A versatile approach to alcohol, aldehyde, ketone and amine derivatives starting from β-allyl C-glycosides of D-ribofuranose and 2-deoxy-D-ribofuranose

Article abstract of DOI:10.1055/s-0030-1260200

An efficient preparative procedure is described, leading from β-allyl C-glycosides of d-ribofuranose to alcohols by a hydroboration-oxidation procedure. The corresponding aldehydes were obtained by Swern or Dess-Martin oxidation. Alternatively, two of the alcohols were mesylated to gain access to azides and amines. Treatment of the aldehydes with ethynylmagnesium bromide or phenylethynyllithium and consecutive oxidation of the diastereomeric alcohols provided the acetylenic ketones in good to excellent yields. The obtained derivatives serve as important intermediates for the synthesis of various heterocyclic systems. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0030-1260200

PAPER
3099
A Versatile Approach to Alcohol, Aldehyde, Ketone and Amine Derivatives
Starting from b-Allyl C-Glycosides of D-Ribofuranose and 2-Deoxy-D-ribo-
furanose
A
V
ersatile
Appro
e
achtoRibo
i
furanos
k
e
D
erivative
e
s
Wächtler,a,b Dilver Peña Fuentes,a Dirk Michalik,c Martin Köckerling,a Alexander Villinger,a Udo Kragl,a
Quirino Arias Cedeño,d Christian Vogel*a
a
University of Rostock, Institute of Chemistry, Albert-Einstein-Str. 3a, 18059 Rostock, Germany
Fax +49(381)4986412; E-mail: christian.vogel@uni-rostock.de
Agilent Technologies, Hewlett-Packard-Str. 8, 76337 Waldbronn, Germany
Leibniz Institute for Catalysis at the University of Rostock, Albert-Einstein-Str. 29a, 18059 Rostock, Germany
Universidad de Granma, Carretera Manzanillo Km. 17.5, Bayamo Granma, Cuba
b
c
d
Received 30 May 2011; revised 21 June 2011
Dedicated to Professor Dr. Rainer Beckert on the occasion of his 60th birthday
dation of the olefins 4 and 5 to produce the alcohols 6 and
Abstract: An efficient preparative procedure is described, leading
from b-allyl C-glycosides of D-ribofuranose to alcohols by a hy-
droboration–oxidation procedure. The corresponding aldehydes
were obtained by Swern or Dess–Martin oxidation. Alternatively,
7 in 72 and 82% yield, respectively. As side-products, the
corresponding sec alcohols were observed (<10%), which
were easily removed by column chromatography. X-ray
two of the alcohols were mesylated to gain access to azides and diffraction studies of compound 7 (Figure 1) established
amines. Treatment of the aldehydes with ethynylmagnesium bro-
its structure and confirmed the presence of the tetrahydro-
mide or phenylethynyllithium and consecutive oxidation of the
diastereomeric alcohols provided the acetylenic ketones in good to
excellent yields. The obtained derivatives serve as important inter-
furan ring as well as the b-linkage to the hydroxy alkyl
residue, with C-1¢ possessing S-configuration.
mediates for the synthesis of various heterocyclic systems.
2
Key words: ribofuranose, C-nucleosides, hydroboration, oxida-
tion, amines, aldehydes, alkynes
1
5'
3
AcO
OAc
RO
O
O
i
1'
4'
2'
3'
O
O
O
O
As part of an ongoing research programme that focuses on
C-nucleosides, we described recently the first safe, short,
and efficient synthetic route to peracetylated b-allyl C-
glycosides of D-ribofuranose and 2-deoxy-D-ribofura-
nose. At present, the best pathway to prepare a b-allyl C-
glycoside of D-ribofuranose proceeds via the 2,3-O-iso-
propylidene diacetate 11–3 by treatment with allyltrimeth-
ylsilane (AllTMS) and zinc bromide in nitromethane as
solvent (Scheme 1).4,5 Here, we report the synthesis of a
series of products, for example alcohols, amines, alde-
hydes, and acetylenic ketones that are potentially useful
for the preparation of a broad range of nucleoside ana-
logues. In view of the diverse application of C-nucleo-
sides, we wished to develop a versatile synthetic route to
these types of compounds. It was decided to attempt this
by applying a hydroboration–oxidation procedure. How-
ever, initial investigations showed that the ester group of
C-glycoside 2 is not stable enough for such reaction con-
ditions. Thus, the acetyl group was replaced by a tert-bu-
tyldimethylsilyl group (TBDMS) and by a tert-butyl-
diphenylsilyl group (TBDPS), providing compounds 4
and 5,5 respectively. Deacetylation was simply achieved
1
2: R = Ac
3: R = H
ii
iii
4: R = TBDMS
5: R = TBDPS
iv
OH
O
1
1
2
2
3
3
RO
RO
O
O
v
O
O
O
O
8: R = TBDMS
9: R = TBDPS
6: R = TBDMS
7: R = TBDPS
Scheme 1 Consecutive synthesis of alcohols 6, 7, and aldehydes 8
and 9 starting from the b-allyl C-glycoside of D-ribofuranose 2.
Reagents and conditions: (i) AllTMS, ZnBr2, MeNO2; (ii) cat. NaO-
Me in MeOH, 75 min, 20 °C; (iii) TBDMSCl or TBDPSCl, py, 12 h;
(iv) B2H6–THF, 3 h, 0 °C, followed by H2O2, NaOH; (v) Swern oxi-
under Zémplen conditions, furnishing 3 nearly quantita- dation.
tively. Subsequent transformation of the double bond in
the terminal alcohol was realized by hydroboration–oxi-
Next, Swern oxidation6 of the primary alcohols 6 and 7
gave the best results compared to other selective oxidation
procedures, and aldehydes 8 and 9 were each obtained in
83% yield (Scheme 1).
SYNTHESIS 2011, No. 19, pp 3099–3108
Advanced online publication: 01.09.2011
DOI: 10.1055/s-0030-1260200; Art ID: T55711SS
x
x.
x
x
.
2
0
1
1
© Georg Thieme Verlag Stuttgart · New York

3100
H. Wächtler et al.
PAPER
of crown ether (18-crown-6) in anhydrous N,N¢-dimethyl-
formamide (DMF) to provide azides 13 and 14 in 85 and
89% yield, respectively. Catalytic hydrogenation of 13 af-
forded amine 15 in 65% yield. Comparable results were
obtained by using a Staudinger reaction7 to furnish amine
16 in 64% yield.
Optimal conditions for the alkylation of imidazole were
found by using its sodium salt and mesylate 10 as
coupling agent. Both reactions — mesylation of 6 as well
as formation of 17 — were achieved in nearly quantitative
yields.
To prepare comparable key intermediates based on 2-
deoxyribofuranose, a slightly modified synthetic route to
20 was applied starting from C-glycoside 2. The total
yield over four steps, including cleavage of the protecting
groups of 2, introduction of the 1,1,3,3-tetraisopropyldi-
siloxane group (TIPDS, 19), exchange of the hydroxy
group by iodine, and its reduction (20), was improved
from 36 to 67% (Scheme 3). Gratifyingly, compound 19
provided suitable crystals, so that a single crystal X-ray
analysis (Figure 2) confirmed our previous results.5
Figure 1 Molecular structure of alcohol 7 with atom labeling
scheme. Thermal ellipsoids are drawn at the 30% probability level.
Puckering parameters are q2 = 0.2602(2) and F2 = –62.77(4) for the
tetrahydrofuran ring. Only one orientation of the disordered atoms C8
and O4 are shown.
On the other hand, introduction of N-functionality was
achieved via the sulfonates 10–12, which are easily acces-
sible in good to quantitative yield (Scheme 2). Mesylates
10 and 11 were treated with sodium azide in the presence
Employing the same conditions for the hydroboration–ox-
idation used for the preparation of 6 or 7 on olefin 20 pro-
vided the primary alcohol 21 in 69% yield. Consecutive
Swern oxidation was also attempted to furnish aldehyde
22. However, this proved unsuccessful, with many side-
products being observed. Alternatively, the Dess–Martin
variant8,9 gave aldehyde 22 in 79% yield (Scheme 3).
OR2
R1O
i
O
6, 7
To allow further variation in heterocyclic chemistry,
which will be described in future publications, the chem-
istry was expanded to include acetylenic ketones.10,11
O
O
10: R1 = TBDMS, R2 = Ms
11: R1 = TBDPS, R2 = Ms
12: R1 = TBDMS, R2 = Ts
HO
O
O
O
Si
i
ii
2
O
HO
OH
O
R
Si
iii
ii
18
19
R = OH
N
2
iii
4
20 R = H
N
R2
1''
5
1
iv
2''
2
5'
3''
TBDMSO
R1O
5'
3
O
O
1'
O
OH
4'
3'
4'
1'
2'
2'
3'
O
O
O
O
O
O
O
O
v
Si
Si
O
O
= TBDMS, R2 = N3
17
13: R1
O
O
iv
v
Si
14: R1 = TBDPS, R2 = N3
15: R1 = TBDMS, R2 = NH2
16: R1 = TBDPS, R2 = NH2
Si
22
21
Scheme 2 Synthesis of sulfonates 10–12 and their transformation
into nitrogen derivatives 13–17. Reagents and conditions: (i) MsCl,
Et3N, CH2Cl2, 20 min, 5 °C, and PTSCl, py,12 h, 5–20 °C; (ii) NaN3,
18-crown-6, DMF, 24 h, 20 °C; (iii) Na imidazolide, DMF, 3 h,
60 °C; (iv) Pd/C, MeOH, H2 atmosphere, 8 h, 20 °C; (v) Ph3P, THF,
90 min, 20 °C, then H2O, 24 h, 20 °C.
Scheme 3 Consecutive synthesis of alcohol 21 and aldehyde 22
starting from the b-allyl C-glycoside of 2-deoxy-D-ribofuranose 20.
Reagents and conditions: (i) aq HCl, EtOH, 2 d, 20 °C; (ii) TIPDSCl,
imidazole, DMF, 1 h, 5 °C; (iii) I2, Ph3P, imidazole, toluene, then
Bu3SnH, AIBN, toluene,10 h, reflux; (iv) B2H6–THF, 3 h, 0 °C, fol-
lowed by H2O2, NaOH; (v) Dess–Martin oxidation.
Synthesis 2011, No. 19, 3099–3108 © Thieme Stuttgart · New York

PAPER
A Versatile Approach to Ribofuranose Derivatives
3101
plished by using Dess–Martin reagent, whereas oxidation
of 24 and 26 was achieved by treatment with pyridinium
chlorochromate (PCC) to provide the ethynyl ketones 27
and 29 in 82 and 90% yield, respectively, and ketones 28
and 30 were obtained in 54 and 50% yield, respectively.
