Synthesis of homochiral pentadentate sulfonamide-based ligands

Article abstract of DOI:10.1016/S0957-4166(01)00292-0

A two-step synthesis of pentadentate, tetraionic ligands based on sulfonamide, amide, and pyridyl groups is reported. These ligands are easily accessible in good to excellent yield from commercially available materials.

Full text of DOI:10.1016/S0957-4166(01)00292-0

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 12 (2001) 1719–1722
Synthesis of homochiral pentadentate sulfonamide-based ligands
,†
Karno Ng,a Ratnasamy Somanathanb,* and Patrick J. Walshb,c,
*
aDepartment of Chemistry, San Marcos State University, San Marcos, CA 92096, USA
bCentro de Graduados e Investigacio´n, Instituto Tecnolo´gico de Tijuana, Apartado Postal 1166, 22000 Tijuana, BC Mexico
cDepartment of Chemistry, San Diego State University, San Diego, CA 92182-1030, USA
Received 10 May 2001; accepted 18 June 2001
Abstract—A two-step synthesis of pentadentate, tetraionic ligands based on sulfonamide, amide, and pyridyl groups is reported.
These ligands are easily accessible in good to excellent yield from commercially available materials. © 2001 Elsevier Science Ltd.
All rights reserved.
The goal of the work reported herein is to design
pentadentate tetraionic ligands for use in asymmetric
catalysis. It was envisaged that a pentadentate ligand
could coordinate to metals and leave an open coordi-
nation site that could bind and activate a substrate in
a Lewis acid catalyzed reaction. The core of the lig-
and is based on the pyridine bis(amide), which is
known to bind well to transition metal complexes, as
shown in Fig. 1.40
1. Introduction
The development of novel chiral ligands is crucial to
the advancement of asymmetric catalysis. Classifica-
tion of ligands that have been successfully used in
enantioselective catalysis by denticity, that is the num-
ber of points of attachment of the ligand to the metal
and by the formal charge of the closed shell form of
the ligand, can be informative. Many of the most
common ligands are bidentate and neutral, including
chelating phosphines such as DIOP and BINAP.1
Others like TADDOL2–5 and BINOL6,7 are bidentate
and dianionic. Ligands of higher denticity have been
less well developed. One of the most useful classes of
ligands is the tetradentate salen ligands, which have
The synthesis of the ligands was realized in two easy
steps as outlined in Eqs. (1) and (2). The first step is
identical to that used in the synthesis of sulfonamide/
Schiff base ligands that have been used in the asym-
metric cyclopropanation of allylic alcohols.41,42
Dissolving the tartrate salt of (R,R)-trans-1,2-
diaminocyclohexane in water with two equivalents of
NaOH followed by addition of dichloromethane, tri-
ethylamine, and a sulfonyl chloride led to the forma-
tion of the amino-sulfonamides. The work-up
procedure involved acidic extraction followed by
raising the pH of the solution to 9. Using this proce-
dure any bis(sulfonamide) complex formed was easily
removed.42
been
successfully
employed
in
asymmetric
epoxidation8–10 and asymmetric epoxide ring opening
reactions,11–13 for example. Chiral tetradentate, dian-
ionic porphyrin ligands have also been used with
great success in asymmetric oxidation reactions.14–22
Other tetradentate dianionic23–29 and trianionic ligands
also are promising.30,31 Chiral tetradentate32–34 and
pentadentate tetraanionic ligands are an under repre-
sented class of ligands in asymmetric catalysis despite
the use of achiral analogs in stabilizing reactive metal
centers.35–39
* Corresponding authors. E-mail: somantha@sundown.sdsu.edu;
pwalsh@sas.upenn.edu
† Present address: University of Pennsylvania, Department of Chem-
istry, 231 South 34th Street, Philadelphia, PA 19104–6323, USA.
Figure 1.
