Rhodium-catalyzed arylation of α-amido sulfones with arylboronic acids in a water-toluene biphasic system

Article abstract of DOI:10.1016/j.ica.2010.09.056

An efficient method for the synthesis of N-protected diaryl-methyl-amines was developed through a rhodium-catalyzed arylation of α-amido sulfones with arylboronic acids in a water-toluene biphasic system. The use of a base combined with a surfactant playe

Full text of DOI:10.1016/j.ica.2010.09.056

Inorganica Chimica Acta 369 (2011) 284–287
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Rhodium-catalyzed arylation of
water–toluene biphasic system
a-amido sulfones with arylboronic acids in a
a,
Xiao-Yong Dou a,b, Qi Shuai a, Liang-Nian He b, , Chao-Jun Li
⇑
⇑
a Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, Quebec, Canada H3A 2K6
b State Key Laboratory and Institute of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, People’s Republic of China
a r t i c l e i n f o
a b s t r a c t
Article history:
Available online 8 October 2010
An efficient method for the synthesis of N-protected diaryl-methyl-amines was developed through a rho-
dium-catalyzed arylation of
The use of a base combined with a surfactant played a key role in this biphasic reaction. A diverse range of
-branched amine derivatives bearing different functional groups were obtained within 10 min under the
present conditions.
a-amido sulfones with arylboronic acids in a water–toluene biphasic system.
Dedicated to R.G. Bergman and
R.J. Puddephatt
a
Ó 2010 Elsevier B.V. All rights reserved.
Keywords:
Rhodium
Arylboronic acids
a-Amido sulfones
Imines
Aqueous media
1. Introduction
array of sensitive functional groups and can even work well in
water and air. Among them, arylboronic acids are extremely power-
ful organometallic reagents in organic synthesis because they are
moisture-stable, easy to handle, commercially available and com-
patible with many functional groups. Additions of arylboronic acids
to imines have already been intensively studied recently; however,
they generally suffer from harsh reaction conditions, a long reaction
time and poor functional group compatibility [10–23]. Such restric-
tions undoubtedly limited the application of these reactions.
Due to the abundance of water as well as the inherent advanta-
ges of using water as a solvent, recent interest has been growing in
studying organic reactions in water [24–26]. Many reactions that
are traditionally carried out in organic solvent can be conducted
in water with additional beneficial features: (1) water-soluble sub-
strates such as carbohydrates can be used directly without deriva-
tization, (2) the aqueous catalyst solution can be recycled easily,
and (3) water-insoluble products can be separated conveniently
by simple phase separations. Among them, we and others have
reported that organometallic reagents including organoboron,
organotin, organobismuth and organolead reagents were effective
for carbonyl addition and conjugated addition reactions in air
and water [27–39]. In addition, we also reported the copper-
mediated or catalyzed direct nucleophilic additions of alkynes to
reactive N-acylimines and N-acyliminium ions (generated in situ
The addition reactions of various organometallic reagents to the
C@N bond of imines and their derivatives have attracted consider-
able attention of organic chemists [1,2]. Such reactions can provide
practical methods for the synthesis of a-branched amines and their
derivatives, which are prevalent and important building blocks of
many biological and pharmaceutical agents. However, most imines
are unstable and prone to decomposition during workup. Further-
more, many functional groups are not tolerated with the classical
organometallic reagents and need to be protected. Thus, methods
involving the generation of the imine in situ are highly desirable.
a-Amido sulfones are stable precursors of reactive imino deriva-
tives, which can be easily synthesized by the three-components
coupling of carbamate, aldehyde, and sodium sulfinates under
acidic conditions [3]. Subsequent elimination of sulfinic acid leads
to the in situ generation of reactive N-acylimines, which can react
with nucleophilic reagents to give the corresponding addition prod-
ucts [3–6]. Recently, Ollevier’s group developed a Bi(OTf)3 catalyzed
addition of allylsilanes and silyl enolates to N-alkoxycarbonylamino
sulfones [7–9].
