1086 R. Csuk et al. ■Chiral Pool Synthesis of 4a-Substituted Carboxyclic Cyclopentanoid Nucleoside Presursors. II
of BH3 .THF (4.2 ml. 1.1 equiv.) was slowly added.
After stirring at this temperature for an additional
(.s, C9 (ar)), 128.45, 127.77, 127.72 (d, Q(ar)),
111.17 ( 5, Ct/(isopropyl)), 84.56, 79.89 {d, C(2),
3 h. methanol (5 ml) was added, the mixture al- C(3)), 77.76 ( 5, C(4)), 73.54 ( f , CH2 (ar)), 72.45 {t,
lowed to warm to 25 °C and 3
m
NaOH solution
C(5)), 71.58 (d, C (l)), 39.79 (t, C(4a)), 26.23 {q,
CH3 (isopropyl)), 26.01 (q, CH3 (terr-butyl)), 24.55
{q, CH3(isopropyl)), 18.41 (5 , Cf/(rm-butyl)), -4.48
{q, CH3-Si), -4.68 (q, CH3-Si); MS (ei, 80 eV,
102 °C): 408 (M. 0.2%), 351 (4.0%), 129 (5.7), 101
(4.6%), 92 (7.6%), 91 (100%); HRMS calcd. for
C22H360 ,S i (408.61): 408.2333; found: 408.2332.
(10 ml) and 30% H20 2 (30%, 1 0 ml) were added
in succession. Stirring at 55 °C was continued for
lh, then the mixture was diluted with diethyl ether
(50 ml) and water (30 ml), the phases were sepa-
rated, the aqueous layer was extracted with diethyl
ether (3 x 50 ml), the combined organic layers
were washed with brine (20 ml), dried (M gS04),
the solvents removed under reduced pressure and
the residue was subjected to chromatography (sil-
ica gel, hexane/ethyl acetate 2 0 : 1 —* 1 0 :1 ) to afford
10 (0.97 g, 61.8%) and 11 (0.16 g, 10.2%). Data for
10. - [aß0 -23.6° (c, 0.6 CHC13); RF = 0.22 (hex-
ane/ethyl acetate 1:1); 'H NMR (250 MHz,
CDCI3): <3 = 7.37-7.28 (m, 5 H, H-C(ar)), 4.54 (s,
2 H, CH2 (ar)), 4.50 (t, 1 H , / = 5.6 Hz, H-C(2)),
4.36 (t, 1 H, J = 5.6 Hz, H-C(3)), 3.91 (dd, 1 H, J =
8 .6 , 10.1 Hz, H-C(4a)), 3.83 (dd, l H , / = 6.9, 9.0
Hz, HaC(5)), 3.72 {t, 1 H, J = 8.0 Hz, HBC(5)),
3.67 (dd, 1 H, / = 5.4, 8.4Hz, H -C (l)), 2.50 (bs, 1
H, OH), 1.96-1.86 (m, 1 H, H-C(4)), 1.40 (s, 3
H, CH3(isopropyl)), 1.26 (5 , 3 H, CH3(isopropyl)),
(4a R) 5-0-Benzyl-l-0-(tert-butyldimethylsilyl)-
4a-carba-4a-0-(4-nitrobenzoyl)-2,3-0-isopropyl-
idene-ß-L-lyxofuranose = [(3a R, 4 S, 5 R, 6 S,
6a R) 4-(benzyloxy-methyl)-4-hydroxy-6-(tert-
butyldimethylsilyl-oxy)-2,2-dimethyl-tetrahydro-
cyclopenta[l,3]dioxol-5-yl] 4-nitro-benzoate (13)
Compound 10 (100 mg, 0.25 mmol) was acylated
in dry dichloromethane (5 ml) with pyridine
(0.2 ml)
and 4-nitrobenzoylchloride
(55 mg,
0.27 mmol); after usual work up (vide supra) and
chromatography (silica gel, hexane/ethyl acetate
20:1) 13 (127 mg, 93%) was obtained; m.p. I l l °C;
RF = 0.40 (hexane/ethyl acetate 5:1); ’H NMR
(300 MHz, CDC13): (3 = 8.22 (td, 2 H, J = 2.1, 9.0
