A modular methodology for the synthesis of 4- and 3-substituted benzene and aniline C-ribonucleosides

FULL PAPER

DOI: 10.1002/ejoc.200701168

A Modular Methodology for the Synthesis of 4- and 3-Substituted Benzene and

Aniline C-Ribonucleosides

[a]

ˇ

Martin Stefko, Radek Pohl, Blanka Klepetárová, and Michal Hocek*

Keywords: Nucleosides / Cross-coupling / Amination / Arene

A modular, efficient, and practical methodology for the prep-

aration of 4- and 3-substituted benzene and aniline C-ribo-

nucleosides was developed. Addition of 4- or 3-bromophen-

yllithium (2 or 12) to TBDMS-protected ribonolactone 3 gave

intermediates 6 and 15 were subjected to a series of palla-

dium-catalyzed cross-coupling, alkoxylation, and amination

reactions to give a series of protected 1β-(3- and 4-substi-

tuted phenyl)ribonuleosides 9 and 18. Deprotection of si-

hemiacetal adducts 4 or 13 as pure β-anomers. Their re- lylated nucleosides 9 or 18 by Et₃N·3HF afforded a series of

duction with Et₃SiH and BF₃·Et₂O afforded the desired pro-

tected 4- or 3-bromophenyl-C-ribonucleosides 6 or 15 in 66

and 75%, respectively, over two steps from 3. Bromophenyl

free C-ribonucleosides 10 or 19 (20 examples).

Germany, 2008)

trast, incorporation of bulky biaryl C-nucleosides into a du-

plex opposite to a purine or pyrimidine nucleobase causes

local disruption of the stacking.^[12]Very recently, donor-

and acceptor-modified biphenyl C-nucleoside-containing

oligonucleotide was used^[13]for recognition of another

hydrophobic modification in the opposite strand or even of

a bulge position. Moreover, oligoaryl C-nucleosides have

been used by Kool at al.^[14]for the construction of fluores-

cent oligonucleotide probes.

There are several synthetic approaches to C-nucleosides:

(i) addition reactions of organometallics to ribono- or 2-

deoxyribonolactones,^[3,9,15](ii) coupling of a halogenose

with organometallics,^[16](iii) electrophilic substitution reac-

tions of electron-rich aromatics with sugars under Lewis

acid catalysis,^[17]or (iv) Heck-type coupling of aryl iodides

with glycals.^[18]However, none of them is truly general,

and many of them suffer from poor selectivity and low

yields.

We are currently involved in development of modular

methodologies based on larger-scale syntheses of a versatile

C-nucleoside intermediates and their further use for the

generation of a series of diverse derivatives. We have already

developed modular syntheses of 3- and 4-substituted ben-

zene,^[19]6-substituted pyridin-2-yl,^[20]and 6-substituted pyr-

idin-3-yl^[21]C-2Ј-deoxyribonucleosides by the preparation

of a general halogenated C-arylnucleoside intermediate, fol-

lowing by displacement of the bromine atom by alkyl, aryl,

or amino substituents by cross-coupling reactions. An anal-

ogous modular approach was also used by Leumann^[22]to

prepare some biaryl C-2Ј-deoxyribonucleosides. However,

so far no application in the synthesis of C-ribonucleosides

has been published. Therefore, we report here on an ef-

ficient and modular synthesis of diverse 4- or 3-substituted

benzene C-ribonucleosides.

Introduction

C-Nucleosides bearing hydrophobic aryl groups as nu-

cleobase are interesting compounds with a wide range of

applications in chemical biology, in particular in the exten-

sion of the genetic alphabet.^[1]If incorporated to oligonu-

cleotide duplexes, they usually selectively pair with the same

type of hydrophobic nucleobase as a owing to increased

packing interactions and favorable desolvation energy in

comparison to canonical hydrophilic nucleobases.^[2]Tri-

phosphates of some of the C-nucleosides are efficiently in-

corporated into DNA by DNA polymerase.^[3]Most studies

were performed on 2Ј-deoxyribonucleosides and addressed

the stability of DNA duplexes and the specificity of incor-

poration by DNA polymerases. Much less work has been

done on C-ribonucleosides, which represents the second

step in the extension of the genetic alphabet Ϫ the tran-

scription. Some C-ribonucleosides that have been prepared

have been used for studying the stability of modified

RNA,^[4]RNA interference,^[5]or active sites of ribozymes;^[6]

some others have been studied as potential antitumor or

antiviral agents.^[7]C-nucleoside analogues of nicotin-

amide riboside were studied as IMP dehydrogenase inhibi-

tors.^[8]

Biaryl C-nucleosides are of particular interest because of

largely extended stacking and formation of very stable du-

plexes.^[9]Both theoretical calculations^[10]and experimental

(NMR spectroscopic structure) results^[11]confirmed that

they form a stacked-pair within the B-DNA duplex. In con-

[a] Institute of Organic Chemistry and Biochemistry, Academy

of Sciences of the Czech Republic, Gilead & IOCB Research

Center,

Flemingovo nám. 2, 16610 Prague 6, Czech Republic

Fax: +420-220183559

E-mail: hocek@uochb.cas.cz

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M. Stefko, R. Pohl, B. Klepetárˇová, M. Hocek

FULL PAPER

Results and Discussion

Our selected approach for the synthesis of a series of 4-

and 3-substituted benzene C-nucleosides was based on the

synthesis of a suitably protected 4- or 3-halophenyl C-nucleo-

side intermediate and on its further transformation (cross-

coupling, amination, alkoxylation). Therefore, our first ef-

forts were focused on the preparation of the protected bro-

mophenyl nucleoside intermediate. As a starting material,

we chose TBS-protected ribonolactone 3,^[23]which is easily

available in two steps from -ribose. First, oxidation of -

ribose by aqueous bromine generates the corresponding -

ribonolactone and subsequent reaction of this crude prod-

uct with TBSCl and imidazole produces the TBS-protected

ribonolactone in very good overall yield (75%) on a

multigram scale. The first addition reaction was performed

in analogy to a related literature example in the 2Ј-deoxy-

ribo series.^[22]Thus, 4-bromophenyllithium (2) was gener-

ated from 1,4-dibromobenzene (1) by its initial treatment

with nBuLi, followed by its reaction with lactone 3 at

–78 °C for 1 h. This reaction gave desired hemiketal 4 (51%)

and side product 5 (34%), which was identified as a product

resulting from the migration of the TBS group from the

hydroxy group in the 2-position of the sugar moiety to the

hemiketal hydroxy group (Scheme 1). The addition reac-

tions proceeded stereoselectively Ϫ exclusive formation of

the β-anomers of hemiketals 4 and 5 was observed and

proved by ROESY spectra. In addition, the structure of side

product 5 was determined by X-ray diffraction (Figure 1).

Shortening of the reaction time to 30 min after the addition

of bromophenyllithium resulted in a decrease in the forma-

tion of side product 5 (17%) and desired product 4 was

isolated in 77% yield.

Figure 1. ORTEP drawing of 5 with the atom numbering scheme.

Thermal ellipsoids are drawn at the 50% probability level; hydrogen

atoms on the TBS groups are omitted for clarity.

Reduction of hemiketal 4 was then performed with Et₃-

SiH/BF₃·Et₂O in analogy to the literature procedures.^[20,22]

Here we found that the use of Et₃SiH (3.3 equiv.) and

BF₃·Et₂O (1.2 equiv.) in CH₂Cl₂at –10 °C for just 5 min is

sufficient for total conversion of starting hemiketal 4 to de-

sired C-nucleoside 6 in 85% yield. We then tried the analo-

gous reduction of 1Ј-O-TBS derivative 5 under the same

conditions. This silyl acetal reacted in the same way to give

2Ј-unprotected C-nucleoside 7 in 89% yield. The very short

reaction time was crucial for the selectivity, as prolongation

of the reaction time resulted in partial cleavage of the TBS

protecting groups and degradation of the desired product.

In both cases, β-anomeric nucleosides 6 and 7 were isolated

as the only products. Treatment of silylated nucleoside 6

with Et₃N·3HF gave the free bromophenyl-C-nucleoside 8

in 85% yield (for discussion of the deprotection protocol

vide infra).

The TBS-protected 4-bromophenyl-C-nucleoside key in-

termediate 6 was then subjected to a series of Pd-catalyzed

cross-coupling, amination, and alkoxylation reactions at the

4-position (Scheme 2). Cross-coupling reactions with or-

ganoaluminum or organozinc reagents were used for the

introduction of sp³(alkyl and benzyl) substituents. The re-

actions of 6 with trimethylaluminum, triethylaluminum,

and benzylzinc bromide were performed under standard

conditions^[19]in the presence of Pd(PPh₃)₄in THF at 55 °C

without any optimization (Table 1, Entries 1-3). In all cases,

desired nucleosides 9a–c were obtained in good-to-excellent

yields (67–90%; Table 1, Entries 1–3).

