Friedel-Crafts and modified Vorbrüggen ribosylation. A short synthesis of aryl and heteroaryl-C-nucleosides

Article abstract of DOI:10.1016/j.tetlet.2008.04.105

A direct coupling of aryl donor and tetra-O-acetylribose in the presence of Lewis acid led to β-C-nucleosides in good yields. In contrast, for deactivated electron-poor aromatics, a modified Vorbru?ggen ribosylation reaction was investigated and successfully applied in the case of 2-trimethylsilyl-thiazole.

Full text of DOI:10.1016/j.tetlet.2008.04.105

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 3967–3971
Friedel–Crafts and modified Vorbruggen ribosylation.
¨
A short synthesis of aryl and heteroaryl-C-nucleosides
Marie Spadafora, Mohamed Mehiri, Alain Burger, Rachid Benhida *
ˆ
Laboratoire de Chimie des Mole´cules Bioactives et des Aromes UMR CNRS-UNSA 6001, Institut de Chimie de Nice,
Universite´ de Nice-Sophia Antipolis, Parc Valrose, 06108 Nice Cedex 2, France
Received 18 March 2008; revised 14 April 2008; accepted 16 April 2008
Available online 22 April 2008
Abstract
A direct coupling of aryl donor and tetra-O-acetylribose in the presence of Lewis acid led to b-C-nucleosides in good yields. In
contrast, for deactivated electron-poor aromatics, a modified Vorbruggen ribosylation reaction was investigated and successfully applied
¨
in the case of 2-trimethylsilyl-thiazole.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Friedel–Crafts ribosylation; Modified Vorbruggen reaction; C-Nucleosides
¨
C-Nucleosides are important targets in organic synthesis
due to their high potential value as therapeutic agents and
biochemical probes. They have been found in a lot of nat-
urally occurring and synthetic products with potent antivi-
ral or antitumour activities. Among them, tiazofurin has
recently been approved as an orphan drug for the treat-
ment of chronic myelogenous leukemia in accelerated
phase or blast crisis.1 The benzamide riboside is another
tiazofurin analogue with improved biological properties.1
Recently, several synthetic C-nucleosides have been studied
not only as chemotherapeutic agents, but also as building
blocks in DNA and RNA containing artificial bases and
in a number of other biochemical applications.2 Another
attractive feature of C-nucleosides arises from the presence
of C–C glycosidic bond which confers to these analogues a
greater resistance towards chemical and enzymatic hydro-
lysis than to the classical N-nucleosides. Therefore, efficient
and short synthetic methods which allow access to suitable
precursors are of great importance.
Various routes have been recently developed for the syn-
thesis of C-aryl-nucleosides, among them, the addition of
aryl-metallated species to an appropriate activated sugar.
However, this methodology led in many cases to the unde-
sired a-anomer as the major product.3 The coupling
between lithiated aryls and the ribonolactone followed by
Lewis acid-mediated hemiacetal 10-deoxygenation is also
a well known procedure developed in the synthesis of aryl
and heteroaryl series. Unfortunately, the 10-deoxygenation
led, in many cases, to poor yields and diastereoselectivity.4
Other stereocontrolled procedures have been successfully
developed to overcome these drawbacks.5 The palladium-
catalyzed coupling of halogenated aryls with glycals is
another well-utilized procedure but this approach is only
applicable in 20-deoxy series.6 Otherwise, most of the avail-
able procedures have some limitations in terms of yield and
the number of steps required to assess the suitable C-
nucleosides (Fig. 1).
On the other hand, the Friedel–Crafts reaction is an effi-
cient and attractive procedure which has been particularly
developed in pyranose series with aryl donors and glycosyl
acceptors.7 Surprisingly, only limited examples were
reported in ribofuranose series for the elaboration of C-
nucleosides.8 Moreover, in our knowledge, the analogous
*
Corresponding author. Tel.: +33 0 4 92 07 61 74; fax: +33 0 4 92 07 61
51.
