Synthesis and reactivity of sulfonamides containing boronate esters

Article abstract of DOI:10.1002/hc.20025

Sulfonamides containing pinacol protected boronate ester groups have been prepared by the addition of H₂NC₆H₄Bpin (pin = O₂C₂Me₄) to sulfonyl chlorides p-RC ₆H₄SO

Full text of DOI:10.1002/hc.20025

Heteroatom Chemistry
Volume 15, Number 5, 2004
Synthesis and Reactivity of Sulfonamides
Containing Boronate Esters
Xiao-Feng He,1 Haiwen Zhang,1 Christopher M. Vogels,1
Andreas Decken,2 and Stephen A. Westcott1
1Department of Chemistry, Mount Allison University, Sackville, New Brunswick E4L 1G8, Canada
2Department of Chemistry, University of New Brunswick, Fredericton, New Brunswick E3B 5A3,
Canada
Received 11 November 2003; revised 24 March 2004
macrocyclic chemistry [3], organometallic and or-
ABSTRACT: Sulfonamides containing pinacol pro-
ganic synthesis [4], and as glucose sensors for di-
tected boronate ester groups have been prepared by
abetes therapy [5]. Interest in these compounds
the addition of H2NC6H4Bpin (pin = O2C2Me4) to sul-
also arises from their potent biological activities [6–
fonyl chlorides p-RC6H4SO2Cl (R = CH3, NO2). Hy-
15]. For instance, sulfonamides containing boronic
drogenation of the nitro derivatives afford the corre-
acids have been examined for their ability to in-
sponding sulfanilamides without compromising the
hibit ꢀ-lactamases, enzymes responsible for the
aryl-Bpin bond. The sulfanilamides were further func-
widespread resistance mechanisms of ꢀ-lactam an-
tionalized to afford novel platinum complexes con-
tibiotics. These properties, along with the ability of
ꢀ
C
taining boranosulfonamides. 2004 Wiley Periodicals,
boronic acid groups to transport water insoluble
Inc. Heteroatom Chem 15:369–375, 2004; Published online
reagents through membranes [16], prompted us to
in Wiley InterScience (www.interscience.wiley.com). DOI
investigate the use of boronate ester sulfonamide
10.1002/hc.20025
compounds as carrier ligands for biologically-active
metal complexes.
Cisplatin, cis-[PtCl2(NH3)2], and a few related
INTRODUCTION
platinum-based complexes are currently used as
anticancer agents against testicular and ovarian
malignancies [17–20]. There are several limitations
to platinum therapy, however, such as neural and
kidney toxicity as well as intrinsic and acquired resis-
tance of tumor cells to the drugs [17]. These compli-
cations have provided incentive for further research
in the development of platinum-based complexes
with increased solubilities in physiological media
that show enhanced specificity toward cancer cells.
Recent studies have shown that cis-amminedichloro
(2-methylpyridine)platinum(II) (AMD473 or ZD0473,
Fig. 1) shows considerable cytotoxicity in cisplatin
resistant cell lines [21,22]. Steric crowding from the
methyl group is believed to decrease the rates of
hydrolysis and substitution reactions of AMD473
thereby permitting high selectivity in binding with
Compounds containing boronic acids (RB(OH)2) or
boronate esters (RB(ORꢁ)2) have received consid-
erable attention in catalyzed carbon-carbon bond
formation reactions [1], solid-phase synthesis [2],
Correspondence to: S. A. Westcott; e-mail: swestcott@mta.ca.
Contract grant sponsor: Natural Science and Engineering Re-
search Council (Canada).
Contract grant number: 184044.
Contract grant sponsor: NSERC.
Contract grant sponsor: American Chemical Society-Petroleum
Research Fund.
Contract grant number: 37824-B1.
Contract grant sponsor: Canada Research Chairs pro-
gram/Canadian Foundation for Innovation/Atlantic Innovation
Fund.
Contract grant sponsor: Mount Allison University.
2004 Wiley Periodicals, Inc.
c
ꢀ
369

370 He et al.
nitrogen donors in biomolecules, interactions be-
lieved responsible for some of the adverse side ef-
fects associated with cisplatin [17]. We report herein
our results on the synthesis of cis-dichloro(pyridin-2-
ylcarboxaldimine)platinum(II) compounds contain-
ing sulfonamide boronate esters.
FIGURE 1 AMD473.
RESULTS AND DISCUSSION
DNA [23]. The primary mechanism of action in
these platinum drugs is believed to arise, at least in
part, from the metal’s interaction with DNA.
