2H), 3.79-3.81 (m, 1H), 3.52-3.49 (m, 3H), 3.42-3.41 (m, 2H),
1.68 (s, 3H), 1.58 (s, 3H), 1.42 (s, 3H), 1.38 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 189.9, 188.4, 171.4, 170.9, 136.8, 135.6,
131.5, 129.6, 129.2, 125.1, 124.5, 64.3, 63.3, 61.6, 60.6, 60.2, 60.0,
54.7, 52.4, 39.3, 37.9, 20.1, 20.0, 19.4, 19.6; HRMS (FAB) calcd
for C15H18NO4SSe 388.0122 (M + H)+, found m/z 388.0109.
2-[[1,3]Dioxolan-2-yl(phenylselenyl)methyl]-3,3-dimeth-
yl-4,4-dioxo-4-thia-1-azabicyclo[3.2.0]heptan-7-one (14). To
a solution of 13 (2.5 g, 6.5 mmol) in anhyd C6H6 (30 mL) were
added ethylene glycol (1 mL, 13 mmol) and cat. PTSA. The
reaction mixture was refluxed for 3.5 h using a Dean-Stark
apparatus. The solution was concentrated and purified by flash
chromatography (100% CH2Cl2 to 20% EtOAc/CH2Cl2) to give a
mixture of diastereomers (2.23 g, 80%): IR (neat, cm-1) ν 1797,
1593; 1H NMR (400 MHz, CDCl3) δ 7.64-7.60 (m, 4H), 7.31-
7.26 (m, 6H), 5.31-5.30 (m, 2H), 4.45-4.44 (m, 2H), 4.20-4.00
(m, 10H), 3.28-3.40 (m, 6H), 1.67 (s, 6H), 1.28 (s, 6H); 13C NMR
(100 MHz, CDCl3) δ 188.9, 187.4, 141.5, 139.7, 136.8, 135.6,
129.6, 129.2, 125.1, 124.5, 65.2, 65.3, 64.7, 64.8, 63.3, 62.3, 61.6,
60.6, 59.8, 59.2, 54.7, 52.4, 39.2, 37.8, 20.3, 20.1, 19.3, 19.6;
HRMS (FAB) calcd for C17H22NO5SSe 432.0384 (M + H)+, found
m/z 432.0379.
2E-[1,3]Dioxolan-2-ylmethylene-3,3-dimethyl-4,4-dioxo-
4-thia-1-azabicyclo[3.2.0]heptan-7-one (15) and 2Z-[[1,3]-
Dioxolan-2-ylmethylene]-3,3-dimethyl-4,4-dioxo-4-thia-1-
azabicyclo[3.2.0]heptan-7-one (16). To a solution of 14 (2 g,
4.8 mmol) in anhyd CH2Cl2 (6 mL) under N2 were added
NaHCO3 (1.0 g, 10 mmol) and m-CPBA (1.2 g, 14.8 mmol) at
0 °C. The mixture was stirred for 45 min at rt. The mixture was
diluted with CH2Cl2, washed with aq sodium metabisulfite
solution, aq NaHCO3, and brine, dried over Na2SO4, and
evaporated. The residue was purified by chromatography (100%
CH2Cl2 to 15% EtOAc/CH2Cl2) to give the E-isomer 15 (120 mg,
10.95%) and Z-isomer 16 (685 mg, 62%) in a 15:85 ratio.
E-Isomer (15): IR (neat, cm-1) ν 1811, 1320; 1H NMR
(400 MHz, CDCl3) δ 5.79 (d, J ) 7.8 Hz, 1H, olefin CH), 5.05
(d, J ) 7.8 Hz, 1H, CH), 4.71-4.69 (m, 1H, C5 CH), 4.06-3.90
(m, 4H, CH2CH2), 3.59-3.54 (m, 2H, CH2), 1.59 (s, 3H, CH3)
1.54 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3) δ 165.5, 141.5,
109.8, 99.9, 65.3, 65.1, 62.9, 60.9, 38.3, 26.6, 17.9; HRMS (FAB)
calcd for C11H16NO5S 274.0749 (M + H)+, found m/z 274.0753.