Following the above strategy, alcohols 31 and 32 were ob-
tained in 75 and 66% isolated yield, respectively. The
corresponding alkynyl ketones 33 and 34 were synthe-
sized by Dess–Martin oxidation and isolated in 77 and
60% yield, respectively (Scheme 5).
R
OH
Figure 2 Molecular structure of C-allyl derivative 19 with atom la-
beling scheme. Thermal ellipsoids are drawn at the 30% probability
level. Puckering parameters are q2 = 0.420(1) and F2 = –62.7(2) for
the tetrahydrofuran ring.
O
i
O
22
Si
O
O
Si
Treatment of aldehydes 8 or 9 with ethynylmagnesium
bromide or phenylethynyllithium in anhydrous tetrahy-
drofuran (THF) afforded pentynols 23–26 as an insepara-
ble diastereomeric mixture in 64, 83, 67, and 69% yield,
respectively (Scheme 4). The stereogenic center giving
rise to diastereoisomers will be destroyed in the subse-
quent step. Thus, oxidation of 23 and 25 was accom-
31: R = H
32: R = Ph
ii
R
O
R2
5
4
OH
O
O
3
2
Si
O
R1O
5'
3'
1
O
O
4'
1'
i
Si
8, 9
2'
O
O
33: R = H
34: R = Ph
23: R1 = TBDMS, R2 = H
24: R1 = TBDPS, R2 = H
25: R1 = TBDMS, R2 = Ph
26: R1 = TBDPS, R2 = Ph
Scheme 5 Synthesis of acetylenic ketones 33 and 34 derived from
2-deoxy-D-ribofuranose C-glycoside. Reagents and conditions: (i)
ethynylmagnesium bromide or phenylethynyllithium, THF, 4 h,
20 °C; (ii) Dess–Martin oxidation.
ii
In conclusion, we have developed a versatile synthetic ap-
proach to key intermediates of nucleoside analogues. The
route allows the synthesis of a broad variety of heterocyc-
lic b-C-glycosidic moieties connected to D-ribofuranose
and 2-deoxy-D-ribofuranose. Examples of such structures
will be reported in due course.
R2
5
4
O
3
2
R1O
5'
1
O
4'
1'
2'
3'
Melting points were determined with a Boetius micro-heating plate
BHMK 05 (Rapido, Dresden) and are not corrected. Optical rotation
was measured for solutions in a 2-cm cell with an automatic pola-
O
O
1
rimeter GYROMAT (Dr. Kernchen Co.). H NMR (250.13 MHz
27: R1 = TBDMS, R2 = H
28: R1 = TBDPS, R2 = H
29: R1 = TBDMS, R2 = Ph
and 300.13 MHz) and 13C NMR (62.9 MHz and 75.5 MHz) spectra
were recorded with Bruker AV 250 and AV 300 instruments, re-
spectively, with CDCl3 as solvent. Calibration of the spectra was
carried out with solvent signals (CDCl3: dH = 7.26 ppm,
dC = 77.0 ppm). 1H and 13C NMR signals were assigned by DEPT,
two-dimensional 1H,1H COSY and 1H,13C correlation spectra
(HMBC and HSQC). For NMR numbering of atoms see Scheme 1,
Scheme 2, and Scheme 4. Mass spectra were recorded with an
AMD 402/3 spectrometer (AMD Intectra GmbH). Elemental anal-
30: R1 = TBDPS, R2 = Ph
Scheme 4 Synthesis of acetylenic ketones 27–30 derived from D-
ribofuranose C-glycoside. Reagents and conditions: (i) ethynylmag-
nesium bromide or phenylethynyllithium, THF, 4 h, 20 °C; (ii) Dess–
Martin oxidation gave 27 and 29, PCC oxidation provided 28 and 30.
Synthesis 2011, No. 19, 3099–3108 © Thieme Stuttgart · New York

3102
H. Wächtler et al.
PAPER
ysis was performed with a CHNS-Flash-EA-1112 instrument
(Thermoquest).
Anal. Calcd for C17H32O4Si (328.52): C, 62.15; H, 9.82. Found: C,
61.99; H, 9.73.
For X-ray structure determination of compounds 7 and 19, an
X8Apex system with CCD area detector was used (l = 0.71073 Å;
graphite monochromator). The structures were solved by direct
methods (Bruker-SHELXTL). The refinement calculations were
performed by the full-matrix least-squares method of Bruker
SHELXTL (Version 5.10, Bruker Analytical X-ray Systems). All
non-hydrogen atoms were refined anisotropically. The hydrogen at-
oms were placed in idealized positions and refined using riding
models. Crystallographic data for the structure analysis has been de-
posited with the Cambridge Crystallographic Data Centre, CCDC
No 827041 and 825615 for compounds 7 and 19, respectively. Cop-
ies of this information may be obtained free of charge from: The Di-
rector, CCDC, 12 Union Road, Cambridge, CB2 1EZ UK; Fax
+44(1223)336033 or via Email: deposit@ccdc.cam.ac.uk or online
at http://www.ccdc.cam.ac.uk.
Compound 5 was previously obtained by the reaction of allyltri-
methylsilane with 1-O-acetyl-5-O-tert-butyldiphenylsilyl-2,3-O-
isopropylidene-b-D-ribofuranose.5 In principle, the procedure
above can be used analogously for its preparation by using tert-bu-
tylchlorodiphenylsilane.
Hydroboration–Oxidation of Compounds 4 and 5
Borane–tetrahydrofuran complex (0.1 M in THF, 50.0 mL) was
added dropwise to a stirred soln of 4 (5.91 g, 18.0 mmol) or 5 (8.15
g, 18.0 mmol) in anhyd THF (50 mL) at 0 °C, and stirring was con-
tinued at that temperature. After 3 h, the excess of borane complex
was destroyed by adding a few drops of H2O. NaOH (3 M, 215 mL)
and 30% H2O2 (215 mL) were then added successively to the reac-
tion mixture at 0 °C. The ice-bath was removed and the mixture was
stirred for 90 min at ambient temperature (reaction monitored by
TLC). The reaction mixture was poured into ice–water (600 mL),
the aqueous phase was extracted with CH2Cl2 (4 × 300 mL), and the
combined organic phases were washed with brine (250 mL), dried,
and concentrated. Purification by flash chromatography (solvent
A2) afforded 6 and 7.
All washing solutions were cooled to ~5 °C. The NaHCO3 solution
was saturated. Reactions were monitored by thin-layer chromatog-
raphy (TLC; Silica Gel 60, F254, Merck KGaA). The following sol-
vent systems (v/v) were used: (A1) 1.5:1, (A2) 2:1, (A3) 2.5:1, (A4)
3:1, (A5) 4:1, (A6) 5:1, (A7) 6:1, (A8) 7:1, (A9) 8:1, (A10) 10:1, (A11)
11:1, (A12) 12:1, (A13) 80:1 n-hexane–EtOAc; (B1) 1:1, (B2) 2:1,
(B3) 15:1 EtOAc–MeOH. TLC spots were made visible by dipping
the TLC plates into a methanolic 10% H2SO4 solution and charring
with a heat gun for 3–5 min. Preparative flash chromatography was
performed by elution from columns of slurry-packed Silica Gel 60
(Merck, 63–200 mm). All solvents and reagents were purified and
dried according to standard procedures.12 After classical workup of
the reactions mixtures, the organic layer was dried over MgSO4, and
then concentrated under reduced pressure (rotary evaporator).
3-(5-O-tert-Butyldimethylsilyl-2,3-O-isopropylidene-1-deoxy-b-
D-ribofuranos-1-yl)propan-1-ol (6)
Purified by flash chromatography (solvent A2).
24
Yield: 3.92 g (66%); colorless syrup; [a]D –7.4 (c 1.2, CHCl3);
Rf = 0.2 (solvent A2).
1H NMR (300.13 MHz, CDCl3): d = 0.05, 0.05 [2 × s, 6 H,
Si(CH3)2], 0.88 [s, 9 H, C(CH3)3], 1.32, 1.51 [2 × s, 6 H, C(CH3)2],
1.55–1.81 (m, 4 H, H-2,3), 2.25 (br s, 1 H, OH), 3.63 (m, 2 H, H-1),
3.70 (m, 2 H, H-5¢), 3.83–3.90 (m, 1 H, H-1¢), 4.00 (app q, 3J3¢,4¢
≈
3-(5-O-tert-Butyldimethylsilyl-2,3-O-isopropylidene-b-D-ribo-
furanosyl)prop-1-ene (4)
3J4¢,5¢ = 3.6 Hz, 1 H, H-4′), 4.26 (dd, 3J2¢,3¢ = 6.7 Hz, 3J1¢,2¢ = 5.0 Hz,
1 H, H-2¢), 4.61 (dd, 3J2¢,3¢ = 6.7 Hz, 3J3¢,4¢ = 3.6 Hz, 1 H, H-3¢).
NaOMe (0.5 M in MeOH, 0.8 mL) was added to a soln of 2 (7.30 g,
28.5 mmol) in anhyd MeOH (40 mL). After stirring at ambient tem-
perature for 75 min (TLC; solvent A2), the reaction mixture was
neutralized with IR120 (H+) Amberlite resin, filtered, dried, and
concentrated. Compound 3 was obtained quantitatively and used in
the next step without further purification.
13C NMR (62.9 MHz, CDCl3): d = –5.5, –5.4 [Si(CH3)2], 18.3
[C(CH3)3], 25.5, 27.4 [C(CH3)2], 25.8 [C(CH3)3], 29.3, 30.5 (C-2,3),
62.5, 63.5 (C-1,5¢), 81.7 (C-3¢), 84.4, 84.6, 84.9 (C-1¢,2¢,4¢), 114.0
[C(CH3)2].
Anal. Calcd for C17H34O5Si (346.53): C, 58.92; H, 9.89. Found: C,
58.80; H, 9.94.
A soln of tert-butylchlorodimethylsilane (5.43 g, 36.0 mmol) in an-
hyd pyridine (12 mL) was added dropwise to a stirred soln of 3 (6.10
g, 28.5 mmol) in anhyd pyridine (60 mL) at 0 °C. The mixture was
allowed to come to r.t. and stirring was continued overnight (reac-
tion monitored by TLC). The reaction mixture was diluted with
EtOH–heptane–CHCl3 (1:1:5, v/v/v; 100 mL) and concentrated. Af-
ter dissolving the residue in heptane–CHCl3 (2:1, v/v; 360 mL), the
organic phase was washed successively with aq 15% NaHSO4
(2 × 120 mL), ice–water (120 mL), and NaHCO3 (2 × 120 mL),
dried, and concentrated. Purification by flash chromatography (sol-
vent A10) afforded compound 4.
