1058
H. Yoneyama et al.
PAPER
The mixture was stirred at 50 °C for 3 h. EtOAc (100 mL) was add-
ed to the mixture, which was subsequently washed with H2O (5 × 10
mL), dried (Na2SO4), filtered, and then evaporated. The residual oil
was purified by column chromatography (EtOAc–hexane, 1:19) to
give 9; yield: 490 mg (93%); oil.
1H NMR (400 MHz, CDCl3): δ = 0.10 (s, 6 H), 0.84 (s, 9 H), 1.00
(s, 9 H), 1.03 (s, 9 H), 1.22 (s, 9 H), 3.11 (dd, J = 14.8, 7.2 Hz, 1 H),
3.18 (dd, J = 14.8, 6.4 Hz, 1 H), 3.65 (dd, J = 9.6, 4.8 Hz, 1 H), 3.78
(dd, J = 9.6, 9.2 Hz, 1 H), 3.98 (td, J = 10.0, 5.2 Hz, 1 H), 4.19 (d,
J = 5.2 Hz, 1 H), 4.31 (t, J = 6.8 Hz, 1 H), 4.37 (dd, J = 9.2, 5.2 Hz,
1 H), 6.42 (s, 2 H).
evaporated. The residue was purified using column chromatogra-
phy (EtOAc–hexane, 1:9) to give 3v; yield: 62 mg (83%); oil.
1H NMR (400 MHz, CDCl3): δ = 0.13–0.17 (m, 6 H), 0.92–0.98 (m,
12 H), 1.15–1.20 (m, 18 H), 2.10–2.24 (m, 1 H), 2.54–2.68 (m, 1 H),
2.90–3.04 (m, 1 H), 3.15–3.44 (m, 3 H), 3.46–3.60 (m, 2 H), 3.75–
3.93 (m, 8 H), 3.94–4.06 (m, 0.5 H), 4.10–4.20 (m, 1.5 H), 4.22–
4.38 (m, 2 H), 6.17–6.34 (m, 2 H), 6.79–6.86 (m, 4 H), 7.16–7.42
(m, 9 H).
13C NMR (100 MHz, CDCl3): δ = –4.7, –4.1, 18.0, 18.1, 19.9, 20.4,
24.4, 24.6, 25.7, 25.9, 26.8, 29.1, 29.3, 29.5, 34.3, 38.8, 42.8, 42.9,
43.4, 43.5, 55.2, 57.3, 57.5, 58.6, 58.7, 63.5, 63.7, 63.9, 71.4, 72.4,
73.5, 73.7, 74.4, 75.5, 75.7, 76.0, 79.3, 79.7, 83.4, 84.0, 85.9, 86.1,
110.0, 113.1, 117.2, 117.6, 126.7, 127.8, 128.2, 130.1, 135.8, 136.0,
136.2, 144.9, 158.4, 164.3, 164.8, 176.3.
13C NMR (100 MHz, CDCl3): δ = 18.0, 18.2, 20.3, 22.7, 25.6, 25.8,
26.8, 27.0, 27.5, 27.7, 30.7, 38.9, 68.5, 71.5, 74.0, 74.1, 77.2, 85.9,
163.9, 176.4.
HRMS (FAB): m/z [M + H]+ calcd for C27H53N4O6Si2: 585.3504;
31P NMR (120 MHz, CDCl3): δ = 148.5, 151.5.
found: 585.3504.
HRMS (FAB: TEOA + NaCl):11 m/z [M + Na]+ calcd for
C49H71N6O9PSi + Na: 969.4687; found: 969.4679.