Hz, H-C(3'), H-C(5')), 8.09 (td, 2 H , / = 2.1, 9.0
Hz, H-C(2')), H-C(6')), 7.16(5, 5 H, H-C(ar)), 5.46
(dd, 1 H, J = 8.6, 10.7 Hz, H-C(4a)), 4.66 (t, 1 H,
J = 5.5 Hz, H-C(3)), 4.45 (t, 1 H, J = 5.6 Hz, H-
C(2)), 4.44 (d, 1 H, J = 11.6 Hz, HA-CH2(ar)), 4.39
(d, 1 H, / = 11.7 Hz, HB-CH2(ar)), 4.04 (dd, 1 H,
J = 5.6, 8.6 Hz, H -C(l)), 3.88 (dd, l H , / = 7.2, 9.2
Hz, Ha -C(5)), 3.62 (dd, 1 H, J = 6.7, 9.2 Hz, HB-
C(5)), 2.21-2.18 (m, 1 H, H-C(4)), 1.52 (s, 3 H,
CH3(isopropyl)), 1.33 (s, 3 H, CH3(isopropyl)),
0.82 (5 , 9 H, CH3(rrn-butyl)), 0.07 (s, 6 H, CH3-
Si); 13C NMR (75 MHz, CDC13): ö = 164.01 (s,
CO), 150.15 (s, C9(ar)), 138.08 (s, C9(ar)), 128.45,
127.77,127.72 (d, Q(ar)), 111.17 (s, C^isopropyl)),
84.56, 79.89 (d, C(2), C(3)), 77.76 (s, C(4)), 73.54
(t, CH2(ar)), 72.45 (t, C(5)), 71.58 (d, C (l)), 39.79
(t, C(4a)), 26.23 (q, CH3(isopropyl)), 26.01 (q,
CH3(rerf-butyl)), 24.55 (q, CH3(isopropyl)), 18.41
(s, C9(terf-butyl)), -4.48 (q, CH3-Si), -4.68 (q, CH3-
Si); MS (ei, 80 eV, 72 °C): 557 (1.4%), 500
(11.4%), 275 (2.1%), 225 (2.4%), 224 (11.2%), 150
(8.3%), 120 (3.9%), 92 (9.1%), 91 (100%).
0.92 (s, 9 H, CH3 (terr-butyl)), 0.12 (s,
6
H, CH3-
Si); 13C NMR (62 MHz, CDC13): (3 = 138.20 (s,
C9 (ar)), 128.39 (d, Cf(ar)), 127.64 (d, Q(ar)),
110.28 (s, C^(isopropyl)), 78.67, 77.72, 77.47, 76.34
(d, C(2), C(3), C (l), C(4a)), 73.48 (t, CH2 (ar)),
69.48 (t, C(5)), 44.17 (s, C(4)), 25.92 (q, CH3 (iso-
propyl)), 25.90 {q, CH3 (terr-butyl)), 24.23 (q,
CH3 (isopropyl)), 18.41 (s, C^/err-butyl)), -4.57 (q,
CH3-Si), -4.55 (q, CH3-Si); MS (ei, 80 eV, 130 °C):
408 (0.3%), 351 (14.7%), 245 (3.7%), 185 (9.7%),
171 (3.8%), 159 (4.6%), 157 (4.8%), 143 (4.0%),
131 (5.4%), 129 (16.2%), 117 (10.5%), 116 (4.9%),
105 (3.3%), 101 (4.0%), 92 (20.5%), 91 (100%).
Analysis for C22H360 5Si (408.61)
Calcd
C 64.67
H 8 .8 8 %,
Found C 64.44 H8.99% .
Data for 11. - [ct]g* -4.7° (c, 0.8 CHC13); RF =
0.44 (hexane/ethyl acetate 1:1); ]H NMR (250
MHz, CDC13): Ö = 7.35-7.28 (m, 5 H, H-C(ar)),
4.63 (d, 1 H, J = 12.2 Hz. HA-CH?(ar)), 4.55 (d, 1
H, J = 11.9 Hz, HB-CH2 (ar)), 4.53 (f, 1 H, J = 5.2
Hz, H-C(2)), 4.41-4.32 (m, 1 H, H -C (l)), 4.22 (d,
1 H, J = 4.9 Hz. H-C(3)), 3.68 (d, 1 H, J = 9.0 Hz,
Ha -C(5)), 3.43 (d, 1 H. J = 8.2 Hz. HB-C(5)), 2.61
(s, 1 H, OH), 1.47-1.26 (m, 2 H, HA/BC(4a)), 1.43
(s, 3 H, CH3 (isopropyl)), 1.31 (5 , 3 H, CH3 (isopro-
Analysis for C ,9H39N 0 8Si (557.71)
Calcd
C 62.45 H 7.05 N2.51%,
pvl)), 0.90 0, 9 H, CH3 (rm-butyl)), 0.09 (s,
6
H.
CH3-Si); 13C NMR (62 MHz, CDC13): (3 = 138.08
Found C 62.80 H 6.76 N2.36%.
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