Bicyclic Sultam HaVing Sulfur at the Apex Position
in H2O (18 mol) heated to 60 °C was added 17 (4.64 g, 28.6 mmol).
The reaction mixture was stirred at 60 °C for 20 h, concentrated,
and placed under high vacuum for 24 h. To the residue was added
a 1:1 solution of THF/CH2Cl2 (72 mL), DMF (10 drops), and, after
cooling to 0 °C, oxalyl chloride (3.1 mL, 35.8 mmol). After being
stirred for 4 h, the reaction mixture was filtered and concentrated
and the sulfonyl chloride was dissolved in CH2Cl2 (30 mL) and
added to a 0 °C solution of allylamine (2.7 mL, 35.8 mmol) and
triethylamine (8.0 mL, 57.2 mmol) in CH2Cl2 (150 mL) over 4 Å
molecular sieves. The solution was stirred for 16 h while warming
to room temperature. The reaction mixture was filtered, then washed
with water (100 mL), saturated NaHCO3, (100 mL) and brine (100
mL). The aqueous phases were back-extracted with CH2Cl2 (2 ×
50 mL), and the organic phases were combined, dried, and
concentrated to leave a yellowish solid. The residue was purified
via column chromatography on silica gel (elution with 99:1 CH2-
Cl2/EtOAc) to give 19 as a light yellow oil (3.0 g, 40%): IR (thin
film, cm-1) 1642, 1439, 1312; 1H NMR (400 MHz, CDCl3) δ 5.94-
5.78 (m, 2H), 5.31 (dq, J ) 1.2, 16.8 Hz, 1H), 5.25-5.16 (m, 3H),
4.26 (bt, J ) 5.6 Hz, 1H), 3.86-3.76 (m, 3H), 3.69 (dt, J ) 6.4,
12.8 Hz, 1H), 3.32-3.25 (m, 1H), 2.75-2.68 (m, 1H), 2.49-2.33
(m, 2H), 2.19-2.10 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 133.6,
133.2, 119.0, 118.0, 58.8, 46.1, 42.1, 33.7, 31.4; HRMS m/z (C9H16-
ClNO2SNa+) calcd 260.0482, obsd 260.0489.
6-Chloro-1-hexene-4-sulfonic Acid Allylamide (19). B. LiCl
as Reactant. To a solution of lithium chloride (3.19 g, 75.2 mmol)
in THF (160 mL) heated to 60 °C was added 17 (10.2 g, 62.7
mmol). The reaction mixture was stirred at 60 °C for 20 h, then
concentrated under vacuum. A portion of the crude sulfonate (1.02
g, 5.0 mmol) dissolved in a 1:1 solution of THF/CH2Cl2 (5 mL)
and DMF (5 drops) was cooled to 0 °C and treated with oxalyl
chloride (0.54 mL, 6.25 mmol). After 4 h of stirring, the crude
sulfonyl chloride was added to a 0 °C solution of allylamine (1.5
mL, 20.0 mmol) and triethylamine (2.8 mL, 20.0 mmol) in CH2-
Cl2 (25 mL) over 4 Å molecular sieves. The solution was stirred
for 16 h while warming to room temperature. The reaction mixture
was filtered and washed with H2O (100 mL), saturated NaHCO3
solution (100 mL), and brine (100 mL). The aqueous phases were
back-extracted with CH2Cl2 (2 × 50 mL), and the combined organic
phases were dried and concentrated to leave a yellowish solid. The
residue was purified via column chromatography over silica gel
(elution with 99:1 CH2Cl2/EtOAc), and 19 was isolated as a light
yellow oil (0.21 g, 18%).
6-Chloro-1-hexene-4-sulfonic Acid Allylamide (19). C. KCl
as Reactant. To a solution of potassium chloride (2.90 g, 38.9
mmol) in H2O (35 mL) heated to 60 °C was added 17 (5.73 g,
35.3 mmol). The reaction mixture was stirred at 60 °C for 16 h,
concentrated, and freed of residual water by distillation from
toluene. To the crude sulfonate was added a 1:1 solution of THF/
CH2Cl2 (100 mL), DMF (10 drops), and, after cooling to 0 °C,
oxalyl chloride (3.75 mL, 43.8 mmol). After being stirred for 4 h,
the reaction mixture was filtered and concentrated to leave an oil.
