Rhodium catalyzed three-component reaction of aldehyde, boronic acid, and sulfonamides: A facile one-pot synthesis of diarylmethylamines

Article abstract of DOI:10.1016/j.tetlet.2014.08.003

Rhodium(I) catalyzed three-component reaction for the one pot synthesis of diarylmethylamines in excellent yields were achieved by using aldehyde, boronic acid, and sulfonamides. The use of hyper-valent bis(trifluoroacetoxy)iodobenzene as an additive plays a key role in the chemo selective formation of amines instead of alcohols.

Full text of DOI:10.1016/j.tetlet.2014.08.003

Tetrahedron Letters xxx (2014) xxx–xxx
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Rhodium catalyzed three-component reaction of aldehyde, boronic
acid, and sulfonamides: a facile one-pot synthesis of
diarylmethylamines
Ponnam Satyanarayana, Ganapam Manohar Reddy, Hariharasarma Maheswaran,
⇑
Mannepalli Lakshmi Kantam
Inorganic and Physical Chemistry Division, Indian Institute of Chemical Technology, Hyderabad 500 007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Rhodium(I) catalyzed three-component reaction for the one pot synthesis of diarylmethylamines in
excellent yields were achieved by using aldehyde, boronic acid, and sulfonamides. The use of hyper-
valent bis(trifluoroacetoxy)iodobenzene as an additive plays a key role in the chemo selective formation
of amines instead of alcohols.
Received 25 April 2014
Revised 31 July 2014
Accepted 2 August 2014
Available online xxxx
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Bis(1,5-cyclooctadiene)-rhodium(I)-
tetrafluoroborate
Diaryl methylamines
Bis(trifluoroacetoxy)-iodobenzene
Three component reaction
Homogeneous catalysis
Construction of carbon–carbon and carbon–nitrogen bonds is of
prime importance in organic synthesis1 due to their prevalence in
wide array of pharmaceuticals,2 biologically active compounds,3
natural products,4 agrochemicals, fine chemicals, and materials.5
The synthesis of diarylmethylamines is important because these
amines are subunits of biologically significant compounds.2 Variety
of methods were reported for the synthesis of diarylmethylamines
such as addition of organometallic reagent to an imine,6
substitution of a hydroxyl group using amine nucleophiles,7 and
direct benzylic C–H amination via dehydrogenative coupling.8
Recently, Renhua et al. reported amination of sp3 C–H bonds via
C–H activation using sulfonamides9 and Kaneda et al. reported
additives, phosphorus ligands, and solvents were altered to find
the best conditions. Rhodium based catalysts like bis(1,5-cycloocta-
diene)rhodium(I)tetrafluoroborate (catalyst 1) and chloro(1,5-
cyclooctadiene)rhodium(catalyst2), inconjunctionwithphosphine
ligands, 1,5-bis(diphenylphosphino)pentane (L1) and 1,2-bis[bis(-
penta-fluorophenylphosphino)ethane (L2) (see Fig. 1) were tested
for the reaction in the presence of additives that include silver oxide,
silver carbonate, copper(II) acetate, hypervalent iodine reagent
[bis(trifluoroacetoxy)iodo]benzene and [bis(acetoxy)iodo]benzene.
The reaction performed using catalyst 1 and L1 in the presence
of silver oxide in toluene afforded the desired product diarylmeth-
ylamine in very poor yields (10%) (Table 1; entry 1). Moreover, the
reaction failed when catalyst 2 was employed under similar reac-
tion conditions (Table 1; entry 2). The use of hypervalent iodine
based [bis(trifluoroacetoxy)iodo]benzene as additive along with
catalyst 1 and L1 improved the yield to 25% (Table 1; entry 3). In
contrast, the reaction performed with catalyst 2 under similar
reaction conditions failed to furnish the desired products (Table 1;
entry 4). Notably, when the reaction was conducted using L2
instead of L1, excellent yield of the desired product was obtained
(Table 1; entry 5). Remarkably, when the reaction was performed
in the absence of bis(trifluoro-acetoxy)iodo]benzene additive, the
formation of diarylmethyl alcohol in significant amount was
observed [(Table 1; entry 6). The use of acetonitrile as solvent
C–N bond formations catalyzed by
a
proton-exchanged
montmorillonite as a heterogeneous catalyst.10 Herein, we report
rhodium-(I)-phosphine complex catalyzed three-component
reaction between aryl aldehyde, boronic acid, and sulfonamide
for the synthesis of diarylmethylamines.