With the advances in organic chemistry, many stable organome-
tallic compounds are developed as substitutes for Grignard and
organolithium reagents. Such alternative reagents can tolerate an
from
a-amido sulfones or methoxyl groups as stable precursors),
affording propargylamine derivatives in aqueous media [40].
Based on our intensive interest in organic reactions in aqueous
media and the excellent properties of boronic acids, we envisioned
⇑
Corresponding authors. Fax: +1 514 398 3797 (C.-J. Li), +86 22 2350 4216 (L.-N.
He).
E-mail addresses: heln@nankai.edu.cn (L.-N. He), cj.li@mcgill.ca (C.-J. Li).
0020-1693/$ - see front matter Ó 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.ica.2010.09.056

X.-Y. Dou et al. / Inorganica Chimica Acta 369 (2011) 284–287
285
that arylation of
ous media will be a direct and practical method for the synthesis of
-branched amines and their derivatives. To the best of our knowl-
edge, such a reaction has not been achieved. Herein, we reported
our results on the rapid arylation of -amido sulfones with arylbo-
a
-amido sulfones with arylboronic acids in aque-
(m, 6H), 7.30–7.34 (m, 4H). 13C NMR (CDCl3, 75 MHz) d 28.3,
58.4, 79.8, 127.2, 127.3, 128.6, 142.0, 155.0. HRMS APCI (m/z):
[M+H]+ calcd for C18H22O2N, 284.16451; found, 284.16457.
Compound 3d was obtained as a white solid. 1H NMR (CDCl3,
400 MHz) d 1.25 (bs, 3H), 4.10–4.16 (q, J = 7.2 Hz, 2H), 5.28 (bs,
1H), 5.97 (d, J = 6.8 Hz, 1H), 7.23–7.28 (m, 6H), 7.31–7.35 (m,
4H). 13C NMR (CDCl3, 75 MHz) d 14.5, 58.6, 61.1, 127.2, 127.4,
128.6, 141.8, 155.8. HRMS APCI (m/z): [M+H]+ calcd for
a
a
ronic acids in a water–toluene biphasic system.
2. Experimental
C
16H18O2N, 256.13321; found, 256.13323.
Compound 3e was obtained as a white solid. 1H NMR (CDCl3,
2.1. General
400 MHz) d 3.69 (s, 3H), 5.32 (bs, 1H), 5.98 (d, J = 6.8 Hz, 1H),
7.23–7.28 (m, 6H), 7.31–7.35 (m, 4H). 13C NMR (CDCl3, 75 MHz)
d 52.3, 58.8, 127.2, 127.5, 128.6, 141.6, 156.2. HRMS APCI (m/z):
[M+H]+ calcd for C15H16O2N, 242.11756; found, 242.11779.
Compound 3f was obtained as a white solid. 1H NMR (CDCl3,
400 MHz) d 0.91 (bs, 3H), 1.36 (bs, 2H), 1.57 (bs, 2H), 2.32 (s,
3H), 4.07 (t, J = 6.4 Hz, 2H), 5.25 (bs, 1H), 5.92 (bs, 1H), 7.13 (s,
4H), 7.23–7.34 (m, 5H). 13C NMR (CDCl3, 75 MHz) d 13.7, 19.0,
21.0, 31.0, 58.4, 65.0, 127.1, 127.3, 128.5, 129.3, 137.1, 138.9,
142.0, 155.9. HRMS APCI (m/z): [M+H]+ calcd for C19H24O2N,
298.18016; found, 298.18022.