E-mail address: benhida@unice.fr (R. Benhida).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.04.105

3968
M. Spadafora et al. / Tetrahedron Letters 49 (2008) 3967–3971
did not efficiently afford the desired ribosylated product
CONH2
(entries 4–9). The use of TiCl4 and a couple of TMSCl/
AgClO4 only afforded low yields (entries 10–12). The best
results were obtained with SnCl4 at low temperature
(entries 14 and 15). Under these conditions, the protected
C-nucleosides 2a was obtained in 70% yield together with
a small amount of the a-anomer (65%).10 Concerning the
stereo- and regio-chemistry of 2ab, this was unambiguously
attested by NOESY and HMBC experiments. Indeed, the
1H 2D NOESY spectrum shows correlations between
Y
O
O
CONH2
X
HO
HO
HO
OH
HO OH
X = S, Y = N
Tiazofurin
Thiophenfurin
Selenazofurin
Benzamide riboside
X = S, Y = CH
X = Se, Y = N
Fig. 1. Structure of tiazofurin and analogues.
0
0
0
H1 –H4 , and the HMBC experiment shows H5 –C1 (C–
0
OMe) and H5 –C3 cross coupling, in accordance with the
Friedel–Crafts reaction with electron-deficient aryls and
ribosyl acceptors was not reported in the literature.
proposed structure for 2ab (Fig. 2).
To get further information on the scope of this proce-
dure, other aryl and heteroaryl donors were subjected to
the same reaction conditions (Scheme 1). Both methoxya-
ryl derivatives and pyrene underwent clean conversion giv-
ing the desired products in 45–72% yields (2b, 2c and 2g).
The five-membered ring heterocycles (thiophene, bromo-
thiophene and furan) also gave the requisite compounds
in satisfactory yields (2d–f, 55–70%).10 However, in the
case of electron-rich aryls such as methoxynaphthalene
and furan, when the reaction time was prolonged, a con-
comitant double arylation was observed leading to the
bis-arylated products, which decreased the overall yield.
As proposed in Scheme 2 for the methoxynaphthalene, this
double arylation reaction probably resulted from Lewis
acid-promoted ring opening of 2c, favoured by aryl assis-
tance, followed by a second aryl addition on intermediate
I to afford 3c (Scheme 2).11
In continuation of our studies aimed at the development
of efficient synthetic routes of aryl and heteroaryl-C-
nucleosides for their incorporation into oligonucleotides
and to assess their biological activities,9 we report herein
a direct ribosylation based on Friedel–Crafts and modified
Vorbrugguen reactions. These methodologies provide a
¨
direct two-step access to aryl and heteroaryl C-nucleosides.
First, we examined the survey of the Friedel–Crafts
reaction conditions by using the commercially available
tetra-O-acetylribose 1 and p-bromoanisole to avoid ortho/
para selectivity. Different conditions were studied for the
optimization of Lewis acid-mediated ribosylation reaction.
The results are listed in Table 1.
We started our study with BF3–Et2O, a classically used
Lewis acid. In this case, no reaction was observed between
p-bromoanisole and ribose 1 (entries 1–3) even under
forced conditions (large excess of Lewis acid, elevated tem-
peratures and a longer reaction time). Moreover, the use of
other Lewis acids such as SnBr4, AlCl3 and metal triflates
Interestingly, this concomitant double alkylation was
overcome by using a catalytic amount of the promoter
(20% molar of SnCl4) and 1.2 equiv of 1-methoxynaphtha-
lene. Under these conditions, compound 2c as well as the
ortho isomer was obtained in 69% yield (ortho/
para = 40:60).
Table 1
Survey of the ribosylation conditions
MeO
While this process appears to be efficient in terms of cost
and time, for example, one step and rapid access to C-
nucleosides in the case of aryl donors, the use of elec-
tron-deficient aryls resulted in no glycosylation reaction.
