Xantphos as an efficient ligand for palladium-catalyzed cross-coupling reactions of aryl bromides and triflates with allyl acetates and indium

Article abstract of DOI:10.1021/jo702279t

(Chemical Equation Presented) Xantphos was found to be an efficient ligand for palladium-catalyzed allyl cross-coupling reactions of aryl bromides and triflates with allylindium reagents generated in situ from allyl acetates and indium. These reactions occur in high yield with good functional group tolerance.

Full text of DOI:10.1021/jo702279t

SCHEME 1. Allyl Cross-Coupling Reactions with Xantphos
Xantphos as an Efficient Ligand for
Palladium-Catalyzed Cross-Coupling Reactions of
Aryl Bromides and Triflates with Allyl Acetates
and Indium
Dong Seomoon and Phil Ho Lee*
National Research Laboratory for Catalytic Organic Reaction,
Department of Chemistry, and Institute for Basic Science,
Kangwon National UniVersity, Chunchon 200-701, Republic of
Korea
cross-coupling reactions using a variety of organoindium
reagents,2,5 we demonstrated inter- and intramolecular Pd-
catalyzed allyl cross-coupling reactions using aryl iodides and
vinyl bromides and triflates via π-allylpalladium(II) complexes
and their transmetalation with indium and indium trichloride
in the presence of catalytic Pd(PPh3)4.6 However, we failed
unexpectedly to get the allyl cross-coupling products in the case
of aryl bromides and triflates. Therefore, there is still a strong
need for efficient catalytic systems for the cross-coupling
reactions of aryl bromides and triflates with allylindiums derived
from allyl acetates. Herein, we report Xantphos as an efficient
ligand for palladium-catalyzed allyl cross-coupling reactions of
aryl bromides and triflates with allylindium obtained from allyl
acetates (Scheme 1).
phlee@kangwon.ac.kr
ReceiVed October 22, 2007
In a test reaction of trifluoromethanesulfonate (1) derived
from 2-naphthol with allyl acetate (2), we found that cross-
coupling reactions could be largely affected by ligands in the
presence of Pd catalyst (Table 1). A variety of ligands with
varied structural and electronic properties was scrutinized.
Among the ligands tested, Xantphos gave the best results (entry
9). Generally, diphosphines have a marked influence on the
reactivity and selectivity of a catalyst. Due to the effects of wide
Xantphos was found to be an efficient ligand for palladium-
catalyzed allyl cross-coupling reactions of aryl bromides and
triflates with allylindium reagents generated in situ from allyl
acetates and indium. These reactions occur in high yield with
good functional group tolerance.
Palladium-catalyzed cross-coupling reactions are among the
most useful synthetic methods for carbon-carbon bond forma-
tion.1 Among them, allyl cross-coupling reactions with allylin-
dium reagents have received much attention due not only to
further applicability of the double bond in allyl groups but also
their reactivity and selectivity, ease of preparation and handling,
and operational simplicity.2 Allylindium reagents are easily
prepared from allyl halides and indium metal in polar solvents,
including water.3 Recently, new methods for the preparation of
allylindiums via a reductive transmetalation of π-allylpalladium-
(II) complexes from allyl alcohols and its derivatives have been
reported, and many successful examples of palladium and