All work-up and purification procedures were carried out with
reagent-grade solvents. Analytical thin-layer chromatography
(TLC) was performed using E. Merck silica gel 60 F254 pre-coated
plates (0.25 mm) or Sorbent silica gel 60 F254 plates. The devel-
oped chromatography was analyzed by UV lamp (254 nm). Flash
column chromatography was performed with E. Merck silica gel
60 (230–400 mesh) or Sorbent silica gel 30–60 lm. High-resolu-
tion mass spectra (HRMS) were obtained from a JEOL JMS-700
instrument (ACPI). Nuclear magnetic resonance (NMR) spectra
were recorded on Varian MERCURY plus-300 spectrometer (1H
300 MHz, 13C 75 MHz), a Varian MERCURY plus-400 spectrometer
(1H 400 MHz, 13C 100 MHz), or a Varian MERCURY plus-500 spec-
trometer (1H 500 MHz, 13C 125 MHz). Chemical shifts for 1H NMR
spectra are reported in parts per million (ppm) with the solvent
resonance as the internal standard (CDCl3: d 7.26 ppm). Chemical
shifts for 13C NMR spectra are reported in parts per million
Compound 3g was obtained as a white solid. 1H NMR (CDCl3,
400 MHz) d 0.91 (bs, 3H), 1.36 (bs, 2H), 1.56 (bs, 2H), 4.07 (t,
J = 6.4 Hz, 2H), 5.24 (bs, 1H), 5.92 (bs, 1H), 7.18–7.20 (m, 4H),
7.25–7.35 (m, 5H). 13C NMR (CDCl3, 75 MHz) d 13.7, 19.0, 30.9,
58.2, 65.1, 127.2, 127.7, 128.5, 128.7, 128.8, 133.2, 140.3, 141.2,
155.8. HRMS APCI (m/z): [M+H]+ calcd for C18H21O2NCl,
318.12553; found, 318.12548.
(ppm) with the solvent as the internal standard (CDCl3:
d
Compound 3h was obtained as a white solid. 1H NMR (CDCl3,
400 MHz) d 0.91 (bs, 3H), 1.36 (bs, 2H), 1.58 (bs, 2H), 4.07 (t,
J = 6.4 Hz, 2H), 5.25 (bs, 1H, 5.90 (bs, 1H), 7.13(d, J = 8.4 Hz, 2H),
7.21 (d, J = 6.8 Hz, 2H),7.26–7.35 (m, 3H), 7.43–7.46 (m, 2H). 13C
NMR (CDCl3, 75 MHz) d 13.6, 18.09, 30.9, 58.2, 65.1, 121.3, 127.2,
127.7, 128.7, 128.8, 131.6, 140.9, 141.1, 155.8. HRMS APCI (m/z):
[M+H]+ calcd for C18H21O2NBr, 362.07502; found, 362.07573.
Compound 3i was obtained as a white solid. 1H NMR (CDCl3,
400 MHz) d 0.93 (t, J = 6.8 Hz, 3H), 1.37–1.39 (m, 2H), 1.58–1.59
(m, 2H), 2.31 (s, 3H), 4.08 (t, J = 6.8 Hz, 2H), 5.26 (d, J = 6.4 Hz,
1H), 6.15 (d, J = 7.6 Hz, 1H), 7.14–7.23 (m, 6H), 7.25–7.33 (m,
3H). 13C NMR (CDCl3, 75 MHz) d 13.7, 19.0, 19.4, 31.0, 55.5, 65.0,
126.2, 126.5, 127.3, 127.4, 128.6, 130.7, 136.0, 139.8, 140.9,
141.2, 155.8. HRMS APCI (m/z): [M+H]+ calcd for C19H24O2N,
298.18016; found, 298.17998.
77.0 ppm). Data are reported as following: chemical shift, multi-
plicity (s = singlet, d = doublet, dd = doublet of doublets, t = triplet,
q = quartet, m = multiplet, br = broad signal), coupling constant
(Hz), and integration. Unless stated otherwise, commercial re-
agents were used without further purification. All reagents were
weighed and handled in air at room temperature.
a-Amido sulf-
ones were prepared according to the literature method [41].
2.2. A representative experimental procedure
A reaction vessel was charged with benzenesulfonyl-phenyl-
methyl-carbamic acid benzyl ester 1a (38.1 mg, 0.1 mmol), phenyl-
boronic acid (18.3 mg, 0.15 mmol), sodium dodecyl sulfate
(20 mg), Rh(COD)2BF4 (2.1 mg, 5 mmol%), water (0.3 mL), and tolu-
ene (0.5 mL); sealed and the resulting solution was stirred at
150 °C for 10 min. The resulting mixture was cooled to room tem-
perature and the residue was extracted with ethyl acetate
(3 Â 5 mL). The combined organic extract was dried over MgSO4.
