Application of Solid-Phase Organic Synthesis to the Generation of β-Lactams
FULL PAPER
308.09298; found 308.09209. C12H20O7S (308.35): calcd. C 46.74,
H 6.54, S 10.40; found C 46.65, H 6.51, S 10.38.
1 H, H-5), 4.43 (dd, J ϭ 1.8, 10.6 Hz, 1 H, H-6b), 4.53 (d, J ϭ 3.7
Hz, 1 H, H-2), 5.82 (d, J ϭ 3.7 Hz, 1 H, H-1), 6.00 (dq, J ϭ 6.1,
1.7 Hz, 1 H, H-1Ј), 7.20 (s, 2 H, aryl) ppm. MS (EI, HR): [Mϩ]
(C28H44O8S): calcd. 540.27569; found 540.27692. C28H44O8S
(540.69): calcd. C 62.19, H 8.20; found C 62.28, H 8.31.
1,2-O-Isopropylidene-5-O-isopropylsulfonyl-3-O-(prop-1Ј-enyl)-α-D-
xylofuranose (3): Compound 3 was obtained from 1 using 1-methyl-
ethanesulfonyl chloride. Oil; yield: 90%. [α]2D2 ϭ Ϫ7.2 (c ϭ 1.1,
1
CHCl3). IR (film): ν˜ ϭ 1670 cmϪ1. H NMR (500 MHz, CDCl3):
1,2-O-Isopropylidene-6-O-isopropylsulfonyl-3-O-methyl-5-O-(prop-
1Ј-enyl)-α-
11 using 1-methylethanesulfonyl chloride; 79%; oil. [α]2D2 ϭ Ϫ29.8
(c ϭ 1.5, CHCl3). IR (CHCl3): ν˜ ϭ 1669 cmϪ1 1H NMR
D-glucofuranose (14): Compound 14 was obtained from
δ ϭ 1.33, 1.51 (2s, 6 H, 2 ϫ Me), 1.44 (dd, J ϭ 1.9, 6.9 Hz, 6 H,
(CH3)2CHϪ), 1.55 (dd, J ϭ 1.7, 6.9 Hz, 6 H, CH3), 3.37 [sept, J ϭ
6.9 Hz, 1 H, (CH3)2CHϪ], 4.20 (d, J ϭ 3.1 Hz, 1 H, H-3), 4.41
(dd, J ϭ 7.0, 10.8 Hz, 1 H, H-5a), 4.46 (dd, J ϭ 4.9, 10.8 Hz, 1 H,
H-5b), 4.50Ϫ4.61 (m, 3 H, H-2Ј, H-2, H-4), 5.96 (d, J ϭ 3.8 Hz, 1
H, H-1), 5.95 (dq, J ϭ 6.1, 1.7 Hz, 1 H, H-1Ј) ppm. 13C NMR
(125 MHz, CDCl3): δ ϭ 9.2, 16.5, 16.6, 26.3, 26.8, 52.3, 66.5, 77.8,
82.7, 83.2, 104.6, 105.2, 112.3, 143.1 ppm. HRMS (LSIMS): [Mϩ]
(C14H24O7S): calcd. 336.12428; found 336.12394. C14H24O7S
(336.41): calcd. C 49.99, H 7.19, S 9.53; found C 50.09, H 7.11,
S 9.39.
.
(500 MHz, CDCl3): δ ϭ 1.32, 1.49 (2s, 6 H, 2 ϫ Me), 1.426, 1.432
[2d, 2 ϫ J ϭ 6.9 Hz, 6 H, (CH3)2CHϪ], 1.58 (dd, J ϭ 1.7, 6.8 Hz,
3 H, CH3-3Ј), 3.32 [sept, J ϭ 6.9 Hz, 1 H, (CH3)2CHϪ], 3.39 (s, 3
H, CH3OϪ), 3.76 (d, J ϭ 2.9 Hz, 1 H, H-3), 4.12Ϫ4.19 (m, 2 H,
H-4, H-2Ј), 4.30 (dd, J ϭ 5.9, 11.0 Hz, 3 H, H-6a), 4.44 (m, 1 H,
H-5), 4.54Ϫ4.58 (m, 2 H, H-2, H-6b), 5.86 (d, J ϭ 3.7 Hz, 1 H, H-
1), 6.01 (dq, J ϭ 6.1, 1.7 Hz, 1 H, H-1Ј) ppm. 13C NMR (125 MHz,
CDCl3): δ ϭ 9.2, 16.6, 16.7, 26.2, 26.8, 52.1, 57.5, 70.0, 76.0, 78.1,
81.2, 83.07, 102.1, 105.2, 144.9 ppm. HRMS (LSIMS): [Mϩ ϩ Na]
(C16H28O8SNa): calcd. 403.14026; found 403.14079. C16H28O8S
(380.46): calcd. C 50.52, H 7.42, S 8.43; found C 50.33, H 7.67,
S 8.37.