[5-(2-O-tert-Butyldimethylsilyl-β-D-ribofuranosyl)methyltetra-
zol-2-yl]methyl 2,2-Dimethylpropionate (10)
A solution of 65% HF·pyridine (40 μL) in pyridine (1 mL) was add-
ed dropwise over 5 min to a solution of 9 (223 mg, 0.38 mmol) in
CH2Cl2 (1 mL) at 0 °C. The mixture was stirred at 0 °C for 1 h and
then diluted with CH2Cl2 (60 mL). The resulting mixture was
washed with saturated aq NaHCO3 (30 mL), dried (Na2SO4), fil-
tered, and evaporated. The residue was purified by column chroma-
tography (EtOAc–hexane, 2:3) to give 10; yield: 123 mg (73%); oil.
Acknowledgment
This research was supported in part by a Grant-in-Aid for Scientific
Research [Grant No. 2159030 (to S.H.) and 24590063 (to S.K.)]
from JSPS, 2009–2013.
1H NMR (400 MHz, CDCl3): δ = 0.07 (s, 3 H), 0.09 (s, 3 H), 0.92
(s, 9 H), 1.21 (s, 9 H), 3.16 (dd, J = 15.6, 6.4 Hz, 1 H), 3.32 (dd,
J = 15.6, 4.8 Hz, 1 H), 3.60 (dd, J = 12.0, 1.6 Hz, 1 H), 3.82 (dd,
J = 12.0, 2.8 Hz, 1 H), 3.91–3.95 (m, 1 H), 3.99–4.04 (br m, 1 H),
4.07 (t, J = 5.2 Hz, 1 H), 4.20–4.26 (m, 1 H), 6.44 (s, 2 H).
Supporting Information for this article is available online at
are 1H, 13C, 31P and 195Pt NMR spectra for compounds 1t–x, 2h, 6–
11, and 3v.SnoIufproi
m
tgioSratnnugIifo
maoirt
r
pt
13C NMR (100 MHz, CDCl3): δ = –4.9, –4.7, 17.9, 25.6, 26.7, 28.3,
38.8, 62.1, 71.4, 74.9, 80.1, 84.7, 163.8, 176.4.
References
HRMS (FAB): m/z [M + H]+ calcd for C19H37N4O6Si: 445.2483;
found: 445.2484.
(1) For recent reviews on tetrazoles, see: (a) Bhatt, U. Five-
membered Heterocycles withFour Heteroatoms: Tetrazoles,
In Modern Heterocyclic Chemistry; Vol. 3; Alvarez-Builla,
J.; Vaquero, J. J.; Barluenga, J., Eds.; Wiley-VCH:
Weinheim, 2011, 1401. (b) Herr, R. J. Bioorg. Med. Chem.
2002, 10, 3379. (c) Bräse, S.; Gil, C.; Knepper, K.;
Zimmermann, V. Angew. Chem. Int. Ed. 2005, 44, 5188.
(d) Butler, R. N. Tetrazoles, In Comprehensive Heterocyclic
Chemistry II; Vol. 4; Katritzky, A. R.; Rees, C. W.; Scriven,
E. F. V., Eds.; Pergamon: Oxford, 1996, 621.
{5-[5-O-(4,4-Dimethoxytrityl)-2-O-tert-butyldimethylsilyl-β-D-
ribofuranosyl]methyltetrazol-2-yl}methyl 2,2-Dimethylpropio-
nate (11)
Compound 10 (120 mg, 0.27 mmol) was co-evaporated three times
with pyridine (1 mL) and then redissolved in pyridine (5 mL).
DMAP (4 mg, 0.03 mmol), 4,4-dimethoxytrityl chloride (DMTCl,
139 mg, 0.41 mmol), and Et3N (57 μL) were added and the mixture
was stirred at r.t. for 4 h. MeOH (1 mL) was then added and evapo-
rated to give a residue, which was purified by column chromatogra-
phy (EtOAc–hexane, 1:9) to give 11; yield: 202 mg (quant); oil.