0957-4166/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(01)00292-0

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K. Ng et al. / Tetrahedron: Asymmetry 12 (2001) 1719–1722
(1)
The amino-sulfonamides were then treated with 0.5
equivalent of 2,6-pyridinedicarbonyl dichloride in
dichloromethane in the presence of triethylamine to
furnish the pyridyl bis(amide) bis(sulfonamide) ligands,
as shown in Eq. (2).
ers were combined, dried with anhydrous MgSO4,
filtered, and the solvent was removed under reduced
pressure to obtain 1a as a pale yellow solid (2.01 g, 7.55
mmol, 99%). The characterization of these compounds
has been previously reported.42
(2)
These ligands are easily synthesized and should readily
bind to transition metal complexes to provide chiral
Lewis acids for use in asymmetric catalysis. This work
is currently being pursued in our laboratories.
2.2. Synthesis and characterization of 2a–2f
The preparation of 2a is described below. Compounds
2b–2f were prepared using this procedure.
To a stirred solution of 1a (1.00 g, 3.73 mmol) in
dichloromethane (30 mL) was added 2,6-pyridinedicar-
bonyl dichloride (0.38 g, 1.87 mmol) in dichloro-
methane (25 mL) and triethylamine (0.52 mL, 3.74
mmol). The mixture was stirred at room temperature
for 12 h. The resulting solution was washed with water
(3×50 mL). The organic layer was collected and anhy-
drous MgSO4 was added. The solution was filtered and
the solvent was removed under reduced pressure.
2. Experimental
2.1. Synthesis of 1a–1f
The procedures used to synthesize compounds 1a–1f
were identical to that described for 1a. The syntheses of
1a–1f have been improved since our original report.42
To a stirred solution of
L-tartrate salt of (R,R)-1,2-
Data for 2a: The yield was 72% (0.95 g, 1.35 mmol).
The white solid obtained from the filtrate was purified
by column chromatography using silica. Compound 2a
was eluted using chloroform/ethyl acetate (1:1, v/v).
Mp 262–263°C; [h]D=−171.6 (c=1.2 g/mL, CHCl3);
1H NMR (CDCl3, 200 MHz) l 1.1 (m, 2H), 1.22 (m,
2H), 1.28 (m, 2H), 1.35 (m, 2H), 1.63 (d, J=10.4 Hz,
4H), 1.82 (d, J=8.3 Hz, 2H), 2.24 (m, 8H), 3.25 (m,
2H), 3.78 (m, 2H), 5.20 (d, J=6.3 Hz, 2H), 7.07 (d,
J=8.3 Hz, 4H), 7.65 (d, J=8.3 Hz, 4H), 7.96 (t, J=6.3
Hz, 1H), 8.2 (d, J=6.3 Hz, 2H), 8.5 (d, J=6.3 Hz, 2H)
ppm; 13C{1H} NMR (CDCl3, 50 MHz) l 21.4, 24.3,
25.0, 32.0, 34.2, 53.7, 57.4, 124.5, 126.6, 129.5, 138.4,
138.6, 143, 148.5, 164.3 ppm. IR (KBr) 3340, 3279,
3133, 2933, 2856, 2350, 1671, 1544, 1452, 1329, 1160,
diaminocyclohexane (3.00 g, 11.36 mmol) in aqueous
NaOH (2N, 15 mL) was added triethylamine (2.1 mL,
15.2 mmol) and dichloromethane (110 mL). The mix-
ture was cooled to 0°C and a solution of p-toluene
sulfonyl chloride (1.44 g, 7.6 mmol) in dichloromethane
(76 mL) was added dropwise over 30 min. After the
addition was complete, the mixture was allowed to
warm to room temperature and stirred for 12 h. The
resulting reaction mixture was washed with aqueous
HCl (2N, 3×50 mL) and the organic phase was
removed. The HCl wash liquor was collected and
adjusted to pH 9 by adding NaOH pellets. The basic
aqueous
solution
was
then
extracted
with
dichloromethane (3×30 mL). The dichloromethane lay-

K. Ng et al. / Tetrahedron: Asymmetry 12 (2001) 1719–1722
1721
1083, 886, 800, 729, 700, 676, 557 cm−1; high resolution
mass spectrum m/z 690.2386 [M+Na+; calcd for
C33H41N5O6S2Na: 690.2395].
Data for 2e: The yield was 98% (0.89 g, 2.50 mmol).
The white solid obtained from the filtrate was purified
by column chromatography using silica. Compound 2e
was obtained using chloroform/ethyl acetate (1:1 v/v).
1
Data for 2b: The yield was 80% (1.00 g, 1.37 mmol).