N-Aryl sulfonamides are an important class of phar-
maceutically important compounds [25,26]. Our in-
terest in preparing novel boron compounds
prompted us to investigate the synthesis of sulfon-
amides containing boronate esters [13,27,28]. Pro-
tection of the boronic acid groups in aminophenyl-
boronic acids (H2NC6H4B(OH)2) by transesterifica-
tion with pinacol (HOCMe2CMe2OH), to prevent
unwanted formation of anhydrides [29], gives
quantitative formation of the corresponding organic
soluble aminoboronate ester H2NC6H4Bpin (pin =
O2C2Me4) [30]. Addition of these amines to sulfonyl
chlorides gave the desired sulfonamides in low to
moderate yields (28–62%, Scheme 1).
We have begun to develop AMD473 analogues
by replacing the NH3 group with a pendant imine
group. Previous studies have shown that the plat-
inum complex derived from aniline has shown con-
siderable activity against the hormone independent
human mammary carcinoma cell line MDA-MB 231
[24]. Varying the aniline functionality allows us to
design compounds with a wide range of physical and
chemical properties that may provide steric conges-
tion around the platinum atom. As well, the use of
bidentate ligands prevents trans labilization and un-
desired displacement of the ligands by sulfur and
SCHEME 1 Sulfonamides containing boronate esters.

Synthesis and Reactivity of Sulfonamides Containing Boronate Esters 371
TABLE 1 Summary of Data Collection and Refinement for
The IR spectra for the sulfonamides 1a–c display
absorption bands ranging from 3282–3234 cm−1 as-
signed to ꢁ(N H). The 1H NMR spectra for 1a shows
a broad singlet at δ 8.56 ppm for the NH peak, while
this resonance is observed at δ 6.68 and 7.01 ppm
for 1b and 1c, respectively. This result is interesting
as it suggests that a weak interaction of the amide
hydrogen with the neighbouring boron atom may
be occurring. However, the 11B NMR spectrum for
1a shows a broad peak at δ 29 ppm, signifying that
the boron atom lies in a trigonal environment [31].
An X-ray diffraction study on 1a was conducted to
confirm the formation of these sulfonamides (Fig. 2)
and to see if any significant N H· · ·B interaction was
occurring in the solid state. Crystallographic data
are given in Table 1 and selected bond distances and
angles shown in Table 2. A distance of N H(16)· · ·B
1a
1a
Formula
M
T (K)
C19H24BNO4S
373.26
198(2)
Cryst. syst.
Space group
Monoclinic
P2(1)/c
˚
a (A)
9.8379(10)
˚
b (A)
11.4745(12)
˚
c (A)
16.4414(16)
90.685(2)
1855.9(3)
4
0.199
1.336
β (◦)
3
˚
V (A )
Z
µ (mm−1
)
d (g cm−3
)
˚
λ (A)
0.71073
0.0370
0.1098
R1a
˚
of 2.550(18) A indicates an interaction between the
wR2b
amine hydrogen and the boron atom. The trigonal
environment of the boron atom suggests, however,
that this interaction is weak and testifies to the
reduced Lewis acidity of the Bpin groups compared
to other boronate ester appendages [13]. The B O
ꢀ
ꢀ
aR1 = ||Fo| − |Fc||/ |Fo|.
ꢀ
ꢀ
bAll data, wR2 (F2) = ( [w(Fo2 − Fc2)2]/ [Fo4])1/2, Weight = 1/
[σ2 (Fo2) + (0.0671 ∗ P)2 + (0.263 ∗ P)] where P = (max(Fo2, 0) + 2 ∗
Fc2)/3
˚
bond distances of 1.3514(17) and 1.3649(16) A are
putative nitro sulfonamides 2a–c, which were read-
ily reduced with dihydrogen using 10% Pd/C to give
the sulfanilamides 3a–c. These compounds are of
singular interest owing to their resemblance to the
typical for those observed in other three coordinate
Bpin complexes [13]. The OBO plane is roughly
coplanar with the aromatic ring of the sulfonamide
(12.4◦), indicating that significant overlap is occur-
ring with the ꢂ–system of the ring and the empty p
orbital of the boron atom.
