3,5-Bis(perfluorodecyl)phenylboronic acid as an easily recyclable direct amide condensation catalyst

Article abstract of DOI:10.1055/s-2001-16788

3,5-Bis(perfluorodecyl)phenylboronic acid has been synthesized based on the direct coupling of perfluorodecyl iodide with 1,3-diiodobenzene. This new boronic acid is shown to be a "green" catalyst for the direct amide condensation reaction by virtue of the strong electron-withdrawing effect and the immobility in the fluorous recyclable phase of the perfluorodecyl group.

Full text of DOI:10.1055/s-2001-16788

LETTER
1371
3,5-Bis(perfluorodecyl)phenylboronic Acid as an Easily Recyclable Direct
Amide Condensation Catalyst
Kazuaki Ishihara, Shoichi Kondo, Hisashi Yamamoto*
Graduate School of Engineering, Nagoya University, CREST, Japan Science of Technology Corporation (JST), Furo-cho, Chikusa, Nagoya
464-8603, Japan
Fax +81-52-789-3222; E-mail: yamamoto@cc.nagoya-u.ac.jp
Received 28 May 2001
F3C
F3C
F
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Abstract: 3,5-Bis(perfluorodecyl)phenylboronic acid has been
synthesized based on the direct coupling of perfluorodecyl iodide
with 1,3-diiodobenzene. This new boronic acid is shown to be a
“green” catalyst for the direct amide condensation reaction by virtue
of the strong electron-withdrawing effect and the immobility in the
fluorous recyclable phase of the perfluorodecyl group.
B(OH)2
F
B(OH)2
1
3
2
4
C10F21
Key words: arylboronic acids, recycle, direct amide condensation,
green chemistry, fluorous bi-phasic catalysis
B(OH)2
C10F21
B(OH)2
C10F21
Arylboronic acids bearing electron-withdrawing substitu-
ents at the aryl group behave as water-, acid-, and base-
tolerant thermally stable Lewis acids and can be easily
handled in air. We have succeeded in enhancing the cata-
lytic activities of a chiral acyloxyborane (CAB) derived
from 2,6-di(isopropoxy)benzoyltartaric acid and bo-
rane THF, Corey’s chiral oxazaborolidine catalyst de-
rived from N-(p-toluenesulfonyl)-(S)-tryptophan and
borane THF, and the Brønsted acid-assisted chiral Lewis
acid (BLA) derived from chiral tetrol and borane THF by
a modified method using 3,5-bis(trifluoromethyl)phenyl-
boronic acid (1) instead of borane•THF.1−3 Moreover, we
have found that 1 and 3,4,5-trifluorophenylboronic acid
(2) are highly effective catalysts for the amide condensa-
tion of amines (1 equiv) and carboxylic acids (1 equiv).4
To the best of our knowledge, this is the first example of
a catalytic and direct amide condensation which does not
require excess amounts of substrates.
alkylated phenylboronic acids 3 and 4 (Scheme). Treat-
ment of 4-iodoanisole (5) and perfluorodecyl iodide in
DMSO (120 °C, 40 h) gave the substituted anisole 6 in
90% yield.9 Compound 6 was converted to 7 by demethy-
lation with boron tribromide (70% yield) and subsequent
triflation with triflic anhydride (>99% yield). The palladi-
um-catalyzed cross-coupling of triflate 7 with bis(pinaco-
lato)diboron yielded the corresponding arylboronate 8 in
81% yield.10a Finally, 8 was converted to 311 in 70% yield
by treatment with boron tribromide. Thus, the new boron-
ic acid 3 was prepared from 5 in five steps. In a similar
manner, 3,5-bis(perfluorodecyl)phenylboronic acid (4)12
was prepared from 1,3-diiodobenzene (9) in four steps:
copper-mediated coupling of 9 with perfluorodecyliodide,
electrophilic aromatic bromination of 10 with N-bromo-
succinimide (NBS),13 palladium-catalyzed cross-coupling
of arylbromide 11 with bis(pinacolato)diboron,10b and
deprotection of 12 with boron tribromide.
Most of the above homogeneous catalytic reactions re-
quire relatively large quantities of arylboronic acid cata-
lysts (1~20 mol%), and trace amounts of the catalysts
must be removed from the reaction products. This has
hampered the application of this methodology to large-
scale syntheses. Recently, the concept of fluorous bi-pha-
sic catalysis (FBC) was introduced as an environmentally
benign recycling process.5−7 In this paper, we describe a
convenient and high-yielding route to phenylboronic ac-
ids 3 and 4 bearing perfluorinated ponytails based on the
direct coupling of fluoroalkyl iodides with halobenzenes
and their catalytic and recyclable application in a direct
amide condensation.