The sulfonyl chloride was dissolved in CH2Cl2 (10 mL) and added
to a 0 °C solution of allylamine (5.3 mL, 70.0 mmol) and
triethylamine (9.8 mL, 70.0 mmol) in CH2Cl2 (175 mL) over 4 Å
molecular sieves. The solution was stirred for 16 h while warming
to room temperature, filtered, and washed in turn with H2O (100
mL), saturated NaHCO3 solution (100 mL), and brine (100 mL).
The aqueous phases were back-extracted with CH2Cl2 (2 × 50 mL),
and the organic phases were combined, dried, and concentrated to
leave a yellowish solid. The residue was purified via column
chromatography on silica (elution with CH2Cl2), and 19 was isolated
as a light yellow oil (4.14 g, 50%).
under vacuum and the product was purified over silica gel (elution
with 70:30 hexanes/EtOAc) to leave 20 as a tan oil (5.4 g, 98%):
IR (thin film, cm-1) 3270, 1438, 1312; 1H NMR (400 MHz, CDCl3)
δ 6.07-5-96 (m, 2H), 4.41 (br s, 1H), 3.80 (dt, J ) 6.4, 11.6 Hz,
1H), 3.72-3.63 (m, 3H), 3.52-3.32 (m, 1H), 2.60-2.57 (m, 1H),
2.48 (ddt, J ) 6.0, 7.2, 14.8 Hz, 1H), 2.03-1.94 (m, 1H); 13C NMR
(100 MHz, CDCl3) δ 132.4, 130.6, 59.8, 41.7, 40.1, 31.9, 27.0;
HRMS m/z (C7H12ClNO2SNa+) calcd 232.0169, obsd 232.0175.
Base-Promoted Cyclization of 20. 1-Aza-9-thiatricyclo[4.2.1]-
non-3-ene 9,9-Dioxide (16). Sodium hydroxide (0.34 g, 8.5 mmol)
in a solution of 20 (1.78 g, 8.49 mmol) and triethylamine (1.2 mL,
8.5 mmol) in absolute EtOH (32 mL) was heated to reflux for 2 h,
cooled, concentrated under vacuum, redissolved in CH2Cl2, filtered,
and reconcentrated. The residue was chromatographed on silica gel
(elution with 50:48:2 hexanes/CH2Cl2/EtOAc) to deliver 16 as a
white solid (1.4 g, 95%): mp 112-115 °C; IR (CH2Cl2, cm-1
)
1
1423, 1333, 1270; H NMR (400 MHz, CDCl3) δ 5.73-5.68 (m,
1H), 5.60-5.54 (m, 1H), 4.04 (br d, J ) 18.4 Hz, 1H), 3.57-3.48
(m, 3H), 2.97 (ddd, J ) 5.2, 11.2, 12.4 Hz, 1H), 2.69 (br d, J )
18.0 Hz, 1H), 2.58-2.49 (m, 1H), 2.34 (ddd, J ) 5.2, 6.8, 18.0
Hz, 1H), 2.05-1.98 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 127.8,
126.7, 53.7, 50.5, 45.5, 29.4, 26.6; HRMS m/z (C7H11NO2SNa+)
calcd 196.0403, obsd 196.0407.
Epoxidation of 16. A mixture of NaHCO3 (0.39 g, 4.6 mmol),
m-chloroperbenzoic acid (0.79 g, 4.6 mmol), and 16 (0.40 g, 2.3
mmol) in CH2Cl2 (45 mL) was heated to reflux for 18 h. The
reaction mixture was purified via column chromatography over
silica gel (elution with 50:48:2 hexanes/CH2Cl2/EtOAc) to furnish
21 as a white solid (0.27 g, 62%): mp 197-199 °C; IR (CH2Cl2,
cm-1) 1421, 1335, 1184; 1H NMR (400 MHz, CDCl3) δ 3.83 (dd,
J ) 1.2, 17.2 Hz, 1H), 3.56-3.35 (m, 3H), 3.30 (br s, 1H), 3.16-
3.15 (m, 1H), 2.55 (ddd, J ) 2.0, 3.2, 16.4 Hz, 1H), 2.50-2.33
(m, 3H); 13C NMR (100 MHz, CDCl3) δ 59.3, 56.5, 53.0, 46.2,
45.9, 26.5, 26.3.
