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Vol. 50, No. 5
d, Jϭ2.0, furan), 6.79 (2H, dm, Jϭ9.0, p-methoxyphenyl), 7.20—7.50 (12H,
m, ArH).
plicable to those of the crude product mixture, the diastereoisomeric rela-
tionship of the products was confirmed. 5g: a colorless oil; [a]D24 Ϫ37.3°
(cϭ0.1, CHCl3). 1H-NMR (400 MHz) d: 1.18 (3H, d, Jϭ7.0, Me), 1.25 (3H,
t, Jϭ7.1, Me), 2.36 (3H, s, Me), 3.12 (1H, dq, Jϭ8.2, 7.0, H-2), 3.73 (3H, s,
OMe), 4.20 (2H, q, Jϭ7.1, CH2), 4.5 (1H, br, NH), 4.95 (1H, d, Jϭ8.2, H-
3), 6.16 (1H, d, Jϭ2.0, furan), 6.60 (2H, dm, Jϭ8.8, p-methoxyphenyl), 6.74
(2H, dm, Jϭ8.8, p-methoxyphenyl), 7.18 (2H, d, Jϭ8.5, p-tolyl), 7.21 (2H,
d, Jϭ8.5, p-tolyl), 7.29 (1H, d, Jϭ2.0, furan). EI-MS m/z 441 (Mϩ), 424,
340, 324, 122. IR cmϪ1 (CHCl3) 1730 (CϭO), 1040 (S→O). EI-HR-MS
Calcd for C24H27NO5S: 441.1610. Found 441.1601.
Ethyl (2S,3R)-3-(N-p-Methoxyphenylamino)-2-methyl-3-[(Ss)-3-(p-tolyl-
sulfinyl)-2-furyl]propanoate (4g): 1H-NMR (400 MHz) d: 1.19 (3H, t,
Jϭ7.1, Me), 1.36 (3H, d, Jϭ7.1, Me), 2.36 (3H, s, Me), 3.13 (1H, m, H-2),
3.73 (3H, s, OMe), 4.12 (2H, q, Jϭ7.1, CH2), 4.3 (1H, br, NH), 5.11 (1H, d,
Jϭ5.9, H-3), 6.15 (1H, d, Jϭ2.2, furan), 6.6—7.4 (9H, m, ArH). IR cmϪ1
(CHCl3) (a mixture of 4g and 6g) 1729 (CϭO), 1039 (S→O). EI-MS (a
mixture of 4g and 6g) m/z 441 (Mϩ), 424, 340, 324, 122. EI-HR-MS (a mix-
ture of 4g and 6g) Calcd for C24H27NO5S: 441.1610. Found 441.1601.
Ethyl (2R,3S)-3-(N-p-Methoxyphenylamino)-2-methyl-3-[(Ss)-3-(p-tolyl-
sulfinyl)-2-furyl]propanoate (6g): 1H-NMR (400 MHz) d: 1.23 (3H, t,
Jϭ7.1, Me), 1.40 (3H, d, Jϭ7.2, Me), 2.35 (3H, s, Me), 3.13 (1H, m, H-2),
3.73 (3H, s, OMe), 4.22 (2H, dq, Jϭ7.1, 4.2, CH2), 4.3 (1H, br, NH), 5.03
(1H, d, Jϭ7.2, H-3), 6.16 (1H, d, Jϭ2.2, furan), 6.6—7.4 (9H, m, ArH).
Ethyl (2S,3S)-3-(N-p-Methoxyphenylamino)-2-methyl-3-[(Ss)-3-(p-tolyl-
sulfinyl)-2-furyl]propanoate (7g): 1H-NMR (400 MHz) d: 1.19 (3H, d,
Jϭ6.8, Me), 1.28 (3H, t, Jϭ7.1, Me), 2.35 (3H, s, Me), 3.10 (1H, m, H-2),
3.73 (3H, s, OMe), 4.22 (2H, m, CH2), 4.4 (1H, br, NH), 4.98 (1H, d,
Jϭ9.8, H-3), 6.13 (1H, d, Jϭ2.0, furan), 6.72 (4H, m, p-methoxyphenyl),
7.00 (2H, d, Jϭ7.8, p-tolyl), 7.14 (2H, d, Jϭ7.8, p-tolyl), 7.30 (1H, d,
Jϭ2.0, furan).