3-(5-O-tert-Butyldiphenylsilyl-2,3-O-isopropylidene-1-deoxy-b-
D-ribofuranos-1-yl)propan-1-ol (7)
Purified by flash chromatography (solvent A2).
Yield: 6.95 g (82%); colorless crystals; mp 50–52 °C (EtOAc–
hexane); [a]D23 –2.6 (c 1.0, CHCl3); Rf = 0.28 (solvent A2).
1H NMR (250.13 MHz, CDCl3): d = 1.06 [s, 9 H, C(CH3)3], 1.35,
1.53 [2 × s, 6 H, C(CH3)2], 1.60–1.80 (m, 4 H, H-2,3), 3.66 (m, 2 H,
H-5¢), 3.75 (m, 2 H, H-1), 3.84–3.92 (m, 1 H, H-1¢), 4.06 (app q,
3J3¢,4¢
≈
3J4¢,5¢ = 3.6 Hz, 1 H, H-4¢), 4.31 (dd, 3J2¢,3¢ = 6.7 Hz,
23
3J1¢,2¢ = 5.0 Hz, 1 H, H-2¢), 4.71 (dd, 3J2¢,3¢ = 6.7 Hz, 3J3¢,4¢ = 3.6 Hz,
1 H, H-3¢), 7.34–7.72 (m, 10 H, PhH).
Yield: 8.80 g (94%); colorless syrup; [a]D –12.1 (c 1.1, CHCl3);
Rf = 0.38 (solvent A10).
1H NMR (300.13 MHz, CDCl3): d = 0.06, 0.07 [2 × s, 6 H,
Si(CH3)2], 0.90 [s, 9 H, C(CH3)3], 1.34, 1.52 [2 × s, 6 H, C(CH3)2],
2.37 (m, 2 H, H-3), 3.72 (m, 2 H, H-5′), 3.95 (app dt, 3J1¢,3a = 6.5 Hz,
13C NMR (75.5 MHz, CDCl3): d = 19.2 [C(CH3)3], 25.6, 27.0
[C(CH3)2], 26.5 [C(CH3)3], 29.5, 30.6 (C-2,3), 62.7 (C-1), 64.1 (C-
5¢), 81.8 (C-3¢), 84.2, 84.5, 84.8 (C-1¢,2¢,4¢), 114.2 [C(CH3)2], 127.7
(2), 135.6, 135.7 (o-, m-Ph), 129.7 (2) (p-Ph), 133.2, 133.3 (i-Ph).
3
3
3J1¢,2¢ ≈ J1¢,3b = 4.7 Hz, 1 H, H-1′), 4.00 (app q, 3J3¢,4′ ≈ J4¢,5¢ = 3.6
Hz, 1 H, H-4′), 4.33 (dd, 3J2¢,3¢ = 6.6 Hz, 3J1¢,2¢ = 4.7 Hz, 1 H, H-2′),
4.62 (dd, 3J2¢,3¢ = 6.6 Hz, 3J3¢,4¢ = 3.6 Hz, 1 H, H-3′), 5.05–5.19 (m, 2
H, H-1), 5.84 (m, 1 H, H-2).
MS (EI): m/z (%) = 471 (3) [M + H]+.
Anal. Calcd for C27H38O5Si (470.67): C, 68.90; H, 8.14. Found: C,
68.64; H, 8.15.
13C NMR (75.5 MHz, CDCl3): d = –5.4, –5.3 [Si(CH3)2], 18.4
[C(CH3)3], 25.6, 27.5 [C(CH3)2], 25.9 [C(CH3)3], 38.1 (C-3), 63.6
(C-5¢), 81.8 (C-3¢), 83.9, 84.3, 84.4 (C-1¢,2¢,4¢), 117.4 (C-1), 134.0
(C-2), 113.8 [C(CH3)2].
Swern Oxidation of 6 and 7
DMSO (2.1 mL, 30.0 mmol) was added dropwise to a stirred soln
of oxalyl chloride (1.7 mL, 20.0 mmol) in anhyd CH2Cl2 (4.0 mL)
Synthesis 2011, No. 19, 3099–3108 © Thieme Stuttgart · New York

PAPER
A Versatile Approach to Ribofuranose Derivatives
3103
at –72 °C under an Ar atmosphere. After stirring the mixture for
10 min, a soln of 6 (4.85 g, 14.0 mmol) or 7 (6.59 g, 14.0 mmol) in
anhyd CH2Cl2 (9.0 mL) was added dropwise at –72 °C. Stirring was
continued for a further 15 min before Et3N (8.9 mL, 64 mmol) was
added dropwise. To facilitate stirring, an additional amount of
CH2Cl2 (10 mL) was added and the mixture was warmed to r.t. After
stirring for 1 h at r.t., H2O (30 mL) was added, the organic phase
was separated, and the aqueous phase was extracted with CH2Cl2
(3 × 150 mL). The combined organic phases were then washed with
NaHCO3 (90 mL), dried, and concentrated. The residue was puri-
fied by flash chromatography to afford compound 8 (86%) as a col-
orless syrup or compound 9 (83%) as a colorless solid.
3-(5-O-tert-Butyldimethylsilyl-2,3-O-isopropylidene-1-deoxy-b-
D-ribofuranos-1-yl)prop-1-yl Methanesulfonate (10)
Purified by flash chromatography (solvent A4).
23
Yield: 3.19 g (94%); colorless syrup; [a]D –15.8 (c 1.1, CHCl3);
Rf = 0.17 (solvent A4).
1H NMR (300.13 MHz, CDCl3): d = 0.05, 0.06 [2 × s, 6 H,
Si(CH3)2], 0.89 [s, 9 H, C(CH3)3], 1.33, 1.51 [2 × s, 6 H, C(CH3)2],
1.60–1.80 (m, 2 H, H-3), 1.82–1.96 (m, 2 H, H-2), 2.99 (s, 3 H,
SO2CH3), 3.70 (m, 2 H, H-5¢), 3.84 (app dt, 3J1¢,3a = 7.7 Hz, 3J1¢,2¢
≈
3J1¢,3b = 5.2 Hz, 1 H, H-1¢), 4.00 (app q, 3J3¢,4¢ ≈ 3J4¢,5¢, = 3.6 Hz, 1 H,
H-4¢), 4.19–4.31 (m, 3 H, H-1,2¢), 4.61 (dd, 3J2¢,3¢ = 6.7 Hz,
3J3¢,4¢ = 3.6 Hz, 1 H, H-3¢).
13C NMR (75.5 MHz, CDCl3): d = –5.4, –5.3 [Si(CH3)2], 18.3
[C(CH3)3], 25.5, 27.4 [C(CH3)2], 25.6 (C-2), 25.9 [C(CH3)3], 29.5
(C-3), 37.3 (SO2CH3), 63.5 (C-5¢), 69.6 (C-1), 81.8 (C-3¢), 83.8,
84.4, 84.8 (C-1¢,2¢,4¢), 114.0 [C(CH3)2].
3-(5-O-tert-Butyldimethylsilyl-2,3-O-isopropylidene-1-deoxy-b-
D-ribofuranosyl-1-yl)propanal (8)
Purified by flash chromatography (solvent A5).
22
Yield: 4.15 g (86%); colorless syrup; [a]D –14.4 (c 1.0, CHCl3);
Rf = 0.31 (solvent A5).
Anal. Calcd for C18H36O7SSi (424.62): C, 50.91; H, 8.55; S, 7.55.
Found: C, 51.17; H, 8.45; S, 7.50.
1H NMR (300.13 MHz, CDCl3): d = 0.05, 0.05 [2 × s, 6 H,
Si(CH3)2], 0.89 [s, 9 H, C(CH3)3], 1.33, 1.51 [2 × s, 6 H, C(CH3)2],
1.80–2.03 (m, 2 H, H-3), 2.47–2.66 (m, 2 H, H-2), 3.69 (m, 2 H, H-
3-(5-O-tert-Butyldiphenylsilyl-2,3-O-isopropylidene-1-deoxy-b-
D-ribofuranos-1-yl)prop-1-yl Methanesulfonate (11)
Purified by flash chromatography (solvent A1).
5¢), 3.86 (app dt, 3J1¢,3a = 8.0 Hz, 3J1¢,2¢ ≈ 3J1¢,3b = 5.0 Hz, 1 H, H-1¢),
3
3.99 (app q, J3¢,4¢
≈
3J4¢,5¢ = 3.5 Hz, 1 H, H-4¢), 4.27 (dd,
3J2¢,3¢ = 6.6 Hz, J1¢,2¢ = 5.0 Hz, 1 H, H-2¢), 4.62 (dd, 3J2¢,3¢ = 6.6 Hz,
3
Yield: 4.04 g (92%); colorless syrup. Compound 11 was used in the
next step without further analytical characterization.
3J3¢,4¢ = 3.5 Hz, 1 H, H-3¢), 9.77 (t, 3J1,2 = 1.4 Hz, 1 H, H-1).
13C NMR (62.9 MHz, CDCl3): d = –5.5, –5.3 [Si(CH3)2], 18.3
[C(CH3)3], 25.5, 27.5 [C(CH3)2], 25.9 [C(CH3)3], 26.1 (C-3), 40.2
(C-2), 63.6 (C-5¢), 81.9 (C-3¢), 83.6, 84.5, 84.8 (C-1¢,2¢,4¢), 114.0
[C(CH3)2], 201.6 (C-1).
3-(5-O-tert-Butyldimethylsilyl-2,3-O-isopropylidene-1-deoxy-b-
D-ribofuranos-1-yl)prop-1-yl 4-Methylbenzenesulfonate (12)
A soln of 4-methylbenzenesulfonyl chloride (763 mg, 4.0 mmol) in
anhyd pyridine (3 mL) was added dropwise to a stirred soln of 6
(692 mg, 2.0 mmol) in anhyd pyridine (11 mL) at 5 °C. The ice bath
was removed and the mixture was stirred for 12 h at r.t. After adding
toluene–heptane (5:1, 60 mL), the reaction mixture was concentrat-
ed, the residue was dissolved in CH2Cl2 (100 mL), and the organic
phase was successively washed with aq 15% NaHSO4 (2 × 40 mL),
ice-water (40 mL), NaHCO3 (2 × 40 mL), dried, and concentrated.
Purification by flash chromatography (solvent A6) afforded com-
pound 12.
Anal. Calcd for C17H32O5Si (344.52): C, 59.27; H, 9.36. Found: C,
57.71; H, 8.93.
3-(5-O-tert-Butyldiphenylsilyl-2,3-O-isopropylidene-1-deoxy-b-
D-ribofuranosyl-1-yl)propanal (9)
Purified by flash chromatography (solvent A5).
21
Yield: 5.45 g (83%); colorless solid; mp 54–56 °C; [a]D –3.1 (c
1.0, CHCl3); Rf = 0.20 (solvent A2).