◦
˚
TABLE 2 Selected Bond Lengths (A) and Angles ( ) for 1a
The pinacol protected boronic acid derivatives of
aniline added readily to 4-O2NC6H4SO2Cl to give the
B O(5)
1.3514(17)
B O(2)
B C(10)
1.3649(16)
1.5491(19)
O(2) C(3)
C(4) O(5)
1.4630(15)
1.4587(15)
C(11) N(16)
N(16) S
S O(7)
1.4169(16)
1.6369(11)
1.4214(10)
S O(6)
S C(17)
1.4223(10)
1.7480(13)
B H(16)
2.550(18)
113.55(11) O(7) S O(6)
O(5) B O(2)
O(5) B C(10)
O(2) B C(10)
B O(2) C(3)
O(2) C(3) C(7)
O(2) C(3) C(6)
O(2) C(3) C(4)
O(5) C(4) C(8)
O(5) C(4) C(9)
O(5) C(4) C(3)
B O(5) C(4)
C(11) C(10) B
C(15) C(10) B
120.31(7)
122.07(11) O(7) S N(16) 108.35(6)
124.32(12) O(6) S N(16) 104.05(6)
107.05(10) O(7) S C(17) 108.11(6)
108.39(11) O(6) S C(17) 109.03(6)
106.09(11) N(16) S C(17) 106.13(6)
102.48(9) C(22) C(17) S 120.69(10)
107.93(11) C(18) C(17) S 118.78(10)
106.96(11)
102.31(10)
108.01(10)
124.58(11)
117.95(12)
C(12) C(11) N(16) 120.35(12)
C(10) C(11) N(16) 118.79(11)
FIGURE 2 The molecular structure of 1a with ellipsoids
drawn at 30% probability level. Hydrogen atoms have been
omitted for clarity with the exception of H(16).
C(11) N(16) S
124.55(9)

372 He et al.
antibiotics sulfapyridine and sulfadimidine [32]. Re-
lated boranosulfonamides have recently been exam-
ined as potential ꢀ-lactamase inhibitors [33]. Once
again, a significant downfield shift is observed in the
1H NMR data for the amide NH bond in 3a (δ 8.54
ppm) compared to 3b (6.33 ppm) and 3c (6.44 ppm).
The 11B NMR spectra for all three compounds are at
ca δ 30 ppm, meaning the boron retains its trigonal
planar configuration.
EXPERIMENTAL
Reagents and solvents used were obtained from
Aldrich Chemicals. K2PtCl4 was purchased from Pre-
cious Metals Online Ltd. 2-H2NC6H4Bpin [36], 3-
H2NC6H4Bpin [30], and [PtCl2(coe)]2 [34,37] were
prepared as described in the literature. NMR spec-
tra were recorded on a JEOL JNM-GSX270 FT NMR
1
spectrometer. H NMR chemical shifts are reported
in ppm and are referenced to residual protons in
deuterated solvent at 270 MHz. 11B NMR chemical
shifts are referenced to external BF3·OEt2 at 87 MHz.
13C NMR chemical shifts are referenced to solvent
carbon resonances as internal standards at 68 MHz.
Multiplicities are reported as singlet (s), doublet (d),
triplet (t), multiplet (m), broad (br), and overlap-
ping (ov). Infrared spectra were obtained using a
Mattson Genesis II FT-IR spectrometer and are re-
ported in cm−1. Melting points were measured uncor-
rected with a Mel-Temp apparatus. Microanalyses
for C, H, and N were carried out at Guelph Chemical
Laboratories Ltd. (Guelph, ON).
As part of our investigation into preparing bio-
logically active boron-metal complexes, we decided
to examine the use of boranosulfonamides (3a–c)
as ligands for platinum dichloride complexes. Addi-
tion of 2-pyridinecarboxaldehyde to 3a–c afforded
the iminopyridyl ligands, which reacted further with
organic soluble [PtCl2(coe)]2 (coe = cis-cyclooctene)
[34] to give 4a–c in moderate yields (38–67%,
Scheme 1). Complexes 4a–c have been character-
ized by a number of physical methods, including
multinuclear NMR spectroscopy. A significant down-
field shift in the 1H NMR spectra is observed for the
imine sp2 proton upon coordination of the ligand to
the metal center. For instance, the singlet at δ 8.54
ppm for the 3-Bpin derivative shifts to 9.38 ppm in
complex 4b. Platinum satellites are also observed
for this resonance (JH-Pt = 81 Hz) upon complexa-
tion of the ligand to the metal. Similar trends are ob-
served for the pyridine hydrogen alpha to the nitro-
gen atom as the chemical shift changes from δ 8.73
to 9.46 ppm (JH-Pt = 43 Hz). Unfortunately, attempts
to produce single crystals of these complexes for X-
ray diffraction studies proved unsuccessful. Related
metal complexes derived from iminopyridyl ligands
containing sulfonamide appendages have been re-
ported [35]. We will examine the biological activity
of these novel metal complexes for their efficacy to
act as anticancer agents and will report our findings
in due course.