Z-Isomer (16): IR (neat, cm-1) ν 1799.6, 1326; 1H NMR
(400 MHz, CDCl3) δ 5.69 (d, J ) 5.8 Hz, 1H), 5.64 (d, J )
5.8 Hz, 1H), 4.62-4.60 (m, 1H), 4.03-4.99 (m, 2H), 3.91-3.89
(m, 2H), 3.62-3.52 (m, 2H), 1.65 (s, 3H), 1.61 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 166.05, 139.7, 114.4, 97.9, 65.03, 64.1, 60.3,
39.2, 25.3, 17.7; HRMS (FAB) calcd for C11H16NO5S 274.0749
(M + H)+, found m/z 274.0743.
5% aq NaH2PO4 (0.5 mL), sodium chlorite (113 mg, 1.25 mmol),
and sulfamic acid (121, 1.25 mmol) at 0 °C. The solution was
stirred at rt for 45 min. MeOH was removed, and the residue
was dissolved in EtOAc (5 mL), washed with water and brine,
dried over Na2SO4, and concentrated. Purification by flash
chromatography (1% MeOH/CH2Cl2 to 20% MeOH/CH2Cl2)
afforded product (41 mg, 68%): IR (neat, cm-1) ν 3347.05, 1806.5,
1
1707.5, and 1637.4; H NMR (400 MHz, CDCl3) δ 11.0 (s, 1H),
6.07 (d, J ) 6.7 Hz, 1H), 4.66-4.4.65 (m, 1H), 3.76-3.71 (m,
1H), 3.63-3.58 (m, 1H) 1.78 (s, 3H), 1.62 (s, 3H); HRMS (FAB)
calcd for C9H12NO5S 246.0436 (M + H)+, found m/z 246.0443.
Forthy milligrams of this acid was dissolved in EtOAc (4 mL),
extracted with aq NaHCO3 (25 mg of sodium bicarbonate was
dissolved in 4 mL of deionized H2O), and purified on a column
of CHP-20P-deionized water as eluent to give product (25 mg):
1H NMR (400 MHz, D2O) δ 6.04 (s, 1H), 5.00-4.98 (m, 1H), 3.63
(dd, J ) 12.4 Hz, J ) 4.5 Hz, 1H), 3.46 (dd, J ) 15.5 Hz, J )
1.9 Hz, 1H) 1.53 (s, 3H), 1.44 (s, 3H).
(3,3-Dimethyl-4,4,7-trioxo-4-thia-1-azabicyclo[3.2.0]hept-
2Z-ylidene)acetaldehyde (19). To a solution of 16 (229 mg,
1 mmol) in acetone (5 mL) was added PTSA (200 mg, 1 mmol)
at 0 °C. The reaction mixture was stirred at rt for 30 min. The
solvent was removed and the mixture diluted with EtOAc
(30 mL), washed with aq NaHCO3 and brine, dried over Na2-
SO4, and concentrated. Purification by flash chromatography
(100% CH2Cl2 to 10% EtOAc/CH2Cl2) afforded product (196 mg,
86%): IR (neat, cm-1) ν 1810.9, 1673.5, 1622.0; 1H NMR
(400 MHz, CDCl3) δ 9.85 (d, J ) 7.5 Hz, 1H), 5.60 (d, J ) 7.5
Hz, 1H), 4.93-4.91 (m, 1H), 3.82-3.70 (m, 2H, C6), 1.62 (s, 3H),
1.56 (s, 3H); 13C NMR (400 MHz, CDCl3) δ 189.7, 165.7, 153.1,
112.0, 64.2, 61.9, 39.5, 26.2, 17.4; HRMS (FAB) calcd for
C9H12NO4S 230.0487 (M + H)+, found m/z 230.0490.
