Leung et al.
65) and then by HPLC (EtOAc/hexane 6:4) to afford 34 (48.0 mg,
64%) and 33 (18.6 mg, 25%) as colorless oils.
m, CHCH2OTr), 1.95 (1H, m, CHaHbCHOSi), 1.80 (1H, m,
CHaHbCH2CHOSi), 1.44 (1H, m, CHaHbCHOSi), 1.34 (1H, m,
CHaHbCH2CHOSi), 0.85 (9H, s, SiC(CH3)3), 0.01 (3H, s, SiCH3),
Data for 34: [R]D +23.5 (c 0.66, CHCl3, 26 °C); IR 2954 (w),
1741 (s), 1695 (s), 1648 (vs), 1599 (w), 1441 (m), 1367 (m), 1240
0.00 (3H, s, SiCH3); 13C NMR (100 MHz, CDCl3) 144.7 (CAr
×
1
(s) cm-1; H NMR (400 MHz, CDCl3) 7.94-7.91 (2H, m, CHAr),
3), 139.2 (CAr), 129.0 (CHAr × 6), 128.3 (CHAr × 2), 128.0 (CHAr
× 6), 127.5 (CHAr × 2), 127.4 (CHAr), 126.9 (CHAr × 3), 86.7
(CHOBn), 86.6 (CPh3), 76.9 (CHOSi), 71.9 (CH2Ph), 63.2
(CH2OTr), 41.7 (CHCH2OTr), 32.4 (CH2CHOSi), 26.0 (SiC(CH3)3),
25.2 (CH2CH2CHOSi), 18.4 (SiC), -4.5 (SiCH3 × 2); ES+ m/z
601 ((M + Na)+, 100); HRMS (ES+) for C38H46O3SiNa (M + Na)+
calcd 601.3108, measured 601.3119.
7.64 (1H, m, CHAr), 7.52-7.47 (2H, m, CHAr), 7.14 (1H, q, J )
1.0 Hz, C)CH), 4.91 (1H, dtd, J ) 11.0, 9.0, 7.5 Hz, CHN), 4.09
(2H, d, J ) 6.5 Hz, CH2OAc), 2.42-2.24 (2H, m, CHCH2OAc +
CHCHaHbCH), 2.15 (1H, m, CH2CHaHbCH), 2.08 (3H, s, COCH3),
2.00 (3H, s, CH3), 1.91 (1H, m, CHaHbCH2CH), 1.77 (1H, m,
CH2CHaHbCH), 1.61 (1H, dddd, J ) 13.0, 9.5, 7.5, 6.0 Hz,
CHaHbCH2CH), 1.45 (1H, dt, J ) 12.0, 10.0 Hz, CHCHaHbCH);
13C NMR (100 MHz, CDCl3) 171.2 (CdO), 169.3 (CdO), 162.8
(CdO), 150.1 (CdO), 136.4 (CdCH), 135.0 (CHAr), 131.9 (CAr),
130.6 (CHAr × 2), 129.2 (CHAr × 2), 111.3 (C)CH), 67.9
(CH2OAc), 56.6 (CHN), 36.8 (CHCH2OAc), 35.1 (CHCH2CH),
29.8 (CH2CH2CH), 27.0 (CH2CH2CH), 21.0 (COCH3), 12.8 (CH3);
ES+ m/z 393 ((M + Na)+, 82), 371 ((M + H)+, 100); HRMS (ES+)
for C20H22N2O5Na (M + Na)+ calcd 393.1421, measured 393.1417.
Data for O2-(1′R,4′S)-3-benzoyl-1-(4′-acetoxymethylcyclopen-
tan-1′-yl)thymine (33): IR 2960 (m,br), 1737 (s), 1611 (m), 1552
(1S,2R,3R)-(2-Benzyloxy-3-trityloxymethylcyclopentyloxy)-
tert-butyldimethylsilane (36b). Raney nickel (slurry in water,
rinsed with EtOH; ∼1 cm3) was added to a solution of 17b (94.0
mg, 0.138 mmol) in ethanol (1.46 mL), and the mixture was stirred
at reflux for 4 h. The suspension was cooled, filtered through Celite,
and concentrated in vacuo. The crude was purified by column
chromatography (EtOAc/petroleum ether 1:9) to afford 36b as a
colorless oil (70 mg, 88%): [R]D +36.0 (c 0.50, CHCl3, 24 °C); IR
3058 (w), 3027 (w), 2950 (m), 2853 (m), 1489 (m), 1447 (m), 1358
(m) cm-1. 1H NMR (400 MHz, CDCl3) 7.36-7.32 and 7.23-7.13
(20H, m, ArH), 4.60 (1H, d, J ) 12.0 Hz, CHaHbPh), 4.40 (1H, d,
J ) 12.0 Hz, CHaHbPh), 4.07 (1H, m, CHOSi), 3.52 (1H, dd, J )
6.0, 4.0 Hz, CHOBn) see spectrum, 3.02 (1H, dd, J ) 9.0, 6.0 Hz,
CHaHbOTr), 3.00 (1H, dd, J ) 9.0, 5.5 Hz, CHaHbOTr), 2.32 (1H,