Synthesis of Sulfonamides 1a–c
The appropriate {4,4,5,5-tetramethyl-[1,3,2]-dioxa-
borolan-2-yl}phenylamine (200 mg, 0.91 mmol) in
CH2Cl2 (3 ml) was added to a CH2Cl2 (3 ml) solution
of p-toluenesulfonyl chloride (86 mg, 0.45 mmol)
and the reaction mixture was heated at reflux for
18 h. Extraction with CH2Cl2 (3 × 5 ml) from H2O
(10 ml) followed by removal of the solvent under vac-
uum afforded compounds 1a–c.
Sulfonamide 1a. Yield: 56 mg (33%) of an
off-white solid; mp 164–166◦C. Anal. Calcd for
C19H24NBO4S: C, 61.12; H, 6.49; N, 3.75. Found: C,
1
61.58; H, 6.43; N, 3.84%. H NMR (CDCl3): δ 8.56
(br s, 1H, NH), 7.63–7.58 (ov m, 4H, Ar), 7.38 (t d,
J = 7, 2 Hz, 1H, Ar), 7.14 (d, J = 8 Hz, 2H, Ar), 7.03
(t, J = 7 Hz, 1H, Ar), 2.32 (s, 3H, CH3Ar), 1.28 (s,
12H, O2C2(CH3)4); 11B NMR (CDCl3): δ 29.4 (br); 13
C
CONCLUSION
NMR (acetone-d6): δ 143.9, 136.5, 132.9, 130 (br, C-
B), 129.6, 129.1, 127.3, 124.8, 123.8, 119.6, 84.8, 24.3,
20.5. IR (Nujol): 3282, 2931, 2858, 1604, 1577, 1493,
1458, 1377, 1346, 1319, 1265, 1169, 1138, 1090, 1070,
1039, 962, 912, 854, 825, 758, 669, 565.
We have prepared a number of sulfonamides con-
taining pinacol protected boronate ester groups,
which can be used to generate a wide range of
new sulfonamides using the Suzuki–Miyaura cross-
coupling reaction. A weak interaction of the amide
N H bond with the neighboring ortho boron atom is
observed in solution and in the solid state as evident
by 1H NMR spectroscopy and X-ray crystallography.
The sulfanilamides were further functionalized with
2-pyridinecarboxaldehyde to give pyridyl imine lig-
ands, which were subsequently used to give the cor-
responding platinum complexes.
Sulfonamide 1b. Yield: 47 mg (28%) of an
off-white solid; mp 144–146◦C. Anal. Calcd for
C19H24NBO4S: C, 61.12; H, 6.49; N, 3.75. Found: C,
1
61.67; H, 6.89; N, 3.99%. H NMR (CDCl3): δ 7.64
(d, J = 8 Hz, 2H, Ar), 7.51 (d, J = 7 Hz, 1H, Ar),
7.33–7.18 (ov m, 5H, Ar), 6.68 (br s, 1H, NH), 2.35
(s, 3H, CH3Ar), 1.29 (s, 12H, O2C2(CH3)4); 11B NMR

Synthesis and Reactivity of Sulfonamides Containing Boronate Esters 373
(CDCl3): δ 29.8 (br); 13C NMR (acetone-d6): δ 143.6,
137.6, 137.3, 130.7, 130 (br, C-B), 129.6, 128.6, 127.2,
126.9, 123.5, 83.8, 24.4, 20.5. IR (Nujol): 3253, 2926,
2856, 1454, 1377, 1358, 1338, 1207, 1165, 1146, 1092,
968, 937, 850, 820, 791, 706, 673, 569, 544.
C, 57.75; H, 6.21; N, 7.49. Found: C, 57.85; H, 6.33;
N, 7.60%. 1H NMR (CDCl3): δ 7.52 (d, J = 8 Hz, 2H,
Ar), 7.32–7.20 (ov m, 4H, Ar), 6.56 (d, J = 8 Hz, 2H,
Ar), 6.33 (br s, 1H, NH), 4.06 (br s, 2H, NH2), 1.30
(s, 12H, O2C2(CH3)4); 11B NMR (CDCl3): δ 30.5 (br);
13C NMR (acetone-d6): δ 152.8, 138.3, 130.1, 130 (br,
C-B), 129.2, 128.4, 126.6, 126.3, 123.1, 113.0, 83.8,
24.4. IR (Nujol): 3460, 3369, 3228, 2912, 2864, 1633,
1595, 1462, 1377, 1155, 1090, 968, 945, 849, 721.