1H NMR (250.13 MHz, CDCl3): d = 1.06 [s, 9 H, C(CH3)3], 1.34,
1.53 [2 × s, 6 H, C(CH3)2], 1.77–2.07 (m, 2 H, H-3), 2.54–2.61 (m,
Yield: 651 mg (65%); colorless syrup; [a]D23 –15.5 (c 1.0, CHCl3);
Rf = 0.17 (solvent A6).
2 H, H-2), 3.77 (m, 2 H, H-5¢), 3.86 (app dt, 3J1¢,3a = 8.2 Hz, 3J1¢,2¢
≈
1H NMR (300.13 MHz, CDCl3): d = 0.03, 0.04 [2 × s, 6 H,
Si(CH3)2], 0.87 [s, 9 H, C(CH3)3], 1.31, 1.49 [2 × s, 6 H, C(CH3)2],
1.54–1.67 (m, 2 H, H-3), 1.70–1.84 (m, 2 H, H-2), 2.44 (s, 3 H,
3J1¢,3b = 5.2 Hz, 1 H, H-1¢), 4.03 (app q, 3J3¢,4¢ ≈ 3J4¢,5¢ = 3.7 Hz, 1 H,
H-4¢), 4.30 (dd, 3J2¢,3¢ = 6.7 Hz, 3J1¢,2¢ = 5.2 Hz, 1 H, H-2¢), 4.71 (dd,
3J2¢,3¢ = 6.7 Hz, 3J3¢,4¢ = 3.7 Hz, 1 H, H-3¢), 7.34–7.44 (m, 6 H),
7.65–7.71 (m, 4 H, Ph), 9.76 (t, 3J1,2 = 1.4 Hz, 1 H, H-1).
13C NMR (62.9 MHz, CDCl3): d = 19.3 [C(CH3)3], 25.6, 27.5
[C(CH3)2], 26.1 (C-3), 26.8 [C(CH3)3], 40.2 (C-2), 64.1 (C-5¢), 81.9
(C-3¢), 83.4, 84.2, 84.7 (C-1¢,2¢,4¢), 114.3 [C(CH3)2], 127.2, 127.7,
135.6, 135.6 (o-, m-Ph), 129.7, 129.8 (p-Ph), 133.2, 133.3 (i-Ph),
201.6 (C-1).
PhCH3), 3.67 (m, 2 H, H-5¢), 3.75 (app dt, 3J1¢,3a = 7.4 Hz, 3J1¢,2¢
≈
3J1¢,3b = 5.2 Hz, 1 H, H-1¢), 3.94 (app q, 3J3¢,4¢ ≈ 3J4¢,5¢, = 3.6 Hz, 1 H,
3
H-4¢), 4.05 (m, 2 H, H-1), 4.19 (dd, J2¢,3¢ = 6.6 Hz, 3J1¢,2¢ = 5.2 Hz,
1 H, H-2¢), 4.58 (dd, 3J2¢,3¢ = 6.6 Hz, 3J3¢,4¢ = 3.6 Hz, 1 H, H-3¢), 7.33
(m, 2 H), 7.78 (m, 2 H, Ph).
13C NMR (75.5 MHz, CDCl3): d = –5.4, –5.3 [Si(CH3)2], 18.3
[C(CH3)3], 21.6 (PhCH3), 25.3 (C-2), 25.5, 27.4 [C(CH3)2], 25.9
[C(CH3)3], 29.5 (C-3), 63.6 (C-5¢), 70.2 (C-1), 81.8 (C-3¢), 83.7,
84.4, 84.8 (C-1¢,2¢,4¢), 114.0 [C(CH3)2], 127.9, 129.8 (o-, m-Ph),
133.2 (i-Ph), 144.6 (p-Ph).
MS (EI): m/z (%) = 469 (5) [M + H]+.
Anal. Calcd for C27H36O5Si (468.66): C, 69.20; H, 7.74. Found: C,
69.45; H, 7.74.
Anal. Calcd for C24H40O7SSi (500.72): C, 57.57; H, 8.05; S, 6.40.
Found: C, 57.81; H, 7.86; S, 6.17.
Mesylation of Compounds 6 and 7
Methanesulfonyl chloride (5.9 mL, 42.0 mmol) was added dropwise
to a stirred soln of 6 (2.77 g, 8.0 mmol) or 7 (3.77 g, 8.0 mmol) in
anhyd CH2Cl2 (130 mL) and Et3N (1.4 mL, 18.0 mmol) at 5 °C. Af-
ter stirring for 20 min at r.t. (reaction monitored by TLC), the reac-
tion mixture was diluted with CH2Cl2 (270 mL), and the organic
phase was washed successively with NaHCO3 (160 mL) and brine
(160 mL), dried, and concentrated. Purification by flash chromatog-
raphy afforded compound 10 (94%) and 11 (92%), both as colorless
syrups.
Azides 13 and 14
Mesylate 10 (2.12 g, 5.0 mmol) or 11 (2.74 g, 5.0 mmol), NaN3 (3.9
g, 60 mmol), and crown ether (18-crown-6; 1.6 g, 6.0 mmol) in an-
hyd DMF (25 mL) was stirred for 24 h at r.t. The reaction mixture
was diluted with EtOAc (250 mL), and the organic phase was
washed with H2O (2 × 150 mL), dried, and concentrated. Purifica-
tion by flash chromatography afforded azide 13 (85%) or azide 14
(89%) both as colorless syrups.
Synthesis 2011, No. 19, 3099–3108 © Thieme Stuttgart · New York

3104
H. Wächtler et al.
PAPER
3-(5-O-tert-Butyldimethylsilyl-2,3-O-isopropylidene-1-deoxy-b-
D-ribofuranos-1-yl)propyl-1-azide (13)
Purified by flash chromatography (solvent A12).
3-(5-O-tert-Butyldiphenylsilyl-2,3-O-isopropylidene-1-deoxy-b-
D-ribofuranos-1-yl)propan-1-amine (16)
A soln of azide 14 (991 mg, 2.0 mmol) and Ph3P (551 mg, 2.1
mmol) in THF (20 mL) was stirred for 90 min at r.t. (reaction mon-
itored by TLC). After adding H2O (8 mL, 0.44 mmol), the reaction
mixture was stirred for 24 h at r.t. and then concentrated. The resi-
due was purified by flash chromatography (solvent B2) to provide
compound 16.
24
Yield: 1.58 g (85%); colorless syrup; [a]D –23.3 (c 1.0, CHCl3);
Rf = 0.31 (solvent A10).
1H NMR (250.13 MHz, CDCl3): d = 0.06, 0.06 [2 × s, 6 H,
Si(CH3)2], 0.89 [s, 9 H, C(CH3)3], 1.34, 1.52 [2 × s, 6 H, C(CH3)2],
1.57–1.82 (m, 4 H, H-2,3), 3.31 (m, 2 H, H-1), 3.71 (m, 2 H, H-5¢),
3.84 (m, 1 H, H-1¢), 3.99 (app q, 3J3¢,4¢ ≈ 3J4¢,5¢ = 3.6 Hz, 1 H, H-4¢),
4.26 (dd, 3J2¢,3¢ = 6.7 Hz, 3J1¢,2¢ = 5.0 Hz, 1 H, H-2¢), 4.62 (dd,
3J2¢,3¢ = 6.7 Hz, 3J3¢,4¢ = 3.6 Hz, 1 H, H-3¢).
13C NMR (75.5 MHz, CDCl3): d = –5.4, –5.3 [Si(CH3)2], 18.3
[C(CH3)3], 25.3, 30.8 (C-2,3), 25.5, 27.5 [C(CH3)2], 25.9 [C(CH3)3],
51.3 (C-1), 63.6 (C-5¢), 81.9 (C-3¢), 84.0, 84.4, 84.9 (C-1¢,2¢,4¢),
114.0 [C(CH3)2].
Yield: 600 mg (64%); colorless syrup; [a]D24 –3.0 (c 1.0, MeOH);
Rf = 0.16 (solvent B1).
1H NMR (300.13 MHz, CDCl3): d = 1.05 [s, 9 H, C(CH3)3], 1.34,
1.53 [2 × s, 6 H, C(CH3)2], 1.56–1.67 (m, 4 H, H-2,3), 1.90 (br s,
2 H, NH2), 2.73 (m, 2 H, H-1), 3.77 (m, 2 H, H-5¢), 3.86 (m, 1 H, H-
3
1¢), 4.02 ( app q, J3¢,4¢
≈
3J4¢,5¢ = 3.8 Hz, 1 H, H-4¢), 4.30 (dd,
3J2¢,3¢ = 6.7 Hz, J1¢,2¢ = 5.1 Hz, 1 H, H-2¢), 4.70 (dd, 3J2¢,3¢ = 6.7 Hz,
3J3¢,4¢ = 3.8 Hz, 1 H, H-3¢), 7.34–7.45 (m, 6 H), 7.66–7.72 (m, 4 H,
Ph).
3
Anal. Calcd for C17H33N3O4Si (371.55): C, 54.95; H, 8.95; N, 11.31.
Found: C, 55.20; H, 9.00; N, 11.58.
13C NMR (75.5 MHz, CDCl3): d = 19.3 [C(CH3)3], 25.6, 27.5
[C(CH3)2], 26.8 [C(CH3)3], 29.5 (C-2), 31.1 (C-3), 41.9 (C-1), 64.2
(C-5¢), 81.9 (C-3¢), 84.1 (C-4¢), 84.3 (C-1¢), 85.0 (C-2¢), 114.1
[C(CH3)2], 127.6, 127.7, 135.6, 135.7 (o-, m-Ph), 129.7, 129.7 (p-
Ph), 133.3, 133.4 (i-Ph).
3-(5-O-tert-Butyldiphenylsilyl-2,3-O-isopropylidene-1-deoxy-b-
D-ribofuranos-1-yl)propyl-1-azide (14)
Purified by flash chromatography (solvent A10).
24
Yield: 2.21 g (89%); colorless syrup; [a]D +0.6 (c 0.7, CH2Cl2);
MS (CI): m/z (%) = 470 (100) [M + H]+.
Rf = 0.44 (solvent A6).
Anal. Calcd for C27H39NO4Si (469.69): C, 69.04; H, 8.37; N, 2.98.
Found: C, 68.76; H, 8.30; N, 2.88.