(3R,4R)-3-Benzyloxy-1-(p-methoxyphenyl)-4-[(Ss)-3-(p-tolylsulfinyl)-2-
furyl]-2-azetidinone (10h) To a solution of lithium diisopropylamide
[prepared from diisopropylamine (0.04 ml, 0.3 mmol) and n-BuLi (0.19 ml,
0.3 mmol, 1.58 mol dmϪ3 in hexane)] in dry THF (3 ml) at Ϫ78 °C was
added ethyl (benzyloxy)acetate60—62) (58 mg, 0.3 mmol) via syringe. After
being stirred for 0.5 h at Ϫ78 °C, a solution of 2 (68 mg, 0.2 mmol) in dry
THF (3 ml) was slowly added. After being stirred for 1 h at the same temper-
ature, the mixture was slowly warmed up to room temperature (during
45 min). The reaction mixture was then quenched with saturated NH4Cl
(5 ml), and the aqueous layer was extracted with EtOAc (7 mlϫ3). The com-
bined organic phase was washed with brine, dried, and concentrated. The
crude product was purified by column chromatography on silica
(hexane–EtOAc 5 : 2) to give a mixture of 10h—13h (65 mg, 67%) as a col-
orless oil. The product mixture was further purified by preparative TLC
(hexane–EtOAc 3 : 1, 6 developments) to afford anti-isomers (11h and 13h,
46%) and syn-isomers (10h and 12h, 8%). The product ratio was determined
by integration of methine signals (H-3 and H-4) of the crude mixture in the
1H-NMR spectrum. 10h: 1H-NMR (270 MHz) d: 2.37 (3H, s, Me), 3.77
(3H, s, OMe), 4.58 (1H, d, Jϭ11.7, PhCHH), 4.69 (1H, d, Jϭ11.7, PhCHH),
5.11 (1H, d, Jϭ4.9, H-3 or H-4), 5.62 (1H, d, Jϭ4.9, H-4 or H-3), 6.41 (1H,
d, Jϭ2.0, furan), 6.77 (2H, dm, Jϭ9.0, p-methoxyphenyl), 7.15—7.45 (12H,
m, ArH). IR cmϪ1 (CHCl3) (a mixture of 10h and 12h) 1759 (CϭO), 1043
(S→O). EI-MS (a mixture of 10h and 12h) m/z 487 (Mϩ), 470, 380, 324,
323, 322, 231, 91. EI-HR-MS (a mixture of 10h and 12h) Calcd for
C28H25NO5S: 487.1453. Found 487.1459.
Methyl (2S,3R)-2-(tert-Butyldimethylsilyloxy)-3-(N-p-methoxyphenyl-
amino)-3-[(Ss)-3-(p-tolylsulfinyl)-2-furyl]propanoate (4i) To a solution
of lithium diisopropylamide [prepared from diisopropylamine (0.29 ml,
2.2 mmol) and n-BuLi (1.5 ml, 2.2 mmol, 1.47 mol dmϪ3 in hexane)] in dry
THF (10 ml) at Ϫ78 °C was added methyl (tert-butyldimethylsilyloxy)ac-
etate76) (451 mg, 2.2 mmol) in dry THF (5 ml) via syringe. After being
stirred for 0.5 h at Ϫ78 °C, a solution of 2 (500 mg, 1.47 mmol) in dry THF
(5 ml) was slowly added. After being stirred for 0.5 h at the same tempera-
ture, the reaction mixture was warmed up to Ϫ30 °C (during 0.5 h). The re-
action mixture was then quenched with saturated NH4Cl solution (15 ml),
and the aqueous layer was extracted with EtOAc (20 mlϫ3). The combined
organic phase was washed with brine, dried, and concentrated. The crude
product was purified by column chromatography on silica (hexane–EtOAc
3 : 1) to give a mixture of the products. The ester 4i (534 mg, 67%) and the
anti-b-lactam 11i (68 mg, 8%) were purely isolated; however, other isomers,
5i and 10i (13% and 0.6% yields, respectively), were inseparable from each
other by chromatographic separation. The products 6i, 7i, 12i and 13i were
not obtained in substantial yield. The product ratio of 10i, 11i, 12i and 13i
was thus calculated on the basis of the integration of pertinent signals due to
the furan ring (d: 6.41, 6.35, 6.45 and 6.37, respectively) in the 1H-NMR
spectrum. 4i: mp 82—84 °C (hexane–Et2O). [a]D22 Ϫ117.1° (cϭ1.0, CHCl3).