In order to introduce hetaryl-substituents, Stille cross-

coupling reactions were used. The reactions were carried

out in DMF by using PdCl₂(PPh₃)₂as a catalyst. Reaction

of 6 with 2-thienyl(tributyl)stannane (Table 1, Entry 4) pro-

ceeded very smoothly within 10 min at 100 °C to give de-

sired 4-(2-thienyl)benzene-C-nucleoside 9d in 79% yield. In

contrast, reaction of 6 with 2-pyridyl(tributyl)stannane re-

quired a longer time to reach complete conversion, and

Scheme 1. Synthesis of 4-bromophenyl C-nucleosides. Reagents

and conditions: (a) BuLi, THF, –78 °C, 30 min; (b) 3 (addition over

30 min), THF, –78 °C, 30 min, 4 (77%) and 5 (17%); (c) Et₃SiH,

BF₃·Et₂O, CH₂Cl₂, –10 °C, 5 min, 6 (85% from 4), 7 (89% from

5); (d) Et₃N·3HF, THF, 40 °C, 2 d, 8 (85% from 6).

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Eur. J. Org. Chem. 2008, 1689–1704

Synthesis of 4- and 3-Substituted Benzene and Aniline C-Ribonucleosides

Scheme 2. Cross-coupling, amination, and alkoxylation reactions of intermediate 6 and deprotection.

Table 1. Cross-coupling, amination, and alkoxylation reactions of intermediate 6 and deprotection.

Entry Reagent

Catalyst

Ligand/base

Solvent

Other conditions Product (yield, %)^[g]Product (yield, %)^[h]

1

2

3

4

5

6

7

8

9

10

Me₃Al

Et₃Al

BnZnBr

Pd(PPh₃)₄

Pd(PPh₃)₂Cl₂

Pd(PPh₃)₄

THF

DMF

toluene

THF

48 h, 55 °C

10 min, 100 °C

32 h, 100 °C

10 min, 110 °C

3.5 h, 110 °C

48 h, 60 °C

72 h, 37 °C

8 h, 90 °C

9a (90)

9b (77)

9c (67)

9d (79)

9e (56)

9f (85)

9g (72)

9h (84)

9i (82)

9j (69)

10a (95)

10b (85)

10c (84)

10d (95)

10e (86)

10f (95)

10g (95)

10h (68)

10i (86)

10j (95)

2-Bu₃Sn-thiophene^[a]

2-Bu₃Sn-pyridine^[b]

4-F-C₆H₄-boronic acid^[c]

K₂CO₃

bdCyp^[e],

4-MeO-C₆H₄-boronic acid^[d]Pd(PPh₃)₄

LiN(SiMe₃)₂

Me₂NH·HCl

tBuONa

Pd₂dba₃

bdtbp,^[f]tBuONa toluene

bdtbp^[f]

toluene

[a] 2-Bu₃Sn-thiophene = 2-(tributylstannyl)thiophene. [b] 2-Bu₃Sn-pyridine = 2-(tributylstannyl)pyridine. [c] 4-F-Ph-boronic acid = 4-

fluorophenylboronic acid. [d] 4-MeO-Ph-boronic acid = 4-methoxyphenylboronic acid. [e] bdCyp = (2-biphenyl)dicyclohexylphosphane.

[f] bdtbp = (2-biphenyl)di-tert-butylphosphane. [g] Cross-coupling/amination product. [h] Deprotection product.

moreover, formation of some byproducts were observed. oxy)phenyl C-nucleoside 9j was observed as a side product

The extraction and column chromatography isolation of re- in 7%. In order to obtain this compound on a preparative

sulting nucleoside 9e from lipophilic tin-containing side scale, we performed the reaction of 6 with tBuONa in tolu-

products was more complicated, which is reflected in the ene by using Pd₂dba₃and dbtbp (virtually the same condi-

lower isolated yield of 56% (Table 1, Entry 5).

tions as above but in the absence of dimethylamine). The 4-

Substituted biphenyl-C-nucleosides were prepared by the (tert-butoxy)phenyl derivative 9j was obtained in this way

Suzuki–Miyaura cross coupling of 6 with the corresponding in 63% yield (Table 1, Entry 10).

substituted phenylboronic acid in toluene in the presence of

After successful preparation of the whole series of TBS-

K₂CO₃and Pd(PPh₃)₄as a catalyst. In both cases, the reac- protected C-ribonucleosides, we turned our attention to the

tion proceeded very smoothly. In the case of 4-fluorophen- final deprotection step. Trying to find a general deprotec-

ylboronic acid (Table 1, Entry 6), the reaction was complete tion protocol for all the synthesized C-ribonucleosides was

within 10 min and yielded desired nucleoside 9f in 85% not easy. Three reagents known to cleave O-TBS groups

yield. The reaction with 4-methoxyphenylboronic acid re- under mild conditions were tried. TBAF (tetrabutylammo-

quired a somewhat longer time and more difficult isolation nium fluoride) in THF worked perfectly for bromo deriva-

to afford target nucleoside 9g in 72% yield (Table 1, En- tive 6, but in the case of 9b, we were unable to separate

try 7).

TBAF from the final free nucleoside. Next, we tried TFA

Hartwig–Buchwald reactions^[24]were used to introduce (trifluoroacetic acid) in water (TFA/H₂O, 9:1). Deprotec-

the N-substituents. Unsubstituted aminophenyl derivative tion again proceeded smoothly and was complete at room

9h was prepared by the reaction of 6 with lithium bis(tri- temperature within 30 min. This method was successfully

methylsilyl)amide in the presence of Pd₂dba₃and P(tBu)₃used for compounds 9a–c, but we encountered serious

[generated in situ from P(tBu)₃·HBF₄] in a low yield of only problems with compound 9j, where epimerization and de-

24%. The use of Buchwald-type ligand (2-biphenyl)dicyclo- composition was observed. Finally, we turned to Et₃N·3HF,

hexylphosphane (bdCyp)^[25]under the same conditions gave which is a favorite reagent for deprotection of TBS-pro-

desired aniline nucleoside 9h in a very good yield of 84% tected nucleosides.^[26]The reactions required 6 d to go to

(Table 1, Entry 8). The Buchwald reaction was also used for completion when they were carried out in THF at room

the introduction of the dimethylamino group. The reaction temperature. However, the reactions were clean and no de-

of 6 with dimethylamine hydrochloride (Me₂NH·HCl) was gradation or epimerization was observed. Only in case of

performed under standard conditions by using Pd₂dba₃, 2- the amino derivative 9h was formation of a complex be-

(di-tert-butylphosphanyl)biphenyl (bdtbp), and tBuONa as tween Et₃N·3HF and the amino group observed, but this

a base at 37 °C for 3 d to give target dimethylaniline C- could be easily cleaved by treatment with NaHCO₃. This

nucleoside 9i in 82% yield (Table 1, Entry 9). When this re- treatment was then also used for all other compounds to

action was performed at 80 °C, formation of 4-(tert-but- make the isolation of the products easier and more efficient.

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M. Stefko, R. Pohl, B. Klepetárˇová, M. Hocek

FULL PAPER

The last problem to be overcome was the unacceptably long

reaction time required for deprotection. An increase in the

concentration of Et₃N·3HF in the reaction mixture also

brought no improvement. However, simple heating of the

reaction mixture to 40 °C resulted in a decrease in the reac-

tion time to an acceptable 2 d, during which time there was

no influence on the purity of the prepared free C-ribonucle-

osides. Finally, deprotection under these general conditions

yielded free C-nucleosides 10a–j in good-to-excellent yields

(Table 1, Entries 1–10; last column).

After finishing the first series of 4-substituted benzene

C-ribonucleosides, we turned our attention to the prepara-

tion of analogous 3-substituted benzene nucleosides. Again,

the key protected 3-bromophenyl C-nucleoside intermediate

15 must have been prepared very efficiently. For its prepara-

tion, we adopted analogous conditions to those used in the

first series. The addition of 3-bromophenyllithium (12, gen-

erated from 11) to lactone 3 was performed as described

above (Scheme 3) to give desired hemiketal 13 in excellent

89% yield. In this case, 1Ј-O-TBS side product 14 was

formed in only very low yield of 4%. Again, the addition

was stereoselective and gave both products 13 and 14 as

pure β-anomers. Also, the subsequent reduction was ac-

complished under the same conditions as those used in the

first series, which included the use of Et₃SiH/BF₃·Et₂O as

a reducing system, to result in formation of desired key in-

termediate 15 in 84% yield (Scheme 3). Reduction of 14 was

Scheme 3. Synthesis of 3-bromophenyl C-nucleosides. Reagents

and conditions: (a) BuLi, THF, –78 °C, 30 min; (b) 3 (addition over

30 min), THF, –78 °C, 30 min, 13 (89%) and 14 (4%); (c) Et₃SiH,

BF₃·Et₂O, CH₂Cl₂, –10 °C, 5 min, 15 (84% from 13), 16 (73% from

14); (d) Et₃N·3HF, THF, 40 °C, 2 d, 17 (88% from 15).