1H NMR (400 MHz, CDCl3): δ = 0.17 (s, 6 H), 0.94 (s, 9 H), 1.18
(s, 9 H), 2.63 (d, J = 3.6 Hz, 1 H), 3.01 (dd, J = 10.4, 3.2 Hz, 1 H),
3.24 (dd, J = 14.8, 6.4 Hz, 1 H), 3.31 (dd, J = 10.4, 2.8 Hz, 1 H),
3.37 (dd, J = 14.8, 4.0 Hz, 1 H), 3.79 (s, 6 H), 4.00–4.06 (m, 2 H),
4.25–4.34 (m, 2 H), 6.21 (d, J = 10.4 Hz, 1 H), 6.26 (d, J = 10.4 Hz,
1 H), 6.80–6.84 (m, 4 H), 7.15–7.30 (m, 7 H), 7.35–7.40 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = –4.8, –4.6, 17.9, 25.7, 26.7, 29.1,
38.8, 55.1, 63.9, 71.3, 72.3, 75.6, 79.7, 84.0, 85.9, 113.1, 126.7,
127.8, 128.1, 130.0, 135.9, 136.1, 144.9, 158.4, 164.3, 176.3.
HRMS (FAB): m/z [M + H]+ calcd for C40H54N4O8Si: 746.3711;
found: 746.3700.
(2) Finnegan, W. G.; Henry, R. A.; Lofquist, R. J. Am. Chem.
Soc. 1958, 80, 3908.
(3) Demko, Z. P.; Sharpless, K. B. J. Org. Chem. 2001, 66,
7945.
(4) (a) Alterman, M.; Hallberg, A. J. Org. Chem. 2000, 65,
7984. (b) Schmidt, B.; Meid, D.; Kieser, D. Tetrahedron
2007, 63, 492. (c) Myznikov, L. V.; Roh, J.; Artamonova, T.
V.; Hrabalek, A.; Koldobskii, G. I. Russ. J. Org. Chem.
2007, 43, 765. (d) Shie, J.-J.; Fang, J.-M. J. Org. Chem.
2007, 72, 3141. (e) Zhao, Z.; Leister, W. H.; Robinson, R.
G.; Barnett, S. F.; Defeo-Jones, D.; Jones, R. E.; Hartman, G.
D.; Huff, J. R.; Huber, H. E.; Duggan, M. E.; Lindsley, C. W.
Bioorg. Med. Chem. Lett. 2005, 15, 905. (f) Marvi, O.;
Alizadeh, A.; Zarrabi, S. Bull. Korean Chem. Soc. 2011, 32,
4001. (g) Patil, V. S.; Nandre, K. P.; Borse, A. U.; Bhosale,
S. V. E-J. Chem. 2012, 9, 1145. (h) Myznikov, L. V.;
Efimova, Y. A.; Artamonova, T. V.; Koldobskii, G. I. Russ.
J. Org. Chem. 2011, 47, 728. (i) Sakhuja, R.; Panda, S. S.;
Bajaj, K. Curr. Org. Chem. 2012, 16, 789. (j) Kappe, C. O.;
Stadler, A.; Dallinger, D. Microwaves in Organic and
Medicinal Chemistry, In Methods and Principles in
Medicinal Chemistry; Vol. 52; Mannhold, R.; Kubinyi, H.;
Folkers, G., Eds.; Wiley-VCH: Weinheim, 2012, 487.
{5-[5-O-(4,4-Dimethoxytrityl)-2-O-tert-butyldimethylsilyl-3-O-
(2-cyanoethoxy-N,N-diisopropylaminophosphino)-β-D-ribofu-
ranosyl]methyltetrazol-2-yl}methyl 2,2-Dimethylpropionate
(3v)
4,5-Dicyanoimidazole (DCI) (12 mg, 0.10 mmol) and 2-cyanoethyl
N,N,N′,N′-tetraisopropylphosphordiamidite (50 μL, 0.16 mmol)
were added to a solution of 11 (59 mg, 0.08 mmol) in dichloroeth-
ane (5 mL). The mixture was stirred at 40 °C for 30 min and then
Synthesis 2013, 45, 1051–1059
© Georg Thieme Verlag Stuttgart · New York