5-O-(1ЈЈ,1ЈЈ-Dimethyl-2ЈЈ-phenyl)ethylsulfonyl-1,2-O-isopropylidene-
3-O-(prop-1Ј-enyl)-α-D-xylofuranose (4): nBuLi (2.5 . in hexane,
1.1 mL, 2.74 mmol) was added with stirring to a mixture of com-
pound 3 (0.70 g, 2.1 mmol), N,NЈ-dimethylpropyleneurea (DMPU;
5 mL) and dry THF (20 mL) under argon at Ϫ70 °C. The mixture
was then warmed up slowly to Ϫ50 °C (15Ϫ30 min) and treated
with BnCl (0.27 mL, 2.13 mmol). Stirring was continued for 1.5 h
while warming up to room temperature. The excess reagents were
decomposed by addition of isopropyl alcohol (3 mL). The reaction
mixture was poured into saturated NaCl solution and extracted
with diethyl ether (3 ϫ 50 mL). The combined extracts were washed
with water, dried (Na2SO4), filtered and concentrated. The residue
was purified on a silica gel column using hexane/ethyl acetate (4:1,
v/v) as eluent to give 4 (1.072 g, 63%). [α]2D2 ϭ Ϫ16.9 (c ϭ 1.3,
CHCl3). IR (film): ν˜ ϭ 1670 1346, 1128, 1082, 981 cmϪ1. 1H NMR
(500 MHz, CDCl3): δ ϭ 1.32, 1.51 (2s, 6 H, 2 ϫ Me), 1.368, 1.371
[2s, 6 H, Ϫ(CH3)2CϪ], 1.55 (dd, J ϭ 1.7, 6.9 Hz, 3 H, CH3-3Ј),
3.14 (s, 2 H, Bn), 4.20 (d, J ϭ 2.8 Hz, 1 H, H-3), 4.47 (dd, J ϭ
8.4, 11.9 Hz, 1 H, H-5a), 4.50Ϫ4.63 (m, 4 H, H-2Ј, H-2, H-4, H-
5b), 5.95Ϫ5.97 (m, 2 H, H-1, H-1Ј) ppm. 13C NMR (125 MHz,
CDCl3): δ ϭ 9.2, 21.1, 21.2, 26.3, 26.8, 41.4, 66.4, 77.9, 82.7, 83.2,
104.6, 105.3, 127.1, 128.2, 131.0, 143.2 ppm. HRMS (LSIMS): [Mϩ
6-O-(1ЈЈ,1ЈЈ-Dimethyl-2ЈЈ-phenyl)ethylsulfonyl-1,2-O-isopropylidene-
3-O-methyl-5-O-(prop-1Ј-enyl)-α-D-glucofuranose (15): Compound
15 was obtained from 14 according to the procedure described for
compound 4; 54%; oil. [α]2D2 ϭ Ϫ17.1 (c ϭ 1.1, CHCl3). IR (film):
1
ν˜ ϭ 1669 cmϪ1. H NMR (500 MHz, CDCl3): δ ϭ 1.32, 1.48 (2s,
6 H, 2 ϫ Me), 1.35 [s, 6 H, Bn(CH3)2CϪ], 1.59 (dd, J ϭ 1.7, 6.8
Hz, 3 H, CH3-3Ј), 3.15 (s, 2 H, Bn), 3.40 (s, 3 H, CH3OϪ), 3.77
(d, J ϭ 2.4 Hz, 1 H, H-3), 4.16Ϫ4.21, 4.33Ϫ4.37 (2m, 3 H, H-2Ј,
H-4, H-6a), 4.45 (m, 1 H, H-5), 4.58 (d, J ϭ 3.7 Hz, 1 H, H-2),
4.64 (dd, J ϭ 1.7, 11.5 Hz, 1 H, H-6b), 5.88 (d, J ϭ 3.7 Hz, 1 H,
H-1), 6.03 (dq, J ϭ 6.1, 1.7 Hz, 1 H, H-1Ј), 7.16Ϫ7.32 (m, 5 H,
Ph) ppm. 13C NMR (125 MHz, CDCl3): δ ϭ 9.2, 21.0, 21.0, 26.2,
26.8, 41.2, 57.5, 70.0, 76.1, 78.2, 81.2, 83.1, 101.9, 105.3, 127.0,
128.1, 131.0, 145.1 ppm. HRMS (LSIMS): [Mϩ
ϩ Na]
(C23H34O8SNa): calcd. 493.18721; found 493.18643. C23H34O8S
(470.59): calcd. C 58.70, H 7.28; found C 58.58, H 7.38.
[2؉2]-Cycloaddition of Chlorosulfonyl Isocyanate to Vinyl Ethers
2؊4, 12؊15 was performed according to the procedure described
in the literature.[5,6,7]
ϩ
Na] (C21H30O7SNa): calcd. 449.16100; found 449.16288.
C21H30O7S (426.53): calcd. C 59.13, H 7.09, S 7.52; found C 59.01,
H 6.89, S 7.44.