For example, no reaction occurred between free thiazole
and ribose 1 in the presence of SnCl4. Therefore, to over-
come the lower reactivity of the thiazole in the C-glycosyl-
O
O
Lewis acid / CH2Cl2
see table
OAc
OAc
AcO
AcO
Br
AcO
AcO
OAc
1
2
a
Entries
Lewis acida
T (°C)
Yieldb (%)
1
2
3
BF3ꢀEt2O
BF3ꢀEt2O
BF3ꢀEt2O
AlCl3
rt
0
0
0
ation process, we investigated a modified Vorbruggen
¨
ꢁ78
0
0
<5
0
0
reaction. The Vorbruggen method is a well-known N-gly-
¨
4
—
cosylation procedure that involved the coupling between
silylated forms of nitrogen- or amide-containing hetero-
cycles and activated sugars, in the presence of Lewis acid
5
6
7
8
SnBr4
0 or rt
—
—
—
—
Sn(OTf)2
Zn(OTf)2
Cu(OTf)2
TMSOTf
TiCl4
TiCl4
TMSCl/AgClO4
SnCl4
0
9
<10
20
15
28
60
70
68
10
11
12
13
14
15
a
0
Br
ꢁ78
0 or rt
rt
0 to rt
ꢁ78 to rt
H
H
2a
O
(HMBC)
SnCl4
SnCl4
(NOESY) AcO
OMe
OAc
AcO
Conditions: 1 (1 mmol), Lewis acid (1.1 equiv), aryl (2.1 equiv), 16 h.
Yield of isolated product.
b
Fig. 2. Significant NOESY and HMBC (J3) correlations (2ab).

M. Spadafora et al. / Tetrahedron Letters 49 (2008) 3967–3971
3969
MeO
O
O
O
S
O
AcO
AcO
AcO
AcO
I
AcO
OAc
OAc
OAc
OAc
AcO
AcO
2b (72%)
(2d 64%)
2f (55%)
SnCl4 / CH2Cl2 / 0 °C
1
Aryl donor
OMe
O
O
O
Br
S
AcO
AcO
AcO
AcO
OAc
AcO
OAc
2e (70%)
2c (45%, ortho/para = 2/3)
2g (65%)
Scheme 1. Reagents and conditions: 1 (1 mmol), Lewis acid (1.1 equiv), aryl (2.1 equiv), 0 °C to rt.
-
Cl4Sn
SnCl4
O
O AcO
Nu
OMe
OMe
-
HO AcO
AcO
SnCl4
AcO
1
AcO
CH2Cl2
AcO
AcO
OAc
AcO
3c
2c
I
+OMe
OMe
Scheme 2. Plausible mechanism for the double arylation with methoxynaphthalene.
(Scheme 3). It has been extensively explored with a large
number of N-heterocycles including the natural
nucleobases.12
In the modified version, we used 2-TMS-thiazole instead
of thiazole to activate the C2 position. Interestingly, the
treatment of 2-TMS-thiazole and ribose 1 with SnCl4 in
CH2Cl2 led to 75% of the ribosylated product 2h (Scheme
3).13,14 This result clearly shows the potential application
of this modified reaction for the ribosylation of deactivated
heteroaryl systems.
Lewis acid
Me Si
3
+
O
E
O
N
E
N
N
E
N
SiMe
3
Vorbrüggen reaction
N
N
S
O
SnCl / CH Cl
2
4
2
S
SiMe
AcO
3
O °C to rt / 1
OAc
AcO
75%
2h
In summary, we developed an efficient one-step synthe-
sis of new C-nucleosides featuring aryl and heteroaryl rings
Scheme 3. Example of modified Vorbru¨ggen reaction.
H3CO
O
RO
ZnCN2 / toluene
CN
Pd(PPh3)4
RO
OR
H3CO
78%
H3CO
O
4b : R = Ac
5b : R = H
NH3 / MeOH
92%
NH3 / MeOH
O
HO
AcO
AcO
Br
95%
X
H3CO
HO
OH
OAc
90%
3a : X = Br
3b : X = I
O
2a : X = Br
2b : X = I
phenylacetylene
RO
Pd(Ph3)4 5% molar
CuI, Et3N
RO
OR
THF
6b : R = Ac
7b : R = H
NH3 / MeOH
95%
Scheme 4. Example of post-synthetic transformations of compounds 2a and 2b.

