A new strategy for the synthesis of benzylic sulfonamides: Palladium-catalyzed arylation and sulfonamide metathesis

Article abstract of DOI:10.1021/jo701431j

(Chemical Equation Presented) An efficient two-step strategy has been developed to access diversely functionalized benzylic sulfonamides. Execution of this strategy required the development of two reaction methods: the palladium-catalyzed cross-coupling of aryl halides with CH-acidic methanesulfonamides and a metathesis reaction between the resulting α-arylated sulfonamides and diverse amines. The broad scope of the cross-coupling process combined with a versatile sulfonamide metathesis constitutes an efficient strategy for the synthesis of various benzylic sulfonamides.

Full text of DOI:10.1021/jo701431j

to build benzylic sulfonamides that met three essential require-
ments: (1) the sulfonamide moiety must be introduced at a late
stage of the syntheses in the presence of sensitive functionality;
(2) removable functional handles must be present to allow
diversification of substituents on both the carbon and the
nitrogen atoms bonded to sulfur as a final step of the synthesis;
and (3) the diversification steps must be sufficiently mild and
generally applicable to allow for incorporation of a range of
sterically and electronically diverse substituents. As conventional
approaches to preparing benzylic sulfonamides typically rely
on free-radical processes, harsh oxidation conditions, and
unstable sulfonyl chloride intermediates,4 we decided to devise
a new strategy for their construction. As shown in Scheme 1,
our strategy required the development of the two new procedures
that are the subject of this communicationsa cross-coupling
between an R-C-H activated, yet hydrolytically stable, sulfonyl
chloride equivalent 1 and aryl halides (Step A) and a method
for converting stable sulfonyl chloride equivalent 2 to the desired
sulfonamides 3 (Step B).
A New Strategy for the Synthesis of Benzylic
Sulfonamides: Palladium-Catalyzed Arylation
and Sulfonamide Metathesis
Jonathan B. Grimm, Matthew H. Katcher,
David J. Witter, and Alan B. Northrup*
Department of Drug Design and Optimization, Merck Research
Laboratories, Boston, Massachusetts 02115
alan_northrup@merck.com
ReceiVed July 2, 2007
SCHEME 1. Strategy for Preparing Benzylic Sulfonamides
An efficient two-step strategy has been developed to access
diversely functionalized benzylic sulfonamides. Execution
of this strategy required the development of two reaction
methods: the palladium-catalyzed cross-coupling of aryl
halides with CH-acidic methanesulfonamides and a meta-
thesis reaction between the resulting R-arylated sulfonamides
and diverse amines. The broad scope of the cross-coupling
process combined with a versatile sulfonamide metathesis
constitutes an efficient strategy for the synthesis of various
benzylic sulfonamides.
The central C-C bond-forming event in our strategy relies
on extending the scope of the palladium-catalyzed R-arylation
of carbonyl compounds5 to include substrates, such as 1,
containing a removable activating group, E, and a stable sulfonyl
chloride equivalent (SO2Z). The early, pioneering efforts of
Buchwald, Hartwig and others focused largely on the arylation
of ketones.6 Since that time, the R-arylation chemistry has been
expanded to include esters,7 amides,8 aldehydes,9 nitriles,10
nitroalkanes,11 malonates,12 sulfones,13 and sulfoximines.14 There
are even two reports concerning sulfonamide C-arylations.
The sulfonamide is a key functional group in organic
chemistry that is present both in the structures of natural products
and also in marketed therapeutics such as Celecoxib for pain
and inflammation,1 Tipranavir for HIV/AIDS,2 and Zonisamide
for seizure.3 During the course of two distinct medicinal
chemistry programs we required access to diversely substituted
benzylic sulfonamides. To enable rapid exploration of structure/
activity relationships, we searched the literature for a strategy
(4) (a) Hill, B.; Liu, Y.; Taylor, S. D. Org. Lett. 2004, 6, 4285. (b)
Abdellaoui, H.; Depreux, P.; Lesieur, D.; Pfeiffer, B.; Bontempelli, P. Synth.
Commun. 1995, 25, 1301. (c) Anderson, K. K. In ComprehensiVe Organic
Chemistry; Jones, D. N., Ed.; Pergamon Press: Oxford, 1979; Vol. 3, p
345. (d) For a creative and useful strategy limited to ammonia-derived
benzylic and alkyl sulfonamides, see: Baskin, J. M.; Wang, Z. Tetrahedron
Lett. 2002, 43, 8479.