Sulfonamide 1c. Yield: 104 mg (62%) of an
off-white solid; mp 201–202◦C. Anal. Calcd for
C19H24NBO4S: C, 61.12; H, 6.49; N, 3.75. Found: C,
60.88; H, 6.10; N, 3.63%. 1H NMR (CDCl3): δ 7.67 (d,
J = 8 Hz, 2H, Ar), 7.64 (d, J = 8 Hz, 2H, Ar), 7.19
(d, J = 8 Hz, 2H, Ar), 7.06 (d, J = 8 Hz, 2H, Ar), 7.01
(br s, 1H, NH), 2.34 (s, 3H, CH3Ar), 1.29 (s, 12H,
O2C2(CH3)4); 11B NMR (CDCl3): δ 30.1 (br); 13C NMR
(acetone-d6): δ 143.8, 140.9, 137.2, 135.8, 130 (br, C-
B), 129.6, 127.2, 118.8, 83.6, 24.4, 20.5. IR (Nujol):
3234, 2918, 2860, 1608, 1460, 1373, 1336, 1146, 1092,
922, 854, 819, 571.
Sulfonamide 3c. Yield: 69 mg (41%) of a white
solid; mp 220–224◦C. Anal. Calcd for C18H23N2BO4S:
C, 57.75; H, 6.21; N, 7.49. Found: C, 57.51; H, 6.37;
N, 7.46%. 1H NMR (CDCl3): δ 7.65 (d, J = 8 Hz, 2H,
Ar), 7.54 (d, J = 8 Hz, 2H, Ar), 7.03 (d, J = 8 Hz, 2H,
Ar), 6.56 (d, J = 8 Hz, 2H, Ar), 6.44 (br s, 1H, NH),
4.05 (br s, 2H, NH2), 1.30 (s, 12H, O2C2(CH3)4); 11B
NMR (CDCl3): δ 28.6 (br); 13C NMR (CDCl3): δ 150.8,
139.7, 136.0, 130 (br, C-B), 129.5, 127.2, 119.4, 114.0,
83.9, 24.9. IR (Nujol): 3444, 3361, 3232, 2926, 2856,
1651, 1597, 1458, 1375, 1362, 1269, 1144, 1090, 962,
918, 833, 706.
Synthesis of Sulfonamides 3a–c
A solution of the appropriate {4,4,5,5-tetramethyl-
[1,3,2]-dioxaborolan-2-yl}phenylamine (200 mg,
0.91 mmol) in CH2Cl2 (3 ml) was added to a solution
of p-nitrobenzenesulfonyl chloride (100 mg, 0.45
mmol) in CH2Cl2 (3 ml). The reaction mixture was
heated at reflux for 18 h. Extraction with CH2Cl2
(3 × 5 ml) from H2O (10 ml) followed by removal
of the solvent under vacuum afforded compounds
2a–c. Compounds 3a–c were prepared by dissolving
the appropriate sulfonamide 2a–c in EtOH (5 ml) in
the presence of a catalytic amount of Pd/C (10%).
The mixture was shaken under an atmosphere of
H2 for 4 h, at which point, the catalyst was removed
by suction filtration and the solvent removed under
vacuum. The products were isolated by crystalliza-
tion from a solution of CH2Cl2 (2 ml) and hexane
(3 ml) stored at 5◦C.
Synthesis of Platinum Complexes 4a–c
Compounds 3a–c were added to a CH2Cl2 solution of
2-pyridinecarboxaldehyde (1 equivalent) in the pres-
ence of activated molecular sieves. The reaction was
allowed to proceed for 5 days, at which point, the
molecular sieves were removed by suction filtration
and the solvent removed under vacuum. The desired
pyridinyl-carboxaldimine (2 equivalents), used with-
out further purification, was added drop-wise to a
stirred CH2Cl2 solution of [PtCl2(coe)]2. Solvent was
removed after 2 h under vacuum to afford an orange
residue. Compounds 4a–c were crystallized from sat-
urated THF solutions which were stored overnight at
5◦C.
Sulfonamide 3a. Yield: 62 mg (37%) of a white
solid; mp 138–140◦C. Anal. Calcd for C18H23N2BO4S:
C, 57.75; H, 6.21; N, 7.49. Found: C, 57.31; H, 6.18;
Platinum Complex 4a. Yield: 28 mg (38%) of a
yellow solid; mp 230◦C (decomp.). Anal. Calcd for
1
.