With key intermediate 15 in hand, we performed a series

accomplished under the same conditions, which resulted in of cross-coupling, amination, and alkoxylation reactions in

the smooth formation of nucleoside 16 in 73% yield. De- analogy to the first series (Scheme 4, Table 2). Generally, we

protection of 15 with Et₃N·3HF gave free nucleoside 17 in used analogous conditions (i.e., catalyst type and loading,

88% yield.

ligands, solvents etc., with only slight modifications to the

Scheme 4. Cross-coupling, amination, and alkoxylation reactions of intermediate 15 and deprotection.

Table 2. Cross-coupling, amination, and alkoxylation reactions of intermediate 15 and deprotection.

Entry

Reagent

Catalyst

Ligand/base

Solvent

Other conditions Product (yield,%)^[g]Product (yield,%)^[h]

1

2

3

4

5

6

7

8

9

10

Me₃Al

Et₃Al

BnZnBr

Pd(PPh₃)₄

Pd(PPh₃)₂Cl₂

Pd(PPh₃)₄

THF

DMF

toluene

48 h, 55 °C

0.5 h, 100 °C

17 h, 100 °C

0.5 h, 100 °C

2 h, 95 °C

48 h, 60 °C

72 h, 40 °C

8 h, 50 °C

18a (95%)

18b (73%)

18c (67%)

18d (73%)

18e (46%)

18f (69%)

18g (81%)

18h (73%)

18i (77%)

18j (68%)

19a (72%)

19b (77%)

19c (80%)

19d (72%)

19e (68%)

19f (77%)

19g (73%)

19h (84%)

19i (77%)

19j (78%)

2-Bu₃Sn-thiophene^[a]

2-Bu₃Sn-pyridine^[b]

4-F-C₆H₄-boronic acid^[c]

K₂CO₃

4-MeO-C₆H₄-boronic acid^[d]Pd(PPh₃)₄

LiN(SiMe₃)₂

Me₂NH·HCl

tBuONa

Pd₂dba₃

bdCyp,^[e]tBuONa THF

bdtbp^[f]

toluene

[a] 2-Bu₃Sn-thiophene = 2-(tributylstannyl)thiophene. [b] 2-Bu₃Sn-pyridine = 2-(tributylstannyl)pyridine. [c] 4-F-Ph-boronic acid = 4-

fluorophenylboronic acid. [d] 4-MeO-Ph-boronic acid = 4-methoxyphenylboronic acid. [e] bdCyp = (2-biphenyl)dicyclohexylphosphane.

[f] bdtbp = (2-biphenyl)di-tert-butylphosphane. [g] Cross-coupling/amination product. [h] Deprotection product.

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Synthesis of 4- and 3-Substituted Benzene and Aniline C-Ribonucleosides

are given in 10^–1°cm²g^–1. NMR spectra were measured at

reaction temperatures and times) to get the series of TBS-

protected 3-substituted benzene and aniline C-ribonucleo-

sides 18a–j in yields comparable to those obtained for the

4-substituted series. Desilylation of the TBS-protected C-

ribonucleosides 18a–j was performed by the general pro-

cedure on the basis of the reaction with Et₃N·3HF, in THF

for 2 d at 40 °C and subsequent treatment with NaHCO₃.

This methodology was highly efficient and yielded free C-

ribonucleosides 19a–j in good yields (68–84%; Table 2, En-

tries 1–10).

400 MHz for ¹H and 100.6 MHz for ¹³C nuclei, at 500 MHz for ¹H

1

and 125.8 MHz for ¹³C, or at 600 MHz for H and 151 MHz for

¹³C in CDCl₃, for protected nucleosides and [D₆]DMSO for depro-

tected ones. (TMS was used as internal standard), [D₆]DMSO (ref-

erenced to the residual solvent signal). Chemical shifts are given in

ppm (δ scale) and coupling constants (J) in Hz. Complete assign-

ment of all NMR signals was performed by using a combination

of H, H-COSY, H,H-ROESY, H,C-HSQC, and H,C-HMBC ex-

periments. Mass spectra were measured by using FAB (ionization

by Xe, accelerating voltage 8 kV, glycerol +thioglycerol matrix) of

EI (electron energy 70 eV). DMF was degassed in vacuo and stored

over molecular sieves under an atmosphere of argon.

All the final 4-substituted benzene and aniline C-ribonu-

cleosides 10a–j were crystalline compounds. The crystal

structure of 10i was determined by X-ray diffraction (Fig-

1β-(4-Bromophenyl)-2,3,5-tri-O-(tert-butyldimethylsilyl)-D-ribo-

ure 2), and it provides evidence for the 3Ј-exo conformation furanose (4) and 1β-(4-Bromophenyl)-1,3,5-tri-O-(tert-butyldi-

methylsilyl)-D-ribofuranose (5): To a stirred solution of p-di-

of the sugar. In contrast, the 3-substituted benzene C-nu-

cleosides 19a–j were all oily compounds and all attempts to

crystallize them failed (only in some cases solid precipitates

were obtained). All the final nucleosides were tested for

anti-HCV activity. None of them showed any considerable

activity or cytotoxicity.

bromobenzene (8.07 g, 0.034 mol, 1.7 equiv.) in dry THF (80 mL)

at –72 °C was quickly added nBuLi (1.6  in hexanes, 20.5 mL,

0.033 mol, 1.65 equiv.), and mixture was stirred for 30 min. Then,

a solution of TBS protected ribonolactone 3 (10 g, 0.020 mol) in

dry THF (80 mL) was slowly added over 30 min and stirred for an

additional 30 min at –72 °C. The reaction mixture was than poured

into a saturated NH₄Cl solution and extracted with AcOEt. The

combined organic phase was washed with a saturated NH₄Cl solu-

tion, dried (MgSO₄), and concentrated under vacuum. Purification

on silica gel (gradient hexane to hexane/toluene, 1:1 to toluene)

gave desired hemiketal 4 (10.14 g, 77%) as a colorless oil and 5

(2.27 g, 17%) as a white solid, which was crystallized from MeOH,

to obtain fine needles. Compound 4: ¹H NMR (400 MHz, CDCl₃):

δ = –0.53, –0.14, 0.12, 0.126, 0.13 and 0.133 (6 s, 6ϫ3 H, CH₃Si),

0.83, 0.94 and 0.95 [3 s, 3ϫ9 H, (CH₃)₃C], 3.80 (dd, J_gem= 11.0 Hz,

´

J_´= 2.6 Hz, 1 H, 5b-H), 3.84 (dd, J

= 11.0 Hz, J_´= 3.4 Hz,

´

5b,4

gem

5a,4

1 H, 5Јa-H), 4.00 (d, J_2Ј,3Ј= 4.7 Hz, 1 H, 2Ј-H), 4.17 (dd, J_3Ј,2Ј

=

4.7 Hz, J_3Ј,4Ј= 0.8 Hz, 1 H, 3Ј-H), 4.20 (ddd, J_4Ј,5Ј= 3.4, 2.6 Hz,

J_4Ј,3Ј= 0.8 Hz, 1 H, 4Ј-H), 5.07 (s, 1 H, OH), 7.43 (m, 2 H, 3,5-

H), 7.53 (m, 2 H, 2,6-H) ppm. ¹³C NMR (100.6 MHz, CDCl₃): δ

= –5.82, –5.62, –5.47, –4.83, –4.57 and –4.53 (CH₃Si), 17.83, 17.90

and 18.29 [C(CH₃)₃], 25.74, 25.77 and 25.93 [(CH₃)₃C], 63.66

(CH₂-5Ј), 74.98 (CH-3Ј), 77.88 (CH-2Ј), 85.14 (CH-4Ј), 103.79 (C-

1Ј), 122.21 (C-4), 128.79 (CH-2,6), 130.68 (CH-3,5), 140.13 (C-1)

Figure 2. ORTEP drawing of 10i with the atom numbering scheme.

Thermal ellipsoids are drawn at the 50% probability level.

ppm. IR (CCl ): ν = 3507, 2955, 2930, 2897, 2859, 1590, 1472,

˜

4

1362, 1257, 1171, 1149, 1106, 1096, 1012, 961 cm^–1. HRMS (FAB):

calcd. for C₂₉H₅₅O₅Si₃BrNa [M + Na] 669.2438; found 669.2400.

Compound 5: M.p. 82–84 °C. ¹H NMR (600 MHz, C₆D₆): δ =

–0.20, –0.03, –0.02, 0.15, 0.17 and 0.25 (6 s, 6ϫ3 H, CH₃Si), 0.83,

0.997 and 1.001 [3 s, 3ϫ9 H, (CH₃)₃C], 3.18 (d, J_OH,2Ј= 12.2 Hz,

1 H, OH), 3.60 (dd, J_gem= 10.9 Hz, J_5Јb,4Ј= 3.0 Hz, 1 H, 5Јb-H),

3.63 (dd, J_gem= 10.9 Hz, J_5Јa,4Ј= 3.4 Hz, 1 H, 5Јa-H), 3.90 (dd,

Conclusions

A general modular methodology for the synthesis of 4-

or 3-substitutred benzene C-ribonucleosides was developed.