1H NMR (250.13 MHz, CDCl3): d = 1.06 [s, 9 H, C(CH3)3], 1.35,
1.54 [2 × s, 6 H, C(CH3)2], 1.64–1.80 (m, 4 H, H-2,3), 3.30 (m, 2 H,
H-1), 3.78 (m, 2 H, H-5¢), 3.85 (m, 1 H, H-1¢), 4.03 (app q, 3J3¢,4¢
≈
1-[3-(5-O-tert-Butyldiphenylsilyl-2,3-O-isopropylidene-1-
deoxy-b-D-ribofuranos-1-yl)propyl]-1H-imidazole (17)
Methanesulfonate 10 (3.40 g, 8.0 mmol) was added to a soln of so-
dium imidazolide (1.01 g, 11.2 mmol) in anhyd DMF (55 mL). Af-
ter stirring at 60 °C for 3 h (reaction monitored by TLC), the
reaction mixture was diluted with CH2Cl2 (270 mL) and stored in a
refrigerator overnight. The reaction mixture was filtered and the fil-
trate was washed with brine (200 mL), dried, and concentrated. The
residue was purified by flash chromatography (solvent B3) to pro-
vide compound 17. Using tosylate 12 under the same conditions
gave compound 17 in 75% yield.
3J4¢,5¢ = 3.7 Hz, 1 H, H-4¢), 4.29 (dd, 3J2¢,3¢ = 6.7 Hz, 3J1¢,2¢ = 5.2 Hz,
1 H, H-2¢), 4.72 (dd, 3J2¢,3¢ = 6.7 Hz, 3J3¢,4¢ = 3.7 Hz, 1 H, H-3¢),
7.35–7.44 (m, 6 H), 7.66–7.72 (m, 4 H, Ph).
13C NMR (75.5 MHz, CDCl3): d = 19.3 [C(CH3)3], 25.4, 30.8 (C-
2,3), 25.7, 27.5 [C(CH3)2], 26.8 [C(CH3)3], 51.3 (C-1), 64.1 (C-5¢),
81.8 (C-3¢), 83.9, 84.2, 84.9 (C-1¢,2¢,4¢), 114.2 [C(CH3)2], 127.6,
127.7, 135.6, 135.6 (o-, m-Ph), 129.7, 129.8 (p-Ph), 133.2, 133.3 (i-
Ph).
MS (CI): m/z (%) = 496 (40) [M + H]+.
Anal. Calcd for C27H37N3O4Si (495.69): C, 65.42; H, 7.52; N, 8.48.
Found: C, 65.21; H, 7.76; N, 8.54.
24
Yield: 2.95 g (93%); pale-yellow syrup; [a]D –16.7 (c 1.0,
MeOH); Rf = 0.33 (solvent B3).
1H NMR (300.13 MHz, CDCl3): d = 0.03, 0.04 [2 × s, 6 H,
Si(CH3)2], 0.87 [s, 9 H, C(CH3)3], 1.30, 1.50 [2 × s, 6 H, C(CH3)2],
1.56, 1.89 (2 × m, 4 H, H-2¢¢,3¢¢), 3.68 (m, 2 H, H-5¢), 3.78 (m, 1 H,
H-1¢), 3.90–4.00 (m, 3 H, H-4¢,1¢¢), 4.19 (dd, 3J2¢,3¢ = 6.7 Hz,
3J1¢,2¢ = 5.2 Hz, 1 H, H-2¢), 4.57 (dd, 3J2¢,3¢ = 6.7 Hz, 3J3¢,4¢ = 3.6 Hz,
1 H, H-3¢), 6.89 (br s, 1 H), 7.03 (br s, 1 H), 7.44 (br s, 1 H) (H-
2,4,5).
13C NMR (62.9 MHz, CDCl3): d = –5.5, –5.3 [Si(CH3)2], 18.3
[C(CH3)3], 25.4, 27.4 [C(CH3)2], 25.8 [C(CH3)3], 27.5, 30.4 (C-
2¢¢,3¢¢), 46.7 (C-1¢¢), 63.5 (C-5¢), 81.7 (C-3¢), 83.9, 84.3, 84.8 (C-
1¢,2¢,4¢), 114.1 [C(CH3)2], 118.7 (br), 129.4 (br), 137.0 (br, C-2,4,5).
3-(5-O-tert-Butyldimethylsilyl-2,3-O-isopropylidene-1-deoxy-b-
D-ribofuranos-1-yl)propan-1-amine (15)
10% Pd/C (ca. 170 mg) was added to a soln of azide 13 (743 mg, 2.0
mmol) in MeOH (55 mL). The suspension was stirred for 8 h at r.t.
under an atmosphere of H2 (reaction monitored by TLC). The mix-
ture was then filtered through Celite, eluted with MeOH, and the
combined filtrates were concentrated. The crude product was puri-
fied by flash chromatography (solvent B2) to give compound 15.
Yield: 449 mg (65%); colorless syrup; [a]D25 –12.5 (c 1.0, MeOH);
Rf = 0.1 (solvent B2).
1H NMR (300.13 MHz, CDCl3): d = 0.05, 0.05 [2 × s, 6 H,
Si(CH3)2], 0.88 [s, 9 H, C(CH3)3], 1.32, 1.51 [2 × s, 6 H, C(CH3)2],
Anal. Calcd for C20H36N2O4Si (396.60): C, 60.57; H, 9.15; N, 7.06.
Found: C, 60.36; H, 9.16; N, 7.05.
1.54–1.65 (m, 4 H, H-2,3), 1.80 (br s, 2 H, NH2), 2.72 (m, 2 H, H-
3
1), 3.70 (m, 2 H, H-5¢), 3.84 (m, 1 H, H-1¢), 3.97 (app q, J3¢,4¢
≈
3J4¢,5¢ = 3.7 Hz, 1 H, H-4¢), 4.25 (dd, 3J2¢,3¢ = 6.7 Hz, 3J1¢,2¢ = 4.9 Hz,
1 H, H-2¢), 4.60 (dd, 3J2¢,3¢ = 6.7 Hz, 3J3¢,4¢ = 3.7 Hz, 1 H, H-3¢).
3-(b-D-Ribofuranosyl)prop-1-ene (18)
Starting from 2 (4.10 g, 16.0 mmol), compound 18 (2.59 g, 93%)
was obtained according to the procedure of Otero Martinez et al. as
a colorless solid.5
13C NMR (75.5 MHz, CDCl3): d = –5.4, –5.3 [Si(CH3)2], 18.3
[C(CH3)3], 25.5, 27.5 [C(CH3)2], 25.9 [C(CH3)3], 29.7, 31.1 (C-2,3),
41.9 (C-1), 63.6 (C-5¢), 81.9 (C-3¢), 84.3, 84.4 (C-1¢,4¢), 85.0 (C-2¢),
113.9 [C(CH3)2].
3-[3,5-O-(Tetraisopropyldisiloxane-1,3-diyl)-b-D-ribofurano-
syl]prop-1-ene (19)
1,3-Dichloro-1,1,3,3-tetraisopropyldisiloxane (5.3 mL, 17.0 mmol)
was added to a soln of 2 (2.79 g, 16.0 mmol) and imidazole (4.63 g,
68.0 mmol) in anhyd DMF (40 mL). After stirring at 5 °C for 1 h
(reaction monitored by TLC), the reaction mixture was poured into
Anal. Calcd for C17H35NO4Si (345.55): C, 59.09; H, 10.21; N, 4.05.
Found: C, 59.30; H, 9.92; N, 3.87.
Synthesis 2011, No. 19, 3099–3108 © Thieme Stuttgart · New York

PAPER
A Versatile Approach to Ribofuranose Derivatives
3105
ice-water (500 mL). The aqueous phase was extracted with CH2Cl2
(4 × 150 mL), and the combined organic phases were washed with
NaHCO3 (150 mL), dried, and concentrated. Purification by flash
chromatography (solvent A11) afforded compound 19.
2 H, H-1¢,5¢b), 4.36 (app dt, 3J2¢a,3¢ = 7.9 Hz, 3J3¢,4¢ = 4.5 Hz,
3J2¢b,3¢ = 4.2 Hz, 1 H, H-3¢), 9.77 (t, 3J1,2 = 1.5 Hz, 1 H, H-1).
13C NMR (62.9 MHz, CDCl3): d = 12.5, 12.9, 13.3, 13.5
[CH(CH3)2], 16.9, 17.0, 17.1, 17.3, 17.4, 17.4 (2), 17.6 [CH(CH3)2],
27.8, 30.3 (C-2,3), 40.3 (C-2¢), 63.7 (C-5¢), 73.5 (C-3¢), 76.5 (C-1¢),
86.0 (C-4¢), 202.1 (C-1).
Yield: 7.08 g (68%); colorless solid; mp 28 °C; Rf = 0.30 (solvent
A11). NMR data and elemental analysis were in agreement with re-
ported data.5
MS (ESI): m/z (%) = 417 (3) [M + H]+.
Anal. Calcd for C20H40O5Si2 (416.70): C, 57.65; H, 9.68. Found: C,
57.70; H, 9.57.
3-[2-Deoxy-3,5-O-(tetraisopropyldisiloxane-1,3-diyl)-b-D-eryth-
ro-pentofuranosyl]prop-1-ene (20)
Exchange of the hydroxy group of 19 by iodine to furnish 3-[2-
deoxy-2-iodo-3,5-O-(tetraisopropyldisiloxane-1,3-diyl)-b-D-ara-
binofuranosyl]prop-1-ene (95%) was carried out as described by
Otero Martinez et al., and the analytical data were in agreement with
the published data.5
Alkynylation of Aldehydes 8, 9, and 22
A soln of ethynylmagnesium bromide (0.5 M, 12 mL, 6.0 mmol) or
lithium phenylacetylide (1.0 M, 10 mL, 10 mmol) in anhyd THF
was added dropwise to a stirred soln of 8 (1.72 g, 5.0 mmol), 9 (2.34
g, 5.0 mmol), or 22 (2.09 g, 5.0 mmol) in anhyd THF (24 mL) at r.t.
After stirring for 4 h (reaction monitored by TLC), H2O (0.3 mL)
and silica gel were successively added, and the suspension was con-
centrated. The residue was loaded onto a silica gel column and pu-
rified by flash chromatography to provide the desired ethynyl
alcohols 23–26, 31, and 32 as diastereomeric mixtures.
A mixture of the 2-iodo-compound (6.32 g, 12.0 mmol), tri-n-butyl-
tin hydride (6.98 g, 24.0 mmol), and azobisisobutyronitrile (AIBN;
493 mg, 3.0 mmol) in toluene (150 mL) was stirred at reflux for 5 h,
after which time, additional tri-n-butyltin hydride (3.48 g, 12.0
mmol) and AIBN (493 mg, 3.0 mmol) were added. Stirring under
reflux was continued for a further 5 h, and the reaction mixture was
then filtered and concentrated. The residue was dissolved in Et2O
(200 mL) and the organic phase was washed with 10% KF (50 mL),
dried, and concentrated. Purification by flash chromatography (sol-
vent A13) afforded compound 20 (4.42 g, 92%) as a colorless syrup.