We first investigated the catalytic activities of arylboronic
acids 1 4 (5 mol%), which promote the model reaction of
4-phenylbutyric acid (1 equiv) with 3,5-dimethylpiperi-
dine (1 equiv) in toluene at azeotropic reflux with removal
of water (4-Å molecular sieves in a Soxhlet thimble) for 1
h, and its recovery by extraction with fluorous solvents
(Table 1). As expected, 3,5-bis(perfluorodecyl)phenylbo-
ronic acid 4 was more active than 4-(perfluorodecyl)phe-
nylboronic acid 3, and was recovered in quantitative yield
by extraction with perfluoromethylcyclohexane. Al-
though 1 and 2 were more active than 4, they could not be
recovered by extraction with any fluorous solvents. The
amide condensation proceeded cleanly in the presence of
5 mol% of 4, the desirable amide was obtained in 95%
yield by azeotropic reflux for 15 h. In addition, the corre-
sponding N-benzylamide was obtained in quantitative
Cross-coupling of fluoroalkyl iodides with iodoaromatic
compounds to give fluoroalkyl-substituted aromatics in
the presence of copper was reported by McLoughlin and
Thrower more than three decades ago.8 Prompted by this
early finding, we attempted the synthesis of perfluoro-
Synlett 2001, No. 9, 1371–1374 ISSN 0936-5214 © Thieme Stuttgart · New York

1372
K. Ishihara et al.
LETTER
Table 1 Catalytic Activities and Recovery of Arylboronic Acid for
Direct Amide Condensation
C
10F21I (1.1 equiv)
Cu (3.3 equiv)
2,2'-dipyridyl (20 mol%)
I
OMe
C
10F21
6 (90% yield)
OMe
DMSO
120 °C, 40 h
5
+
HN
Ph
CO2H
1. BBr3 (3 equiv)
CH2Cl2, 0°C to rt, 2 h; H2O
C10F21
OTf
2. Tf2O (1.2 equiv)
i-Pr2EtN (1.5 equiv)
CH2Cl2, 0°C to rt, 2 h
ArB(OH)2 (5 mol%)
7 (70% yield)
N
toluene
azeotropic reflux
(–H2O), 1 h
Ph
O
O
O
O
O
(1.1 equiv)
B
B
Yield of amide (%)a
Recovery of ArB(OH)2 (%)b
ArB(OH)2
1
59
60
0
0
PdCl2(dppf) (5 mol%)
dppf (5 mol%), KOAc (3 equiv)
2
O
O
3
4
39
57
>99
0
47 (95)c
23
C10F21
B
PhB(OH)2
1,4-dioxane, 120 °C, 32 h
d
–
<2
–
8 (81% yield)
a Isolated yield. b Extraction with perfluoromethylcyclohexane. c Yield after
heating at azeotropic reflux for 15 h is indicated in parenthesis. d No catalyst
was added.
1. BBr3 (3 equiv)
CH2Cl2, 0 °C to rt
3 (70% yield after recrystallization from CHCl3)
H
2. H2O
99% yield, >99% recovery of 4
[Reaction conditions: 4 (2 mol%),
toluene, azeotropic reflux for 4 h]
N
Ph
Ph
O
C
10F21I (2.2 equiv)
Cu (3.3 equiv)
C10F21
I
I
NBS (1.5 equiv)
2,2'-dipyridyl (40 mol%)
H2SO4–CF3CO2H
(3:7.5 (v:v))
DMSO
120 °C, 68 h
Table 2 Recovery and Reuse of 4 in the Recyclable Fluorous Im-
C10F21
mobilized Phasea
50 °C, 8 h
9
10 (57% yield)
CO2H
PhCH2NH2
+
O
B
O
B
O
(1.1 equiv)
O
O
4 (3 mol%)
N
Ph
C10F21
H
PdCl2(dppf) (6 mol%)
dppf (6 mol%), KOAc (3 equiv)
o-xylene–toluene-perfluorodecaline (1:1:1)
azeotropic reflux, 12 h
Br
DMSO
100 °C, 12 h
Cyclea
Conversion (%)b >99 (99)
1
2
>99
3
>99
4
5c
>99 (99)
C10F21
>99 (98)
11 (94% yield after recrystallization from CHCl3)
aReaction conditions (See Scheme 2): 4 (0.03 mmol), cyclohexane-
carboxylic acid (1 mmol), benzylamine (1 mmol), o-xylene (2.5 mL),
toluene (2.5 mL), and perfluorodecaline (2.5 mL). After the reaction,
a solution of the amide in the upper phase was decanted and the cata-
C10F21
1. BBr3 (3 equiv)
CH2Cl2, 0 °C to rt
O
O
4 (74% yield)
B
b
lyst 4 in the lower phase was recycled successively. Values in par-
2. H2O
entheses refer to the isolated yields. cCatalyst 4 was recovered in 98%
C10F21
yield from the perfluorodecalin phase.