Key TBS-protected bromobenzene nucleoside intermediates

6 and 15 were efficiently and stereoselectively prepared

from easily available ribonolactone in two steps. Pd-cata-

lyzed cross-coupling and amination reactions proceeded

well to give a series of protected benzene and aniline C-

ribonucleosides. Et₃N·3HF was used for final deprotection

of the whole series of C-nucleosides. As these nucleosides

are not cytotoxic, they might be good candidates for con-

version to triphosphates and tested as substrates for RNA

polymerases.

J_2Ј,OH= 12.2 Hz, J_2Ј,3Ј= 6.4 Hz, 1 H, 2Ј-H), 4.26 (dd, J_3Ј,2Ј

=

6.4 Hz, J_3Ј,4Ј= 2.0 Hz, 1 H, 3Ј-H), 4.29 (br. ddd, J_4Ј,5Ј= 3.4, 3.0 Hz,

J_4Ј,3Ј= 2.0 Hz, 1 H, 4Ј-H), 7.37 (m, 2 H, 3,5-H), 7.65 (m, 2 H, 2,6-

H) ppm. ¹³C NMR (151 MHz, C₆D₆): δ = –5.66, –5.43, –4.84,

–4.50, –3.48 and –2.58 (CH₃Si), 18.26, 18.31 and 18.59 [C(CH₃)₃],

25.84, 26.05 and 26.29 [(CH₃)₃C], 63.92 (CH₂-5Ј), 73.56 (CH-3Ј),

79.27 (CH-2Ј), 86.72 (CH-4Ј), 104.43 (C-1Ј), 122.43 (C-4), 128.05

(CH-2,6), 131.17 (CH-3,5), 143.45 (C-1) ppm. IR (CCl ): ν = 3554,

˜

4

2955, 2927, 2894, 2857, 1594, 1471, 1256, 1132, 1088, 1048, 1021,

963, 929, 836 cm^–1. HRMS (FAB): calcd. for C₂₉H₅₅O₅Si₃BrNa [M

+ Na] 669.2438; found 669.2465.

1β-(4-Bromophenyl)-1-deoxy-2,3,5-tri-O-(tert-butyldimethylsilyl)-D-

Experimental Section

ribofuranose (6): Et₃SiH (3.4 mL, 21.1 mmol, 3.33 equiv.) was

added in one portion to a stirred solution of hemiketal 4 (4.1 g,

6.33 mmol) in dry CH₂Cl₂(23.3 mL) in an ice–brine bath (–10 °C)

General Methods: Melting points were determined with a Kofler

block. Optical rotations were measured at 25 °C, [α]²_D⁰, and values

Eur. J. Org. Chem. 2008, 1689–1704

www.eurjoc.org

1693

ˇ

M. Stefko, R. Pohl, B. Klepetárˇová, M. Hocek

FULL PAPER

under an atmosphere of argon. After 5 min, BF₃·Et₂O (0.9 mL,

7.59 mmol, 1.2 equiv.) was added over 1 min by syringe. The re-

sulting mixture was stirred for an additional 5 min, then poured

into saturated NaHCO₃, extracted with CH₂Cl₂, dried with

MgSO₄, and concentrated under vacuum. The crude product was

chromathographed on silica gel (hexane/toluene, 2:1 to toluene) to

obtain 6 (3.4 g, 85 %) as a colorless oil. ¹H NMR (500 MHz,

CDCl₃): δ = –0.44, –0.12, 0.087, 0.09, 0.11 and 0.12 (6 s, 6ϫH,

CH₃Si), 0.81, 0.93 and 0.94 [3 s, 3ϫ9 H, (CH₃)₃C], 3.76 (dd, J_gem

= 11.0 Hz, J_5Јb,4Ј= 2.9 Hz, 1 H, 5Јb-H), 3.80 (dd, J_gem= 11.0 Hz,

4.0, 3.2 Hz, J_4Ј,3Ј= 2.3 Hz, 1 H, H-4Ј), 4.13 (ddd, J_3Ј,2Ј= 4.4 Hz,

J_3Ј,4Ј= 2.3 Hz, J_3Ј,1Ј= 0.4 Hz, 1 H, H-3Ј), 4.74 (d, J_1Ј,2Ј= 7.3 Hz,

1 H, H-1Ј), 7.10 (m, 2 H, H-3,5), 7.29 (m, 2 H, H-2,6) ppm. ¹³C

NMR (125.7 MHz, CDCl₃): δ = –5.50, –5.39, –5.31, –4.53 and

–4.43 (CH₃Si), 17.97, 18.10 and 18.40 [C(CH₃)₃], 21.28 (CH₃),

25.88, 25.92 and 26.02 [C(CH₃)₃], 63.67 (CH₂-5Ј), 73.71 (CH-3Ј),

79.51 (CH-2Ј), 83.07 (CH-1Ј), 85.52 (CH-4Ј), 126.84 (CH-2,6),

128.63 (CH-3,5), 137.14 (C-4), 137.59 (C-1) ppm. IR (CCl ): ν =

˜

4

3099, 3054, 3030, 3013, 2896, 1618, 1516, 1472, 1463, 1406, 1389,

1373, 1361, 1304, 1280, 1257, 1213, 1187, 1021, 937 cm^–1. HRMS

(FAB): calcd. for C₃₀H₅₉O₄Si₃[M + H] 567.3721; found 567.3713.

J_5Јa,4Ј= 3.7 Hz, 1 H, 5Јa-H), 3.81 (dd, J_2Ј,1Ј= 7.8 Hz, J_2Ј,3Ј

=

4.4 Hz, 1 H, 2Ј-H), 4.02 (ddd, J_4Ј,5Ј= 3.7, 2.9 Hz, J_4Ј,3Ј= 1.9 Hz, 1

H, 4Ј-H), 4.11 (ddd, J_3Ј,2Ј= 4.4 Hz, J_3Ј,4Ј= 1.9 Hz, J_3Ј,1Ј= 0.5 Hz,

1 H, 3Ј-H), 4.72 (d, J_1Ј,2Ј= 7.8 Hz, 1 H, 1Ј-H), 7.31 (m, 2 H, 2,6-

H), 7.43 (m, 2 H, 3,5-H) ppm. ¹³C NMR (125.7 MHz, CDCl₃): δ

= –5.52, –5.43, –5.40, –4.48, –4.46 and –4.41 (CH₃Si), 17.92, 18.07

and 18.35 [C(CH₃)₃], 25.83, 25.88 and 25.98 [C(CH₃)₃], 63.63

(CH₂-5Ј), 73.89 (CH-3Ј), 79.57 (CH-2Ј), 82.28 (CH-1Ј), 86.13 (CH-

4Ј), 121.36 (C-4), 128.59 (CH-2,6), 131.06 (CH-3,5), 139.88 (C-1)

1β-(4-Ethylphenyl)-1-deoxy-2,3,5-tri-O-(tert-butyldimethylsilyl)-D-

ribofuranose (9b): Et₃Al (1  in hexanes, 1.8 mmol, 2 equiv.,

1.8 mL) was added in one portion to a vigorously stirred solution

of 6 (566 mg, 0.895 mmol) and Pd(PPh₃)₄(5 mol-%, 52 mg,

0.045 mmol) in THF (10 mL) under an atmosphere of argon. The

mixture was stirred at 55 °C for 48 h and then worked up by pour-

ing into saturated NaH₂PO₄and extracting with EtOAc. The crude

product was chromatographed on silica gel (hexane/EtOAc, 95:3)

ppm. IR (CCl ): ν = 3084, 3049, 3032, 2897, 1595, 1577, 1492,

˜

4

1

to give 9b (398 mg, 77%) as a colorless oil. H NMR (500 MHz,

1488, 1472, 1463, 1408, 1389, 1362, 1308, 1254, 1220, 1188, 1071,

1012, 937, 838 cm^–1. HRMS (FAB): calcd. for C₂₉H₅₆O₄Si₃Br [M

+ H] 631.2670; found 631.2680.