All analytical data were identical to those reported previously.5
(3R,S)-1-(5-O-tert-Butyldimethylsilyl-2,3-O-isopropylidene-1-
deoxy-b-D-ribofuranos-1-yl)pent-4-yn-3-ol (23)
Purified by flash chromatography (solvent A4).
23
Yield: 1.19 g (64%); colorless syrup; [a]D –18.5 (c 1.0, CHCl3);
Rf = 0.3 (solvent A4).
1H NMR (300.13 MHz, CDCl3): d (ratio ca. 1:1) = 0.06, 0.06 [2 × s,
6 H, Si(CH3)2], 0.89 [s, 9 H, C(CH3)3], 1.33, 1.52 [2 × s, 6 H,
C(CH3)2], 1.79–1.91 (m, 4 H, H-1,2), 2.42 (d, 4J3,5 = 2.1 Hz), 2.44
(d, 4J3,5 = 2.1 Hz) (1 H, H-5), 2.59 (br s), 2.82 (br d, 3J3,OH = 5.9 Hz,
1 H, OH), 3.71 (m, 2 H, H-5¢), 3.84–3.92 (m, 1 H, H-1¢), 4.01 (m,
1 H, H-4¢), 4.28 (dd, 3J2¢,3¢ = 6.6 Hz, 3J1¢,2¢ = 5.2 Hz, 1 H, H-2¢),
3-[3,5-O-(Tetraisopropyldisiloxane-1,3-diyl)-1,2-dideoxy-b-D-
ribofuranos-1-yl]propan-1-ol (21)
Prepared as described for the preparation of 6. Compound 20 (4.00
g, 10.0 mmol) gave alcohol 21 after purification by flash chroma-
tography (solvent A3).
Yield: 3.01 g (72%); colorless syrup; [a]D22 –23.0 (c 1.0, CH2Cl2);
Rf = 0.29 (solvent A3).
3
3
4.37–4.48 (m, 1 H, H-3), 4.62 (dd, J2¢,3¢ = 6.6 Hz, J3¢,4¢ = 3.6 Hz),
4.63 (dd, 3J2¢,3¢ = 6.6 Hz, 3J3¢,4¢ = 3.6 Hz) (1 H, H-3¢).
1H NMR (250.13 MHz, CDCl3): d = 0.84–1.10 [m, 28 H,
CH(CH3)2], 1.52–1.70 (m, 4 H, H-2,3), 1.79 (app dt,
13C NMR (62.9 MHz, CDCl3): d = –5.4 (2), –5.3 (2) [Si(CH3)2],
18.3 (2) [C(CH3)3], 25.5 (2), 27.5 (2) [C(CH3)2], 25.9 (2) [C(CH3)3],
28.9, 29.4 (C-1), 34.2 (C-2), 61.6, 62.0 (C-3), 63.5 (C-5¢), 72.8, 72.9
(C-5), 81.8 (2) (C-3¢), 84.2, 84.4, 84.5, 84.5, 84.7, 84.9 (C-1¢,2¢,4¢),
84.7, 84.7 (C-4), 114.0 [C(CH3)2].
3
3
2J2¢a,2¢b = 12.8 Hz, J1¢,2¢a ≈ J2¢a,3¢ = 8.0 Hz, 1 H, H-2¢a), 2.04 (ddd,
2J2¢a,2¢b = 12.8 Hz, 3J1¢,2¢b = 6.5 Hz, 3J2¢b,3¢ = 4.2 Hz, 1 H, H-2¢b), 2.10
(br, 1 H, OH), 3.57–3.78 (m, 4 H, H-1,4¢,5¢a), 3.96–4.13 (m, 2 H,
H-1¢,5¢b), 4.37 (app dt, 3J2¢a,3¢ = 8.0 Hz, 3J3¢,4¢ = 4.4 Hz,
3J2¢b,3¢ = 4.2 Hz, 1 H, H-3¢).
Anal. Calcd for C19H34O5Si (370.56): C, 61.58; H, 9.25. Found: C,
61.56; H, 9.23.
13C NMR (62.9 MHz, CDCl3): d = 12.5, 13.0, 13.4, 13.5
[CH(CH3)2], 16.9, 17.0, 17.1, 17.3, 17.4, 17.4 (2), 17.5 [CH(CH3)2],
29.4, 32.3 (C-2,3), 40.6 (C-2¢), 62.8 (C-1), 63.9 (C-5¢), 73.7 (C-3¢),
77.8 (C-1¢), 86.2 (C-4¢).
(3R,S)-1-(5-O-tert-Butyldiphenylsilyl-2,3-O-isopropylidene-1-
deoxy-b-D-ribofuranos-1-yl)pent-4-yn-3-ol (24)
Purified by flash chromatography (solvent A5).
MS (ESI): m/z (%) = 419 (100) [M + H]+.
23
Yield: 2.05 g (83%); colorless syrup; [a]D –1.1 (c 1.0, CH2Cl2);
Anal. Calcd for C20H42O5Si2 (418.72): C, 57.37; H, 10.11. Found:
C, 57.17; H, 9.97.
Rf = 0.45 (solvent A2).
1H NMR (250.13 MHz, CDCl3): d (ratio ca. 1:1) = 1.06 [s, 9 H,
C(CH3)3], 1.34, 1.53 [2 × s, 6 H, C(CH3)2], 1.81–1.94 (m, 4 H, H-
3-[3,5-O-(Tetraisopropyldisiloxane-1,3-diyl)-1,2-dideoxy-b-D-
ribofuranos-1-yl]propanal (22)
4
1,2), 2.00 (br, 1 H, OH), 2.38 (d, J3,5 = 2.1 Hz), 2.42 (d,
4J3,5 = 2.1 Hz) (1 H, H-5), 3.78 (m, 2 H, H-5¢), 3.83–3.94 (m, 1 H,
H-1¢), 4.02–4.08 (m, 1 H, H-4¢), 4.32 (m, 1 H, H-2¢), 4.37–4.48 (m,
1 H, H-3), 4.70 (m, 1 H, H-3¢), 7.36–7.45 (m, 6 H), 7.65–7.72 (m,
4 H, Ph).
A soln of 12-I-5-triacetoxyperiodinane (5.30 g, 12.5 mmol) in an-
hyd CH2Cl2 (25 mL) was added to a stirred soln of alcohol 21 (4.61
g 11.0 mmol) in anhyd CH2Cl2 (25 mL) at r.t. under an Ar atmo-
sphere. After stirring for 5 h (reaction monitored by TLC), solid
NaHCO3 (2.1 g, 25.0 mmol) and silica gel were successively added
and the suspension was concentrated. The residue was loaded onto
a silica gel column, and purified by chromatography (solvent A7) to
provide the desired aldehyde 22.
Yield: 3.63 g (79%); colorless syrup; [a]D22 –24.1 (c 1.0, CH2Cl2);
Rf = 0.42 (solvent A6).
1H NMR (250.13 MHz, CDCl3): d = 0.88–1.10 [m, 28 H,
CH(CH3)2], 1.72–1.93 (m, 3 H, H-2¢a,3), 1.99–2.10 (m, 1 H, H-2¢b),
2.42–2.59 (m, 2 H, H-2), 3.72 (m, 2 H, H-4¢,5¢a), 3.95–4.13 (m,
13C NMR (62.9 MHz, CDCl3): d = 19.2 (2) [C(CH3)3], 25.5 (2), 27.5
(2) [C(CH3)2], 26.8 (2) [C(CH3)3], 29.0, 29.4 (C-1), 34.2, 34.2 (C-
2), 61.7, 62.0 (C-3), 64.0 (2) (C-5¢), 72.9, 73.0 (C-5), 81.8 (2) (C-
3¢), 84.1, 84.2, 84.3, 84.4, 84.8, 84.8 (C-1¢,2¢,4¢), 84.6, 84.6 (C-4),
114.2, 114.2 [C(CH3)2], 127.8 (4) (m-Ph), 129.7 (4) (p-Ph), 133.1,
133.2, 133.3, 133.3 (i-Ph), 135.6 (4) (o-Ph).
MS (CI): m/z (%) = 495 (3) [M + H]+.
Anal. Calcd for C29H38O5Si (494.69): C, 70.41; H, 7.74. Found: C,
70.21; H, 7.86.
Synthesis 2011, No. 19, 3099–3108 © Thieme Stuttgart · New York

3106
H. Wächtler et al.
PAPER
(3R,S)-1-(5-O-tert-Butyldimethylsilyl-2,3-O-isopropylidene-1-
deoxy-b-D-ribofuranos-1-yl)-5-phenylpent-4-yn-3-ol (25)
Purified by flash chromatography (solvent A5).
73.6, 73.7 (C-3¢), 77.4, 77.7 (C-1¢), 84.7, 84.8 (C-4), 86.2, 86.2 (C-
4¢).
MS (EI): m/z (%) = 456 (3) [M]+.
23
Yield: 1.50 g (67%); pale-yellow syrup; [a]D –16.4 (c 1.0,
Anal. Calcd for C23H44O5Si2 (456.76): C, 60.48; H, 9.71. Found: C,
60.72; H, 9.80.
CH2Cl2); Rf = 0.26 (solvent A5).
1H NMR (300.13 MHz, CDCl3): d (ratio ca. 1:1) = 0.05, 0.06, 0.06,
0.06 [4 × s, 6 H, Si(CH3)2], 0.88, 0.89 [2 × s, 9 H, C(CH3)3], 1.34,
1.53 [2 × s, 6 H, C(CH3)2], 1.76–1.99 (m, 4 H, H-1,2), 2.57 (d,
3J3,OH = 5.3 Hz), 2.72 (d, 3J3,OH = 6.3 Hz) (1 H, OH), 3.72 (m, 2 H,
H-5¢), 3.88–3.96 (m, 1 H, H-1¢), 4.02 (m, 1 H, H-4¢), 4.31 (dd,
(3R,S)-1-[3,5-O-(Tetraisopropyldisiloxane-1,3-diyl)-1,2-
dideoxy-b-D-ribofuranos-1-yl]-5-phenylpent-4-yn-3-ol (32)
Reaction time ca. 3 h; purified by flash chromatography (solvent
A6).
3
3J2¢,3¢ = 6.6 Hz, J1¢,2¢ = 5.1 Hz, 1 H, H-2¢), 4.60–4.71 (m, 2 H, H-
22
Yield: 1.76 g (66%); pale-yellow syrup; [a]D –12.3 (c 1.0,
3,3¢), 7.27–7.32 (m, 3 H, m-, p-Ph), 7.40–7.43 (m, 2 H, o-Ph).
CH2Cl2); Rf = 0.30 (solvent A6).