m, CHCH2OTr), 1.87 (1H, m, CHaHbCH2CHOSi), 1.69-1.64 (2H,
m, CH2CHOSi), 1.29 (1H, m, CHaHbCH2CHOSi), 0.84 (9H, s,
SiC(CH3)3), 0.00 (3H, s, SiCH3), -0.01 (3H, s, SiCH3); 13C NMR
1
(m), 1429 (s), 1335 (m), 1236 (s), 1052 (s) cm-1; H NMR (400
MHz, CDCl3) 8.39 (1H, d, J ) 1.0 Hz, CH)C), 8.21-8.18 (2H,
m, CHPh), 7.67 (1H, m, CHPh), 7.55-7.51 (2H, m, CHPh), 5.37 (1H,
tt, J ) 6.0, 4.0 Hz, CHO), 4.08 (1H, dd, J ) 11.0 6.5 Hz,
CHaHbOAc), 4.05 (1H, dd, J ) 11.0, 6.5 Hz, CHaHbOAc),
2.37-2.25 (2H, m, CHCH2OAc + CHCHaHbCH), 2.15 (3H, d, J
) 1.0 Hz, CH3), 2.04 (3H, s, COCH3) 2.00-1.92 (2H, m,
CHaHbCHO), 1.84 (1H, m, CHaHbCH2CH), 1.70-1.57 (2H, m,
CHCHaHbCH + CHaHbCH2CH); 13C NMR (100 MHz, CDCl3)
171.2 (C), 165.4 (C), 164.0 (C), 163.3 (C), 161.9 (C)CH), 134.3
(CHAr), 130.6 (CHPh × 2), 129.2 (CHPh × 2), 128.6 (CPh), 115.5
(CdCH), 79.5 (CHO), 68.6 (CH2OAc), 37.4 (CHCH2OAc), 35.9
(CHCH2CH), 32.4 (CH2CH2CHO), 27.4 (CH2CH2CHO), 21.1
(COCH3), 12.3 (CH3); ES+ m/z 231 (100), 371 ((M + H)+, 88),
393 ((M + Na)+, 70); HRMS (ES+) for C20H23N2O5Na (M + H)+
calcd 371.1601, measured 371.1603.
(100 MHz, CDCl3) 144.5 (CAr × 3), 139.3 (CAr), 128.9 (CHAr
×
6), 128.3 (CHAr × 2), 127.8 (CHAr × 6), 127.7 (CHAr × 2), 127.3
(CHAr), 127.0 (CHAr × 3), 86.4 (CPh3), 83.1 (CHOBn), 73.5
(CHOSi), 71.8 (CH2Ph), 64.9 (CH2OTr), 42.6 (CHCH2OTr), 31.5
(CH2CHOSi), 26.1 (SiC(CH3)3), 23.2 (CH2CH2CHOSi), 18.4 (SiC),
-4.4 (SiCH3), -4.5 (SiCH3); ES+ m/z 601 ((M + Na)+, 100);
HRMS (ES+) for C38H46O3SiNa (M + Na)+ calcd 601.3108,
measured 601.3119.
The reaction requires careful monitoring in order to avoid benzyl
hydrogenolysis leading to (1R,2S,5R)-2-tert-butyldimethylsilany-
loxy-5-trityloxymethylcyclopentanol (37b): [R]D +34.9 (c 0.78,
CHCl3, 27 °C); IR 3546 (m,br), 3058 (w), 2953 (m), 2928 (m),
2857 (m), 1597 (w), 1490 (m), 1448 (m), 1101 (s) cm-1; 1H NMR
(400 MHz, CDCl3) 7.49-7.46 and 7.34-7.23 (15H, m, ArH), 4.11
(1H, q, J ) 5.5 Hz, CHOSi), 3.73 (1H, q, J ) 5.5 Hz, CHOH),
3.15 (1H, dd, J ) 9.0, 5.0 Hz, CHaHbOTr), 3.10 (1H, dd, J ) 9.0,
6.0 Hz, CHaHbOTr), 2.54 (1H, d, J ) 5.5 Hz, OH), 2.17 (1H, m,
CHCH2OTr), 1.96 (1H, dtd, J ) 13.0, 8.5, 4.0 Hz, CHaHbCHCH2),
1.85 (1H, m, CHaHbCHOSi), 1.66 (1H, m, CHaHbCHOSi), 1.34
(1H, dq, J ) 13.0 8.5 Hz, CHaHbCHCH2), 0.92 (9H, s, SiC(CH3)3),
(1′R,4′S)-1-(4′-Hydroxymethylcyclopentan-1′-yl)thymine (6′-
Carba-2′,3′-dideoxythymidine) (35). A mixture of 34 (38.2 mg,
0.103 mmol) and NH3 (7 N solution in MeOH; 1.5 mL, 10.5 mmol)
was stirred at rt for 24 h. The solvent was evaporated in vacuo,
and the crude was purified by column chromatography (acetone/
petroleum ether 6:4) to afford 35 as white crystals (20.6 mg, 89%):
[R]D +13.3 (c 2.08, MeOH, 29 °C) [lit.30e +11.30 (c 0.18, MeOH,
28 °C)]; 1H NMR (400 MHz, DMSO-d6) 11.14 (1H, s), 7.55 (1H,