indium-mediated allylation have been described.4 With regard
to our ongoing research interest in transition metal-catalyzed
(3) (a) Li, C.-J. Chem. ReV. 1993, 93, 2023-2035. (b) Cintas, P. Synlett
1995, 1087-1096. (c) Li, C.-J. Tetrahedron 1996, 52, 5643-5668. (d) Li,
C.-J.; Chan, T.-H. Organic Reactions in Aqueous Media; Wiley: New York,
1997. (e) Li, C.-J.; Chan, T.-H. Tetrahedron 1999, 55, 11149-11176. (f)
Babu, G.; Perumal, P. T. Aldrichim. Acta 2000, 33, 16-22. (g) Chauhan,
K. K.; Frost, C. G. J. Chem. Soc., Perkin Trans. 1 2000, 3015-3020. (h)
Pae, A. N.; Cho, Y. S. Curr. Org. Chem. 2002, 6, 715-737. (i) Podlech,
J.; Maier, T. C. Synthesis 2003, 633-655. (j) Li, C.-J. Chem. ReV. 2005,
105, 3095.
(4) (a) Araki, S.; Kamei, T.; Hirashita, T.; Yamamura, H.; Kawai, M.
Org. Lett. 2000, 2, 847-849. (b) Jang, T.-S.; Keum, G.; Kang, S. B.; Chung,
B. Y.; Kim, Y. Synthesis 2003, 775-779. (c) Miyabe, H.; Yamaoka, Y.;
Naito, T.; Takemoto, Y. J. Org. Chem. 2003, 68, 6745-6751. (d) Miyabe,
H.; Yamaoka, Y.; Naito, T.; Takemoto, Y. J. Org. Chem. 2004, 69, 1415-
1418. (e) Hirashita, T.; Kambe, S.; Tsuji, H.; Omori, H.; Araki, S. J. Org.
Chem. 2004, 69, 5054-5059. (f) Nguyen, V. C.; Kim, Y.-T.; Yu, Y.-K.;
Kang, H.-Y. Bull. Korean Chem. Soc. 2005, 26, 711-712.
(1) (a) Trost, B. M.; Verhoeven, T. R. In ComprehensiVe Organometallic
Chemistry; Wilkinson, G., Stone, F. G., Abel, E. W., Eds.; Pergamon:
Oxford, UK, 1982; Vol. 8, pp 799-938. (b) Heck, R. F. Palladium Reagents
in Organic Synthesis; Academic Press: New York, 1985. (c) Farina, V. In
ComprehensiVe Organometallic Chemistry II; Wilkinson, G., Stone, F. G.,
Abel, E. W., Eds.; Pergamon: Oxford, UK, 1995; Vol. 12, pp 161-240.
(d) Tsuji, J. Palladium Reagents and Catalyst; Wiley: Chichester, UK, 1995;
Chapter 4. (e) Metal-Catalyzed Cross-Couplings Reactions; Diederich, F.,
Stang, P. J., Eds.; Wiley-VCH: Weinheim, Germany, 1998. (f) Malleron,
J.; Fiaud, J.; Legros, J. Handbook of Palladium-Catalyzed Organic
Reactions; Academic Press: San Diego, CA, 1997. (g) Negishi, E.
Organopalladium Chemistry; Wiley-Interscience: New York, 2002; Vols.
I and II.
(5) (a) Lee, K.; Seomoon, D.; Lee, P. H. Angew. Chem., Int. Ed. 2002,
41, 3901-3903. (b) Lee, P. H.; Sung, S.-Y.; Lee, K.; Chang, S. Synlett
2002, 146-148. (c) Lee, P. H.; Lee, S. W.; Lee, K. Org. Lett. 2003, 5,
1103-1106. (d) Lee, P. H.; Lee, S. W.; Seomoon, D, Org. Lett. 2003, 5,
4963-4966. (e) Lee, S. W.; Lee, K.; Seomoon, D.; Kim, S.; Kim, H.; Kim,
H.; Shim, E.; Lee, M.; Lee, S.; Kim, M.; Lee, P. H. J. Org. Chem. 2004,
69, 4852-4855. (f) Lee, P. H.; Lee, K. Angew. Chem., Int. Ed. 2005, 44,
3253-3256. (g) Lee, P. H.; Seomoon, D.; Lee, K. Org. Lett. 2005, 7, 343-
345. (h) Lee, P. H.; Shim, E.; Lee, K.; Seomoon, D.; Kim, S. Bull. Korean
Chem. Soc. 2005, 26, 157-160. (i) Lee, P. H.; Lee, K.; Kang, Y. J. Am.
Chem. Soc. 2006, 128, 1139-1146.
(6) (a) Lee, P. H.; Seomoon, D.; Lee, K.; Kim, S.; Kim. H.; Kim, H.;
Shim, E.; Lee, M.; Lee, S.; Kim, M.; Sridhar, M. AdV. Synth. Catal. 2004,
346, 1641-1645. (b) Seomoon, D.; Lee, K.; Kim, H.; Lee, P. H. Chem.
Eur. J. 2007, 13, 5197-5206.
(2) (a) Lee, P. H.; Sung, S.-Y.; Lee, K. Org. Lett. 2001, 3, 3201-3204.
(b) Lee, K.; Lee, J.; Lee, P. H. J. Org. Chem. 2002, 67, 8265-8268.
10.1021/jo702279t CCC: $40.75 © 2008 American Chemical Society
Published on Web 01/09/2008
J. Org. Chem. 2008, 73, 1165-1168
1165