After removal of the solvent, the residue was purified by flash chro-
matography on silica gel (eluent: hexane/diethyl ether = 10:1) to
give benzyl benzhydrylcarbamate 3a.
Compound 3j was obtained as a white solid. 1H NMR (CDCl3,
400 MHz) d 0.92 (t, J = 6.8 Hz, 3H), 1.36–1.38 (m, 2H), 1.59 (bs,
2H), 3.77 (s, 3H), 4.07 (t, J = 6.8 Hz, 2H), 5.29 (bs, 1H), 5.93 (d,
J = 6.8 Hz, 1H), 6.79–6.84 (m, 3H), 7.22–7.34 (m, 6H). 13C NMR
(CDCl3, 75 MHz) d 13.7, 19.0, 31.0, 55.2, 58.6, 65.0, 112.5, 113.1,
119.5, 127.2, 127.4, 128.6, 129.6, 141.6, 143.4, 155.9, 159.7. HRMS
APCI (m/z): [M+H]+ calcd for C19H24O3N, 314.17507; found,
314.17558.
2.3. 1H, 13C NMR spectra and HR/MS data
Compound 3k was obtained as a white solid. 1H NMR (CDCl3,
400 MHz) d 0.92 (bs, 3H), 1.38 (bs, 2H), 1.59 (bs, 2H), 4.08 (t,
J = 6.4 Hz, 2H), 5.29 (bs, 1H), 6.00 (bs, 1H), 7.20–7.22 (m, 2H),
7.27–7.40 (m, 5H), 7.59 (d, J = 8.0 Hz, 2H). 13C NMR (CDCl3,
75 MHz) d 13.7, 19.0, 30.9, 58.5, 65.2, 125.5, 125.6, 127.3, 127.9,
128.9, 129.4, 140.8, 145.8, 155.8. HRMS APCI (m/z): [M+H]+ calcd
for C19H21O2NF3, 352.15189; found, 352.15213.
Compound 3a was obtained as a white solid [42]. 1H NMR
(CDCl3, 400 MHz) d 5.12 (s, 2H), 5.41 (bs, 1H), 6.00 (d, J = 7.6 Hz,
1H), 7.24–7.29 (m, 6H), 7.31–7.35 (m, 9H). 13C NMR (CDCl3,
125 MHz) d 58.8, 67.0, 127.2, 127.5, 128.2, 128.5, 128.6, 136.2,
141.6, 155.5.
Compound 3b was obtained as a white solid. 1H NMR (CDCl3,
400 MHz) d 0.92 (bs, 3H), 1.38 (bs, 2H), 1.61 (bs, 2H), 4.08 (t,
J = 6.4 Hz, 2H), 5.31 (bs, 1H), 5.98 (d, J = 6.0 Hz, 1H), 7.24–7.28
(m, 6H), 7.31–7.35 (m, 4H). 13C NMR (CDCl3, 75 MHz) d 13.7,
19.0, 31.0, 58.6, 65.0, 127.2, 127.4, 128.6, 141.8, 155.9. HRMS APCI
(m/z): [M+H]+ calcd for C18H22O2N, 284.16451; found, 284.16441.
Compound 3c was obtained as a white solid. 1H NMR (CDCl3,
400 MHz) d 1.44 (s, 9H), 5.16 (bs, 1H), 5.91 (bs, 1H), 7.23–7.27
Compound 3l was obtained as a white solid. 1H NMR (CDCl3,
400 MHz) d 0.93 (bs, 3H), 1.39 (bs, 2H), 1.61 (bs, 2H), 4.10 (t,
J = 6.8 Hz, 2H), 5.42 (bs, 1H), 6.14 (bs, 1H), 7.26–7.36 (m, 6H),
7.45–7.50 (m, 2H), 7.73 (s, 1H), 7.79–7.83 (m, 3H). 13C NMR (CDCl3,
75 MHz) d 13.7, 19.0, 31.0, 58.8, 65.1, 125.4, 125.7, 126.0, 126.3,
127.4, 127.5, 127.6, 128.0, 128.5, 128.7, 132.7, 133.2, 139.1,
141.6, 156.0. HRMS APCI (m/z): [M+H]+ calcd for C22H24O2N,
334.18016; found, 334.18052.