s), 4.72 (1H, m), 4.53 (1H, t, J ) 5.5 Hz), 3.39 (2H, t, J ) 5.5
Hz), 2.06 (1H, m), 1.95 (1H, dt, J ) 12.0, 7.5 Hz), 1.86 (1H, m),
1.78 (3H, s), 1.75-1.62 (2H, m), 1.53 (1H, m), 1.37 (1H, m); 13
C
NMR (100 MHz, DMSO-d6) 163.7 (CdO), 150.9 (CdO), 137.6
0.10 (6H, s, Si(CH3)2); 13C NMR (100 MHz, CDCl3) 144.5 (CAr
×
(CH), 109.0 (CH), 64.8 (CH2), 55.3 (CH), 39.5 (CH), 33.9 (CH2),
3), 128.9 (CHAr × 6), 127.9 (CHAr × 6), 127.0 (CHAr × 3), 86.5
(CPh3), 76.2 (CHOH), 74.6 (CHOSi), 65.3 (CH2OTr), 45.0
(CHCH2OTr), 31.6 (CH2CHOH), 26.0 (SiC(CH3)3), 24.1
(CH2CH2CH), 18.3 (SiC), -4.4 (SiCH3), -4.8 (SiCH3); ES+ m/z
511 ((M + Na)+, 20); HRMS (ES+) for C31H40O3SiNa (M + Na)+
calcd 511.2639, measured 511.2653.
1
29.1 (CH2), 26.1 (CH2), 12.0 (CH3); H NMR corresponds to the
previously reported values.30b,e 13C NMR corresponds to the
previously reported values.30c
(1S,2S,3R)-(2-Benzyloxy-3-trityloxymethylcyclopentyloxy)-
tert-butyldimethylsilane (36a). Raney nickel (slurry in water, rinsed
with EtOH; ∼2 mL) was added to a solution of 17a (126.0 mg,
0.184 mmol) in ethanol (1.85 mL). The mixture was stirred at reflux
with the addition of Raney nickel (∼2 mL) every 30 min until
complete conversion was evident by TLC (∼4 h). The suspension
was cooled and filtered through Celite. The resulting solution was
concentrated in vacuo and purified by column chromatography
(EtOAc/petroleum ether 3:97) to afford 36a as a colorless oil (92.0
mg, 86%): [R]D +11.6 (c 2.1, CHCl3, 24 °C); IR 3057 (w), 3029 w,
(1S,2S,3R)-2-Benzyloxy-3-trityloxymethylcyclopentan-1-ol (38a).
TBAF (1.0 M solution in THF; 0.285 mL, 0.285 mmol) was added
to a solution of 36a (110 mg, 0.190 mmol) in THF (1.9 mL). The
mixture was stirred at rt for 16 h. The solvent was removed in
vacuo, and the residue was purified by column chromatography
(EtOAc/petroleum ether 3:7) to afford 38a as a white solid (81.0
mg, 92%): mp 38-40 °C; [R]D +9.2 (c 0.80, CHCl3, 24 °C); IR
3388 (w, br), 3059 (w), 3031 (w), 2931 (w), 2873 (w), 1490 (m),
1448 (m), 1067 (s) cm-1; 1H NMR (400 MHz, CDCl3) 7.49-7.43
and 7.30-7.12 (20H, m, ArH), 4.52 (1H, d, J ) 12.0 Hz, CHaHbPh),
4.46 (1H, d, J ) 12.0 Hz, CHaHbPh), 4.25 (1H, m, CHOH), 3.87
(1H, dd, J ) 5.5, 2.5 Hz, CHOBn), 3.27 (1H, dd, J ) 9.0, 7.5 Hz,
CHaHbOTr), 3.21 (1H, dd, J ) 9.0, 6.5 Hz, CHaHbOTr), 2.57 (1H,
m, CHCH2OTr), 2.11 (1H, m, CHaHbCH2CHOH), 1.88 (1H, m,
2949 (m), 2854 (m), 1490 (m), 1447 (m), 1359 (w), 1064 (s) cm-1
;
1H NMR (400 MHz, CDCl3) 7.43-7.39 and 7.24-7.07 (20H, m,
ArH), 4.46 (1H, d, J ) 12.0 Hz, CHaHbPh), 4.36 (1H, d, J ) 12.0
Hz, CHaHbPh), 4.14 (1H, dt, J ) 6.0, 2.5 Hz, CHOSi), 3.72 (1H,
dd, J ) 5.0, 2.5 Hz, CHOBn), 3.18 (1H, dd, J ) 9.0, 7.5 Hz,
CHaHbOTr), 3.16 (1H, dd, J ) 9.0, 6.5 Hz, CHaHbOTr), 2.45 (1H,
9204 J. Org. Chem. Vol. 73, No. 23, 2008