N, 7.42%. H NMR (CDCl3): δ 8.54 (br s, 1H, NH),
C24H26N3BCl2O4PtS THF: C, 41.95; H, 4.28; N, 5.24.
7.61 (t, J = 8 Hz, 2H, Ar), 7.53 (d, J = 8 Hz, 2H, Ar),
7.37 (t d, J = 7, 2 Hz, 1H, Ar), 7.01 (t d, J = 7, 2 Hz,
1H, Ar), 6.61 (d, J = 8 Hz, 2H, Ar), 4.05 (br s, 2H,
NH2), 1.30 (s, 12H, O2C2(CH3)4); 11B NMR (CDCl3): δ
29.4 (br); 13C NMR (acetone-d6): δ 152.8, 144.5, 136.4,
132.7, 130 (br, C-B), 129.3, 125.5, 123.2, 119.3, 112.9,
84.6, 24.3. IR (Nujol): 3483, 3383, 3255, 2924, 2854,
1628, 1579, 1495, 1456, 1377, 1358, 1315, 1265, 1147,
1120, 1088, 928, 833, 766, 677, 567.
Found: C, 41.23; H, 4.26; N, 5.37%. 1H NMR (DMSO-
d6): δ 9.46 (br m, 1H, Ar), 9.36 (br m, 1H, Ar), 9.12 (br
s, 1H, NH), 8.44 (br m, 1H, Ar), 8.24 (br m, 1H, Ar),
8.00 (br m, 1H, Ar), 7.79 (br m, 2H, Ar), 7.58 (br m,
3H, Ar), 7.43 (br m, 1H, Ar), 7.28 (br m, 1H, Ar), 7.14
(br m, 1H, Ar), 1.31 (s, 12H, O2C2(CH3)4); 11B NMR
(DMSO-d6): δ 30.3 (br); 13C NMR (DMSO-d6): δ 174.2,
157.5, 150.5, 149.7, 142.7, 141.3, 139.5, 136.6, 133.0,
130.7, 130.5, 130 (br, C-B), 129.4, 127.6, 125.9, 125.2,
121.3, 112.9, 84.9, 25.2. IR (Nujol): 3257, 3238, 2924,
2856, 1608, 1556, 1485, 1435, 1348, 1267, 1169, 1142,
1070, 920, 856, 773, 706, 669, 627.
Sulfonamide 3b. Yield: 94 mg (56%) of a white
solid; mp 160–162◦C. Anal. Calcd for C18H23N2BO4S:

374 He et al.
Platinum Complex 4b. Yield: 49 mg (67%) of
ACKNOWLEDGMENTS
a yellow solid; mp 250◦C (decomp.). Anal. Calcd
for C24H26N3BCl2O4PtS: C, 39.51; H, 3.60; N, 5.76.
Found: C, 39.10; H, 3.49; N, 5.52%. 1H NMR (DMSO-
d6): δ 10.43 (s, 1H, NH), 9.46 (d, JH-Pt = 43 Hz, J = 5
Hz, 1H, Ar), 9.38 (s, JH-Pt = 81 Hz, 1H, C(H)N), 8.44
(t, J = 7 Hz, 1H, Ar), 8.19 (d, J = 7 Hz, 1H, Ar),
8.00 (t, J = 7 Hz, 1H, Ar), 7.86 (d, J = 8 Hz, 2H,
Ar), 7.62 (d, J = 8 Hz, 2H, Ar), 7.46 (s, 1H, Ar),
7.36 (t, J = 5 Hz, 1H, Ar), 7.28–7.26 (ov m, 2H, Ar),
We thank Dan Durant and Roger Smith for expert
technical assistance and an anonymous reviewer for
helpful comments.
REFERENCES
[1] Miyaura, N.; Suzuki, A. Chem Rev 1995, 95,
2457.
[2] Carboni, B.; Pourbaix, C.; Carreaux, F.; Deleuze,
H.; Maillard, B. Tetrahedron Lett 1999, 40,
7979.
[3] Farfan, N.; Ho¨pfl, H.; Barba, V.; Ochoa, M. E.;
Santillan, R.; Gomez, E.; Gutierrez, A. J Organomet
Chem 1999, 581, 70.
[4] Tailor, J.; Hall, D. G. Org Lett 2000, 2, 3715.
[5] Eggert, H.; Frederiksen, J.; Morin, C.; Chr. Norrild, J.