3970
M. Spadafora et al. / Tetrahedron Letters 49 (2008) 3967–3971
7. See, for example: (a) Hanessian, S. Chem. Rev. 2000, 100, 4443; (b)
Kumazawa, T.; Onda, K.; Okuyama, H.; Matsuba, S.; Sato, S.;
Onodera, J. Carbohydr. Res. 2002, 337, 1007; (c) Li, Y.; Wei, G.; Yu,
B. Carbohydr. Res. 2006, 341, 2717.
8. Hainke, S.; Arndt, S.; Seitz, O. Org. Biomol. Chem. 2005, 3, 4233. and
references therein (in 20-deoxy series)..
9. (a) Guianvarc’h, D.; Fourrey, J.-L.; Sun, J.-S.; Maurisse, R.; Benhida,
R. Bioorg. Med. Chem. 2003, 11, 2751; (b) Guianvarc’h, D.; Fourrey,
J.-L.; Maurisse, R.; Sun, J.-S.; Benhida, R. Org. Lett. 2002, 4, 4209;
(c) El Akri, K.; Bougrin, K.; Balzarini, J.; Faraj, A.; Benhida, R.
Bioorg. Med. Chem. Lett. 2007, 17, 6656.
as aglycone moiety. We found that the Friedel–Crafts reac-
tion could be directly applied to assess C-nucleosides with
electron-rich aromatics, whereas deactivated aryls required
Si-metallation to undergo clean ribosylation. Generally
good, although not optimized, yields were obtained. More-
over, the process is compatible with functional groups such
as halogens and offers several possibilities for further post-
synthetic transformations. For example, bromo- and iodo-
derivatives 2a and 2b were subjected to different conditions
to assess their reactivities (Scheme 4). Thus, the treatment
of 2a and 2b with NH3 in MeOH gave the corresponding
free nucleosides 3a and 3b, respectively (95%). On the other
hand, cyanation of 2b was also efficiently achieved using
Pd-coupling (ZnCN2, Pd(PPh3)4) to give 4b (78%), which
upon NH3 treatment led to the free nucleoside 5b (95%).
Finally, the new C-nucleoside 7b was prepared following
Sonogashira coupling between 2b and phenylacetylene to
give 6b and subsequent protecting group cleavage (85%
in two steps, Scheme 4).15 Taken together, our results illus-
trate the efficiency of the given synthetic methodology for
the supply of a variety of C-nucleosides for further bio-
physical and biological applications. The development of
10. Typical procedure: To a stirred solution of tetra-O-acetylribose
(3 mmol) in CH2Cl2 (15 ml) and aryl (2.1 equiv) was added dropwise,
at 0 °C, SnCl4 (1.1 equiv). The mixture was stirred and warmed to
room temperature and monitored by TLC (in general, the colour of
the reaction mixture changes as the reaction progresses). The mixture
was quenched with saturated aqueous NaHCO3 solution and
extracted with methylene chloride (3 ꢂ 50 ml). The combined organic
layers were dried (MgSO4), concentrated and subjected to silica gel
chromatography (cyclohexane/AcOEt: 80:20 to 50:50). Selected
spectral data: 2a: 1H NMR (200 MHz, CDCl3) d ppm 1.77 (s, 3H,
Ac), 2.02 (s, 3H, Ac), 2.09 (s, 3H, Ac), 3.74 (s, 3H, OMe), 4.15 (dd,
1H, J = 12.8 and 5.5 Hz, H-50), 4.40 (m, 2H, H-50 and H-40), 5.37 (dd,
1H, J = 8.2 and 4.4 Hz, H-30), 5.44 (d, 1H, J = 3.2, H-10), 5.77 (dd,
1H, J = 4.4 and 3.2 Hz, H-20), 6.64 (d, 1H, J = 8.7 Hz, H-6 Ar), 7.31
(dd, 1H, J = 8.7 and 2.6 Hz, H-5 Ar), 7.63 (d, 1H, J = 2.6, H-3 Ar).
13C NMR (50 MHz, CDCl3) d ppm 20.38, 20.56, 20.91, 26.95, 55.62,
63.64, 71.92, 72.55, 111.46, 112.64, 126.58, 130.38, 131.41, 155.01,
169.41, 169.88, 170.81. MS (ES+) m/z: 467–469 (MNa)+, 484–486
(MK)+. HRMS (ES+) calcd for C18H22O8Br [M+H]+, 447.04779
the modified C–C Friedel–Crafts/Vorbruggen reactions is
¨
underway.