(3ЈR,4ЈS)- and (3ЈS,4ЈR)-1,2-O-Isopropylidene-3-O-(3Ј-methyl-2Ј-
oxoazetidin-4Ј-yl)-5-O-methylsulfonyl-α-
D-xylofuranose (5/6):
A
1,2-O-Isopropylidene-3-O-methyl-6-O-methylsulfonyl-5-O-(prop-1Ј-
mixture of stereoisomers 5 and 6, in a ratio of 1.2:1, respectively,
was obtained from 2, 30%; solid foam. IR (KBr): ν˜ ϭ 3193, 1775
cmϪ1. 1H NMR (500 MHz, CDCl3) selected data taken for the mix-
ture of diastereomers: δ ϭ 1.14, 1.16 (2d, 2 ϫ J ϭ 6.7 Hz, 6 H,
CH3), 4.15 (dd, J ϭ 5.2, 9.7 Hz, 1 H, H-5a), 4.16 (dd, J ϭ 5.5, 9.8
Hz, 1 H, H-5a), 4.28 (dd, J ϭ 7.3, 9.8 Hz, 1 H, H-5b), 4.29 (dd,
J ϭ 7.7, 9.7 Hz, 1 H, H-5b), 4.51 and 4.57 (2d, J ϭ 3.7 Hz, 2 H,
H-2), 5.10 (d, J ϭ 4.4 Hz, 1 H, H-4Ј), 5.13 (d, J ϭ 4.2 Hz, 1 H,
H-4Ј), 5.87 and 5.88 (2d, J ϭ 3.6 Hz, 2 H, H-1), 6.43 and 6.57 (2
br. s, 2 H, NH) ppm. MS (LSIMS, HR): [Mϩ ϩ H] (C13H21NO8S):
calcd. 352.10741; found 352.10661. Analytical data taken for the
mixture: C13H21NO8S (351.36): calcd. C 44.44, H 6.02, N 3.99;
found C 44.85, H 6.59, N 3.76.
enyl)-α-
using methanesulfonyl chloride; 85%; oil. [α]2D2 ϭ Ϫ40.4 (c ϭ 0.7,
CH2Cl2). IR (CHCl3): ν˜ ϭ 1669 cmϪ1 1H NMR (200 MHz,
D-glucofuranose (12): Compound 12 was obtained from 11
.
CDCl3): δ ϭ 1.31, 1.50 (2s, 6 H, 2 ϫ Me), 1.58 (dd, J ϭ 1.7, 6.8
Hz, 3 H, CH3-3Ј), 3.03 (s, 3 H, Ms), 3.39 (s, 3 H, CH3OϪ), 3.76
(d, J ϭ 2.8 Hz, 1 H, H-3), 4.14Ϫ4.57 (m, 5 H, H-2Ј, H-4, H-5, H-
6a, H-6b), 4.59 (d, J ϭ 3.7 Hz, 1 H, H-2), 5.86 (d, J ϭ 3.7 Hz, 1
H, H-1), 6.00 (dq, J ϭ 6.1, 1.7 Hz, 1 H, H-1Ј) ppm. C14H24O8S
(352.41): calcd. C 47.72, H 6.86; found C 48.25, H 7.07.
1,2-O-Isopropylidene-3-O-methyl-6-O-(2ЈЈ,4ЈЈ,6ЈЈ-triisopropyl-
phenylsulfonyl)-5-O-(prop-1Ј-enyl)-α-
pound 13 was obtained from 11 using 2,4,6-triisopropylbenzenesul-
fonyl chloride; 81%; oil. [α]2D2 ϭ Ϫ41.5 (c ϭ 0.6, CH2Cl2). IR (3ЈR,4ЈS)- and (3ЈS,4ЈR)-1,2-O-Isopropylidene-5-O-isopropylsulfonyl-
(CH2Cl2): ν˜ ϭ 1669 cmϪ1. 1H NMR (500 MHz, CDCl3): δ ϭ 1.30, 3-O-(3Ј-methyl-2Ј-oxoazetidin-4Ј-yl)-α-
-xylofuranose (7/8): A mix-
ture of stereoisomers 7 and 8, in a ratio of 1.8:1, respectively, was
D-glucofuranose (13): Com-
D
1.50 (2s, 6 H, 2 ϫ Me), 1.52 (dd, J ϭ 1.7, 6.8 Hz, 3 H, CH3-3Ј),
2.89 [sept, J ϭ 6.9 Hz, 1 H, (CH3)2CHϪ], 3.35 (s, 3 H, CH3OϪ),
obtained from 3, 66%; solid foam. IR (KBr): ν˜ ϭ 3336, 1776 cmϪ1
;
3.71 (d, J ϭ 3.1 Hz, 1 H, H-3), 4.07Ϫ4.21 [m, 4 H, H-4, H-2Ј, 2 Compound 7 (major isomer): 1H NMR (500 MHz, CDCl3) selected
ϫ (CH3)2CHϪ], 4.13 (dd, J ϭ 7.4, 10.6 Hz, 1 H, H-6a), 4.37 (m, signals taken for the mixture: δ ϭ 4.60 (d, J ϭ 3.7 Hz, 1 H, H-2),
Eur. J. Org. Chem. 2004, 4177Ϫ4187
2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4183