J Org Chem 1999, 64, 3846.
1.27 (s, 12H, O2C2(CH )4); 11B NMR (DMSO-d6): δ
3
32.2 (br); 13C NMR (DMSO-d6): δ 174.5, 157.5, 150.4,
149.8, 141.3, 140.1, 137.6, 130.9, 130.6, 130 (br, C-B),
129.5, 129.4, 127.4, 126.8, 126.0, 123.6, 84.4, 25.2. IR
(Nujol): 3248, 2933, 2868, 1581, 1556, 1460, 1414,
1377, 1267, 1155, 1090, 968, 947, 891, 850, 773, 721,
627.
[6] James, T. D.; Linnane, P.; Shinkai, S. J Chem Soc,
Chem Commun 1996, 281.
[7] Yang, W.; Gao, X.; Wang, B. Med Res Rev 2003, 23,
346.
[8] Morin, C. Tetrahedron 1994, 50, 12521.
[9] Cama, E.; Colleluori, D. M.; Emig, F. A.; Shin,
H.; Kim, S. W.; Kim, N. N.; Traish, A. M.; Ash,
D. E.; Christianson, D. W. Biochemistry 2003, 42,
8445.
[10] Stolowitz, M. L.; Ahlem, C.; Hughes, K. A.; Kaiser,
R. J.; Kesicki, E. A.; Li, G.; Lund, K. P.; Torkelson,
S. M.; Wiley, J. P. Bioconjugate Chem 2001, 12,
229.
[11] Kullberg, E. B.; Bergstrand, N.; Carlsson, J.; Edwards,
K.; Johnsson, M.; Sjo¨berg, S.; Gedda, L. Bioconjugate
Chem 2002, 13, 737.
[12] Soloway, A. H.; Tjarks, W.; Barnum, B. A.; Rong,
F.-G.; Barth, R. F.; Codogni, I. M.; Wilson, J. G. Chem
Rev 1998, 98, 1515.
[13] Decken, A.; Singh, A.; Vogels, C. M.; Westcott, S. A.
Acta Cryst 2002, E58, o1213.
[14] Gronowitz, S.; Dalgren, T.; Namtvedt, J.; Roos, C.;
Sjo¨berg, B.; Forsgren, U. Acta Pharm Suecica 1971,
8, 377.
Platinum Complex 4c. Yield: 28 mg (38%) of
a yellow solid; mp 280◦C (decomp.). Anal. Calcd
for C24H26N3BCl2O4PtS: C, 39.51; H, 3.60; N, 5.76.
Found: C, 39.51; H, 3.16; N, 5.67%. 1H NMR (DMSO-
d6): δ 10.71 (s, 1H, NH), 9.45 (d, JH-Pt = 43 Hz, J = 5
Hz, 1H, Ar), 9.38 (s, JH-Pt = 85 Hz, 1H, C(H)N), 8.44
(t, J = 8 Hz, 1H, Ar), 8.18 (d, J = 8 Hz, 1H, Ar), 8.00
(t, J = 5 Hz, 1H, Ar), 7.90 (d, J = 8 Hz, 2H, Ar), 7.62
(d, J = 7 Hz, 2H, Ar), 7.54 (d, J = 7 Hz, 2H, Ar), 7.15
(d, J = 8 Hz, 2H, Ar), 1.24 (s, 12H, O2C2(CH3)4); 11
B
NMR (DMSO-d6): δ 32.7 (br); 13C NMR (DMSO-d6): δ
174.4, 157.5, 150.5, 149.7, 141.3, 140.9, 139.9, 136.2,
130.5, 130 (br, C-B), 129.3, 129.0, 127.4, 126.0, 122.3,
119.2, 118.2, 113.1, 84.2, 25.2. IR (Nujol): 3178, 2931,
2858, 1608, 1558, 1456, 1362, 1340, 1300, 1273, 1159,
1140, 1090, 1020, 916, 849, 775, 733, 662, 637, 600,
561.
[15] Powers, R. A.; Shoichet, B. K. J Med Chem 2002, 45,
3222.
[16] Westmark, P. R.; Smith, B. D. J Am Chem Soc 1994,
116, 9343.
X-Ray Data
Crystals of 1a were grown from a saturated so-
lution of THF at 5◦C. Single crystals were coated
with Paratone-N oil, mounted using a glass fibre,
and frozen in the cold stream of the goniometer.