13C NMR (75.5 MHz, CDCl3): d = –5.4, –5.4, –5.3, –5.3 [Si(CH3)2],
18.3, 18.3 [C(CH3)3], 25.5 (2), 27.5 (2) [C(CH3)2], 25.9 (2)
[C(CH3)3], 29.2, 29.6 (C-1), 34.3, 34.4 (C-2), 62.4, 62.7 (C-3), 63.5
(2) (C-5¢), 81.8, 81.8 (C-3¢), 84.2, 84.4, 84.4, 84.5, 84.8, 84.9 (C-
1¢,2¢,4¢), 84.8, 84.8 (C-5), 89.9, 89.9 (C-4), 114.1 (2) [C(CH3)2],
122.7, 122.7 (i-Ph), 128.2 (2) (m-Ph), 128.3, 128.3 (p-Ph), 131.7 (2)
(o-Ph).
1H NMR (250.13 MHz, CDCl3): d (ratio ca. 1:0.8) = 1.00–1.08 [m,
28 H, CH(CH3)2], 1.69–1.97 (m, 5 H, H-1,2,2¢a), 2.01–2.12 (m,
1 H, H-2¢b), 2.53 (d, 3J3,OH = 5.2 Hz), 2.77 (d, 3J3,OH = 6.5 Hz) (1 H,
OH), 3.69–3.80 (m, 2 H, H-4¢,5¢a), 3.98–4.20 (m, 2 H, H-1¢,5¢b),
4.40, 4.65 (2 × m, 2 H, H-3,3¢), 7.27–7.34 (m, 3 H, m-, p-Ph), 7.39–
7.44 (m, 2 H, o-Ph).
13C NMR (75.5 MHz, CDCl3): d = 12.5 (2), 12.9 (2), 13.4 (2), 13.5
(2) [CH(CH3)2], 16.9 (2), 17.0 (2), 17.1 (2), 17.3 (2), 17.4 (2), 17.4
(4), 17.5 (2) [CH(CH3)2], 31.0, 31.3 (C-1), 34.4, 34.5 (C-2), 40.5,
40.7 (C-2¢), 62.5, 62.8 (C-3), 63.9 (2) (C-5¢), 73.7, 73.7 (C-3¢), 77.4,
77.7 (C-1¢), 84.8, 84.9 (C-4), 86.2, 86.2 (C-4¢), 89.9 (2) (C-5),
122.7, 122.7 (i-Ph), 128.2 (2) (m-Ph), 128.3, 128.3 (p-Ph), 131.7,
131.7 (o-Ph).
Anal. Calcd for C25H38O5Si (446.65): C, 67.23; H, 8.58. Found: C,
67.11; H, 8.71.
(3R,S)-1-(5-O-tert-Butyldiphenylsilyl-2,3-O-isopropylidene-1-
deoxy-b-D-ribofuranos-1-yl)-5-phenylpent-4-yn-3-ol (26)
Purified by flash chromatography (solvent A6).
Yield: 1.97 g (69%); pale-yellow syrup; [a]D22 –0.9 (c 1.0, CH2Cl2);
Rf = 0.45 (solvent A2).
Anal. Calcd for C29H48O5Si2 (532.86): C, 65.37; H, 9.08. Found: C,
65.63; H, 8.88.
1H NMR (250.13 MHz, CDCl3): d (ratio ca. 1:1) = 1.04, 1.05 [2 × s,
9 H, C(CH3)3], 1.35, 1.54 [2 × s, 6 H, C(CH3)2], 1.80–2.05 (m, 4 H,
H-1,2), 2.00 (br, 1 H, OH), 3.79 (m, 2 H, H-5¢), 3.87–3.98 (m, 1 H,
Oxidation of Alkynole 23–26, 31, and 32
Method A. Pyridinium Chlorochromate (PCC) Oxidation
PCC (800 mg, 3.7 mmol) was added to a soln of alkynol 24 (495
mg, 1.0 mmol) or 26 (571 mg, 1.0 mmol) in anhyd CH2Cl2 (40 mL).
After stirring for 2 h (reaction monitored by TLC) at r.t., silica gel
was added and the suspension was concentrated. The residue was
loaded onto a silica gel column followed by flash chromatography
to provide the desired ethynyl ketones 28 and 30 in 54 and 50%
yield, respectively.
3
3
H-1¢), 4.05 (app q, J3¢,4¢ ≈ J4¢,5¢ = 3.8 Hz, 1 H, H-4¢), 4.33 (dd,
3J2¢,3¢ = 6.8 Hz, 3J1¢,2¢ = 5.2 Hz), 4.35 (dd, 3J2¢,3¢ = 6.8 Hz,
3J1¢,2¢ = 5.2 Hz) (1 H, H-2¢), 4.60–4.75 (m, 2 H, H-3,3¢), 7.25–7.32
(m, 3 H), 7.35–7.43 (m, 8 H), 7.65–7.73 (m, 4 H, Ph).
13C NMR (62.9 MHz, CDCl3): d = 19.2, 19.2 [C(CH3)3], 25.5 (2),
27.5 (2) [C(CH3)2], 26.8 (2) [C(CH3)3], 29.2, 29.6 (C-1), 34.4, 34.4
(C-2), 62.5, 62.7 (C-3), 64.1 (2) (C-5¢), 81.8, 81.8 (C-3¢), 84.1, 84.2,
84.2, 84.3, 84.8, 84.8 (C-1¢,2¢,4¢), 84.9, 84.9 (C-5), 89.8, 89.9 (C-4),
114.2, 114.3 [C(CH3)2], 122.6, 122.7 (i-PhC≡C), 127.7 (4) (m-Ph),
128.2 (2) (m-PhC≡C), 128.3, 128.3 (p-PhC≡C), 129.7 (4) (p-Ph), 131.7
(2) (o-PhC≡C), 133.2 (2), 133.3 (2) (i-Ph), 135.6 (2), 135.7 (2) (o-
Ph).
Method B. Dess–Martin Oxidation
A soln of alcohol 23 (3.71 g 10.0 mmol), 25 (4.47 g, 10.0 mmol), 31
(4.57 g, 10.0 mmol), or 32 (5.33 g, 10.0 mmol) in anhyd CH2Cl2 (20
mL) was added dropwise to a stirred soln of 12-I-5-triacetoxyperi-
odinane (10.60 g, 25.0 mmol), solid NaHCO3 (1.6 g), and molecular
sieves (4 Å, 15 g) in anhyd CH2Cl2 (400 mL) at 0 °C under an Ar
atmosphere. After stirring for 4 h at r.t. (reaction monitored by
TLC), solids were filtered off, and the filtrate was concentrated. The
residue was purified by flash chromatography to provide the ethy-
nyl ketones 27, 29, 33, and 34 in 82, 90, 77, and 60%, respectively.
MS (CI): m/z (%) = 571 (7) [M + H]+.
Anal. Calcd for C35H42O5Si (570.79): C, 73.65; H, 7.42. Found: C,
73.62; H, 7.43.
(3R,S)-1-[3,5-O-(Tetraisopropyldisiloxane-1,3-diyl)-1,2-
dideoxy-b-D-ribofuranos-1-yl]pent-4-yn-3-ol (31)
Reaction time ca. 3 h; purified by flash chromatography (solvent
A6).
Yield: 1.71 g (75%); colorless syrup; [a]D22 –22.1 (c 1.0, CH2Cl2);
Rf = 0.29 (solvent A6).
1-(5-O-tert-Butyldimethylsilyl-2,3-O-isopropylidene-1-deoxy-b-
D-ribofuranos-1-yl)pent-4-yn-3-one (27)
Method B. Purified by flash chromatography (solvent A8).
24
Yield: 3.02 g (82%); colorless syrup; [a]D –28.4 (c 1.0, CHCl3);
Rf = 0.25 (solvent A8).
1H NMR (250.13 MHz, CDCl3): d = (ratio ca. 1:0.7) = 1.00–1.09
[m, 28 H, CH(CH3)2], 1.61–1.89 (m, 5 H, H-1,2,2¢a), 2.00–2.10 (m,
1 H, H-2¢b), 2.43 (d, 4J3,5 = 2.2 Hz), 2.44 (d, 4J3,5 = 2.2 Hz) (1 H, H-
1H NMR (300.13 MHz, CDCl3): d = 0.05, 0.06 [2 × s, 6 H,
Si(CH3)2], 0.89 [s, 9 H, C(CH3)3], 1.33, 1.51 [2 × s, 6 H, C(CH3)2],
1.83–2.05 (m, 2 H, H-1), 2.72 (m, 2 H, H-2), 3.21 (s, 1 H, H-5), 3.69
(m, 2 H, H-5¢), 3.85 (app dt, 3J1a,1¢ = 8.0 Hz, 3J1b,1¢ ≈ 3J1¢,2¢ = 5.0 Hz,
1 H, H-1¢), 4.00 (app q, 3J3¢,4¢ ≈ 3J4¢,5¢ = 3.5 Hz, 1 H, H-4¢), 4.27 (dd,
3
3
5), 2.57 (d, J3,OH = 5.2 Hz), 2.83 (d, J3,OH = 6.6 Hz) (1 H, OH),
3.67–3.79 (m, 2 H, H-4¢,5¢a), 3.97–4.16 (m, 2 H, H-1¢,5¢b), 4.35–
4.50 (m, 2 H, H-3,3¢).
3
3J2¢,3¢ = 6.6 Hz, J1¢,2¢ = 5.0 Hz, 1 H, H-2¢), 4.62 (dd, 3J2¢,3¢ = 6.6 Hz,
13C NMR (75.5 MHz, CDCl3): d = 12.5 (2), 12.9 (2), 13.4 (2), 13.5
(2) [CH(CH3)2], 16.9 (2), 17.0 (2), 17.1 (2), 17.3 (2), 17.4 (4), 17.4
(2), 17.5 (2) [CH(CH3)2], 30.8, 31.1 (C-1), 34.2, 34.3 (C-2), 40.4,
40.6 (C-2¢), 61.7, 62.1 (C-3), 63.8, 63.8 (C-5¢), 72.7, 72.8 (C-5),
3J3¢,4¢ = 3.5 Hz, 1 H, H-3¢).
13C NMR (62.9 MHz, CDCl3): d = –5.5, –5.3 [Si(CH3)2], 18.3
[C(CH3)3], 25.5, 27.5 [C(CH3)2], 25.9 [C(CH3)3], 27.4 (C-1), 41.6
Synthesis 2011, No. 19, 3099–3108 © Thieme Stuttgart · New York

PAPER
A Versatile Approach to Ribofuranose Derivatives
3107
(C-2), 63.6 (C-5¢), 78.5 (C-5), 81.3 (C-4), 81.9 (C-3¢), 83.3, 84.5,
84.7 (C-1¢,2¢,4¢), 114.0 [C(CH3)2], 186.3 (C-3).