The initial optimization studies for the one pot synthesis of dia-
rylmethylamine were conducted by using 4-nitrobenzaldehyde,
phenylboronic acid, and p-toluenesulfonamide as the model
substrates. Various reaction parameters such as rhodium catalysts,
⇑
Corresponding author. Tel.: +91 4027193234; fax: +91 4027193030.
E-mail address: mlakshmi@iict.res.in (M.L. Kantam).
http://dx.doi.org/10.1016/j.tetlet.2014.08.003
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Satyanarayana, P.; et al. Tetrahedron Lett. (2014), http://dx.doi.org/10.1016/j.tetlet.2014.08.003

2
P. Satyanarayana et al. / Tetrahedron Letters xxx (2014) xxx–xxx
F
product was observed when the reaction was carried out with
imine and boronic acid as substrates under standard reaction con-
ditions (Table 1; entry 15). Therefore, among various optimization
studies listed in Table 1 the most promising result was shown to be
Table 1; entry 5.
F
F
F
F
F
F
F
F
F
F
P
F
F
P
Using the optimized reaction conditions in hand the scope of
the reaction was evaluated for various types of substrates and
the results from these studies are presented in Table 2. Among var-
ious sulfonamide substrates that were studied, we have found that
the reaction proceeded smoothly, and excellent yields were
obtained with various structurally diverse aldehydes and boronic
acids substrates. At first, the reaction of 4-nitrobenzaldehyde with
phenylboronic acid and 4-methylbenzenesulfonamide was
executed in the presence of 2.0 mol % of Rh(I) catalyst
bis(1,5-cyclooctadiene)rhodium(I)tetrafluoroborate (catalyst 1),
25.0 mol % of hypervalent iodine based additive, PhI(OCOCF3)2,
and 3.0 mol % of phosphorous ligand 1,2-bis[bis(penta-fluor-
ophenylphosphino)ethane (L2) in toluene at 110 °C for 12 h. This
reaction gave the corresponding diarylmethylamine product in
yields as high as 95% in 12 h (Table 2; entry 1). Similarly, the reac-
tion of 4-nitrobenzaldehyde has also gave good yields (86%) for the
desired product in the reaction with 4-methoxyphenylboronic acid
and 4-methylbenzenesulfonamide (Table 2; entry 2). As was the
case earlier, 4-nitrobenzaldehyde also smoothly reacts with p-tol-
ylboronic acid, and benzenesulfonamide, and gave corresponding
diarylmethylamine product in good yields of 78% (Table 2; entry
3). When the reaction was carried out using 4-nitrobenzaldehyde,
phenylboronic acid, and benzenesulfonamide as substrates under
optimized reaction conditions, the corresponding diarylmethyl-
amine was obtained in good yields of 86% (Table 2; entry 4). When
the reaction was carried out using 4-cyano-benzaldehyde, 4-meth-
oxyphenylboronic acid, and 4-methylbenzenesulfonamide, an
excellent yield of 93% was obtained for the corresponding diarylm-
ethylamine product (Table 2; entry 5). For the reaction between
4-cyanobenzaldehyde, 4-methoxyphenylboronic acid, and benzene
sulfonamide, an excellent yield of 89% was obtained for the
corresponding diarylmethylamine product (Table 2; entry 6). The
reaction between 4-cyanobenzaldehyde, 4-methoxyphenylboronic
acid, and 4-nitrobenzenesulfonamide also proceeded smoothly,
and gave excellent yield of 93% for the corresponding
diarylmethylamine product (Table 2; entry 7). Similarly, when
4-cyanobenzaldehyde was treated with phenylboronic acid and
4-methoxysulfonamide, desired diarylmethylamine product was
isolated in yields as high as 95% (Table 2; entry 8). When 4-chloro-
benzaldehyde was reacted with 4-methoxyphenylboronic acid and
4-methylbenzene-sulfonamide, the corresponding diarylmethyl-
amine product was isolated in 91% yield (Table 2; entry 9). When
6-methoxy naphthaldehyde was treated with p-tolyl boronic acid
and benzenesulfonamide, the desired diarylmethylamine was
obtained in 89% yield (Table 2; entry 10). As was the case above,
1-naphthaldehyde also smoothly reacted with phenyl boronic acid
and 4-methylbenzenesulfonamide and gave good yield of corre-
sponding product in 86% yield (Table 2; entry 11).