CDCl₃): δ = –0.42, –0.14, 0.089, 0.090, 0.11 and 0.13 (6 s, 6ϫ3 H,

CH₃Si), 0.79, 0.93 and 0.95 [3 s, 3ϫ9 H, (CH₃)₃C], 1.20 (t, J_vic

7.6 Hz, 3 H, CH₃CH₂), 2.62 (q, J_vic= 7.6 Hz, 2 H, CH₂CH₃), 3.77

(dd, J_gem= 10.9 Hz, J_5Јb,4Ј= 3.3 Hz, 1 H, 5Јb-H), 3.80 (dd, J_gem

=

1β-(4-Bromophenyl)-1-deoxy-3,5-di-O-(tert-butyldimethylsilyl)-D-

=

ribofuranose (7): Et₃SiH (1 mL, 6.12 mmol, 3.33 equiv.) was added

in one portion to a stirred solution of 5 (1.19 g, 1.84 mmol) in dry

CH₂Cl₂(6.7 mL) in an ice–brine bath (–10 °C) under an atmo-

sphere of argon. After 5 min, BF₃·Et₂O (0.26 mL, 2.20 mmol,

1.2 equiv.) was added over 1 min by syringe. The resulting mixture

was stirred for an additional 5 min, then poured into saturated

NaHCO₃, extracted with CH₂Cl₂, dried with MgSO₄, and concen-

trated under vacuum. Purification on silica gel (hexane/toluene,

1:1) furnished 7 (853 mg, 89 %) as a colorless oil: ¹H NMR

(500 MHz, CDCl₃): δ = 0.093, 0.095, 0.14 and 0.15 (4 s, 4ϫ3 H,

10.9 Hz, J_5Јa,4Ј= 3.8 Hz, 1 H, 5Јa-H), 3.85 (dd, J_2Ј,1Ј= 7.4 Hz, J_2Ј,3Ј

= 4.4 Hz, 1 H, 2Ј-H), 4.01 (ddd, J_4Ј,5Ј= 3.9, 3.3 Hz, J_4Ј,3Ј= 2.3 Hz,

1 H, 4Ј-H), 4.13 (ddd, J_3Ј,2Ј= 4.4 Hz, J_3Ј,4Ј= 2.3 Hz, J_3Ј,1Ј= 0.5 Hz,

1 H, 3Ј-H), 4.74 (d, J_1Ј,2Ј= 7.4 Hz, 1 H, 1Ј-H), 7.12 (m, 2 H, 3,5-

H), 7.32 (m, 2 H, 2,6-H) ppm. ¹³C NMR (125.7 MHz, CDCl₃): δ

= –5.50, –5.39, –4.55 and –4.43 (CH₃Si), 15.80 (CH₃CH₂), 17.99,

18.10 and 18.40 [C(CH₃)₃], 25.87, 25.92 and 26.02 [C(CH₃)₃], 28.65

(CH₂CH₃), 63.70 (CH₂-5Ј), 73.73 (CH-3Ј), 79.56 (CH-2Ј), 83.03

(CH-1Ј), 85.58 (CH-4Ј), 126.92 (CH-2,6), 127.46 (CH-3,5), 137.79

(C-1), 143.74 (C-4) ppm. IR (CCl ): ν = 3095, 3037, 3017, 2896,

˜

4

CH₃Si), 0.91 and 0.95 [2 s, 2ϫ9 H, (CH₃)₃C], 2.75 (d, J_OH,2Ј

=

1617, 1515, 1472, 1423, 1406, 1389, 1374, 1362, 1308, 1282, 1263,

1257, 1213, 1187, 1020, 938 cm^–1. HRMS (FAB): calcd. for

C₃₁H₆₁O₄Si₃[M + H] 581.3878; found 581.3895.

8.3 Hz, 1 H, OH-2Ј), 3.77 (dd, J_gem= 11.1 Hz, J_5Јb,4Ј= 3.2 Hz, 1 H,

5Јb-H), 3.79 (ddd, J_OH,2Ј= 8.3 Hz, J_2Ј,1Ј= 6.8 Hz, J_2Ј,3Ј= 5.5 Hz, 1

H, 2Ј-H), 3.81 (dd, J_gem= 11.1 Hz, J_5Јa,4Ј= 3.9 Hz, 1 H, 5Јa-H),

3.99 (ddd, J_4Ј,5Ј= 3.9, 3.2 Hz, J_4Ј,3Ј= 3.3 Hz, 1 H, 4Ј-H), 4.28 (ddd,

J_3Ј,2Ј= 5.5 Hz, J_3Ј,4Ј= 3.3 Hz, J_3Ј,1Ј= 0.3 Hz, 1 H, 3Ј-H), 4.64 (d,

J_1Ј,2Ј= 6.8 Hz, 1 H, 1Ј-H), 7.33 (m, 2 H, 2,6-H), 7.45 (m, 2 H, 3,5-

H) ppm. ¹³C NMR (125.7 MHz, CDCl₃): δ = –5.53, –5.39, –4.89

and –4.44 (CH₃Si), 18.04 and 18.34 [C(CH₃)₃], 25.75 and 25.91

[C(CH₃)₃], 62.82 (CH₂-5Ј), 72.77 (CH-3Ј), 77.74 (CH-2Ј), 83.73

(CH-1Ј), 84.94 (CH-4Ј), 121.39 (C-4), 127.69 (CH-2,6), 131.31

1β-(4-Benzylphenyl)-1-deoxy-2,3,5-tri-O-(tert-butyldimethylsilyl)-D-

ribofuranose (9c): THF (4.3 mL) was added to a flame-dried and

argon-purged flask containing 6 (143 mg, 0.226 mmol) and

Pd(PPh₃)₄(5 mol-%, 13 mg, 0.011 mmol), and the mixture was

stirred until a clear solution was formed. The commercial solution

of benzylzinc bromide (0.5  solution in THF, 0.9 mL, 0.454 mmol,

2 equiv.) was added in one portion, and the mixture was stirred at

55 °C for 48 h. After workup, the crude product was chromato-

graphed on silica gel (hexane/EtOAc, 50:1) to give 9c (88 mg, 67%)

as colorless oil. ¹H NMR (500 MHz, CDCl₃): δ = –0.43, –0.14,

0.09, 0.10 and 0.11 (5 s, 18 H, CH₃Si), 0.78, 0.931 and 0.934 (3 s,

3ϫ9 H, (CH₃)₃C), 3.77 (d, J_5Ј,4Ј= 3.7 Hz, 2 H, 5Ј-H), 3.84 (dd,

(CH-3,5), 139.57 (C-1) ppm. IR (CCl ): ν = 3624, 3543, 3084, 3049,

˜

4

2898, 1596, 1576, 1489, 1472, 1463, 1407, 1390, 1362, 1310, 1295,

1255, 1220, 1186, 1118, 1088, 1088, 1073, 1012, 939 cm^–1. HRMS:

calcd. for C₂₃H₄₂BrO₄Si₂[M + H] 517.1727; found 517.1805.

1β-(4-Methylphenyl)-1-deoxy-2,3,5-tri-O-(tert-butyldimethylsilyl)-D-

ribofuranose (9a): Me₃Al (2  in hexanes, 0.48 mL, 0.956 mmol, J_2Ј,1Ј= 7.7 Hz, J_2Ј,3Ј= 4.5 Hz, 1 H, 2Ј-H), 3.97 (s, 2 H, CH₂Ph),

2 equiv.) was added in one portion to a vigorously stirred solution

of 6 (302 mg, 0.478 mmol) and Pd(PPh₃)₄(5 mol-%, 28 mg,

0.024 mmol) in THF (10 mL) under an atmosphere of argon. The

mixture was stirred at 55 °C for 48 h, then worked up by pouring

into saturated NaH₂PO₄and extracted with EtOAc. The crude

product was chromatographed on silica gel (hexane/ethyl acetate,

40:1) to give 9a (243 mg, 90 %) as a colorless oil. ¹H NMR

(500 MHz, CDCl₃): δ = –0.41, –0.13, 0.085, 0.088, 0.11 and 0.13 (6

s, 6 ϫ3 H, CH₃Si), 0.81, 0.93 and 0.95 [3 s, 3ϫ9 H, (CH₃)₃C], 2.33

(s, 3 H, CH₃), 3.77 (dd, J_gem= 10.9 Hz, J_5Јb,4Ј= 3.2 Hz, 1 H, H-

5Јb), 3.80 (dd, J_gem= 10.9 Hz, J_5Јa,4Ј= 4.0 Hz, 1 H, H-5Јa), 3.84

4.01 (td, J_4Ј,5Ј= 3.7 Hz, J_4Ј,3Ј= 2.0 Hz, 1 H, 4Ј-H), 4.12 (ddd, J_3Ј,2Ј

= 4.5 Hz, J_3Ј,4Ј= 2.0 Hz, J_3Ј,1Ј= 0.5 Hz, 1 H, 3Ј-H), 4.74 (d, J_1Ј,2Ј

= 7.7 Hz, 1 H, 1Ј-H), 7.12 (m, 2 H, 3,5-H), 7.14 (m, 2 H, o-Ph-H),

7.18 (m, 1 H, p-Ph-H), 7.26 (m, 2 H, m-Ph-H), 7.33 (m, 2 H, 2,6-

H) ppm. ¹³C NMR (125.7 MHz, CDCl₃): δ = –5.51, –5.36, –4.51,

–4.43 and –4.41 (CH₃Si), 17.99, 18.10 and 18.39 [C(CH₃)₃], 25.87,

25.92 and 26.01 [C(CH₃)₃], 41.60 (CH₂Ph), 63.76 (CH₂-5Ј), 73.86

(CH-3Ј), 79.61 (CH-2Ј), 82.83 (CH-1Ј), 85.82 (CH-4Ј), 125.90 (CH-

p-Ph), 127.13 (CH-2,6), 128.29 (CH-m-Ph), 128.81 (CH-3,5),

128.84 (CH-o-Ph), 138.40 (C-1), 140.35 (C-4), 141.47 (C-i-Ph) ppm.