12 (59% yield after recrystallization from CHCl3)
Scheme
corresponding amide in quantitative yield. Catalyst 4 was
completely recovered and reused in the recyclable fluo-
yield by heating 4-phenylbutyric acid with benzylamine rous immobilized phase.
in the presence of 2 mol% of 4 under azeotropic reflux
conditions for 4 h.
Catalyst 4 was insoluble in toluene and o-xylene at room
temperature even in the presence of carboxylic acids,
Based on the above results, the recyclable use of 4 was ex- amines, and amides. However, the amide condensation
amined for direct amide condensation (Table 2 and Figure catalyzed by 4 proceeded homogeneously under reflux
1).14 The reaction of cyclohexanecarboxylic acid and ben- conditions. To demonstrate this advantage of 4 with re-
zylamine in a 1:1:1 mixture of o-xylene, xylene, and per- spect to solubility,16 we attempted to reuse 4 (5 mol%) 10
fluorodecalin was carried out under azeotropic reflux times for the amide condensation reaction of cyclohexan-
conditions with removal of water for 12 h in the presence ecarboxylic acid with benzylamine (Table 3 and Figure
of 3 mol% of 4.15 After cooling to ambient temperature, 2).17 After heating the reaction mixture at reflux with re-
the two heterogeneous phases were separated to give the moval of water for 3 h, the mixture was allowed to stand
Synlett 2001, No. 9, 1371–1374 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
An Easily Recyclable Direct Amide Condensation Catalyst
1373
Table 3 Reuse of Catalyst 4 for the Amide Condensation of Cyclo-
hexanecarboxylic Acid with Benzylamine.a
CO2H
cooling to
azeotropic
R2
NR3
R1CO2H
HNR2R3
+
PhCH2NH2
O
C
room temp. R1
reflux
O
(–H2O)
4
4
4 (5 mol%)
o-xylene
N
H
Ph
(bi-phases, rt)
(bi-phases, rt)
(homogeneous, reflux)
non fluorous phase
azeotropic reflux, 3 h
Total (10 times): 96% isolated yield
fluorous phase
Use of 4a
Conversion (%)
2
3
4
5
6
7
8
9
10
>99
1
>99
decantation
>99 >99 >99 99 >99 >99 >99 >99
flask
aReaction conditions: 4 (0.05 mmol), cyclohexanecarboxylic acid (1
mmol), benzylamine (1 mmol), xylene (5 mL). After the reaction, the
solution was decanted and the residual catalyst 4 was reused without
isolation (see, Scheme 2). bRecovered catalyst 4 was used successive-
ly (Use 2, 3, 4,.)
4
O
C
R2
N
R3
R1CO2H
HNR2R3
R1
(a solution of 4 in
perfluorodecalin, rt)
toluene–o-xylene
toluene–o-xylene
In conclusion, we have shown that 3,5-bis(perfluorode-
cyl)phenylboronic acid 4 is a “green” catalyst by virtue of
the electron-withdrawing effect and the immobility in the
fluorous recyclable phase of the perfluorodecyl group. In
addition, it is noteworthy that 4 was simply recovered by
filtration without using any fluorous solvents. Perfluoro-
decyl groups on 4 increased precipitation properties in
nonfluorous organic solvents. We believe that direct
amide condensation catalyzed by a reusable boronic acid
4 may be useful as an environmentally and industrially
ideal condensation method in the near future.
Figure 1 Recycling of 4 in the recyclable fluorous immobilized
phase
cooling to
azeotropic
O
C
R2
N
R1CO2H
HNR2R3
room temp. R1
reflux
(–H2O)
R3
4 (solid)
References and Notes
(heterogeneous, rt)
(heterogeneous, rt)
decantation
(homogeneous, reflux)
(1) (a) Ishihara, K.; Mouri, M.; Gao, Q.; Maruyama, T.; Furuta,
K.; Yamamoto, H. J. Am. Chem. Soc. 1993, 115, 11490.
