.-J. Xiao, H. Alper J. Org. Chem. 1997,
62, 3422–3423; e) J. A. Marshall, M. A. Wolf J. Org.
Chem. 1996, 61, 3238–3239; f) G. J. Hollingworth, G. Per-
kins, J. B. Sweeney, J. Chem. Soc. Perkin Trans. 1 1996,
1913–1919.
Method A: In a glove-box with an N2 atmosphere, to a mixture
of phenylboronic acid (1.5 mmol), potassium phosphate
(3 mmol), 4-(p-toluenesulfonyloxy)coumarins or 4-(p-tolue-
nesulfonyloxy)-2(5H)-furanone (1 mmol) and 2 mL THF
were added bis(1,5-cyclopentadiene)nickel(0) (8.3 mg,
0.03 mmol) and tricyclohexylphosphine (33 mg, 0.12 mmol).
The mixture was allowed to stir for 4 to 8 hours. After quench-
ing with water, the reaction mixture was extracted with ethyl
acetate. The organic phase was washed with brine and the sol-
vent was evaporated under vacuum. Flash chromatography on
the silica gel (hexane:ethyl acetate¼90:10 to 85:15) yielded
the cross-coupling products.
MethodB:Inaglove-box withanN2 atmosphere, to a mixture
of bis(tricyclohexylphosphine)nickel(II) chloride (11 mg,
0.015 mmol), tricyclohexylphosphine (0.03 mmol ), were added
2 mL THF. After the Ni(II) species had dissolved, n-butyllithi-
um (20 mL, 2.5 M in hexane) was added. After stirring for 1 mi-
nute, to the deep red solution were added phenylboronic acid
(0.75 mmol), potassium phosphate (1.5 mmol) and the 4-(p-tol-
uenesulfonyloxy)coumarin or 4-(p-toluenesulfonyloxy)-2(5H)-
furanone (0.5 mmol) sequentially. The mixture was allowed to
stirfor4hours. Afterquenching withwater, thereactionmixture
was extracted with ethyl acetate. The organic phase was washed
with brine and the solvent was evaporated under vacuum. Flash
chromatography on silica gel (hexane: ethyl acetate¼90:10 to
85:15) yielded the cross-coupling products.
[7] For recent examples of Pd(0)- or Ni(0)-catalyzed 4-substi-
tuted 2(5H)-furanone syntheses from 4-halo- or 4-sulfony-
loxy-2(5H)-furanones: a) J. Wu, Q. Zhu, L. Wang, R. Fa-
thi, Z.Yang, J. Org. Chem. 2003, 68, 670–673; b) R. Rossi,
F. Bellina, E. Raugei, E. Synlett 2000, 1749–1752; c) M.-L.
Yao, M.-Z. Deng, J. Org. Chem. 2000, 65, 5034–5036; d) J.
Boukouvalas, N. Lachance, M. Ouellet, M. Trudeau, M.
Tetrahedron Lett. 1998, 39, 7665–7668.
Acknowledgements
[8] Z.-Y. Tang, Q.-S. Hu, J. Am. Chem. Soc. 2004, 126, 3058–
3059.
[9] K. W. Barnett, J. Chem. Educ. 1974, 51, 422–423.
We thank the National Institutes of Health (GM69704) for sup-
porting this work. Partial support from the Professional Staff
Adv. Synth. Catal. 2004, 346, 1635–1637
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