The pale yellow solid obtained from the filtrate was
purified by column chromatography using silica. Com-
pound 2b was eluted using methanol/hexane/
dichloromethane (1:1:1 v/v). Mp 187–188°C; [h]D=31.9
(c=0.0475 g/mL, CHCl3); 1H NMR (CDCl3, 500 MHz)
l 1.0 (tq, J1=2.2 Hz, J2=10.5 Hz, 2H), 1.22 (tq,
J1=2.2 Hz, J2=11.9 Hz, 2H), 1.28 (dq, J1=2.2 Hz,
J2=11.9 Hz, 2H), 1.43 (dq, J1=2.2 Hz, J2=11.9 Hz,
2H), 1.54 (d, J=10.5 Hz, 2H), 1.6 (d, J=10.5 Hz, 2H),
1.68 (d, J=10.5 Hz, 2H), 2.24 (d, J=10.5 Hz, 2H), 3.22
(m, 2H), 3.78 (m, 2H), 5.5 (d, J=5.1 Hz, 2H), 7.36 (t,
J=6.3 Hz, 2H), 7.48 (t, J=6.3 Hz, 2H), 7.56 (t, J=6.3
Hz, 2H), 7.70 (d, J=7.0 Hz, 2H), 7.86 (t, J=6.3 Hz,
1H), 7.96 (d, J=7.0 Hz, 2H), 8.60 (d, J=7.0 Hz, 2H),
8.22 (d, J=7.0 Hz, 2H), 8.34 (dd, J1=1.3 Hz, J2=6.3
Hz, 2H), 8.51 (d, J=7.0 Hz, 2H) ppm; 13C{1H} NMR
(CDCl3, 125 MHz) l 24.4, 25.1, 32.0, 34.1, 53.6, 57.6,
123.8, 124.3, 124.5, 126.8, 127.9, 128.3, 128.7, 129.0,
134.1, 134.2, 135.5, 138.0, 148.2, 164.1 ppm; IR (KBr)
3361, 3340, 2940, 2849, 2372, 1670, 1537, 1460, 1319,
1165, 1123, 1096, 800, 757, 650, 600 cm−1.
Mp 148°C; [h]D=−130.8 (c=0.0395 g/mL, CHCl3); H
NMR (CDCl3, 300 MHz) l 1.00 (m, 2H), 1.20 (m, 2H),
1.35 (m, 4H), 1.54 (d, J=10.7 Hz, 4H), 1.75 (d, J=10.7
Hz, 2H), 2.10 (d, J=10.7 Hz, 2H), 2.16 (s, 6H), 2.45 (s,
6H), 3.30 (m, 2H), 3.80 (m, 2H), 5.8 (d, J=5.1 Hz, 2H),
6.88 (d, J=8.9 Hz, 2H), 7.00 (d, J=8.9 Hz, 2H), 7.70
(s, 2H), 7.85 (t, J=5.6 Hz, 1H), 8.13 (d, J=7.1 Hz,
2H), 8.60 (d, J=7.1 Hz, 2H) ppm; 13C{1H} NMR
(CDCl3, 125 MHz) l 19.8, 20.7, 24.4, 25.1, 32.1, 33.6,
53.6, 56.7, 124.5, 129.2, 132.4, 133.1, 133.8, 135.6,
138.3, 138.8, 148.5, 164.2 ppm; IR (KBr) 3340, 3200,
2933, 2856, 1674, 1551, 1442, 1321, 1160, 1076, 900,
700, 600 cm−1; high resolution mass spectrum m/z
718.2752 [M+Na+; calcd for C35H45N5O6S2Na:
718.2708].
Data for 2f: The yield was 74% (0.85 g, 1.30 mmol).
