D. H. Martyres et al. / Tetrahedron 57 /2001) 4999±5007
5005
.[MH]1, 9%), 155 .[M2OEt]1, 36%), 127 .[M2CO2Et]1,
23%).
.chloroformate CvO), 171.72 .ester CvO); m/z .APCI1):
185 .[M2OC.O)Cl]1, 60%), 150 .67%), 111 .100%).
2.1.7. *1R, 4S, 5S, 6S)- and *1S, 4R, 5R, 6R)-2-Thiabicyclo-
[3.2.0]heptan-6-ol-4-carboxylic acid ethyl ester *12). To a
stirred solution of .1R, 4S, 5S)- and .1S, 4R, 5R)-2-thia-
bicyclo[3.2.0]heptan-6-one-4-carboxylic acid ethyl ester
.11) .2.00 g, 10.0 mmol) in methanol .60 cm3) at 08C was
added sodium borohydride .0.40 g, 10.5 mmol) portion-
wise. After addition was complete, the reaction was allowed
to warm to room temperature. After 30 min stirring at room
temperature, water .20 cm3) was added and the mixture
acidi®ed to pH 2 with H2SO4 .aq.) .1 M, 2 cm3). Sodium
chloride .ca. 4 g) was added to the mixture and this was
extracted with DCM .4£30 cm3). The organic layers were
combined and washed with saturated brine .2£20 cm3) then
dried and concentrated in vacuo to yield a green oil. Flash
chromatography .1:1 PE 40±60/Et2O) afforded the title
compound .12) .1.51 g, 75%) as a green oil: Rf .4:1
EtOAc/Et2O) 0.5; IR .NaCl plates) nmax: 3441 brs .OH),
2979s .CH), 2936s .CH), 1732brs .CvO), 1444m,
1369m, 1182s, 1030s; dH .400 MHz CDCl3): 1.21 .3H, t,
J7.0 Hz, OCH2CH3), 1.91 .1H, brdt, J14.5, 6.5 Hz,
endo-H of SCHCH2), 2.18 .1H, brs, OH), 2.85±2.91 .1H,
m, exo-H of SCHCH2), 3.28 .1H, dd, J12.0, 6.0 Hz, endo-
H of SCH2), 3.36 .1H, dd, J12.0, 5.0 Hz, exo-H of SCH2),
3.52±3.61 .3H, m, SCH, SCH2CH, and SCHCH), 4.10 .2H,
q, J7.0 Hz, OCH2CH3), 4.33 .1H, brq, J7.0 Hz, CHOH);
dC .100.6 MHz CDCl3): 14.15 .OCH2CH3), 36.91 .SCH2),
39.32 .SCH), 41.91 .SCHCH2), 48.06 .SCH2CH), 53.90
.SCHCH), 61.21 .OCH2CH3), 62.11 .CHOH), 173.20
.CvO); m/z .APCI1): 203 .[MH]1, 100%), 158
.[MH2OEt]1, 25%); HRMS: calculated for C9H15O3S
[MH]1: 203.0742; found: 203.0742.
2.1.9. *1R, 4S, 5S, 6S)- and *1S, 4R, 5R, 6R)-4-Ethoxycar-
bonyl-2-thiabicyclo[3.2.0]heptane-6-azidoformate *14).
To a stirred solution of .1R, 4S, 5S, 6S)- and .1S, 4R, 5R,
6R)-4-ethoxycarbonyl-2-thiabicyclo[3.2.0]heptane-6-chloro-
formate .13) .1.40 g, 5.3 mmol) in dry DMF .30 cm3) was
added sodium azide .1.73 g, 26.5 mmol) in one portion at
08C. After 20 min, the reaction was allowed to warm to
room temperature followed by 3 h further stirring. Water
.20 cm3) was added and the mixture extracted with diethyl
ether .3£20 cm3). The combined organic extracts were
washed with water .2£30 cm3) and saturated brine .2£
30 cm3), and the organic layer was dried and concentrated
in vacuo to yield a yellow oil. Flash chromatography .2:1
PE 40±60/Et2O) afforded the title compound .14) .0.91 g,
63%) as a pale green oil: Rf .1:1 PE 30±40/Et2O) 0.65; IR
.NaCl plates) nmax: 2984s .CH), 2942m .CH), 2187s .N3),
2139s .N3), 1732brs .2xCvO); dH .400 MHz CDCl3): 1.27
.3H, t, J7.0 Hz, OCH2CH3), 2.18 .1H, dtd, J14.0, 8.0,
1.5 Hz, endo-H of SCHCH2), 3.06 .1H, dtd, J14.0, 8.0,
3.0 Hz, exo-H of SCHCH2), 3.22 .1H, dd, J11.5, 6.0 Hz,
endo-H of SCH2), 3.41 .1H, brq, J4.0 Hz, SCH2CH), 3.48
.1H, dd, J11.5, 4.5 Hz, exo-H of SCH2), 3.72 .1H, q,
J7.0 Hz, SCH), 3.90±3.96 .1H, m, SCHCH), 4.16 .2H,
q, J7.0 Hz, OCH2CH3), 5.14 .1H, q, J7.0 Hz,
SCHCH2CH); dC .100.6 MHz CDCl3) 14.06 .OCH2CH3),
36.94 .SCH2), 39.34 .SCHCH2), 40.19 .SCH), 48.68
.SCH2CH), 51.84 .SCHCH), 61.43 .OCH2CH3), 68.13
.SCHCH2CH), 156.47 .azidoformate CvO), 171.89 .ester
CvO); m/z .APCI1): 244 [.MH2N2]1, 100%), 111 .53%);
HRMS: calculated for C10H14N3O4S [MH]1: 272.0705;
found: 272.0711.