Phenylselenation of 21. To a solution of diphenyl diselenide
(0.47 g, 1.5 mmol) in THF (4 mL) was added 1.59 M n-butyllithium
(0.95 mL, 1.5 mmol). After 5 min, a solution of 21 (0.095 g, 0.5
mmol) in THF (4 mL) was added, and the reaction mixture was
stirred at reflux for 48 h, diluted with CH2Cl2 (20 mL), and washed
with 0.2 M HCl (25 mL) and brine (25 mL). The aqueous phases
were back-extracted with CH2Cl2 (2 × 10 mL), and the combined
organic phases were dried and concentrated to leave a yellow
residue. The crude product was purified over silica gel (elution with
90:10 CH2Cl2/EtOAc) to provide the isomeric selenides as a white
waxy solid in a 50:50 ratio (0.10 g, 60%).
For the less polar alcohol: 1H NMR (400 MHz, CDCl3) δ 7.61-
7.58 (m, 2H), 7.42-7.32 (m, 3H), 4.23-4.16 (m, 1H), 4.04 (dd,
J ) 6.8, 15.2 Hz, 1H), 3.77 (ddd, J ) 3.6, 10.4, 13.6 Hz, 1H),
3.31-3.24 (m, 2H), 3.15 (ddd, J ) 6.0, 10.8, 12.8 Hz, 1H), 3.08
(s, 1H), 2.75 (dd, J ) 8.4, 14.8 Hz, 1H), 2.56-2.47 (m, 1H), 2.35
(ddd, J ) 3.2, 5.6, 15.2 Hz, 1H), 2.28-2.20 (m, 1H), 2.09-2.02
(m, 1H); HRMS m/z (C13H17NO3SSeNa+) calcd 369.9987, obsd
369.9985.
For the more polar alcohol: IR (CH2Cl2, cm-1) 3684, 1338, 1280;
1H NMR (400 MHz, CDCl3) δ 7.62-7.60 (m, 2H), 7.41-7.32 (m,
3H), 4.28-4.21 (m, 1H), 3.59-3.45 (m, 4H), 3.34 (dt, J ) 4.4,
11.2 Hz, 1H), 3.20 (d, J ) 2.0 Hz, 1H), 3.05 (ddd, J ) 4.0, 10.8,
12.3 Hz, 1H), 2.84 (pent, J ) 7.2 Hz, 1H), 2.79-2.70 (m, 1H),
2.14-2.06 (m, 1H), 1.56 (ddd, J ) 0.8, 8.4, 14.4 Hz, 1H); 13C
NMR (100 MHz, CDCl3) δ 135.8, 129.6, 129.0, 125.5, 69.8, 54.6,
49.8, 49.8, 43.1, 37.0, 32.2; HRMS m/z (C13H17NO3SSeNa+) calcd
369.9987, obsd 369.9971.
Bromination of 16. A solution of 16 (0.17 g, 1.0 mmol) in CH2-
Cl2 (2 mL) was treated dropwise with bromine until an orange color
persisted. The solvent was evaporated under vacuum, and the
residue was purified by column chromatography on silica gel
(elution with 70:30 hexanes/EtOAc) to provide a mixture of the
Ring-Closing Metathesis of 19. To a degassed solution of 19
(6.25 g, 26.3 mmol) in CH2Cl2 (500 mL) was added a solution of
Grubbs first-generation catalyst (0.21 g, 0.26 mmol) in CH2Cl2 (20
mL). The reaction mixture was stirred at room temperature with
periodic purging of ethylene for 24 h. Lead tetraacetate (0.44 g,
1.0 mmol) was added, and after 24 h, the solvent was evaporated
isomeric dibromides 26 and 27 (0.30 g, 90%): IR (CH2Cl2,cm-1
1342, 1170, 1140; H NMR (400 MHz, CDCl3) δ 4.87 (ddd, J )
)
1
J. Org. Chem, Vol. 71, No. 17, 2006 6577