IR (CCl ): ν = 3087, 3064, 3029, 2897, 1604, 1514, 1495, 1482,

˜

4

(dd, J_2Ј,1Ј= 7.3 Hz, J_2Ј,3Ј= 4.4 Hz, 1 H, H-2Ј), 4.01 (ddd, J_4Ј,5Ј

=

1463, 1454, 1422, 1406, 1389, 1362, 1309, 1286, 1257, 1187, 1031,

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Eur. J. Org. Chem. 2008, 1689–1704

Synthesis of 4- and 3-Substituted Benzene and Aniline C-Ribonucleosides

1020, 939 cm^–1. HRMS (FAB): calcd. for C₃₆H₆₃O₄Si₃[M + H] (CH-4-py), 138.64 (C-4), 141.68 (C-1), 149.61 (CH-6-py), 157.35

643.4034; found 643.4054.

(C-2-py) ppm. IR (CCl ): ν = 2896, 1611, 1588, 1579, 1564, 1468,

˜

4

1468, 1436, 1414, 1408, 1389, 1362, 1308, 1295, 1256, 1220, 1187,

1095, 1080, 1074, 1016, 995, 939 cm^–1. HRMS: calcd. for

C₃₄H₆₀NO₄Si₃[M + H] 630.3830; found 630.3819.

1β-[4-(2-Thienyl)phenyl]-1-deoxy-2,3,5-tri-O-(tert-butyldimethyl-

silyl)-D-ribofuranose (9d): DMF (3.5 mL) was added to a flame-

dried and argon-purged flask containing 6 (480 mg, 0.760 mmol)

and PdCl₂(PPh₃)₂(5 mol-%, 27 mg, 0.038 mmol). After 5 min

stirring at room temperature, tributyl(thiophen-2-yl)stannane

(0.29 mL, 0.912 mmol, 1.2 equiv.) was added, and reaction vessel

was immersed into an oil bath preheated to 100 °C. After 10 min,

the reaction mixture became dark-brown and the reaction was fin-

ished (monitored by TLC; hexanes/EtOAc, 10:1). The crude reac-

tion mixture was diluted with Et₂O, washed with saturated NaCl

solution, and dried with MgSO₄. After evaporation of the solvents

under reduced pressure, the crude product was chromatographed

on silica gel (hexanes/EtOAc, 50:1) to obtain 9d (381 mg, 79%) as

a colorless oil. ¹H NMR (600 MHz, CDCl₃): δ = –0.41, –0.12, 0.10,

0.13 and 0.14 (5 s, 18 H, CH₃Si), 0.81, 0.94 and 0.95 [3 s, 3ϫ9 H,

(CH₃)₃C], 3.79 (dd, J_gem= 10.9 Hz, J_5Јb,4Ј= 3.0 Hz, 1 H, 5Јb-H),

1β-[4-(4-Fluorophenyl)phenyl]-1-deoxy-2,3,5-tri-O-(tert-butyldi-

methylsilyl)-D-ribofuranose (9f): Toluene (4 mL) was added to a

flame-dried and argon-purged flask containing 6 (344 mg,

0.545 mmol), Pd(PPh₃)₄(2.5 mol-%, 16 mg, 0.014 mmol), K₂CO₃

(151 mg, 1.090 mmol, 2 equiv.), and 4-fluorophenylboronic acid

(152 mg, 1.090 mmol, 2 equiv.), and the red mixture was stirred at

110 °C for 10 min. After the reaction was complete (monitored by

TLC; hexanes/toluene, 2:1), the reaction mixture was evaporated

under reduced pressure and chromatographed on silica gel (hex-

anes/toluene, 2:1) to give 9f (301 mg, 85%) as a colorless oil. ¹H

NMR (600 MHz, CDCl₃): δ = –0.42, –0.11, 0.10, 0.13 and 0.14 (5

s, 18 H, CH₃Si), 0.81, 0.94 and 0.95 [3 s, 3ϫ9 H, (CH₃)₃C], 3.80

(dd, J_gem= 10.9 Hz, J_5Јb,4Ј= 2.9 Hz, 1 H, 5Јb-H), 3.83 (dd, J_gem

=

3.82 (dd, J_gem= 10.9 Hz, J_5Јa,4Ј= 3.9 Hz, 1 H, 5Јa-H), 3.87 (dd, 10.9 Hz, J_5Јa,4Ј= 3.9 Hz, 1 H, 5Јa-H), 3.89 (dd, J_2Ј,1Ј= 7.6 Hz, J_2Ј,3Ј

J_2Ј,1Ј= 7.7 Hz, J_2Ј,3Ј= 4.4 Hz, 1 H, 2Ј-H), 4.04 (ddd, J_4Ј,5Ј= 3.9, = 4.4 Hz, 1 H, 2Ј-H), 4.05 (ddd, J_4Ј,5Ј= 3.9, 2.9 Hz, J_4Ј,3Ј= 2.0 Hz,

3.0 Hz, J_4Ј,3Ј= 2.0 Hz, 1 H, 4Ј-H), 4.14 (dd, J_3Ј,2Ј= 4.4 Hz, J_3Ј,4Ј

=

1 H, 4Ј-H), 4.15 (ddd, J_3Ј,2Ј= 4.4 Hz, J_3Ј,4Ј= 2.0 Hz, J_3Ј,1Ј= 0.5 Hz,

2.0 Hz, 1 H, 3Ј-H), 4.78 (d, J_1Ј,2Ј= 7.7 Hz, 1 H, 1Ј-H), 7.08 (dd, 1 H, 3Ј-H), 4.81 (d, J_1Ј,2Ј= 7.6 Hz, 1 H, 1Ј-H), 7.12 (m, 2 H, m-

J_4,5= 5.1 Hz, J_4,3= 3.6 Hz, 1 H, 4-thienyl-H), 7.26 (dd, J_5,4

5.1 Hz, J_5,3= 1.2 Hz, 1 H, 5-thienyl-H), 7.32 (dd, J_3,4= 3.6 Hz,

=

C₆H₄F-H), 7.49 (m, 4 H, 2,3,5,6-H), 7.54 (m, 2 H, o-C₆H₄F-H)

ppm. ¹³C NMR (151 MHz, CDCl₃): δ = –5.51, –5.40, –5.39, –4.50,

J_3,5= 1.2 Hz, 1 H, 3-thienyl-H), 7.43 (m, 2 H, 2,6-H), 7.55 (m, 2 –4.44 and –4.42 (CH₃Si), 17.96, 18.09 and 18.38 [C(CH₃)₃], 25.85,

H, 3,5-H) ppm. ¹³C NMR (151 MHz, CDCl₃): δ = –5.51, –5.38, 25.90 and 26.01 [C(CH₃)₃], 63.67 (CH₂-5Ј), 73.84 (CH-3Ј), 79.61

–5.32, –4.50, –4.45 and –4.43 (CH₃Si), 17.95, 18.09 and 18.38

[C(CH₃)₃], 25.85, 25.90 and 26.01 [C(CH₃)₃], 63.67 (CH₂-5Ј), 73.86

(CH-2Ј), 82.71 (CH-1Ј), 85.92 (CH-4Ј), 115.51 (d, J_C,F= 21 Hz,

CH-m-C₆H₄F), 126.57 (CH-3,5), 127.39 (CH-2,6), 128.58 (d, J_C,F

(CH-3Ј), 79.51 (CH-2Ј), 82.67 (CH-1Ј), 85.92 (CH-4Ј), 122.85 (CH- = 8 Hz, CH-o-C₆H₄F), 137.26 (d, J_C,F= 3 Hz, C-i-C₆H₄F), 139.53

3-thienyl), 124.50 (CH-5-thienyl), 125.49 (CH-3,5), 127.42 (CH- (C-4), 139.83 (C-1), 162.36 (d, J_C,F= 246 Hz, C-p-C₆H₄F) ppm.

2,6), 127.94 (CH-4-thienyl), 133.68 (C-4), 140.08 (C-1), 144.50 (C-

¹⁹F NMR (470.3 MHz, CDCl ): δ = –116.08 ppm. IR (CCl ): ν =

˜

3 4

2-thienyl) ppm. IR (CCl ): ν = 3115, 3077, 3030, 2956, 2897, 1613,

3033, 2956, 2897, 1615, 1605, 1595, 1569, 1525, 1499, 1472, 1463,

1405, 1390, 1362, 1303, 1280, 1236, 1226, 1186, 1158, 1096, 1080,

1026, 1007, 945, 939 cm^–1. HRMS (FAB): calcd. for C₃₅H₅₉FO₄-

Si₃Na [M + Na] 669.3603; found 669.3605.

˜

4

1538, 1504, 1472, 1433, 1418, 1407, 1389, 1362, 1309, 1298, 1263,

1257, 1257, 1215, 1187, 1112, 1095, 1081, 1081, 1046, 1019, 971,

946, 938, 839 cm^–1. HRMS (FAB): calcd. for C₃₃H₅₈O₄SSi₃Na [M

+ Na] 657.3261; found 657.3249.