(b) Ishihara, K.; Maruyama, T.; Mouri, M.; Gao, Q.; Furuta,
K.; Yamamoto, H. Bull. Chem. Soc. Jpn. 1993, 66, 3483.
(2) (a) Ishihara, K.; Kurihara, H.; Yamamoto, H. J. Am. Chem.
Soc. 1996, 118, 3049. (b) Ishihara, K.; Kondo, S.; Kurihara,
H.; Yamamoto, H.; Ohashi, S.; Inagaki, S. J. Org. Chem.
1997, 62, 3026. (c) Ishihara, K.; Kurihara, H.; Matsumoto, M.;
Yamamoto, H. J. Am. Chem. Soc. 1998, 120, 6920.
(3) (a) Ishihara, K.; Kondo, S.; Yamamoto, H. Synlett 1999, 1283.
(b) Ishihara, K.; Kondo, S.; Yamamoto, H. J. Org. Chem.
2000, 65, 9125.
(4) (a) Ishihara, K.; Ohara, S.; Yamamoto, H. J. Org. Chem. 1996,
61, 4196. (b) Ishihara, K.; Ohara, S.; Yamamoto, H.
Macromolecules 2000, 33, 3511.
(5) (a) Horváth, I. T.; Rábai, J. Science 1994, 266, 72.
(b) Horváth, I. T. Acc. Chem. Res. 1998, 31, 641. (c) Vogt, M.
The Application of Perfluorinated Polyethers for
Immobilization of Homogeneous Catalysts, Ph.D. Thesis,
Rheinisch-Wesfälischen Technischen Hochschule, Aachen,
Germany, 1991.
flask
R2
N
R1CO2H
O
C
HNR2R3
R1
(heterogeneous, rt)
toluene or o-xylene
R3
toluene or o-xylene
Figure 2 Recovery of 4 by decantation and its reuse without
isolation
at ambient temperature for 1 h to precipitate 4. The liquid
phase of the resultant mixture was decanted and the resid-
ual solid catalyst 4 was reused without isolation. No loss
of activity was observed for the recovered catalyst, and
26% of 4 remained in the flask in the 10th reaction. This
means that 88% of 4 was retained in each cycle. The total
isolated yield of the amide which was obtained in ten re-
actions was 96%. Moreover, pure compound 4 could be
recovered in 97% yield as a white solid from the above re-
action mixture by filtration and washing with toluene.17
(6) Reviews: (a) Curran, D. P. Angew. Chem. Int. Ed. Engl. 1998,
37, 1174. (b) Fish, R. H. Chem. Eur. J. 1999, 5, 1677.
(c) Cornils, B. Angew. Chem. Int. Ed. Engl. 1997, 36, 2057.
(7) Mikami, K.; Mikami, Y.; Matsumoto, Y.; Nishikido, J.;
Yamamoto, F.; Kakajima, H. Tetrahedron Lett. 2001, 42, 289.
(8) McLoughlin, V. C. R.; Thrower, J. Tetrahedron 1969, 25,
5921.
(9) For the effect of 2,2’-dipyridyl, see: Chen, W.; Xiao, J.
Tetrahedron Lett. 2000, 41, 3697.
Synlett 2001, No. 9, 1371–1374 ISSN 0936-5214 © Thieme Stuttgart · New York

1374
K. Ishihara et al.
LETTER
(10) (a) Ishiyama, T.; Kitano, T.; Miyaura, N. Tetrahedron Lett.
1997, 38, 3447. (b) Ishiyama, T.; Murata, M.; Miyaura, N. J.
Org. Chem. 1995, 60, 7508.
(15) Perfluorodecaline was not miscible with a single non-fluorous
solvent, toluene or o-xylene, even under reflux conditions.
(16) For recent examples of precipitatable catalysts, see:
Bergbreiter, D. E.; Koshti, N.; Franchina, J. G.; Frels, J. D.
Angew. Chem. Int. Ed. 2000, 39, 1040. (b) Janda, K. D.;
Reger, T. S. J. Am. Chem. Soc. 2000, 122, 6029.