(
81Br); found, 447.04721. Compound 2b: 1H NMR (200 MHz,
Acknowledgements
CDCl3) d ppm 1.81 (s, 3H, Ac), 2.05 (s, 3H, Ac), 2.12 (s, 3H, Ac),
3.76 (s, 3H, OMe), 4.19 (dd, 1H, J = 12.8 and 5.3 Hz, H-50), 4.42 (m,
2H, H-50 and H-40), 5.40 (dd, 1H, J = 8.0 and 4.5 Hz, H-30), 5.46 (d,
1H, J = 3.2, H-10), 5.78 (dd, 1H, J = 4.3 and 3.2 Hz, H-20), 6.56 (d,
1H, J = 8.6 Hz, H-6 Ar), 7.53 (dd, 1H, J = 8.6 and 2.3 Hz, H-5 Ar),
7.77 (d, 1H, J = 2.3 Hz, H-3 Ar). 13C NMR (50 MHz, CDCl3) d ppm
20.47, 20.65, 21.00, 53.56, 55.60, 63.74, 72.02, 72.66, 76.95, 82.51,
112.14, 126.91, 136.29, 137.61, 155.93, 169.49, 169.95, 170.90. MS
(ES+) m/z: 514.9 (MNa)+. HRMS (ES+) calcd for C18H22O8I
[M+H]+, 493.03534; found, 493.03539. Compound 2d: 1H NMR
(200 MHz, CDCl3) d ppm 1.99 (s, 3H, Ac), 2.03 (s, 3H, Ac), 2.04 (s,
3H, Ac), 4.13 (dd, 1H, J = 11.7 and 3.8 Hz, H-50), 4.23 (m, 1H, H-40),
4.36 (dd, 1H,J = 11.7 and 3.0 Hz, H-50), 5.15 (m, 2H, H-10 and H-20),
5.26 (t, 1H, J = 4.8 Hz, H-30), 6.90 (dd, 1H, J = 5.0 and 3.5 Hz, H-4),
7.01 (m, 1H, H-3), 7.21 (dd, 1H, J = 5.0 and 1.3 Hz, H-5). 13C NMR
(50 MHz, CDCl3) d ppm 20.46, 20.55, 20.77, 63.44, 71.78, 76.51,
78.54, 79.94, 125.37, 125.73, 126.86, 141.22, 169.56, 169.68, 170.50.
MS (ES+) m/z: 365 (MNa)+, 382 (MK)+. 2e: 1H NMR (200 MHz,
CDCl3) d ppm 2.00 (s, 3H, Ac), 2.03 (s, 3H, Ac), 2.05 (s, 3H, Ac), 4.13
(dd, 1H, J = 11.7 and 3.6 Hz, H-50), 4.24 (m, 1H, H-40), 4.34 (dd, 1H,
J = 11.7 and 2.9 Hz, H-50), 5.07 (br d, 2H, J = 2.6 Hz, H-10 and H-20),
5.22 (dd, 1H, J = 4.4 and 2.6 Hz, H-30), 6.76 (d, 1H, J = 3.7 Hz, H-4),
6.86 (d, 1H, J = 3.8 Hz, H-3). 13C NMR (50 MHz, CDCl3) d ppm
20.62, 20.70, 20.96, 63.45, 71.77, 76.43, 78.83, 80.17, 112.83, 125.71,
129.82, 143.03, 158.17, 169.71, 169.83, 170.67. MS (ES+) m/z: 443-
445 (MNa)+, 459-461 (MK)+. Small amount of the a-anomer was also
observed in these reactions (68%).
The authors thank CNRS, ANR (Agence Nationale de
´
`
la Recherche), Region PACA and Ministere de l’Education
Nationale et de la Recherche for financial support and for a
doctoral fellowship (MENRT) to M. Spadafora.