286
X.-Y. Dou et al. / Inorganica Chimica Acta 369 (2011) 284–287
Compound 3m was obtained as a white solid. 1H NMR (CDCl3,
K2CO3 decreased the yield, whereas further increasing the amount
of K2CO3 above one equivalent did not give significant improvement
of the yield (Table 1, entries 5 and 6). These results can be rational-
ized that the addition of bases facilitate the formation of the reactive
N-acylimines that readily reacted with nucleophilic reagents to give
the corresponding addition products; in addition, phenylboronic
acid could also be activated under basic conditions [28].
400 MHz) d 0.92 (bs, 3H), 1.38 (bs, 2H), 1.60 (bs, 2H), 4.07 (t,
J = 6.4 Hz, 2H), 5.23 (d, J = 10.8 Hz, 1H), 5.28 (bs, 1H), 5.73 (d,
J = 19.2 Hz, 1H), 5.95 (bs, 1H), 6.65–6.73 (dd, J = 17.6 Hz,
J = 10.8 Hz, 1H), 7.20–7.28 (m, 5H), 7.31–7.38 (m, 4H). 13C NMR
(CDCl3, 75 MHz) d 13.7, 19.0, 31.0, 58.4, 65.0, 114.0, 126.4, 127.2,
127.4, 127.5, 128.6, 136.2, 136.7, 141.3, 141.6, 155.9. HRMS APCI
(m/z): [M+H]+ calcd for C20H24O2N, 310.18016; found, 310.18022.
Compound 3n was obtained as a white solid. 1H NMR (CDCl3,
400 MHz) d 0.92 (bs, 3H), 1.37 (bs, 2H), 1.60 (bs, 2H), 2.58 (s,
1H), 4.08 (t, J = 6.8 Hz, 2H), 5.30 (bs, 1H), 5.99 (bs, 1H), 7.20–7.22
(m, 2H), 7.26–7.38 (m, 5H), 7.93 (d, J = 8.4 Hz, 2H). 13C NMR (CDCl3,
75 MHz) d 13.6, 18.9, 26.2, 30.9, 58.6, 65.2, 127.2, 127.3, 127.8,
128.7, 128.8, 136.2, 140.9, 147.1, 155.8, 197.6. HRMS APCI (m/z):
[M+H]+ calcd for C20H24O3N, 326.17507; found, 326.17516.
There are two competitive reactions related to
a-amido sulf-
ones in water: (1) hydrolysis under basic conditions and (2) the
tandem elimination–addition reaction with phenylboronic acid.
In order to overcome hydrolysis of
a-amido sulfones in water,
we hypothesized that the use of a surfactant and an aqueous
two-phase system would decrease the kinetics of hydrolysis by
preventing and/or diminishing the N-acylimines from encounter-
ing water molecules. The use of a water–toluene biphasic system
together with a catalytic amount of sodium laurylsulfate as a sur-
factant and one equivalent of K2CO3 provided the desired product
in 60% yield (Table 1, entry 8). The use of a surfactant together with
a biphasic system is very critical for the success of the reaction.
After further optimization of the reaction conditions, 77% yield of
the arylation product 3a was obtained in a water (0.3 mL)–toluene
(0.5 mL) biphasic system at 70 °C together with sodium laurylsul-
fate (20 mg) (Table 1, entry 12). It is interesting to note that only
a trace amount of the corresponding product was detected when
toluene alone was employed as the solvent (Table 1, entry 14
versus entry 2). Water is an essential co-solvent in the reaction,
possibly by dissolving the K2CO3 that can neutralize the sulfinic
acid generated from the coupling reaction and further driving the
3. Results and discussion
Duo to the high catalytic activity of Rh(cod)2BF4 in the aqueous
reaction in our initial studies, a model reaction employing benzene-
sulfonyl-phenylmethyl-carbamic acid benzyl ester 1a and phenyl-
boronic acid 2a as substrates in water was examined (Scheme 1).