(17) Typical procedure for the direct amide condensation
(Table 3 and Figure 2). A dry, 10-mL round-bottom flask
fitted with a stirring bar and a 5-mL pressure-equalized
addition funnel (containing a cotton plug and ca. 2 g of 4 Å
molecular sieves (pellets) and functioning as a Soxhlet
extractor) surmounted by a reflux condenser was charged with
cyclohexanecarboxylic acid (128.2 mg, 1.0 mmol),
(11) 3: white solid; mp 166 °C; IR (KBr) 3600 3200 (OH), 1406,
1375, 1345, 1240, 1210, 1150 cm; 1H NMR (CDCl3, 300
MHz, 55 °C) 7.63 (d, J = 9.3 Hz, 1H), 7.90 (d, J = 9.3 Hz,
1H); 19F NMR (CDCl3, 282 MHz)
128.17 (s, 3F), 124.61
(s, 2F), 123.51 (s, 10F), 123.06 (s, 2F), 111.91 (s, 2F),
83.33 (s, 2F). Anal. Calcd for C16H6F21BO2: C, 30.03; H,
0.94. Found: C, 30.09; H, 0.89.
(12) 4: white solid; mp 166 °C; IR (KBr) 1375, 1841, 1293, 1225,
1150, 1096, 899 cm−1 (The OH stretching freuency for 4 was
not observed probably because the sample contained varying
amounts of boronic anhydride); 1H NMR (CDCl3, 300 MHz,
55 °C) 7.90 (s, 1H), 8.12 (s, 2H); 19F NMR (CDCl3, 282
benzylamine (109.2 L, 1.0 mmol), and 4 (57.9 mg, 0.05
mmol) in o-xylene (5 mL). The mixture was heated at
azeotropic reflux with removal of water to provide a
homogeneous solution. After 3 h, the resulting mixture was
cooled to ambient temperature to precipitate 4. After 1 h, the
liquid phase of the resultant mixture was decanted and the
residual solid catalyst 4 was reused without isolation. Catalyst
4 remained in the flask in the 10th reaction. Liquid phases
which were obtained in each reactions were combined,
concentrated under reduced pressure, and the residue was
purified by column chromatography on silica gel (eluant:
hexane-ethyl acetate = 3:1) to give the corresponding amide
(2.08 g, 9.6 mmol, 96% yield). The spectral data for the amide
is in agreement with data previously reported by us.4a Typical
Procedure for Recovering of 4. After completing the above
reaction (one cycle), the resulting mixture was cooled to
ambient temperature to precipitate 4. After 1 h, the resultant
mixture was diluted with toluene (3 mL), and 4 was separated
by filtration, washed with toluene (2 mL), and dried under
vacuum (1 torr) to recover 4 (56.0 mg, 97% yield) as a pure
white solid.
MHz, 55 °C)
127.09 (s, 6F), 123.70 (s, 4F), 122.78 (s,
20F), 122.15 (s, 4F), 112.04 (t, J = 15.2 Hz, 4F), 81.96 (t,
J = 9.0 Hz, 4F). Anal. Calcd for C26H5F42BO2: C, 26.97; H,
0.44. Found: C, 27.01; H, 0.35.
(13) (a) Zhang, L. H.; Duan, J.; Xu, Y.; Dolbier, W. R. Jr.
Tetrahedron Lett. 1998, 39, 9621. (b) Duan, J.; Zhang, L. H.;
Dolbier, W. R. Jr. Synlett 1999, 1245.
(14) Typical procedure for the direct amide condensation
(Table 2 and Figure 1). A dry, 10-mL round-bottom flask
fitted with a stirring bar and 15-mL pressure-equalized
addition funnel (containing a cotton plug and ca. 2 g of 4 Å
molecular sieves (pellets) and functioning as a Soxhlet
extractor) surmounted by a reflux condenser was charged with
cyclohexanecarboxylic acid (128.2 mg, 1.0 mmol),
benzylamine (109.2 L, 1.0 mmol), and 4 (34.7 mg, 0.03
mmol) in o-xylene (2.5 mL) and perfluorodecaline (2.5 mL).
The mixture was heated at azeotropic reflux with removal of
water to provide a homogeneous solution. After 3 h, the
resulting mixture was cooled to ambient temperature, and
phase separation occurred immediately. The organic phase
was concentrated under reduced pressure, and the residue was
purified by column chromatography on silica gel (eluant:
hexane-ethyl acetate = 3:1) to give the corresponding amide
(215 mg, 0.99 mmol, 99% yield). The spectral data for the
amide is in agreement with data previously reported by us.4a
The fluorous phase containing the catalyst 4 was recovered
and could be used for further experiments.
Article Identifier:
1437-2096,E;2001,0,09,1371,1374,ftx,en;G09901ST.pdf
Synlett 2001, No. 9, 1371–1374 ISSN 0936-5214 © Thieme Stuttgart · New York