P
P
F
F
F
F
F
F
L1
F
L2
Figure 1. Phosphine based ligands.
Table 1
Optimization of one-pot synthesis of diaryl methylamine through a three component
reaction of aldehyde, boronic acid, and sulfonamidea
O
S
O
O
O
O
NH2
S
B(OH)2
+
HN
RhCatalyst
Addit ive
+
Ligand, Toluene,
O2N
110C, 12h
NO2
Entry
Catalyst
Additive
Ligand
Yieldb (%)
1
2
3
4
5
6
7
8
Catalyst 1
Catalyst 2
Catalyst 1
Catalyst 2
Catalyst 1
Catalyst 1
Catalyst 1
Catalyst 1
RhCl3
Catalyst 1
Catalyst 1
Catalyst 1
—
Ag2O
Ag2O
L1
L1
L1
L1
L2
L2
L2
PPh3
L2
L2
L2
L2
L2
L2
L2
L2
10
n.d.
25
n.d.
95
PhI(OCOCF3)2
PhI(OCOCF3)2
PhI(OCOCF3)2
—
PhI(OCOCF3)2
PhI(OCOCF3)2
PhI(OCOCF3)2
Ag2CO3
Cu(OAC)2
—
PhI(OCOCF3)2
PhI(OCOCH3)2
PhI(OCOCF3)2
PhI(OCOCF3)2
10c
70d
n.d.
n.d.
n.d.
n.d.
n.d.f
n.d.g
35
9e
10
11
12
13
14
15
16i
Catalyst 1
Catalyst 1
Rh(acac)3
n.d.h
n.d.
a
Reaction conditions: 1.0 mmol of aldehyde, 2.0 mmol of boronic acid, 1.0 mmol
of sulfonamide, 2.0 mol % of catalyst, 25.0 mol % of additive, 3.0 mol % of ligand and
2 mL of toluene.
b
Isolated yields.
Diarylmethyl alcohol was isolated.
Acetonitrile was used instead of toluene.
5 mol % of rhodium trichloride was used as catalyst.
Molecular oxygen used as an additive.
Imine was isolated.
1 mmol of imine and 2 mmol of boronic acid were used.
2 mol % of Rh(acac)3 was used as catalyst.
c
d
e
f
g
h
i
considerably reduced the product yield (Table 1; entry 7). When
the reaction was performed using triphenylphosphine as ligand,
no desired product was observed (Table 1; entry 8). In a similar
way, the reaction also failed when conducted in the presence of
either RhCl3 or Rh(acac)3 catalysts under similar reaction condi-
tions (Table 1; entries 9 and 16). Moreover, the use of additives like
silver carbonate and copper(II) acetate in the reaction failed to give
the desired diarylmethylamine product (Table 1; entries 10 and
11). Besides, the reaction carried out by molecular oxygen as an
additive did not proceed to furnish the desired product, (Table 1;
entry 12).
When the reaction was performed by using [bis(trifluoroacet-
oxy)iodo]benzene as additive in the absence of catalyst,
considerable amount of imine was isolated (Table 1; entry 13).
However, the reaction carried out in the presence of [bis(acet-
oxy)iodo]benzene under similar reaction conditions, afforded the
desired amine in moderate yields (Table 1; entry 14). Notably, no
A plausible mechanism11 is explained for the synthesis of dia-
rylmethylamines in Scheme 1. In the first step, a reactive imine
5, is formed by the condensation between amine and the aldehyde
promoted by hyper-valent iodine. Then, an in situ formed Bronsted
acid could protonate the imine 5 to give an even more reactive
iminium ion 6. Simultaneously, the bis(phosphine) complex of rho-
dium(I)tetrafluoroborate could react with the arylboronic acid to
form a more nucleophilic aryl rhodium(I) complex 7. Finally, imine
and aryl rhodium(I) species can subsequently react with each other
to form the desired product 4.