(5) Culkin, D. A.; Hartwig, J. F. Acc. Chem. Res. 2003, 36, 234.
(6) (a) Palucki, M.; Buchwald, S. L. J. Am. Chem. Soc. 1997, 119, 11108.
(b) Hamann, B. C.; Hartwig, J. F. J. Am. Chem. Soc. 1997, 119, 12382. (c)
Åhman, J.; Wolfe, J. P.; Troutman, M. V.; Palucki, M.; Buchwald, S. L. J.
Am. Chem. Soc. 1998, 120, 1918. (d) Kawatsura, M.; Hartwig, J. F. J. Am.
Chem. Soc. 1999, 121, 1473. (e) Fox, J. M.; Huang, X.; Chieffi, A.;
Buchwald, S. J. Am. Chem. Soc. 2000, 122, 1360.
(7) (a) Moradi, W. A.; Buchwald, S. L. J. Am. Chem. Soc. 2001, 123,
7996. (b) Lee, S.; Beare, N. A.; Hartwig, J. F. J. Am. Chem. Soc. 2001,
123, 8410. (c) Jørgensen, M.; Lee, S.; Liu, X.; Wolkowski, J. P.; Hartwig,
J. F. J. Am. Chem. Soc. 2002, 124, 12557.
(8) (a) Shaughnessy, K. H.; Hamann, B. C.; Hartwig, J. F. J. Org. Chem.
1998, 63, 6546. (b) Cossy, J.; de Filippis, A.; Pardo, D. G. Org. Lett. 2003,
5, 3037.
(1) Penning, T. D.; Talley, J. J.; Bertenshaw, S. R.; Carter, J. S.; Collins,
P. W.; Docter, S.; Graneto, M. J.; Lee, L. F.; Malecha, J. W.; Miyashiro,
J. M.; Rogers, R. S.; Rogier, D. J.; Yu, S. S.; Anderson, G. D.; Burton, E.
G.; Cogburn, J. N.; Gregory, S. A.; Koboldt, C. M.; Perkins, W. E.; Seibert,
K.; Veenhuizen, A. W.; Zhang, Y. Y.; Isakson, P. C J. Med. Chem. 1997,
40, 1347.
(2) Thaisrivongs, S.; Skulnick, H. I.; Turner, S. R.; Strohbach, J. W.;
Tommasi, R. A.; Johnson, P. D.; Aristoff, P. A.; Judge, T. M.; Gammill,
R. B.; Morris, J. K.; Romines, K. R.; Chrusciel, R. A.; Hinshaw, R. R.;
Chong, K.-T.; Tarpley, W. G.; Poppe, S. M.; Slade, D. E.; Lynn, J. C.;
Horng, M.-M.; Tomich, P. K.; Seest, E. P.; Dolak, L. A.; Howe, W. J.;
Howard, G. M.; Schwende, F. J.; Toth, L. N.; Padbury, G. E.; Wilson, G.
J.; Shiou, L.; Zipp, G. L.; Wilkinson, K. F.; Rush, B. D.; Ruwart, M. J.;
Koeplinger, K. A.; Zhao, Z.; Cole, S.; Zaya, R. M.; Kakuk, T. J.;
Janakiraman, M. N.; Watenpaugh, K. D. J. Med. Chem. 1996, 39, 4349.
(3) Uno, H.; Kurokawa, M.; Masuda, Y.; Nishimura, H. J. Med. Chem.
1979, 22, 180.
(9) (a) Terao, Y.; Fukuoka, Y.; Satoh, T.; Miura, M.; Nomura, M.
Tetrahedron Lett. 2002, 43, 101. (b) Muratake, H.; Natsume, M.; Nakai,
H. Tetrahedron 2004, 60, 11783.
(10) (a) Culkin, D. A.; Hartwig, J. F. J. Am. Chem. Soc. 2002, 124, 9330.