TABLE 1. Ligand Optimization in Pd-Catalyzed Allyl Cross-Coupling Reactions of 2-Naph-OTf with Allyl Acetatesa
yield (%)
entry
catalyst
ligand
time (h)
3b
4c
1c
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
10% Pd(PPh3)4
5
5
5
5
20
3
20
20
2
20
20
20
20
20
2
35
35
30
0
0
0
41
43
55
81
20
0
96
97
0
39
97
20
94
67
73
77
5% Pd2dba3CHCl3
5% Pd2dba3CHCl3
5% Pd2dba3CHCl3
5% Pd2dba3CHCl3
5% Pd2dba3CHCl3
5% Pd2dba3CHCl3
5% Pd2dba3CHCl3
5% Pd2dba3CHCl3
2.5% Pd2dba3CHCl3
5% Pd2dba3CHCl3
5% Pd2dba3CHCl3
5% Pd2dba3CHCl3
5% Pd2dba3CHCl3
10% PdBr2
40% PPh3
40% P(2-furyl)3
40% PCy3
20% dppe
20% dppf
40% P(DMOP)3
40% P(o-Tolyl)3
20% Xantphos
10% Xantphos
20% [1,2-(Ph2P)-Benzene]
20% dppp
40% P(t-Bu)3
20% DPEphos
20% Xantphos
20% Xantphos
5c
0
0
79
26
0
0
3
0
0
68
4
0
64 (74)c
0
0
84 (97)c
43
0
10c
2c
32
17
15
3
3
5% (π-allyl)2Pd2Cl2
2
a Naph: naphthyl. Reactions performed with 1 (0.5 mmol) in the presence of cat-Pd(0), In (1.0 mmol), InCl3 (0.25 mmol), LiCl (1.5 mmol), and n-BuNMe2
(1.0 mmol) unless otherwise noted. b Isolated yield. c GC yields based on 2-methoxynaphthalene as an internal standard.
bite angle, several groups have reported that palladium-catalyzed
reactions with Xantphos, a ligand developed by van Leeuwen,
could be effective.7 However, P(2-Furyl)3, PCy3, dppe, dppp,
dppf, P(DMOP)3, P(o-Tolyl)3, P(t-Bu)3, DPEphos, and [1,2-
(Ph2P)Benzene] produced the desired product in low yields. Pd2-
dba3CHCl3 was the Pd source of choice for reactions. Of the
catalytic systems examined, the best results were obtained with
5 mol % of Pd2dba3CHCl3, 20 mol % of Xantphos, In (2 equiv),
InCl3 (0.5 equiv), LiCl (3 equiv), and N,N-dimethyl-n-buty-
lamine (2 equiv) in DMF at 100 °C under a nitrogen atmosphere,
producing product 3 in quantitative GC yield (97%) (entry 9).
The use of 2.5 mol % of Pd2dba3CHCl3 and 10 mol % of
Xantphos gave a lower yield (43%) as well as longer reaction
times (20 h, entry 10).
To demonstrate the efficiency and scope of the present
method, we applied the optimum condition to a variety of allyl
acetate and aryl triflates and bromides. The results are sum-
marized in Table 2. For allyl acetates as coupling partners, the
presence of methyl group at the R, â, and γ positions had an
effect on both reaction rates and product yields. Allyl acetate
(2), 2-methylallyl acetate (21), but-1-en-3-yl acetate (22), and
crotyl acetate (23) produced the corresponding allyl cross-
coupling products in good yields. Reactions of triflate (1) and
2-bromonaphthalene (5) with allyl acetate (2) gave 2-allylnaph-
thalene (3) in 84% and 81% yields, respectively, under the
optimized conditions with Xantphos (entries 1 and 3). However,
use of Pd(PPh3)4 afforded 3 in 35% and 33% yields (entries 2
and 4). Treatment of 1 and 5 with 21 gave rise to the allyl cross-
coupling product in 74% and 67% yields (entries 5 and 6).
Exposure of 1 to the allylindium derived from 22 provided the
desired products 25 and 26 in 52% yield, but the product 26
resulting from γ-attack predominated (R:γ ) 1:3.5) (entry 7).
Also, reaction of 1 with 23 furnished the allyl cross-coupling
product in 53% yield and the regioselectivity (1:4) of this
reaction was similar to that of 22 (entry 8). Treatment of triflate
(6) derived from 1-naphthol with 2 gave 1-allylnaphthalene (27)
in 81% yield under the optimized conditions with Xantphos
(entry 9), while use of Pd(PPh3)4 produced 27 in 26% yield
and starting material was recovered in 57% yield (entry 10).
Aryl triflates and bromides bearing ethoxycarbonyl (entries 11-
15), cyano (entries 16 and 17), and N-benzylaminocarbonyl
(entry 18) substituents as electron-withdrawing groups and
methoxy (entries 19-21) and tert-butyl (entry 22) substituents
as electron-donating groups smoothly reacted with allyl acetate
under the optimum conditions to give the corresponding allyl-
substituted aromatic compounds in good yields. In the case of
aryl triflates and bromides bearing an ethoxycarbonyl group,
both the yield and the selectivity are almost independent of the
electronic and steric effect (entries 11-15). Heteroatoms turned
out to be compatible with the employed reaction conditions.
Reaction of 3-bromoquinoline (19) and 4-bromoisoquinoline
(20) with allylindium in the presence of Pd2dba3CHCl3/Xantphos
produced the correspondding allyl cross-coupling products in
76% and 84% yields, respectively (entries 24 and 25). In
contrast, use of Pd(PPh3)4 gave low yields of the allyl cross-
coupling products for aryl triflates and bromides (entries 2, 4,
10, 23, and 26), indicating the Pd-Xantphos catalytic system is
more efficient than Pd(PPh3)4.
In conclusion, we have demonstrated that Xantphos was an
efficient ligand for palladium-catalyzed allyl cross-coupling
reactions of aryl bromides and triflates with allylindium reagents
generated in situ from allyl acetates and indium. These reactions
occur in high yield with good functional group tolerance. The
present method complements the existing synthetic methods
because the previous methods were only successful for aryl
iodides and vinyl bromides and triflates.
(7) (a) Kranenburg, M.; van der Burgt, Y. E. M.; Kamer, P. C. J.; van
Leeuwen, P. W. N. M. Organometallics 1995, 14, 3081-3089. (b) van
Leeuwen, P. W. N. M.; Kamer, P. C. J.; Reek, J. N. H.; Dierkes, P. Chem.
ReV. 2000, 100, 2741-2769. (c) Kamer, P. C. J.; van Leeuwen, P. W. N.
M.; Reek, J. N. H. Acc. Chem. Res. 2001, 34, 895-904.
1166 J. Org. Chem., Vol. 73, No. 3, 2008