[C(CH3)2], 119.9 (i-PhC≡C), 127.7, 127.7, 128.6, 133.0, 135.6, 135.6
(o-, m-Ph), 129.7, 129.7, 130.7 (p-Ph), 133.2, 133.3 (i-Ph), 186.9
(C-3).
MS (CI): m/z (%) = 569 (7) [M + H]+.
Anal. Calcd for C19H32O5Si (368.54): C, 61.92; H, 8.75. Found: C,
62.21; H, 8.93.
Anal. Calcd for C35H40O5Si (568.77): C, 73.91; H, 7.09. Found: C,
73.63; H, 7.16.
1-(5-O-tert-Butyldiphenylsilyl-2,3-O-isopropylidene-1-deoxy-b-
D-ribofuranos-1-yl)pent-4-yn-3-one (28)
Method A. Purified by flash chromatography (solvent A7).
Yield: 266 mg (54%); colorless syrup; [a]D22 –5.6 (c 1.2, CH2Cl2);
Rf = 0.52 (solvent A2).
1-[3,5-O-(Tetraisopropyldisiloxane-1,3-diyl)-1,2-dideoxy-b-D-
ribofuranos-1-yl]pent-4-yn-3-one (33)
Method B. Reaction time 1 h; purified by flash chromatography
(solvent A7).
1H NMR (250.13 MHz, CDCl3): d = 1.06 [s, 9 H, C(CH3)3], 1.34,
24
1.53 [s, 6 H, C(CH3)2], 1.82–2.12 (m, 2 H, H-1), 2.75 (m, 2 H, H-2),
Yield: 3.5 g (77%); colorless syrup; [a]D –26.5 (c 1.0, CH2Cl2);
3.77 (m, 1 H, H-5¢), 3.85 (app dt, 3J1a,1¢ = 8.3 Hz, J1b,1¢
≈
Rf = 0.47 (solvent A6).
3
3J1¢,2¢ = 5.1 Hz, 1 H, H-1¢), 4.03 (app q, 3J3¢,4¢ ≈ 3J4¢,5¢ = 3.7 Hz, 1 H,
H-4¢), 4.30 (dd, 3J2¢,3¢ = 6.7 Hz, 3J1¢,2¢ = 5.1 Hz, 1 H, H-2¢), 4.71 (dd,
3J2¢,3¢ = 6.7 Hz, 3J3¢,4¢ = 3.7 Hz, 1 H, H-3¢), 7.33–7.45, 7.64–7.71
(2 × m, 10 H, Ph).
1H NMR (250.13 MHz, CDCl3): d = 0.98–1.09 [m, 28 H,
CH(CH3)2], 1.72–2.09 (m, 4 H, H-1,2¢), 2.71 (m, 2 H, H-2), 3.21 (s,
1 H, H-5), 3.65–3.76 (m, 2 H, H-4¢,5¢a), 3.95–4.16 (m, 2 H, H-
1¢,5¢b), 4.36 (app dt, 3J2¢a,3¢ ≈ 3J3¢,4¢ = 7.9 Hz, 3J2¢b,3¢ = 4.5 Hz, 1 H, H-
3¢).
13C NMR (62.9 MHz, CDCl3): d = 12.5, 12.9, 13.3, 13.5
[CH(CH3)2], 16.9, 17.0, 17.1, 17.3, 17.4 (2), 17.4, 17.5 [CH(CH3)2],
29.2 (C-1), 40.2 (C-2¢), 41.8 (C-2), 63.7 (C-5¢), 73.5 (C-3¢), 76.2 (C-
1¢), 78.5 (C-5), 81.3 (C-4), 86.0 (C-4¢), 186.6 (C-3).
13C NMR (75.5 MHz, CDCl3): d = 19.2 [C(CH3)3], 25.5, 27.5
[C(CH3)2], 26.8 [C(CH3)3], 27.5 (C-1), 41.7 (C-2), 64.1 (C-5¢), 78.6
(C-5), 81.3 (C-4), 81.8 (C-3¢), 83.1, 84.2, 84.7 (C-1¢,2¢,4¢), 114.2
[C(CH3)2], 127.7, 127.7, 135.6, 135.6 (o-, m-Ph), 129.7 (p-C6H5),
133.2, 133.3 (i-Ph), 186.3 (C-3).
MS (CI): m/z (%) = 493 (3) [M + H]+.
Anal. Calcd For C23H42O5Si2 (454.75): C, 60.75; H, 9.31. Found: C,
60.38; H, 9.24.
Anal. Calcd for C29H36O5Si (492.68): C, 70.70; H, 7.37. Found: C,
70.68; H, 7.42.
1-[3,5-O-(Tetraisopropyldisiloxane-1,3-diyl)-1,2-dideoxy-b-D-
ribofuranos-1-yl]-5-phenylpent-4-yn-3-one (34)
Method B. Reaction time ca. 2 h; purified by flash chromatography
(solvent A9).
1-(5-O-tert-Butyldimethylsilyl-2,3-O-isopropylidene-1-deoxy-b-
D-ribofuranos-1-yl)-5-phenyl-pent-4-yn-3-one (29)
Method B. Purified by flash chromatography (solvent A10).
Yield: 4.0 g (90%); pale-yellow syrup; [a]D23 –28.0 (c 1.0, CH2Cl2);
Rf = 0.39 (solvent A6).
Yield: 3.1 g (60%); pale-yellow syrup; [a]D22 –27.6 (c 1.0, CH2Cl2);
Rf = 0.50 (solvent A6).
1H NMR (300.13 MHz, CDCl3): d = 0.06, 0.07 [2 × s, 6 H,
Si(CH3)2], 0.89 [s, 9 H, C(CH3)3], 1.34, 1.52 [2 × s, 6 H, C(CH3)2],
1.89–2.12 (m, 2 H, H-1), 2.72–2.91 (m, 2 H, H-2), 3.71 (m, 2 H, H-
1H NMR (250.13 MHz, CDCl3): d = 0.98–1.11 [m, 28 H,
CH(CH3)2], 1.75–2.12 (m, 4 H, H-1,2¢), 2.80 (m, 2 H, H-2), 3.73
(m, 2 H, H-4¢,5¢a), 4.02 (dd, 2J5¢a,5¢b = 15.1 Hz, 3J4¢,5¢b = 7.2 Hz, 1 H,
H-5¢b), 4.10 (m, 1 H, H-1¢), 4.38 (app dt, J2¢a,3¢ ≈ J3¢,4¢ = 7.9 Hz,
3J2¢b,3¢ = 4.5 Hz, 1 H, H-3¢), 7.34–7.49 (m, 3 H), 7.35–7.59 (m, 2 H,
Ph).
13C NMR (62.9 MHz, CDCl3): d = 12.5, 12.9, 13.4, 13.5
[CH(CH3)2], 16.9, 17.0, 17.1, 17.3, 17.4, 17.4 (2), 17.5 [CH(CH3)2],
29.6 (C-1), 40.3 (C-2¢), 41.8 (C-2), 63.8 (C-5¢), 73.6 (C-3¢), 76.5 (C-
1¢), 86.0 (C-4¢), 87.7 (C-4), 90.8 (C-5), 120.0 (i-Ph), 128.6, 133.0
(o-, m-Ph), 130.7 (p-Ph), 187.2 (C-3).
3
3
5¢), 3.91 (app dt, 3J1a,1¢ = 8.0 Hz, 3J1b,1¢ ≈ 3J1¢,2¢ = 5.0 Hz, 1 H, H-1¢),
3
4.01 (app q, J3¢,4¢
≈
3J4¢,5¢ = 3.5 Hz, 1 H, H-4¢), 4.31 (dd,
3J2¢,3¢ = 6.6 Hz, J1¢,2¢ = 5.0 Hz, 1 H, H-2¢), 4.64 (dd, 3J2¢,3¢ = 6.6 Hz,
3J3¢,4¢ = 3.5 Hz, 1 H, H-3¢), 7.34–7.48 (m, 3 H, m-, p-Ph), 7.55–7.58
(m, 2 H, o-Ph).
3
13C NMR (75.5 MHz, CDCl3): d = –5.4, –5.3 [Si(CH3)2], 18.3
[C(CH3)3], 25.5, 27.5 [C(CH3)2], 25.9 [C(CH3)3], 27.8 (C-1), 41.6
(C-2), 63.6 (C-5¢), 81.9 (C-3¢), 83.4, 84.5, 84.8 (C-1¢,2¢,4¢), 87.7 (C-
4), 90.7 (C-5), 114.0 [C(CH3)2], 120.0 (i-Ph), 128.6 (m-Ph), 130.6
(p-Ph), 133.0 (o-Ph), 186.9 (C-3).
MS (ESI): m/z (%) = 517 (100) [M + H]+.
Anal. Calcd for C28H44O5Si2 (516.82): C, 65.07; H, 8.58. Found: C,
65.14; H, 8.53.
Anal. Calcd for C25H36O5Si (444.64): C, 67.53; H, 8.16. Found: C,
67.62; H, 8.30.
1-(5-O-tert-Butyldiphenylsilyl-2,3-O-isopropylidene-1-deoxy-b-
D-ribofuranos-1-yl)-5-phenyl-pent-4-yn-3-one (30)
Method A. Purified by flash chromatography (solvent A10).
Acknowledgment
This work was supported by the DFG Research Training Group
1213 ‘New Methods for Sustainability in Catalysis and Technique’.
Yield: 284 mg (54%); colorless crystals; mp 48–50 °C (EtOAc–
hexane); [a]D23 –6.9 (c 1.0, CH2Cl2); Rf = 0.55 (solvent A2).
1H NMR (250.13 MHz, CDCl3): d = 1.06 [s, 9 H, C(CH3)3], 1.34,
References
1.52 [2 × s, 6 H, C(CH3)2], 1.89–2.18 (m, 2 H, H-1), 2.84 (m, 2 H,
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3
H-2), 3.79 (m, H-5¢), 3.91 (app dt, 3J1a,1¢ = 8.2 Hz, J1b,1¢
≈
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3J2¢,3¢ = 6.7 Hz, 3J3¢,4¢ = 3.7 Hz, 1 H, H-3¢), 7.33–7.46 (m, 9 H),
7.52–7.56 (m, 2 H), 7.65–7.72 (m, 4 H, Ph).
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13C NMR (62.9 MHz, CDCl3): d = 19.2 [C(CH3)3], 25.6, 27.5
[C(CH3)2], 26.8 [C(CH3)3], 27.8 (C-1), 41.7 (C-2), 64.1 (C-5¢), 81.8
(C-3¢), 83.2, 84.2, 84.7 (C-1¢,2¢,4¢), 87.7 (C-4), 90.9 (C-5), 114.2
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Synthesis 2011, No. 19, 3099–3108 © Thieme Stuttgart · New York