The white solid was obtained from the filtrate was
purified by column chromatography using silica. Com-
pound 2f was obtained using methanol/ethyl acetate/
dichloromethane (1:1:1 v/v). Mp 170°C; [h]D=−1.1
1
(c=0.028 g/mL, CHCl3); H NMR (CDCl3, 500 MHz)
l 0.75 (t, J=6.4 Hz, 6H), 1.24 (m, 4H), 1.36 (m, 6H),
1.50 (m, 2H), 1.69 (m, 4H), 1.76 (d, J=7.3 Hz, 2H),
1.81 (d, J=7.3 Hz, 2H), 2.17 (d, J=10.1 Hz, 2H), 2.23
(d, J=10.1 Hz, 2H), 2.97 (m, 4H), 3.40 (m, 2H), 3.82
(m, 2H), 5.22 (s, 2H), 7.98 (t, J=7.0 Hz, 1H), 8.27 (d,
J=7.2 Hz, 2H), 8.69 (d, J=7.2 Hz, 2H) ppm; 13C{1H}
NMR (CDCl3, 125 MHz) l 13.4, 21.4, 24.5, 25.3, 25.6,
32.2, 34.6, 53.8, 56.7, 56.9, 124.8, 138.8, 148.6, 164.1
ppm; IR (KBr) 3348, 2934, 2861, 2368, 1677, 1552,
1460, 1321, 1137, 1104 cm−1.
Data for 2c: The yield was 81% (0.94 g, 1.22 mmol).
The white solid obtained from the filtrate was purified
by column chromatography using silica. Compound 2c
was eluted using chloroform/ethyl acetate (1:1, v/v).
Mp 167°C; [h]D=+37.0 (c=0.072 g/mL, CHCl3); 1H
NMR (CDCl3, 300 MHz) l 1.16 (m, 4H), 1.28 (dq,
J1=2.2 Hz, J2=11.9 Hz, 2H), 1.38 (dq, J1=2.2 Hz,
J2=11.9 Hz, 2H), 1.55 (t, J=3.1 Hz, 4H), 1.7 (d,
J=2.2 Hz, 2H), 2.0 (s, 6H), 2.15 (d, J=2.2 Hz, 2H), 2.5
(s, 12H), 3.2 (m, 2H), 3.75 (m, 2H), 5.60 (d, J=5.0 Hz,
2H), 6.60 (s, 4H), 7.80 (t, J=6.2 Hz, 1H), 8.15 (d,
J=7.7 Hz, 2H), 8.30 (d, J=7.7 Hz, 2H) ppm; 13C{1H}
NMR (CDCl3, 125 MHz) l 20.8, 23.1, 24.5, 25.2, 32.1,
34.0, 53.5, 57.1, 124.6, 131.7, 135.7, 138.0, 138.1, 141.4,
148.2, 164.0 ppm; IR (KBr) 3368, 3237, 2941, 2855,
1683, 1545, 1460, 1328, 1157, 1091, 943, 900, 850, 750,
650, 590, 529 cm−1.
Acknowledgements
This work was supported by the Petroleum Research
Fund (PRFc32862-GB1) in the form of a summer
research fellowship to K.N.
Data for 2d: The yield was 98% (1.78 g, 2.26 mmol).
The white solid obtained from the filtrate was purified
by column chromatography using silica. Compound 2d
was obtained using chloroform/ethyl acetate (1:1 v/v).
Mp 193°C; [h]D=+8.3 (c=0.14 g/mL, CHCl3); 1H
NMR (CDCl3, 300 MHz) l 1.05 (m, 2H), 1.20 (s, 18H),
1.22 (m, 2H), 1.37 (m, 4H), 1.60 (d, J=9.47 Hz, 4H),
1.75 (d, J=9.5 Hz, 2H), 2.15 (d, J=9.5 Hz, 2H), 3.40
(m, 2H), 3.75 (m, 2H), 5.55 (d, J=5.1 Hz, 2H), 7.25 (d,
J=7.9 Hz, 4H), 7.75 (d, J=7.9 Hz, 4H), 7.88 (t, J=6.3
Hz, 1H), 8.15 (d, J=7.9 Hz, 2H), 8.75 (d, J=7.9 Hz,
2H) ppm; 13C{1H} NMR (CDCl3, 125 MHz) l 24.4,
25.1, 31.1, 32.0, 33.9, 35.0, 53.8, 57.0, 124.5, 125.7,
126.4, 138.4, 138.7, 148.6, 156.0, 164.1 ppm. IR (KBr)
3354, 3172, 2840, 2863, 2400, 1677, 1544, 1453, 1319,
1158, 1074, 829, 750, 629, 571 cm−1; high resolution
mass spectrum m/e 774.3326 [M+Na+; calcd for
C39H53N5O6S2Na: 7743335].
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