(b) You, J.; Verkade, J. G. Angew. Chem., Int. Ed. 2003, 42, 5051. (c)
You, J.; Verkade, J. G. J. Org. Chem. 2003, 68, 8003. (d) Wu, L.; Hartwig,
J. F. J. Am. Chem. Soc. 2005, 127, 15824.
10.1021/jo701431j CCC: $37.00 © 2007 American Chemical Society
Published on Web 09/20/2007
J. Org. Chem. 2007, 72, 8135-8138
8135

TABLE 1. Optimization of Sulfonamide Arylation with PhBr
TABLE 2. Sulfonamide Arylation Reaction Scope
entry
liganda
base
yieldb (%)
1
2
3
4
5
6
7
8
9
t-Bu3PH‚BF4
t-Bu3PH‚BF4
PCy3
PCy3
dppf
NaOt-Bu
NaH
NaOt-Bu
NaH
NaOt-Bu
NaH
NaOt-Bu
NaH
23
11
31
36
27
42
28
15
58
76
dppf
BINAP
BINAP
PPh3
NaOt-Bu
NaH
10
PPh3
a Similar results were obtained with 15 mol % ligand. b Isolated yield
of chromatographically pure 6.
Middleton et al. described in the patent literature a single
example of coupling an R-cyanosulfonamide to an aryl iodide.15
More recently, Parkinson et al. reported the arylation of simple
methanesulfonamides lacking activating substituents (e.g., CN,
CO2R, and CONR2).16 Neither example afforded the necessary
synthetic flexibility we desired, so we sought to develop sulf-
onamide 5 as a novel substrate in this process (E ) CO2Me, Z
) NMePh). We considered the methyl ester to be an ideal acti-
vating group due to the ease of its removal via decarboxylation
and the rich chemistry of esters. The choice of N-methylaniline
as a chloride surrogate relied on the hypothesis that the increased
acidity of an aniline relative to that of an alkyl amine would
render it a more suitable leaving group in a seldom-used
sulfonamide metathesis reaction (Step B, vide infra).
The equimolar coupling between bromobenzene and sulfona-
mide 5 was employed as a model system to optimize this cross-
coupling process. While other palladium precatalysts (such as
Pd2dba3) were evaluated, uniformly higher yields were obtained
when utilizing Pd(OAc)2 with dioxane as solvent. A representa-
tive set of five ligands (t-Bu3PH‚BF4, PCy3, DPPF, BINAP,
and PPh3) and two bases (NaOt-Bu and NaH) were then selected
for investigation under those conditions (Table 1). An excess
of a strong base (g2.0 eq) was required for deprotonation of
sulfonamide 5 and promotion of the catalytic cycle, as the
arylation product 6 is presumably more acidic than either starting
material. Optimal yield was achieved with PPh3 as ligand and
NaH as base to provide a 76% yield of 6, although reaction
with PPh3 and NaOt-Bu also provided a reasonable yield (58%,
entry 9). In all cases, the yields of 6 were reduced by undesired
side reactions including biphenyl formation, hydrodehalogena-
tion of bromobenzene, and decarboxylation of product 6 to form
an unsubstituted benzylic sulfonamide.
a Product resulted exclusively from coupling at position with bromine.
b Performed at 120 °C. c Performed at 80 °C with 6 mol % PCy3 as ligand.
(11) Vogl, E. M.; Buchwald, S. L. J. Org. Chem. 2002, 67, 106.
(12) Beare, N. A.; Hartwig, J. F. J. Org. Chem. 2002, 67, 541.
(13) (a) Kashin, A. N.; Mitin, A. V.; Beletskaya, I. P.; Wife, R.
Tetrahedron Lett. 2002, 43, 2539. (b) Mitin, A. V.; Kashin, A. N.;
Beletskaya, I. P. Russ. J. Org. Chem. 2004, 40, 802. (c) Mitin, A. V.; Kashin,
A. N.; Beletskaya, I. P. J. Organomet. Chem. 2004, 689, 1085.
(14) (a) Bolm, C.; Okamura, H.; Verrucci, M. J. Organomet. Chem. 2003,
687, 444. (b) Cho, G. Y.; Bolm, C. Org. Lett. 2005, 7, 1351.
(15) Middleton, D. S.; Stobie, A. 1,2,3,4-Tetrahydro-1-naphthalenamine
Compounds Useful in Therapy. (Pfizer Ltd.). WO 00/51972, 2000; Chem.
Abstr. 2000, 133, 222454 .
With these results in mind, the newly optimized sulfonamide
arylation conditions were applied to various substituted aryl
halides (Table 2); however, conditions ideal for bromobenzene
consistently resulted in poor conversions and low yields for a
number of other substratessparticularly those with electron-
withdrawing groups (e.g., aryl halides 7a-h). It was quickly
established that bulky trialkylphosphine ligands, in particular
t-Bu3P, led to increased conversions by reducing the propensity
(16) Zeevaart, J. G.; Parkinson, C. J.; de Koning, C. B. Tetrahedron
Lett. 2005, 46, 1597.