References and notes
1. For the biological and clinical impact of tiazofurin and benzamide
riboside see: (a) Grifantini, M. Curr. Opin. Invest. Drugs 2000, 1, 257;
(b) Szekeres, T.; Sedlak, J.; Novotny, L. Curr. Med. Chem. 2002, 9,
759; (c) Ratcliffe, A. J. Curr. Opin. Drug Discov. Devel. 2006, 9, 595;
(d) Chen, L.; Pankiewicz, K. W. Curr. Opin. Drug Discov. Devel. 2007,
10, 403.
2. For recent reviews on the chemistry and the biochemistry of C-
glycoside analogues, see: (a) Wu, Q.; Simons, C. Synthesis 2004, 1533;
(b) Bililign, T.; Griffith, B. R.; Thorson, J. S. Nat. Prod. Rep. 2005, 22,
742; (c) Lee, D. Y. W.; He, M. S. Curr. Top. Med. Chem. 2005, 5,
1333; (d) Bililign, T.; Griffith, B. R.; Thorson, J. S. Nat. Prod. Rep.
2005, 22, 742; (e) Kool, E. T. Acc. Chem. Res. 2002, 35, 936.
3. (a) Ren, R. X. F.; Chaudhuri, N. C.; Paris, P. L.; Rummey, S.; Kool,
E. T. J. Am. Chem. Soc. 1996, 118, 7671; (b) Chaudhuri, N. C.; Reu,
R. X.; Kool, E. T. Synlett 1997, 341; (c) Hocek, M.; Pohl, R.;
Klepetarova, B. Eur. J. Org. Chem. 2005, 4525.
4. Gudmundsson, K. S.; Drach, J. C.; Townsend, L. B. J. Org. Chem.
1997, 62, 3453; Batoux, N. E.; Paradisi, F.; Engel, P. C.; Migaud, M.
E. Tetrahedron 2004, 60, 6609.
1
11. Compound 3c: H NMR (200 MHz, CDCl3) d ppm 1.20 (s, 3H, Ac),
1.86 (s, 3H, Ac), 1.91 (s, 3H, Ac), 2.34 (br d, 1H, J = 6.7 Hz, OH-40),
3.80 (s, 3H, OMe), 3.95 (s, 3H, OMe), 4.03 (dd, 1H, J = 12.0 and
6.7 Hz, H-50), 4.20 (m, 2H, H-50 and H-40), 5.28 (dd, 1H, J = 7.2 and
2.7 Hz, H-30), 6.07 (dd, 1H, J = 10.6 and 2.7 Hz, H-20), 6.18 (d, 1H,
J = 10.6, H-10), 6.53 (d, 1H, J = 7.1 Hz, H-Ar), 6.87 (d, 1H,
J = 8.1 Hz, H-Ar), 7.31 (m, 3H, H-Ar), 7.41 (m, 1H, H-Ar), 7.57
(ddd, 1H, J = 8.5, 7.0 and 1.5 Hz, H-Ar), 7.83 (d, 2H, J = 8.1 Hz, H-
Ar), 8.20 (m, 2H, H-Ar), 8.48 (d, 1H, J = 8.5 Hz, H-Ar). 13C NMR
(50 MHz, CDCl3) d ppm 20.11, 20.84, 39.80, 55.40, 55.60, 65.88,
´
5. (a) Guianvarc’h, D.; Fourrey, J.-L.; Tran Huu Dau, M.-E.; Gueri-
neau, V.; Benhida, R. J. Org. Chem. 2002, 67, 3724; (b) Singh, I.;
Seitz, O. Org. Lett. 2006, 8, 4319; (c) Harusawa, S.; Matsuda, C.;
Araki, L.; Kurihara, T. Synthesis 2006, 793.
6. For the synthesis of aryl C-glycosides via the Heck reaction, see: (a)
Wellington, K. W.; Benner, S. A. Nucleosides, Nucleotides Nucleic
acids 2005, 1309. review; (b) Oda, H.; Hanami, T.; Iwashita, T.;
Kojima, M.; Itoh, M.; Hayashizaki, Y. Tetrahedron 2007, 63, 12747.