However, no corresponding arylation product was detected (Table 1,
entry 1). When an inorganic base was added, a low yield of benzyl
benzhydrylcarbamate 3a was obtained (Table 1, entries 2–4); and
a better yield (30%) of 3a was obtained when one equivalent of
K2CO3 was added (Table 1, entry 2). Lowering the amount of
O
Ph
O
SO2Ph
Ph
Rh(cod)2BF4
B(OH)2
BnO
N
H
BnO
N
H
3a
1a
2a
Scheme 1. Arylation of benzenesulfonyl-phenylmethyl-carbamic acid benzyl ester.
Table 1
Optimization of the reaction conditions.a
Entry
Time
T (°C)
Solvent
Additive
Yield (%)
1
4 h
70
H2O (0.2 mL)
/
0
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20b
21c
22d
23e
4 h
4 h
4 h
4 h
4 h
4 h
4 h
4 h
4 h
4 h
4 h
4 h
4 h
4 h
4 h
4 h
70
70
70
70
70
70
70
70
70
70
70
70
H2O (0.2 mL)
H2O (0.2 mL)
H2O (0.2 mL)
H2O (0.2 mL)
K2CO3 1 equiv
KOH 1 equiv
Cs2CO3 1 equiv
K2CO3 0.4 equiv
K2CO3 2 equiv
K2CO3 1 equiv
30
26
23
19
31
38
60
65
34
64
77
75
trace
80
94
96
96
94
60
74
51
37
H2O (0.2 mL)
H2O (0.2 mL)/toluene (0.2 mL)
H2O (0.2 mL)/toluene (0.2 mL)
H2O (0.2 mL)/toluene (0.2 mL)
H2O (0.1 mL)/toluene (0.3 mL)
H2O (0.3 mL)/toluene (0.3 mL)
H2O (0.3 mL)/toluene (0.5 mL)
H2O (0.3 mL)/toluene (1.0 mL)
toluene (0.2 mL)
H2O (0.3 mL)/toluene (0.5 mL)
H2O (0.3 mL)/toluene (0.5 mL)
H2O (0.3 mL)/toluene (0.5 mL)
H2O (0.3 mL)/toluene (0.5 mL)
H2O (0.3 mL)/toluene (0.5 mL)
H2O (0.3 mL)/toluene (0.5 mL)
H2O (0.3 mL)/toluene (0.5 mL)
H2O (0.3 mL)/toluene (0.5 mL)
H2O (0.3 mL)/toluene (0.5 mL)
K2CO3 1 equiv, 10 mg SDS
K2CO3 1 equiv, 20 mg SDS
K2CO3 1 equiv, 20 mg SDS
K2CO3 1 equiv, 20 mg SDS
K2CO3 1 equiv, 20 mg SDS
K2CO3 1 equiv, 20 mg SDS
K2CO3 1 equiv
K2CO3 1 equiv, 20 mg SDS
K2CO3 1 equiv, 20 mg SDS
K2CO3 1 equiv, 20 mg SDS
K2CO3 1 equiv, 20 mg SDS
K2CO3 1 equiv, 20 mg SDS
K2CO3 1 equiv, 20 mg TW40
K2CO3 1 equiv, 20 mg N-dodecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate
K2CO3 1 equiv, 20 mg cetyltrimethylammonium bromide
K2CO3 1 equiv, 20 mg cetyltrimethylammonium hydrogensulfate
70
100
135
150
150
150
150
150
150
150
0.5 h
10 min
10 min
10 min
10 min
10 min
a
b
c
Benzyl phenyl(tosyl)methylcarbamate (0.1 mmol), arylboronic acids (0.15 mmol, 150 mol%), sodium dodecyl sulfonate (20 mg), and Rh(cod)2BF4 (0.005 mol, 5 mol%).
Tween 40 (20 mg) as the surfactant.
N-Dodecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate (20 mg) as the surfactant.
Cetyltrimethylammonium bromide (20 mg) as the surfactant.
d
e
Cetyltrimethylammonium hydrogensulfate (20 mg) as the surfactant.