TABLE 2. Palladium-Catalyzed Allyl Cross-Coupling Reactions of Aryl Bromides and Triflates with Allyl Acetates Using Xantphosa
a Naph: naphthyl. Reactions performed with electrophiles (0.5 mmol) in the presence of Pd2dba3CHCl3 (0.025 mmol), Xantphos (0.10 mmol), In (1.0
mmol), InCl3 (0.25 mmol), LiCl (1.5 mmol), and n-BuNMe2 (1.0 mmol) in DMF (2 mL) at 100 °C for 2 h in substrates bearing electron-withdrawing groups
and for 6 h in substrates bearing electron-donating groups unless otherwise noted. Numbers in parentheses are recovered yields of starting material. b Reactions
performed in the presence of Pd(PPh3)4 (0.05 mmol) for 5-16 h. c Yield of homocoupling product. d Ratio of 25 to 26. e GC yields of reduction product of
halide based on 2-methoxynaphthalene as an internal standard. f Diastereomeric ratio of 26: cis:trans ) 1:1. g Diastereomeric ratio of 23: cis:trans ) 1:15.
stirred at 100 °C for 2 h. The reaction mixture was quenched with
NaHCO3 (saturated aqueous). The aqueous layer was extracted with
ether (3 × 20 mL) and the combined organic layers were washed
with water and brine, dried with MgSO4, filtered, and concentrated
under reduced pressure. The residue was purified by silica gel
column chromatography, using n-hexane to give 2-allylnaphthalene
(3) (70.7 mg, 84%). 1H NMR (400 MHz, CDCl3) δ 7.86-7.77 (m,
3H), 7.63 (s, 1H), 7.49-7.40 (m, 2H), 7.33 (dd, J ) 8.46, 1.42
Hz, 1H), 6.05 (ddt, J ) 16.98, 10.09, 6.77 Hz, 1H), 5.16-5.11 (m,
Experimental Section
Typical Experimental Procedure. To a suspension of indium
(114.8 mg, 1.0 mmol), indium trichloride (55.3 mg, 0.25 mmol),
lithium chloride (63.5 mg, 1.5 mmol), Pd2dba3CHCl3 (5 mol%, 10.3
mg), and Xantphos (20 mol%, 57.9 mg) in DMF (1 mL) was added
N,N-dimethylbutylamine (101.2 mg, 2.0 mmol) and allyl acetate
(250.3 mg, 2.5 mmol) at 35 °C under a nitrogen atmosphere. After
30 min, trifluoromethanesulfonic acid naphthalen-2-yl ester (138.1
mg, 0.5 mmol) in DMF (1 mL) was added and the mixture was
J. Org. Chem, Vol. 73, No. 3, 2008 1167

2H), 3.55 (d, J ) 6.66 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ
137.55, 137.32, 133.65, 132.12, 128.04, 127.62, 127.48, 127.39,
126.66, 125.93, 125.27, 40.36; IR (film) 3003, 2916, 1684, 1606,
1414, 1358 cm-1; HRMS (EI) calcd for C13H12 M+ 168.0939, found
168.0934.
by the CMDS at KAIST, and by KOSEF (R01-2006-000-11283-
0). The NMR and mass data were obtained from the central
instrumental facility in Kangwon National University.
Supporting Information Available: Spectral data of all the new
compounds. This material is available free of charge via the Internet
at http://pubs.acs.org.
Acknowledgment. This work was supported by the Korea
Science and Engineering Foundation (KOSEF) through the
National Research Lab. Program funded by the Ministry of
Science and Technology (No. M10600000203-06J0000-20310),
JO702279T
1168 J. Org. Chem., Vol. 73, No. 3, 2008