Sodium Salt of (3,3-Dimethyl-4,4,7-trioxo-4-thia-1-
azabicyclo[3.2.0]hept-2-ylidene)acetic Acid (20). To a solu-
tion of aldehyde (171 mg, 0.75 mmol) in MeOH (6 mL) were
added 5% NaH2PO4 solution (1.5 mL), sodium chlorite (339 mg,
3.75 mmol), and sulfamic acid (363, 3.75 mmol) at 0 °C. The
mixture was stirred at rt for 45 min. MeOH was removed to
give crude product. The residue was dissolved in EtOAc (15 mL),
washed with water and brine, dried over Na2SO4, and concen-
trated to produce the product (80 mg, 63%): IR (neat, cm-1) ν
3351.05, 1802.5, 1701.5, 1630.4; 1H NMR (400 MHz, CDCl3) δ
11.0 (s, 1H), 5.40 (s, 1H), 4.83-4.82 (m, 1H), 3.65-3.62 (m, 2H),
1.63 (s, 3H), 1.57 (s, 3H); HRMS (FAB) calcd for C9H12NO5S
246.0436 (M +H)+, found m/z 246.0431.
Seventy-five milligrams of this acid was dissolved in EtOAc
(4 mL) and extracted with aq NaHCO3 (45 mg of NaHCO3 in
4 mL of deionized H2O). The aqueous layer was purified on CHP-
2OP using water as eluent to give product (20 mg): 1H NMR
(400 MHz, D2O) δ 5.45 (d, J ) 6.7 Hz, 1H), 5.11-5.09 (m, 1H),
3.65 (dd, J ) 12.1 Hz, J ) 4.9 Hz, 1H), 3.39 (dd, J ) 15.3 Hz, J
) 1.7 Hz, 1H) 1.50 (s, 3H), 1.42 (s, 3H).
(3,3-Dimethyl-4,4,7-trioxo-4-thia-1-azabicyclo[3.2.0]hept-
2E-ylidene)acetaldehyde (17). To a solution of dioxolane 15
(109 mg, 0.4 mmol) in acetone (2 mL) was added pTSA (80 mg,
0.4 mmol) at 0 °C. The reaction was stirred at rt for 30 min.
The solvent was removed. The mixture was diluted with EtOAc
(20 mL), washed with aq NaHCO3 solution and brine, dried over
Na2SO4, and concentrated. Purification by flash chromatography
(100% CH2Cl2 to 10% EtOAc/CH2Cl2) afforded product (80 mg,
Acknowledgment. We thank the Robert A. Welch
Foundation and the Texas Higher Education Coordinat-
ing Board for support.
1
87%): IR (neat, cm-1) ν 1811.53, 1663.6, and 1616.5; H NMR
(400 MHz, CDCl3) δ 9.95 (d, J ) 6.7 Hz, 1H), 6.23(d, J ) 6.7 Hz,
1H), 4.78-4.76 (m, 1H), 3.79-3.62 (m, 2H), 1.78 (s, 3H), 1.62
(s, 3H); 13C NMR (400 MHz, CDCl3) δ 188.7, 166.7, 153.2, 112.1,
64.4, 62.1, 39.1, 26.5, 17.2; HRMS (FAB) calcd for C9H12NO4S
230.0487 (M + H)+, found m/z 230.0490.
Sodium Salt of (3,3-Dimethyl-4,4,7-trioxo-4-thia-1-
azabicyclo[3.2.0]hept-2E-ylidene)acetic Acid (18). To a
solution of 17 (57 mg, 0.25 mmol) in MeOH (2 mL) were added
Supporting Information Available: Experimental de-
tails for the preparation of compounds 6 and 7, NMR spectra
of compounds 8-20, and crystal data for compounds 9 and
16. This material is available free of charge via the Internet
JO050004S
J. Org. Chem, Vol. 70, No. 11, 2005 4513