8136 J. Org. Chem., Vol. 72, No. 21, 2007

SCHEME 2. Arylation of Amide-Activated Sulfonamide
SCHEME 4. Proposed Mechanisms for Sulfonamide
Metathesis
SCHEME 3. One-Pot Arylation with Electrophilic Quench
of those aryl halides to partition toward homocoupling and
hydrodehalogenation reaction pathways. For aryl bromides
bearing electron-withdrawing groups, reaction with 5 was
generally complete within 1 h and consistently afforded arylated
products 8a-h in good to excellent yields (Table 2, entries 1-8,
70-85%). Importantly, the arylation conditions were tolerant
of various functionalities including nitriles, esters, and ketones.
Furthermore, couplings of chloro-substituted aryl bromides (7c-
d) were highly halogen-selective, exclusively providing chloro-
phenylated products 8c-d in good yield (entries 3-4, 70-72%).
The scope of the arylation reaction extended beyond electron-
poor aryl bromides to include electron-rich, sterically demand-
ing, and heterocyclic aryl halides. For example, 2-bromotoluene
was a viable substrate for this transformation (entry 9, 39%
yield), although it required an extended reaction time and an
elevated reaction temperature (18 h, 120 °C). As demonstrated
by entry 10, ortho-disubstituted aryl bromides were challenging
substrates providing low conversion (entry 10, 7% yield).
Electron-rich aryl bromides were also tolerated, as exemplified
by reactions with 4-bromo- and 3-bromoanisole (entries 11 and
12, PCy3 ligand, 53% and 45% yields, respectively). Heteroaryl
halides, such as 2-chloropyridine, were also effectively coupled
with sulfonamide 5 to provide pyridylsulfonamide 8m in 53%
yield (entry 13).
excellent yields (66-75% over two steps). This one-pot process
allows for a rapid increase in molecular complexity and affords
useful products containing a diversely functionalized quaternary
carbon.
Having achieved the initial goal of developing a sulfonamide
arylation reaction (Scheme 1, Step A), we next set out to perform
a sulfonamide metathesis reaction (i.e., amine exchange, Scheme
1, Step B) with our coupled products 8a-m to complete a two-
step strategy for preparing diverse benzylic sulfonamides. While
Klamann and co-workers17 established over 50 years ago that
an amine metathesis reaction was possible for C-arylsulfona-
mides and amine salts at elevated temperatures (g200 °C), this
transformation has been largely overlooked by the synthetic
community and has not been previously demonstrated for simple
C-alkylsulfonamides.17d In the present case, the high reaction
temperatures and mildly acidic media of Klamann’s conditions
were unsuitable due to the propensity of compounds 8 to
undergo decarboxylation and other decomposition reactions. In
selecting new conditions for the sulfonamide metathesis reaction,
we considered an alternative mechanistic hypothesis to Kla-
mann’s proposal17c that elimination of N-methylaniline followed
by amine addition to a sulfene intermediate could provide the
desired products under basic conditions (Scheme 4).
While the arylation reactions described in Table 2 employed
the versatile acetate-derived sulfonamide 5, other activated
sulfonamides can be arylated under similar conditions (Scheme
2). For example, dimethylamide-containing sulfonamide 9
underwent a smooth cross-coupling reaction with bromide 7h
to afford arylated sulfonamide 10 in 74% yield, albeit with an
extended reaction time (cf. entry 8, 77% yield, 15 min).
The formation of quaternary carbon centers is an important
goal in synthetic chemistry. A one-pot, two-step process trapping
the arylated products in situ with various electrophiles to form
fully substituted carbon atoms would significantly extend the
utility of this methodology.12 To that end, sulfonamide 5 was
coupled with tert-butyl 4-bromobenzoate (7h) under the opti-
mized cross-coupling conditions in Table 2. After consumption
of sulfonamide 5, the desired electrophile was added to the
reaction mixture (Scheme 3). N-Chlorosuccinimide (NCS),
methyl iodide, and allyl bromide each functioned efficiently as
electrophiles, providing the desired products 11a-c in good to
Gratifyingly, a mild and operationally simple sulfonamide
metathesis procedure was developed that affords useful yields
for a wide range of amine substrates (Table 3). The ease of the
sulfonamide metathesis procedure readily lends itself to rapid
analogue preparation and proved invaluable to our medicinal
chemistry studies. As demonstrated by entries 1-4, primary
amines, electron-deficient amines, and even aniline functioned
efficiently as nucleophiles in this reaction (55-79% yield).