M. Spadafora et al. / Tetrahedron Letters 49 (2008) 3967–3971
3971
68.66, 73.19, 76.00, 103.17, 103.65, 122.61, 122.72, 123.19, 123.78,
124.68, 125.02, 125.66, 125.96, 126.38, 126.64, 127.08, 128.06, 129.35,
132.77, 133.48, 154.35, 154.81, 169.76, 170.40, 171.33. MS (ES+) m/z:
597.4 (MNa)+, 613.3 (MK)+. HRMS (ES+) calcd for C33H34O9Na
[M+Na]+, 597.21002; found, 597.20950.
Comprehensive Organic Chemistry; Barton, D. H. R., Ollis, W. D.,
Eds.; Pergamon: Oxford, 1979; Vol. 3, Chapter 13, p 613.
1
15. Selected spectral data: 5b: H NMR (200 MHz, CD3OD) d ppm 3.57
(dd, 1H, J = 12.1 and 4.6 Hz, H-50), 3.92 (s, 3H, OMe), 3.75–4.02 (m,
2H, H-50 and H-40), 4.13–4.30 (m, 2H, H-30 and H-20), 5.16 (d, 1H,
J = 2.7 Hz, H-10), 6.96 (d, 1H, J = 8.6 Hz, H-6 Ar), 7.52 (dd, 1H,
J = 8.6 and 2.0 Hz, H-5 Ar), 7.69 (d, 1H, J = 1.9 Hz, H-3 Ar). 13C
NMR (50 MHz, CDCl3) d ppm 56.40, 63.14, 73.27, 73.82, 79.09,
83.01, 104.10, 111.73, 120.56, 130.04, 132.81, 134.02, 160.85. MS
(ES+) m/z: 288 (MNa)+, 553 (2MNa)+. Compound 7b: 1H NMR
(200 MHz, MeOD) d ppm 3.17 (dd, 1H, J = 12.1 and 4.6 Hz, H-50),
3.31 (s, 3H, OMe), 3.39 (m, 1H, H-50), 3.52 (m, 1H, H-40), 3.79 (m,
2H, H-30 and H-20), 4.77 (d, 1H, J = 1.6 Hz, H-10), 6.39 (d, 1H,
J = 8.6 Hz, H-6 Ar), 6.88 (m, 6H, H-Ar), 7.18 (d, 1H, J = 1.6 Hz, H-3
Ar). 13C NMR (50 MHz, MeOD) d ppm 55.97, 63.21, 73.42, 73.89,
79.36, 82.93, 88.51, 90.79, 110.94, 116.01, 125.04, 128.31, 128.93,
129.03, 129.45, 132.25, 132.39, 132.58, 157.56. MS (ES+) m/z: 363.3
(MNa)+. HRMS (ES+) calcd for C20H21O5 [M+H]+ 341.13843;
found, 341.13835.
12. Niedballa, U.; Vorbruggen, H. J. Org. Chem. 1976, 41, 2084;
¨
Vorbruggen, H.; Krolikiewicz, K.; Bennua, B. Chem. Ber. 1981,
¨
114, 1234; For review see: Vorbruggen, H.; Ruh-Polenz, C. Org.
¨
React. 2000, 55, 1–630.
13. Compound 2h: 1H NMR (200 MHz, acetone) d ppm 2.05 (br s, 9H,
Ac), 4.47 (dd, 2H, J = 12.8 Hz, 2H-50), 4.76 (m, 1H, H-40), 5.46 (t, 1H,
J = 5.4 Hz, H-30), 5.68 (dd, 1H, J = 5.7 and 4.0 Hz, H-20), 6.69 (d,
J = 4.0 Hz, 1H, H-10), 8.60 (br s, 1H, H-thiazole), 8.73 (br s, 1H, H-
thiazole). 13C NMR (50 MHz, acetone) d ppm 20.49, 20.62, 20.86,
63.18, 70.29, 76.10, 83.38, 95.52, 128.80, 134.87, 158.69, 169.96,
170.37, 170.56. 13C DEPT sequence only shows two CH signals. MS
(ES+) m/z: 344.5 (MH)+.
14. For reviews of arylsilanes in electrophilic aromatic substitutions, see:
(a) Eaborn, C. J. Organomet. Chem. 1975, 100, 43; (b) Fleming, I.. In