1β-[4-(4-Methoxyphenyl)phenyl]-1-deoxy-2,3,5-tri-O-(tert-butyldi-

1β-[4-(Pyridin-2-yl)phenyl]-1-deoxy-2,3,5-tri-O-(tert-butyldimethyl- methylsilyl)-

silyl)- -ribofuranose (9e): DMF (2 mL) was added to a flame-dried

D-ribofuranose (9g): Toluene (4 mL) was added to a

D

flame-dried and argon-purged flask containing 6 (461 mg,

0.731 mmol), Pd(PPh₃)₄(5 mol-%, 43 mg, 0.037 mmol), K₂CO₃

(202 mg, 1.461 mmol, 2 equiv.), and 4-methoxyphenylboronic acid

(222 mg, 1.461 mmol, 2 equiv.), and the yellow mixture was stirred

at 110 °C for 3.5 h. After the reaction was complete (monitored by

TLC; hexanes/toluene, 2:1), the reaction mixture was filtered

though Celite, evaporated under reduced pressure, and chromato-

graphed on silica gel (gradient hexanes/toluene, 4:1 to 1:1) to give

and argon-purged flask containing 6 (273 mg, 0.432 mmol) and

PdCl₂(PPh₃)₂(5 mol-%, 15 mg, 0.022 mmol). After 5 min stirring

at room temperature, 2-(tributylstannyl)pyridine (0.17 mL,

0.605 mmol, 1.4 equiv.) was added in one portion, and the reaction

vessel was immersed into an oil bath preheated at 100 °C. After

32 h, the reaction mixture was diluted with Et₂O and filtered

trough Celite. The filtrate was washed with HCl (2 ) and saturated

NaHCO₃solution and then dried with MgSO₄. After evaporation

of the solvent under reduced pressure, the crude product was chro-

matographed on silica gel (toluene/hexanes, 4:1 to hexanes/EtOAc,

13:1) to obtain 9e (152 mg, 56 %) as a colorless oil. ¹H NMR

(600 MHz, CDCl₃): δ = –0.41, –0.12, 0.10, 0.13 and 0.15 (5 s, 18

H, CH₃Si), 0.82, 0.94 and 0.96 [3 s, 3ϫ9 H, (CH₃)₃C], 3.80 (dd,

1

9g (350 mg, 72%) as a colorless oil. H NMR (600 MHz, CDCl₃):

δ = –0.41, –0.12, 0.10, 0.13 and 0.14 (5 s, 18 H, CH₃Si), 0.81, 0.94

and 0.95 [3 s, 3ϫ9 H, (CH₃)₃C], 3.80 (dd, J_gem= 10.9 Hz, J_5Јb,4Ј

3.0 Hz, 1 H, H-5Јb), 3.83 (dd, J_gem= 10.9 Hz, J_5Јa,4Ј= 4.0 Hz, 1

H, H-5Јa), 3.85 (s, 3 H, CH₃O), 3.89 (dd, J_2Ј,1Ј= 7.5 Hz, J_2Ј,3Ј

4.4 Hz, 1 H, H-2Ј), 4.05 (ddd, J_4Ј,5Ј= 4.0, 3.0 Hz, J_4Ј,3Ј= 2.2 Hz, 1

H, H-4Ј), 4.15 (ddd, J_3Ј,2Ј= 4.4 Hz, J_3Ј,4Ј= 2.2 Hz, J_3Ј,1Ј= 0.4 Hz,

1 H, H-3Ј), 4.81 (d, J_1Ј,2Ј= 7.5 Hz, 1 H, H-1Ј), 6.97 (m, 2 H, H-m-

=

J_gem= 10.9 Hz, J_5Јb,4Ј= 2.9 Hz, 1 H, 5Јb-H), 3.84 (dd, J_gem

=

10.9 Hz, J_5Јa,4Ј= 3.8 Hz, 1 H, 5Јa-H), 3.91 (dd, J_2Ј,1Ј= 7.6 Hz, J_2Ј,3Ј

= 4.4 Hz, 1 H, 2Ј-H), 4.06 (ddd, J_4Ј,5Ј= 3.8, 2.9 Hz, J_4Ј,3Ј= 2.0 Hz, C₆H₄OMe), 7.46 (m, 2 H, H-2,6), 7.49 (m, 2 H, H-3,5), 7.54 (m, 2

1 H, 4Ј-H), 4.16 (ddd, J_3Ј,2Ј= 4.4 Hz, J_3Ј,4Ј= 2.0 Hz, J_3Ј,1Ј= 0.4 Hz,

1 H, 3Ј-H), 4.84 (d, J_1Ј,2Ј= 7.6 Hz, 1 H, 1Ј-H), 7.22 (m, 1 H, 5-py-

H, H-o-C₆H₄OMe) ppm. ¹³C NMR (151 MHz, CDCl₃): δ = –5.50,

–5.39, –5.37, –4.50 and –4.44 (CH₃Si), 17.97, 18.10 and 18.39

H), 7.54 (m, 2 H, 2,6-H), 7.72 –7.77 (m, 2 H, 3,4-py-H), 7.95 (m, [C(CH₃)₃], 25.86, 25.91 and 26.01 [C(CH₃)₃], 55.36 (CH₃O), 63.66

2 H, 3,5-H), 8.70 (ddd, J_6,5= 4.8 Hz, J_6,4= 1.7 Hz, J_6,3= 1.3 Hz, (CH₂-5Ј), 73.79 (CH-3Ј), 79.58 (CH-2Ј), 82.84 (CH-1Ј), 85.78 (CH-

1 H, 6-py-H) ppm. ¹³C NMR (151 MHz, CDCl₃): δ = –5.51, –5.36, 4Ј), 114.12 (CH-m-C₆H₄OMe), 126.27 (CH-3,5), 127.29 (CH-2,6),

–5.27, –4.51, –4.45 and –4.42 (CH₃Si), 17.94, 18.09 and 18.39

[C(CH₃)₃], 25.87, 25.90 and 26.02 [C(CH₃)₃], 63.66 (CH₂-5Ј), 73.87

128.04 (CH-o-C₆H₄OMe), 133.72 (C-i-C₆H₄OMe), 139.13 (C-1),

140.07 (C-1), 159.01 (C-p-C H OMe) ppm. IR (CCl ): ν = 3033,

˜

6

4

(CH-3Ј), 79.55 (CH-2Ј), 82.74 (CH-1Ј), 85.95 (CH-4Ј), 120.51 (CH- 3001, 2956, 2897, 2837, 1612, 1584, 1567, 1527, 1500, 1472, 1442,

3-py), 121.97 (CH-5-py), 126.49 (CH-3,5), 127.31 (CH-2,6), 136.69 1428, 1405, 1389, 1362, 1362, 1310, 1299, 1287, 1270, 1263, 1260,

Eur. J. Org. Chem. 2008, 1689–1704

www.eurjoc.org

1695

ˇ

M. Stefko, R. Pohl, B. Klepetárˇová, M. Hocek

FULL PAPER

1249, 1220, 1215, 1181, 1175, 1110, 1095, 1080, 1044, 1026, 1016,

dried and argon-purged flask containing 6 (387 mg, 0.614 mmol),

949, 939 cm^–1. HRMS (FAB): calcd. for C₃₆H₆₃O₅Si₃[M + H] Pd₂dba₃(14 mg, 0.015 mmol), (2-biphenyl)-di-tert-butylphosphane

659.3983; found 659.3971.

(18 mg, 0.061 mmol), and sodium tert-butoxide (177 mg,

1.84 mmol, 3 equiv.), and the resulting brown-yellow solution was

stirred at 90 °C for 8 h. After the reaction was complete (monitored

by TLC; hexanes/EtOAc, 10:1), the reaction mixture was evapo-

rated under reduced pressure and directly chromatographed on sil-

ica gel (gradient hexanes/toluene, 2:1 to toluene) to give 9j (263 mg,

69%) as a colorless oil. ¹H NMR (600 MHz, CDCl₃): δ = –0.48,

–0.15, 0.09, 0.10, 0.11 and 0.13 (6 s, 6ϫ3 H, CH₃Si), 0.77, 0.937

and 0.941 [3 s, 3ϫ9 H, (CH₃)₃CSi], 1.31 [s, 9 H, (CH₃)₃CO], 3.78

1β-(4-Aminophenyl)-1-deoxy-2,3,5-tri-O-(tert-butyldimethylsilyl)-D-

ribofuranose (9h): LiN(SiMe₃)₂(1  solution in THF, 1.47 mL,

1.468 mmol, 1.3 equiv.) was added to a flame-dried and argon-

purged flask containing 6 (714 mg, 1.129 mmol), (2-biphenyl)dicy-

clohexylphosphane (40 mg, 0.113 mmol), and Pd₂(dba)₃(26 mg,

0.028 mmol), and the mixture was stirred at 60 °C for 48 h. After

cooling to room temperature, the reaction mixture was diluted with

Et₂O (5 mL) and HCl (2 , 1 mL) was added. The resulting hetero-

geneous mixture was stirred for an additional 5 min then transfer-

red into a saturated solution of NaHCO₃and extracted with Et₂O.