1H-NMR (270 MHz) d: Ϫ0.13 (3H, s, SiMe), Ϫ0.03 (3H, s, SiMe), 0.87
(9H, s, Sit-Bu), 2.38 (3H, s, Me), 3.69 (3H, s, OMe), 3.71 (3H, s, OMe),
4.5—4.8 (1H, br, NH), 4.69 (1H, d, Jϭ2.0, H-2), 5.17 (1H, dd, Jϭ10.5, 2.0,
H-3), 6.41 (1H, d, Jϭ2.0, furan), 6.43 (2H, br d, Jϭ9.0, p-methoxyphenyl),
6.67 (2H, br d, Jϭ9.0, p-methoxyphenyl), 7.17 (2H, d, Jϭ8.3, p-tolyl), 7.22
(2H, d, Jϭ8.3, p-tolyl), 7.31 (1H, d, Jϭ2.0, furan). IR cmϪ1 (CHCl3) 1755
(CϭO), 1030 (S→O). EI-MS m/z 543 (Mϩ), 527, 340, 324, 149, 69, 57.
Anal. Calcd for C28H37NO6SiS: C, 61.85; H, 6.86; N, 2.58. Found C, 61.95;
H, 6.91; N, 2.57. EI-HR-MS Calcd: 543.2111. Found 543.2118.
Methyl (2R,3R)-2-(tert-Butyldimethylsilyloxy)-3-(N-p-methoxyphenyl-
amino)-3-[(Ss)-3-(p-tolylsulfinyl)-2-furyl]propanoate (5i): 1H-NMR (400
MHz) d: 0.00 (3H, s, SiMe), 0.09 (3H, s, SiMe), 0.88 (9H, s, Sit-Bu), 2.35
(3H, s, Me), 3.73 (3H, s, OMe), 3.74 (3H, s, OMe), 4.4 (1H, br, NH),
4.70 (1H, d, Jϭ5.9, H-2), 5.15 (1H, br, H-3), 6.15 (1H, d, Jϭ2.0, furan),
6.63 (2H, br d, Jϭ9.0, p-methoxyphenyl), 6.76 (2H, br d, Jϭ9.0, p-
methoxyphenyl), 7.17 (2H, d, Jϭ8.3, p-tolyl), 7.28 (1H, d, Jϭ2.0, furan),
7.29 (2H, d, Jϭ8.3, p-tolyl).
(3R,4R)-3-(tert-Butyldimethylsilyloxy)-1-(N-p-methoxyphenyl)-4-[(Ss)-3-
(p-tolylsulfinyl)-2-furyl]-2-azetidinone (10i): 1H-NMR (400 MHz) d: 0.00
(3H, s, SiMe), 0.16 (3H, s, SiMe), 0.76 (9H, s, Sit-Bu), 2.40 (3H, s, Me),
3.77 (3H, s, OMe), 5.19 (1H, d, Jϭ4.8, H-3 or H-4), 5.66 (1H, d, Jϭ4.8, H-4
or H-3), 6.41 (1H, d, Jϭ2.0, furan), 6.83 (2H, dm, Jϭ9.0, p-methoxy-
phenyl), 7.24 (4H, dϫ2, Jϭ9.0, 8.4, p-methoxyphenylϩp-tolyl), 7.39 (1H,
d, Jϭ2.0, furan), 7.56 (2H, d, Jϭ8.4, p-tolyl).
(3S,4R)-3-(tert-Butyldimethylsilyloxy)-1-(p-methoxyphenyl)-4-[(Ss)-3-(p-
tolylsulfinyl)-2-furyl]-2-azetidinone (11i): A colorless oil; [a]D20 Ϫ62.7°
(cϭ1.3, CHCl3). 1H-NMR (270 MHz) d: 0.02 (3H, s, SiMe), 0.11 (3H, s,
SiMe), 0.90 (9H, s, Sit-Bu), 2.37 (3H, s, Me), 3.75 (3H, s, OMe), 5.12 (1H,
d, Jϭ1.6, H-3 or H-4), 5.24 (1H, d, Jϭ1.6, H-4 or H-3), 6.35 (1H, d, Jϭ2.0,
furan), 6.64 (2H, dm, Jϭ9.0, p-methoxyphenyl), 6.78 (2H, dm, Jϭ9.0, p-
methoxyphenyl), 7.19 (2H, d, Jϭ8.1, p-tolyl), 7.30 (2H, d, Jϭ8.1, p-tolyl),
7.37 (1H, d, Jϭ2.0, furan). IR cmϪ1 (CHCl3) 1750 (CϭO), 1030 (S→O).