Additionally, secondary amines were within the scope of this
metathesis procedure including sterically demanding N,N-
diisopropylamine (entries 5-7, 40-53% yield). As demon-
strated in Scheme 5, a simple one-pot sulfonamide metathesis/
(17) (a) Klamann, D. Oester. Chem. 1953, 54, 299. (b) Klamann, D.
Liebigs Ann. Chem. 1953, 581, 182. (c) Klamann, D.; Fabienke, E. Chem.
Ber. 1959, 92, 712. (d) A survey of the CAS database (SciFinder, 2007) as
well as the ISI Web of Science found a combined 19 publications citing
refs 17a-c at the time of submission of this manuscript.
J. Org. Chem, Vol. 72, No. 21, 2007 8137

TABLE 3. Sulfonamide Metathesis Reaction
(2H, m), 7.30-7.26 (3H, m), 5.16 (1H, s), 3.79 (3H, s), 3.21 (3H,
s); 13C NMR (CDCl3, 150 MHz) δ 165.2, 140.8, 132.8, 131.9 (q,
J ) 32.3 Hz), 131.1, 129.6, 127.8, 126.7, 125.8 (q, J ) 3.9 Hz),
124.0 (q, J ) 273.4 Hz), 70.0, 53.7, 40.3; HRMS (ESI) calcd for
C17H16F3NO4S [M + H]+ 388.0830, found 388.0809.
General Procedure for the Sequential Cross-Croupling and
Electrophilic Quench (Scheme 3). The following procedure for
11a is representative. To a solution of sulfonamide 5 (300 mg, 1.23
mmol) in dioxane (10 mL) was added sodium tert-butoxide (356
mg, 3.70 mmol). After stirring for 15 min at room temperature,
tert-butyl 4-bromobenzoate (476 mg, 1.85 mmol), Pd(OAc)2 (14
mg, 0.06 mmol), and tri-tert-butylphosphonium tetrafluoroborate
(45 mg, 0.19 mmol) were added. The mixture was degassed with
N2 for 20 min at room temperature. It was subsequently heated to
90 °C and stirred for 60 min. The reaction was cooled to room
temperature, and N-chlorosuccinimide (247 mg, 1.85 mmol) in
dioxane (3 mL) was added in one portion. After stirring for an
additional 30 min at room temperature, the reaction was acidifed
with 0.5 N HCl and extracted with CH2Cl2. The organic layer was
washed with brine, dried (MgSO4), and evaporated. Flash chro-
matography on silica gel (0-30% EtOAc/hexanes) afforded 404
mg (72%) of 11a as a yellow gum. 1H NMR (CDCl3, 600 MHz) δ
7.95 (2H, d, J ) 8.6 Hz), 7.84 (2H, d, J ) 8.4 Hz), 7.29-7.19
(5H, m), 3.73 (3H, s), 3.23 (3H, s), 1.58 (9H, s); 13C NMR (CDCl3,
150 MHz) δ 165.1, 165.0, 142.2, 135.7, 133.7, 129.3, 129.1, 129.0,
127.7, 127.5, 88.0, 81.8, 54.6, 43.1, 28.4; HRMS (ESI) calcd for
C21H24ClNO6S [M + Na]+ 476.0911, found 476.0908.
entry
R1
R2
product
yield (%)
1
2
3
4
5
6
7
Ph
Et
H
H
H
H
Me
i-Pr
Bn
12a
12b
12c
12d
12e
12f
79
55
58
65
53
46
40
CH2CF3
CH2CO2Me
Me
i-Pr
Bn
12g
SCHEME 5. One-Pot Metathesis and Decarboxylation
General Procedure for Sulfonamide Metathesis (Table 3). The
following procedure for 12a is representative. To a solution of
sulfonamide 8h (100 mg, 0.238 mmol) in N-methyl-2-pyrrolidine
(2 mL) was added aniline (111 mg, 1.19 mmol). The mixture was
heated to 100 °C on a prewarmed hot plate and allowed to stir for
2 h. The reaction was cooled to room temperature. Flash chroma-
tography on silica gel (EtOAc/hexanes) afforded 12a (76.2 mg,
79%) as a yellow oil. 1H NMR (CDCl3, 600 MHz) δ 7.90 (2H, d),
7.47 (2H, d), 7.28 (2H, dd), 7.14 (4H, m), 5.12 (1H, s), 3.74 (3H,
s), 1.55 (9H, s); 13C NMR (CDCl3, 150 MHz) δ 165.8, 165.2, 136.5,
133.3, 132.5, 130.5, 130.0, 129.8, 125.9, 121.3, 81.7, 70.1, 53.8,
28.3; HRMS (ESI) calcd for C20H23NO6S [M + Na]+ 428.1144,
found 428.1125.