X.-Y. Dou et al. / Inorganica Chimica Acta 369 (2011) 284–287
287
O
SO2Ph
R2
O
R2
Rh(cod)2BF4
R3 B(OH)2
K2CO3, SDS
Toluene/H2O
150 oC, 10 min
R1O
N
H
R1O
N
H
R3
3
1
2
Scheme 2. Rh(cod)2BF4 catalyzed arylation of a-amido sulfones with arylboronic acids in water–toluene biphasic reaction system.
The reaction proceeds very rapidly and can be completed within
10 min. This method allows us to prepare a diverse range of
Table 2
Substrate scope.a
a-branched amines derivatives, and can tolerate different func-
Entry
R1
R2
R3
Product
Yield (%)b
tional groups.
1
2
3
4
5
6
7
8
Bn
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
3a
3b
3c
3d
3e
3f
3g
3h
3i
83
84
82
62
57
69
89
86
85
76
28
79
67
51
n-Bu
t-Bu
Et
Acknowledgments
We are grateful to the Canada Research Chair (Tier I) Founda-
tion (to C.-J. Li), CFI, NSERC, ACS-GCI Pharmaceutical Roundtable
and the program for New Century Excellent Talents in University
(Grant No. NCET-07-0399) for support of our research. X.-Y. Dou
thanks the National Graduate Student Program of Building
World-class Universities Grant (Grant No. [2009]3012) for financial
support.
Mt
Ph
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
4-Me–C6H4
4-Cl–C6H4
4-Br–C6H4
Ph
Ph
Ph
Ph
Ph
Ph
9
2-Me–C6H4
3-MeO–C6H4
4-CF3–C6H4
2-naphthyl
4-CH2@CH–C6H4
4-CH3CO–C6H4
10
11
12
13
14
3j
3k
3k
3m
3n
References
a
a
-Amido sulfones (0.2 mmol), arylboronic acids (0.3 mmol, 150 mol%), sodium
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dodecyl sulfonate (40 mg), K2CO3 (0.2 mmol, 100 mol%) and Rh(cod)2BF4 (0.01 mol,
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5 mol%) in water (0.6 mL), toluene (1.0 mL), 150 °C, 10 min.
b
Isolated yield based on a-amido sulfones 1.
reaction toward the formation of the desired product. The reaction
temperature is another important factor for this reaction. The yield
of 3a increased as the reaction temperature was increased from 70
to 150 °C (entries 12, 15–17), and reached the maximum value of
96% at 150 °C. It is worth mentioning that the reaction proceeded
very rapidly and could be completed within 10 min (Table 1, entry
19). Under the optimized reaction conditions, other surfactants
available in our lab were also examined and gave relatively lower
yields than sodium laurylsulfate under the same reaction condi-
tions (Table 1, entries 20–23).
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Subsequently, various
a-amido sulfones were coupled with
arylboronic acids under the optimized conditions (Scheme 2).
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The reaction was found to be highly sensitive to the carbamate
structural motif of the starting material 1. The
a-phenylsulfonyl-
amine with n-BOC, n-Bu and CBz groups could react smoothly to
afford the desired coupling products in good yields (Table 2, entries
1–3). Relatively low yields of the corresponding products were ob-
tained when using
carbamate (Table 2, entries 4 and 5). The electronic nature of the R2
also has a significant effect on the reaction. The -phenylsulfonyl-
a-amido sulfones derived from methyl or ethyl
a
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amine derived from aromatic aldehydes with electron-withdraw
groups gave higher yields than the ones with electron-donating
substituents (Table 2, entries 6–8). Various arylboronic acids were
subjected to this reaction; and it was found that the nature of the
R3 also has a marked effect on the reactivity. Electron-rich arylbo-
ronic acids gave better yields than the electron-poor ones (Table 2,
entries 9–11). Functional groups (e.g., carbonyl group and carbon–
carbon double bond) are tolerated under the reaction conditions
(Table 2, entries 13–14).
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In conclusion, we have developed an effective arylation of
a-
amido sulfones with arylboronic acids catalyzed by Rh(cod)2BF4
in a water–toluene biphasic system. The uses of K2CO3 as a base
and sodium dodecyl sulfate as a surfactant combined with a
water–toluene biphasic system play a key role in the reaction.