EI-MS m/z 511 (Mϩ), 454, 323, 305, 201, 166. EI-HR-MS Calcd for
C27H33NO5SiS: 511.1849. Found 511.1860.
(3S,4R)-3-Benzyloxy-1-(p-methoxyphenyl)-4-[(Ss)-3-(p-tolylsulfinyl)-2-
furyl]-2-azetidinone (11h): 1H-NMR (270 MHz) d: 2.39 (3H, s, Me), 3.75
(3H, s, OMe), 4.75 (1H, d, Jϭ11.5, PhCHH), 4.89 (1H, d, Jϭ11.5, PhCHH),
5.04 (1H, d, Jϭ1.8, H-3 or H-4), 5.34 (1H, d, Jϭ1.8, H-4 or H-3), 6.32 (1H,
d, Jϭ2.0, furan), 6.80 (2H, dm, Jϭ9.0, p-methoxyphenyl), 7.20—7.50 (12H,
m, ArH). IR cmϪ1 (CHCl3) 1760 (CϭO), 1046 (S→O) (a mixture of 11h
and 13h). EI-MS (a mixture of 11h and 13h) m/z 487 (Mϩ), 470, 380, 324,
323, 322, 231, 91. EI-HR-MS (a mixture of 11h and 13h) Calcd for
C28H25NO5S: 487.1453. Found 487.1452.
(3S,4S)-3-Benzyloxy-1-(p-methoxyphenyl)-4-[(Ss)-3-(p-tolylsulfinyl)-2-
furyl]-2-azetidinone (12h): 1H-NMR (270 MHz) d: 2.35 (3H, s, Me), 3.76
(3H, s, OMe), 4.35 (1H, d, Jϭ11.5, PhCHH), 4.50 (1H, d, Jϭ11.5, PhCHH),
5.07 (1H, d, Jϭ4.4, H-3 or H-4), 5.71 (1H, d, Jϭ4.4, H-4 or H-3), 6.38 (1H,
d, Jϭ2.0, furan), 6.84 (2H, dm, Jϭ9.0, p-methoxyphenyl), 7.15—7.40 (9H,
m, ArH), 7.42 (1H, d, Jϭ2.0, furan), 7. 52 (2H, d, Jϭ8.3, p-tolyl).
Isomerization Experiment of syn-Lactam 10g to anti-Lactam 11g
A
solution of 1,1,1,3,3,3-hexamethyldisilazane (0.034 ml, 0.16 mmol) in dry
THF (1.5 ml) was treated with n-BuLi (0.11 ml, 0.16 mmol, 1.50 mol dmϪ3
in hexane) at 0 °C under nitrogen. After being stirred for 15 min, the solution
was cooled down to Ϫ78 °C, and a solution of 10g (16.5 mg, 0.042 mmol) in
dry THF (0.7 ml) was slowly added. After being stirred for 20 min, the reac-
tion mixture was poured into saturated NH4Cl solution (10 ml). The aqueous
layer was extracted with CHCl3 (7 mlϫ3), and the combined organic phase
was washed with brine, dried, and concentrated. The crude product was puri-
fied by column chromatography on silica (hexane–EtOAc 5 : 2). Early frac-
tions contained a mixture of 10g and 11g (4.2 mg, 25%) in a rough ratio of
1 : 1. Later fractions contained 11g (6.8 mg, 41%), whose spectral data were
in good agreement with those of 11g obtained by the reaction of 2 and 3g.
Cyclization Experiment of b-Amino Ester to b-Lactam To a solution
of lithium hexamethyldisilazide [prepared from 1,1,1,3,3,3-hexamethyldisi-
lazane (0.0086 ml, 0.04 mmol) and n-BuLi (0.032 ml, 0.04 mmol, 1.47
mol dmϪ3 in hexane)] in dry THF (1 ml) at Ϫ10 °C under nitrogen was
(3R,4S)-3-Benzyloxy-1-(p-methoxyphenyl)-4-[(Ss)-3-(p-tolylsulfinyl)-2-
furyl]-2-azetidinone (13h): 1H-NMR (270 MHz) d: 2.38 (3H, s, Me), 3.76
(3H, s, OMe), 4.71 (1H, d, Jϭ11.5, PhCHH), 4.75 (1H, d, Jϭ11.5, PhCHH),
4.93 (1H, d, Jϭ1.7, H-3 or H-4), 5.45 (1H, d, Jϭ1.7, H-4 or H-3), 6.39 (1H,