Penso et al.
and the reaction was monitored by TLC (AcOEt:hexane 1:6)
until completion. The mixture was diluted with water and
extracted with DCM and concentrated; the residue was diluted
with AcOEt (10 mL) and washed with brine (5 × 10 mL), dried
over MgSO4, and filtered. After evaporation of the solvent (RV),
the crude was purified by MPLC (AcOEt:hexane 1:9).
NMR (282 MHz, CDCl3) δ -132.5 (m, 1F), -140.1 (m, 1F),
-144 (m, 1F), -147.9 (m, 1F). 13C NMR (75 MHz, CDCl3) δ
168.0, 144.6 (dt, J ) 262.2, 14.3 Hz), 143.6 (ddd, J ) 261.8,
12.4, 3.3 Hz), 141.6 (dt, J ) 262.1, 14.2 Hz), 140.9 (dd, J )
261.6, 12.5 Hz), 135.4, 129.6, 129.0, 126.2, 121.8 (d, J ) 14.3
Hz), 119.6 (d, J ) 17.8 Hz), 69.9, 54.3. IR (nujol) 3280, 1748,
1637, 1512, 1376, 1319, 1257, 1173, 1035, 914 cm-1. Anal.
Calcd for C15H9F4NO4S: C, 48.01; H, 2.42; N, 3.73. Found: C,
47.96; H, 2.44; N, 3.73.
Synthesis of 7a-f by SL-PTC N-Alkylation of Benzo[d]sul-
tam 8a: General Procedure. To a solution of sultam 8a (375 g,
1 mmol) and TEBA (23 mg, 0.1 mmol) in dry MeCN (2 mL)
at 25 °C was added anhydrous K2CO3 (276 mg, 2 mmol). The
resulting heterogeneous mixture was stirred for 10 min, then
the alkylating agent RX was added (1.5 mmol) and the reaction
was monitored by TLC (AcOEt:hexane 1:6) until completion.
After filtration through a Celite pad and evaporation of the
solvent (RV), the crude was purified by MPLC (AcOEt:hexane
1:9). Alkylating agent RX, reaction times, and product yields
are given in Table 5. Physical and spectroscopic data for 7a-f
match those of products described in the Supporting Information
(SL-PTC “One-Pot” Synthesis of N-Alkyl-benzo[d]sultams
7a-f: General Procedure, p S-9).
Methyl 4,5,6,7-Tetrafluoro-1-methyl-3-phenyl-2,3-dihydroben-
zo[d]isothiazole-3-carboxylate 1,1-Dioxide (7a). 7a (366 mg,
94%), white solid, mp 166 °C. 1H NMR (300 MHz, CDCl3) δ
7.42-7.40 (m, 3H), 7.26-7.23 (m, 2H), 3.91 (s, 3H), 2.84 (s,
3H). 19F NMR (282, MHz, CDCl3) δ -135 (m, 1F), -140.3
(m, 1F), -145.3 (m, 1F), -149 (m, 1F). 13C NMR (125 MHz,
CDCl3) δ 166.8, 144.3 (dt, J ) 261.6, 13.8 Hz), 143.4 (ddd, J
) 261.6, 12.6, 3.8 Hz), 141.5 (dt, J ) 261.6, 13.8 Hz), 141.0
(dd, J ) 262.8, 13.8 Hz), 132.7, 129.9, 129.2, 127.4, 122.3 (dd,
J ) 13.4, 3.5 Hz), 118.2 (dd, J ) 17.5, 3.1 Hz), 71.8, 53.8,
25.4. IR (nujol) 1748, 1638, 1516, 1495, 1296, 1256, 1230,
1170, 1077, 977, 916, 880, 693, 629, 614 cm-1. Anal. Calcd
for C16H11F4NO4S: C, 49.36; H, 2.85; N, 3.60. Found: C, 49.31;
H, 2.81; N, 3.64. HRMS (ESI positive) calcd for
C16H11F4NNaO4S [M + Na]+ 412.02371, found 412.02401.
Synthesis of Benzo[d]sultams 8a-j: General Procedure. The
solution of sulfonamide 4 (1 mmol) and DBU (609 mg, 4 mmol)
in dry DME (5 mL) was stirred at 25 °C until completion (TLC
control). The solution was then diluted with AcOEt (10 mL)
then washed with aqueous 5% citric acid (3 × 10 mL), saturated
NaHCO3 solution (2 × 10 mL), and brine (10 mL). The organic
phase was dried over MgSO4, filtered, and concentrated under
reduced pressure (RV), giving the sultams 8a-j, without any
further purification.
Acknowledgment. This research was carried out within the
framework of the National Project “Nuovi metodi catalitici
stereoselettivi e sintesi stereoselettiva di molecole funzionali”
and is supported by MIUR (Rome) and CNR (Italy).
Supporting Information Available: Detailed experimental
1
procedures, physical and spectral data of new compounds, H,
Methyl 4,5,6,7-Tetrafluoro-3-phenyl-2,3-dihydrobenzo[d]-
isothiazole-3-carboxylate 1,1-Dioxide (8a). In the case of the
synthesis of compound 8a, sulfonamide 4a (3.95 g, 10 mmol),
DBU (6.09 g, 40 mmol), and DME (50 mL) were used. 8a (3.60
19F, and 13C NMR spectra of sulfonamides 4, 5 and benzosul-
tams 7, 8, and chiral HPLC analyses of compounds 4a, S-4a,
7a, and (+)-7a. This material is available free of charge via
1
g, 96%), white solid; mp 98-99 °C. H NMR (300 MHz,
CDCl3) δ 7.42-7.34 (m, 5H), 6.38 (s, 1H), 3.93 (s, 3H). 19F
JO800930G
6690 J. Org. Chem. Vol. 73, No. 17, 2008