In summary we have developed a general protocol for the one
pot synthesis of diaryl methylamines utilizing Rh(I)/bis(phos-
phine) catalyzed three-component reaction of aldehyde, boronic
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P. Satyanarayana et al. / Tetrahedron Letters xxx (2014) xxx–xxx
3
Table 2
Rh(I) catalyzed one-pot synthesis of diarylmethylamine using various aldehydes with boronic acid and sulfonamide substratesa
O
O
O
O
S
Z
B( OH)
S
2
HN
NH
2
O
Rh(COD)2BF4
PhI(OCOCF3)2
Ligand2, Toluene,
110C, 12h
+
+
X
Y
X
Y
Z
X=NO2
CN, Cl,
Z= H, Me,
Ome, NO2
Y=H,Me ,
OMe
Yield75% - 95%
Entry
1
Aldehyde
Boronic acid
Sulfonamide
Diaryl amine
Yieldb (%)
O
B(OH)2
O
O
O
O
O
O
S
S
S
S
NH2
S
O
HN
95
O2N
O2N
O2N
O2N
NO2
O
B(OH)2
O
O
S
NH2
HN
HN
O
2
3
4
5
6
7
8
86
78
86
93
89
93
95
O
NO2
O
O
B(OH)2
O
O
S
O
NH2
NO2
O
B(OH)2
B(OH)2
O
O
S
NH2
HN
O
NO2
O
O
O
O
O
O
S
S
S
NH2
S
O
HN
HN
HN
O
CN
O
NC
NC
NC
O
B(OH)2
O
O
S
NH2
O
O
O
O
CN
O
B(OH)2
O
O
S
O
NH2
NO2
O
CN
O
NO2
B(OH)2
O
O
O
S
S
NH2
O
HN
O
CN
NC
O
(continued on next page)
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P. Satyanarayana et al. / Tetrahedron Letters xxx (2014) xxx–xxx
Table 2 (continued)
Entry
Aldehyde
Boronic acid
Sulfonamide
Diaryl amine
Yieldb (%)
O
B(OH)2
O
O
O
O
O
S
S
S
S
NH2
HN
O
9
91
O
Cl
Cl
O
O
O
B(OH)2
O
S
NH2
HN
O
10
89
86
O
O
O
B(OH)2
O
O
S
NH2
HN
O
11
a
Reaction condition: arylaldehyde (1.0 mmol), boronic acid (2.0 mmol), sulfonamide (1.0 mmol), Rh(COD)2BF4 (2.0 mol %), PhI(OCOCF3)2 (25.0 mol %), and ligand 2
(3.0 mol %), 2 mL toluene used as solvent.
b
Isolated yield.
Ph
Ph
O
O
O
NH2
O
TFA
H+
H
+NH
O
PhI(OCOCF3)2
N
O
H
S
S
+
S
Ph
-H2O
Ar
Ar
O
Ph
Ar
6
2
1
5
O
S
HN
O
Ar2
Rh(COD)BF4
Ligand
5 or 6
Ar2-[Rh]
Ar2-B(OH)2
3
Ar
7
4
Scheme 1. A plausible mechanism for one pot synthesis of diarylmethylamine.
2128; (c) Bishop, M. J.; McNutt, R. W. Bio. Org. Med. Chem. Lett. 1995, 5, 1311–
1314; (d) Sakurai, S.; Ogawa, N.; Suzuki, T.; Kato, K.; Ohashi, T.; Yasuda, S.;
Kato, H.; Ito, Y. Chem. Pharm. Bull. 1996, 44, 765–770.
acid, and sulfonamide in the presence of hyper-valent based iodine
reagent, PhI(OCOCF3)2. The protocol is applicable to a diverse range
of substrate combinations with wide functional group tolerance.
3. (a) Koe, B. K.; Weissman, A.; Welch, W. M.; Browne, R. G. J. Pharmacol. Exp. Ther.
1983, 226, 686–700; (b) Bolshan, Y.; Batey, R. A. Org. Lett. 2005, 7, 1481–1484;
(c) Anderson, J. L.; Mcnutt, R. W.; Xu, H.; Smith, L. E.; Bilsky, E. J.; Davis, P.; Rice,
K. C. J. Med. Chem. 1994, 37, 2125–2128.
Acknowledgments
4. Hili, R.; Yudin, A. K. Nat. Chem. Biol. 2006, 2, 284–287.
5. (a) Amines Synthesis, Properties and Application; Lawrence, S. A., Ed.; Cambridge
University Press: Cambridge, 2004; (b)Modern Amination Reactions; Ricci, A.,
Ed.; Wiley-VCH: Weinheim, 2000; (c) Wu, G.; Cai, Z. W. M.; Bednarz, S.; Kocy,
O. R.; Gavai, A. V.; Godfrey, J. D.; Washbrun, W. N.; Poss, M. A.; Sher, P. M. J.
Comb. Chem. 2005, 7, 99–108.