2.1.8. *1R, 4S, 5S, 6S)- and *1S, 4R, 5R, 6R)-4-Ethoxycar-
bonyl-2-thiabicyclo[3.2.0]heptane-6-chloroformate *13).
To a stirred solution of .1R, 4S, 5S, 6S)- and .1S, 4R, 5R,
6R)-2-thiabicyclo[3.2.0]heptan-6-ol-4-carboxylic acid ethyl
ester .12) .1.40 g, 6.9 mmol) in DCM .30 cm3) was added a
solution of triphosgene .0.74 g, 2.5 mmol) and pyridine
.0.56 cm3, 6.9 mmol) in DCM .30 cm3) dropwise at 08C.
After addition was complete, the reaction was allowed to
warm to room temperature and stirred for a further 2 h. The
reaction mixture was then concentrated in vacuo. Ethyl
acetate .40 cm3) was then added to the orange residue and
this solution was washed with water .20 cm3) and saturated
brine .20 cm3). The organic layer was dried and concen-
trated in vacuo to yield the title compound .13) .1.44 g,
79%) as a yellow oil, which was used without further puri-
2.1.10. *1S, 2R, 6R, 7S, 10S)- and *1R, 2S, 6S, 7R, 10R)-
10-Ethoxycarbonyl-5-aza-3-oxa-8-thiatricyclo[5.3.0.0]-
decan-4-one *15). A stirred solution of .1R, 4S, 5S, 6S)- and
.1S, 4R, 5R, 6R)-4-ethoxycarbonyl-2-thiabicyclo[3.2.0]hep-
tane-6-azidoformate .14) .200 mg, 0.74 mmol) in 1,1,2,2-
tetrachloroethane .400 cm3) was heated to 1478C. After
30 min, the reaction was allowed to cool to room tempera-
ture and was then concentrated in vacuo to give a brown
solid residue. Flash chromatography .3:1 Et2O/EtOAc)
afforded a mixture of the title compound .15) .52 mg,
29%) and the isomeric carbamate .16) in a 14:5 .w/w)
ratio. Further puri®cation of a sample of this mixture for
characterisation purposes provided pure .15) as a pale
yellow oil: Rf .Et2O) 0.2; IR .NaCl plates) nmax: 3340m
.NH), 2982m .CH), 1732brs .urethane CvO and ester
CvO), 1371m, 1211m, 1094m, 1027w; dH .400 MHz
CD3OD): 1.27 .3H, t, J7.0 Hz, OCH2CH3), 3.31 .1H, dd,
J12.0, 7.0 Hz, endo-H of SCH2), 3.45 .1H, dd, J12.0,
2.0 Hz, exo-H of SCH2), 3.54 .1H, dd, J7.0, 2.0 Hz,
SCH2CH), 4.08±4.18 .1H, m, SCH2CHCH), 4.16 .2H, q,
J7.0 Hz, OCH2CH3), 4.27 .1H, ddd, J9.0, 5.0, 2.0 Hz,
SCH), 4.48 .1H, ddd, J9.0, 5.0, 2.0 Hz, CHNH), 5.15 .1H,
ddd, J7.0, 6.0, 2.0 Hz, CHOC.O)NH); dC .100.6 MHz
CDCl3): 14.09 .OCH2CH3), 38.78 .SCH2), 48.32
.SCH2CH), 51.93 .SCH2CHCH), 52.08 .SCH), 54.40
.CHNH), 62.80 .OCH2CH3), 74.77 .CHOC.O)NH),
163.90 .urethane .CvO), 174.20 .ester CvO); m/z
.APCI1): 244 .[MH]1, 100%), 198 .[M2OEt]1, 25%),
®cation: Rf .1:1 PE 40±60/Et2O) 0.3; IR .NaCl plates) nmax
:
2983s .CH), 1778s .chloroformate CvO), 1732s .ester
CvO), 1446m, 1372m; dH .400 MHz CDCl3): 1.29 .3H,
t, J7.0 Hz, OCH2CH3), 2.27 .1H, dt, J13.0, 7.0 Hz,
endo-H of SCHCH2), 3.09 .1H, dtd, J13.0, 7.0, 3.0 Hz,
exo-H of SCHCH2), 3.36 .1H, dd, J11.5, 5.5 Hz, endo-H
of SCH2), 3.46 .brq, J5.5 Hz, SCH2CH), 3.51 .1H, dd,
J11.5, 5.5 Hz, exo-H of SCH2), 3.73 .1H, q, J7.0 Hz,
SCH), 3.92±3.96 .1H, m, SCHCH), 4.18 .2H, q, J
7.0 Hz, OCH2CH3), 5.23 .1H, q, J7.0 Hz, SCHCH2CH);
dC .100.6 MHz CDCl3): 14.07 .OCH2CH3), 37.01 .SCH2),
39.32 .SCHCH2), 40.04 .SCH), 48.86 .SCH2CH), 51.86
.SCHCH), 61.51 .OCH2CH3), 71.72 .SCHCH2CH), 149.50