tert-Butyl 4-{[(dimethylamino)sulfonyl]methyl}benzoate (13).
To a solution of sulfonamide 8h (100 mg, 0.238 mmol) in N-methyl-
2-pyrrolidine (2 mL) was added 2 M dimethylamine in THF (0.6
mL, 1.2 mmol). The solution was heated to 100 °C in a prewarmed
hot plate and allowed to stir for 1 h. The mixture was cooled to
room temperature, and 1 M sodium hydroxide (1.2 mL, 1.2 mmol)
was added. After 30 min, the reaction was added to aqueous sodium
hydrogen carbonate (saturated) and extracted with ethyl acetate.
The combined organic extracts were washed with brine, dried over
anhydrous sodium sulfate, filtered, and concentrated under reduced
pressure. Flash chromatography on silica gel (ethyl acetate/hexanes)
afforded 13 (33.5 mg, 0.112 mmol, 47% yield) as a white solid.
1H NMR (CDCl3, 600 MHz) δ 7.96 (2H, d), 7.43 (2H, d), 4.24
(2H, s), 2.70 (6H, s), 1.56 (9H, s); 13C NMR (CDCl3, 150 MHz) δ
165.4, 133.7, 132.5, 130.7, 130.0, 81.6, 55.9, 38.0, 28.4; HRMS
(ESI) calcd for C14H21NO4S [M + H]+ 300.1270, found 300.1303.
decarboxylation procedure was developed that allows convenient
access to R-unsubstituted benzylic sulfonamides via addition
of NaOH to the metathesis reaction mixture after cooling to
room temperature.
In summary, we have developed a convenient and efficient
strategy for the synthesis of functionalized benzylic sulfona-
mides. Bulky monophosphine-based catalyst systems are uniquely
suited to promoting the R-arylation of activated methanesulfona-
mides with a diverse range of aryl halides. In situ treatment of
the cross-coupled products with various electrophiles afforded
products containing functionalized quaternary carbon centers
in a two-step, one-pot process. Additional derivatization of the
products was accomplished through a novel sulfonamide me-
tathesis procedure that provides synthetically useful benzylic
sulfonamides with convenient functional handles. Future studies
will investigate the mechanism and scope of the new sulfona-
mide metathesis procedure.
Experimental Section
General Procedure for Cross-Coupling with Sulfonamide 5
(Table 2). The following procedure for 8a is representative. To a
solution of sulfonamide 5 (200 mg, 0.82 mmol) in dioxane (5 mL)
was added sodium tert-butoxide (237 mg, 2.47 mmol). After stirring
for 15 min at room temperature, 4-bromobenzotrifluoride (185 mg,
0.82 mmol), Pd(OAc)2 (9 mg, 0.04 mmol), and tri-tert-butylphos-
phonium tetrafluoroborate (35 mg, 0.12 mmol) were added. The
mixture was degassed with N2 for 20 min at room temperature.
The flask was subsequently heated to 90 °C and stirred for 15 min.
The pale yellow slurry was then cooled to room temperature,
acidified with 0.5 N HCl, and extracted with CH2Cl2. The organic
layer was washed with brine, dried (MgSO4), and evaporated. Flash
chromatography on silica gel (0-25% EtOAc/hexanes) afforded
8a (234 mg, 74%) as a colorless solid. 1H NMR (CDCl3, 600 MHz)
δ 7.73 (2H, d, J ) 8.4 Hz), 7.63 (2H, d, J ) 8.2 Hz), 7.37-7.33
Acknowledgment. We thank Naim Nazef for HRMS
analysis of all compounds and Rachael White for the preparation
of sulfonamide 5.
Supporting Information Available: General and detailed
experimental procedures and spectral data for all new compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
JO701431J
8138 J. Org. Chem., Vol. 72, No. 21, 2007