P.S.N. and G.M.R. thank the CSIR-INDIA for research fellowship
and financial assistance.
Supplementary data
6. (a) Bolshan, Y.; Batey, R. A. Org. Lett. 2005, 8, 1481–1484; (b) Duan, H. F.; Xia, Y.
J.; Wang, L. X.; Zhou, Q. Org. Lett. 2006, 8, 2567–2569; (c) Fujihara, H.; Nagai, K.;
Tomioka, K. J. Am. Chem. Soc. 2000, 122, 12055–12056; (d) Hermanns, N.;
Dahmen, S.; Bolm, C.; Brase, S. Angew. Chem., Int. Ed. 2002, 41, 3692–3694; (e)
Bloch, R. Chem. Rev. 1998, 98, 1407–1438; (f) Kobayashi, S.; Ishitani, H. Chem.
Rev. 1999, 99, 1069–1094; (g) Taniyama, D.; Hasegawa, M.; Tomioka, K.
Tetrahedron Lett. 2000, 41, 5533–5536; (h) Pflum, D. A.; Krishnamurthy, D.;
Han, Z.; Wald, S. A.; Senanayake, C. H. Tetrahedron Lett. 2002, 43, 923–926; (i)
Han, Z.; Krishnamurthy, D.; Grover, P.; Fang, Q. K.; Pflum, D. A.; Senanayake, C.
H. Tetrahedron Lett. 2003, 44, 4195–4197; (j) Cabello, N.; Kizirian, J. C.; Alexakis,
A. Tetrahedron Lett. 2004, 45, 4639–4642.
7. (a) Terrasson, V.; Marque, S.; Georgy, M.; Campagne, J. M.; Prim, D. Adv. Synth.
Catal. 2006, 348, 2063–2067; (b) Quin, H.; Yamagiwa, N.; Matsunaga, S.;
Shibasaki, M. Angew. Chem., Int. Ed. 2007, 46, 409–413; (c) Reddy, R. Ch.;
Madhavi, P. P.; Reddy, S. A. Tetrahedron Lett. 2007, 48, 7169–7172.
8. Yang, H. Y.; Zhang, J.; Wang, G.; Chen, S.-Y.; Yu, X. Q. Tetrahedron 2011, 48,
4649–4654.
Supplementary data (general procedure for synthesis,
characterization data and copies of 1H and 13C NMR spectra of all
the compounds) associated with this article can be found, in the
online version, at http://dx.doi.org/10.1016/j.tetlet.2014.08.003.
References and notes
1. (a) Dalko, P. I.; Moisan, L. Angew. Chem., Int. Ed. 2004, 43, 5138–5175; (b) Dalko,
P. I.; Moisan, L. Angew. Chem., Int. Ed. 2001, 40, 3726–3748; (c) Knochel, P.
Handbook of Functionalized Organometallics; Wiley-VCH: Weinheim, 2005; (d)
Brown, B. R. The organic Chemistry of Aliphatic Nitrogen Compounds; University
New York: Oxford, 1994; (e) Buehler, C. A.; Pearson, D. E. Survey of Organic
Synthesis; Wiely-Interscience: New York, 1970; (f) Mitsunbu, O.; Torst, B. M.;
Fleming, I. Comprehensive Organic Synthesis; Pergamon: Oxford, 1991; (g) Insaf,
S. S.; Witiak, D. T. Synthesis 1999, 3, 435–440.
9. Fan, R.; Li, W.; Pu, D.; Zhang, L. Org. Lett. 2009, 11, 1425–1428.
10. Motokura, M.; Nakagiri, N.; Mori, K.; Mizugaki, T.; Ebitani, K.; Jitsukawa, K.;
Kaneda, K. Org. Lett. 2006, 8, 4617–4620.
2. (a) Spencer, C. M.; Foulds, D.; Peters, D. H. Drugs 1993, 46, 1055–1080; (b)
Calderon, S. N.; Rothman, R. B.; Porreca, F.; Anderson, J. L.; McNutt, R. W.; Xu,
H.; Smith, L. E.; Bilsky, E. J.; Davis, P.; Rice, K. C. J. Med. Chem. 1994, 37, 2125–
11. Beisel, T.; Manolikakes, G. Org. Lett. 2013, 15, 6046–6049.
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