A hemisphere of data were collected on a Bruker
AXS P4/SMART 1000 diffractometer using ꢃ and ꢄ
scans with a scan width of 0.3◦ and 10 s exposure
times. The detector distance was 5 cm. The data
were reduced (SAINT) [38] and corrected for ab-
sorption (SADABS) [39]. The structure was solved
by direct methods and refined by full-matrix least
squares on F2 (SHELXTL) [40]. All non-hydrogen
atoms were refined anisotropically. Hydrogen atoms
were located in Fourier difference maps and refined
isotropically.
[17] Jamieson, E. R.; Lippard, S. J. Chem Rev 1999, 99,
2467.
[18] Reedijk, J. Chem Rev 1999, 99, 2499.
[19] Wong, E.; Giandomenico, C. M. Chem Rev 1999, 99,
2451.
[20] Ho, Y.-P.; Au-Yeung, S. C. F.; To, K. K. W. Med Res Rev
2003, 23, 633.
[21] Butour, J. L.; Macquet, J.-P. Biochemistry 1977, 78,
455.
[22] Neplechova´, K.; Kasˇpa´rkova´, J.; Vra´na, O.; Nova´kova´,
O.; Habtemariam, A.; Watchman, B.; Sadler, P. J.;
Brabec, V. Mol Pharmacol 1999, 56, 20.
[23] Hotze, A. C. G.; Chen, Y.; Hambley, T. W.; Parsons,
S.; Kratochwil, N. A.; Parkinson, J. A.; Munk, V. P.;
Sadler, P. J Eur J Inorg Chem 2002, 1035.
[24] Brunner, H.; Schmidt, M.; Scho¨nenberger, H. Inorg
Chim Acta 1968, 123, 201.

Synthesis and Reactivity of Sulfonamides Containing Boronate Esters 375
[25] Romero, D. L.; Morge, R. A.; Genin, M. J.; Biles, C.;
Busso, M.; Resnick, L.; Althaus, I. W.; Reusser, F.;
Thomas, R. C.; Tarpley, W. G. J Med Chem 1993, 36,
1505.
[26] Turner, S. R.; Strohbach, J. W.; Tommasi, R. A.;
Aristoff, P. A.; Johnson, P. D.; Skulnick, H. I.; Dolak,
L. A.; Seest, E. P.; Tomich, P. K.; Bohanon, M. J.;
Horng, M. M.; Lynn, J. C.; Chong, K.-T.; Hinshaw,
R. R.; Watenpaugh, K. D.; Janakiraman, M. N.;
Thaisrivongs, S. J Med Chem 1998, 41, 3467.
[27] Gallop, P. M.; Paz, M. US Patent 4 496 722, 1985.
[28] Calderwood, D. J.; Johnston, D. N.; Rafferty, P.;
Twigger, H. L.; Munschauer, R.; Arnold, L. US Patent
6 001 839, 1999.
[29] Martichonok, V.; Jones, J. B. J Am Chem Soc 1996,
118, 950.
[30] Kennedy, J. W. J.; Hall, D. G. J Organomet Chem
2003, 680, 263.
[31] Medina, J. R.; Cruz, G.; Cabrera, C. R.; Soderquist,
J. A. J Org Chem 2003, 68, 4631 and references
therein.
[32] Mann, J.; Crabbe, J. C. Bacteria and Antibacterial
Agents: Biochemical and Medicinal Chemistry Se-
ries; Spektrum Academic Publishers: Oxford, 1996.
[33] Powers, R. A.; Shoichet, B. K. J Med Chem 2002, 45,
3222.
[34] Otto, S.; Roodt, A.; Elding, L. I. Dalton Trans 2003,
2519.
[35] Congreve, A.; Kataky, R.; Knell, M.; Parker, D.;
Puschmann, H.; Senanayake, K.; Wylie, L. New J
Chem 2003, 27, 98.
[36] Baudoin, O.; Gue´nard, D.; Gue´ritte, F. J Org Chem
2000, 65, 9268.
[37] Vogels, C. M.; Wellwood, H. L.; Hennigar, T. L.;
Biradha, K.; Zaworotko, M. J.; Westcott, S. A. Can J
Chem 1999, 77, 1196.
[38] SAINT 6.02, Bruker AXS, Inc., Madison, Wisconsin,
USA, 1997–1999.
[39] Sheldrick, G. M. SADABS, Bruker AXS, Inc.,
Madison, Wisconsin, USA, 1999.
[40] Sheldrick, G. M. SHELXTL 5.1, Bruker AXS, Inc.,
Madison, Wisconsin, USA, 1997.