The crude product was chromatographed on silica gel (gradient

hexane/EtOAc, 50:1 to 15:1) to gave 9h (641 mg, 84%) as a yellow

(d, J_5Ј,4Ј= 3.5 Hz, 2 H, 5Ј-H), 3.84 (dd, J_2Ј,1Ј= 8.2 Hz, J_2Ј,3Ј

=

4.5 Hz, 1 H, 2Ј-H), 4.01 (td, J_4Ј,5Ј= 3.5 Hz, J_4Ј,3Ј= 1.4 Hz, 1 H,

4Ј-H), 4.12 (ddd, J_3Ј,2Ј= 4.5 Hz, J_3Ј,4Ј= 1.4 Hz, J_3Ј,1Ј= 0.5 Hz, 1

H, 3Ј-H), 4.72 (d, J_1Ј,2Ј= 8.2 Hz, 1 H, 1Ј-H), 6.94 (m, 2 H, 3,5-H),

7.32 (m, 2 H, 2,6-H) ppm. ¹³C NMR (151 MHz, CDCl₃): δ = –5.55,

–5.46, –5.44, –4.51, –4.49 and –4.41 (CH₃Si), 17.97, 18.09 and

18.34 [SiC(CH₃)₃], 25.84, 25.89 and 25.97 [(CH₃)₃CSi], 28.76

[(CH₃)₃CO], 63.88 (CH₂-5Ј), 74.18 (CH-3Ј), 78.40 [OC(CH₃)₃],

79.60 (CH-2Ј), 82.29 (CH-1Ј), 86.26 (CH-4Ј), 124.15 (CH-3,5),

1

oil. H NMR (500 MHz, CDCl₃): δ = –0.38, –0.13, 0.08, 0.10 and

0.12 (5 s, 18 H, CH₃Si), 0.80, 0.93 and 0.94 [3 s, 3 ϫ 9 H,

(CH₃)₃C], 3.60 (br. s, 2 H, NH₂), 3.75 (dd, J_gem= 10.9 Hz, J_5Јb,4Ј

= 3.4 Hz, 1 H, H-5Јb), 3.78 (dd, J_gem= 10.9 Hz, J_5Јa,4Ј= 3.8 Hz, 1

H, H-5Јa), 3.82 (dd, J_2Ј,1Ј= 7.5 Hz, J_2Ј,3Ј= 4.5 Hz, 1 H, H-2Ј), 3.98

(ddd, J_4Ј,5Ј= 3.8, 3.4 Hz, J_4Ј,3Ј= 2.1 Hz, 1 H, H-4Ј), 4.12 (dd, J_3Ј,2Ј

= 4.5 Hz, J_3Ј,4Ј= 2.1 Hz, 1 H, H-3Ј), 4.67 (d, J_1Ј,2Ј= 7.5 Hz, 1 H,

H-1Ј), 6.63 (m, 2 H, H-3,5), 7.19 (m, 2 H, H-2,6) ppm. ¹³C NMR

(125.7 MHz, CDCl₃): δ = –5.51, –5.40, –5.21, –4.50 and –4.44

(CH₃Si), 17.98, 18.10 and 18.39 [C(CH₃)₃], 25.89, 25.92 and 26.02

[C(CH₃)₃], 63.77 (CH₂-5Ј), 73.82 (CH-3Ј), 79.31 (CH-2Ј), 82.96

(CH-1Ј), 85.47 (CH-4Ј), 114.80 (CH-3,5), 126.13 (CH-2,6), 130.62

127.58 (CH-2,6), 135.61 (C-1), 154.79 (C-4) ppm. IR (CCl ): ν =

˜

4

2955, 2930, 2896, 2858, 1609, 1508, 1473, 1463, 1389, 1364, 1257,

1158, 1112, 1045, 1006, 969, 938, 901, 837, 777 cm^–1. HRMS

(FAB): calcd. for C₃₃H₆₅O₅Si₃[M + H] 625.4140; found 625.4150.

1β-(3-Bromophenyl)-2,3,5-tri-O-(tert-butyldimethylsilyl)-

furanose (13) and 1β-(3-Bromophenyl)-1,3,5-tri-O-(tert-butyldi-

methylsilyl)- -ribofuranose (14): To a stirred solution of m-dibro-

D-ribo-

D

(C-1), 145.89 (C-4) ppm. IR (CCl ): ν = 3479, 3395, 3026, 3010,

˜

4

mobenzene (4.05 mL, 8.07 g, 0.034 mol, 1.7 equiv.) in dry THF

(80 mL) cooled to –72 °C was added nBuLi (1.6  in hexanes,

20.5 mL, 0.033 mol, 1.65 equiv.), and the mixture was stirred for

30 min. Then, a solution of TBS-protected ribonolactone 3 (10 g,

0.020 mol) in dry THF (80 mL) was slowly added over 30 min, and

the resulting yellow solution was stirred for additional 30 min at

–72 °C and then quenched with a saturated NH₄Cl solution. After

extraction with AcOEt, the combined organic phase was washed

with saturated NH₄Cl solution, dried (MgSO₄), and concentrated

under vacuum to obtain 14.3 g of colorless oil. Purification on sil-

ica gel (gradient hexane to hexane/toluene, 1:1 to toluene) gave de-

sired hemiketal 13 (11.8 g, 89%) as colorless oil and 14 (0.5 g, 4%)

as a white solid, which was crystallized from MeOH. Compound

13: ¹H NMR (600 MHz, CDCl₃): δ = –0.54, –0.14, 0.128, 0.132,

0.133 and 0.157 (6 s, 6ϫ3 H, CH₃Si), 0.84, 0.94 and 0.95 [3 s, 3ϫ9

H, (CH₃)₃C], 3.81 (dd, J_gem= 11.0 Hz, J_5Јb,4Ј= 2.4 Hz, 1 H, 5Јb-

H), 3.86 (dd, J_gem= 11.0 Hz, J_5Јa,4Ј= 3.3 Hz, 1 H, 5Јa-H), 4.00 (d,

J_2Ј,3Ј= 4.7 Hz, 1 H, 2Ј-H), 4.17 (dd, J_3Ј,2Ј= 4.7 Hz, J_3Ј,4Ј= 0.6 Hz,

1 H, 3Ј-H), 4.23 (ddd, J_4Ј,5Ј= 3.3, 2.4 Hz, J_4Ј,3Ј= 0.6 Hz, 1 H, 4Ј-

H), 5.11 (s, 1 H, OH), 7.18 (t, J_5,4= 7.9 Hz, J_5,6= 7.8 Hz, 1 H, 5-

H), 7.41 (ddd, J_4,5= 7.9 Hz, J_4,2= 2.1 Hz, J_4,6= 1.1 Hz, 1 H, 4-

H), 7.58 (ddd, J_6,5= 7.8 Hz, J_6,2= 1.6 Hz, J_6,4= 1.1 Hz, 1 H, 6-

H), 7.80 (t, J_2,4= 2.1 Hz, J_2,6= 1.6 Hz, 1 H, 2-H) ppm. ¹³C NMR

(151 MHz, CDCl₃): δ = –5.98, –5.64, –5.43, –4.86, –4.58 and –4.53

(CH₃Si), 17.82, 17.90 and 18.27 [C(CH₃)₃], 25.72, 25.76 and 25.95

[C(CH₃)₃], 63.60 (CH₂-5Ј), 75.01 (CH-3Ј), 77.85 (CH-2Ј), 85.35

(CH-4Ј), 103.51 (CH-1Ј), 121.85 (C-3), 125.51 (CH-6), 129.21 (CH-

1956, 1896, 1623, 1588, 1519, 1472, 1406, 1389, 1362, 1331, 1297,

1274, 1263, 1257, 1219, 1175, 1096, 1083, 1013, 940, 928, 838 cm^–1.

HRMS: calcd. for C₂₉H₅₈NO₄Si₃[M + H] 568.3673; found

568.3681.

1β-(4-Dimethylaminophenyl)-1-deoxy-2,3,5-tri-O-(tert-butyldimeth-

ylsilyl)-D-ribofuranose (9i): Toluene (2.0 mL) was added to a flame-

dried and argon-purged flask containing 6 (482 mg, 0.763 mmol),

Pd₂(dba)₃(17 mg, 0.019 mmol), (2-biphenyl)-di-tert-butylphos-

phane (27 mg, 0.076 mmol), sodium tert-butoxide (440 mg,

4.58 mmol, 6 equiv.), and Me₂NH·HCl (311 mg, 3.815 mmol,

5 equiv.). The resulting mixture was stirred at 37 °C for 72 h and

then diluted with Et₂O, poured into water, extracted with Et₂O,

and dried with MgSO₄. After removal of the solvent under reduced

pressure, the crude product was chromatographed on silica gel (gra-

dient hexane/EtOAc, 250:1 to 63:1) to give 9i (455 mg, 82%) as a

yellow oil. ¹H NMR (500 MHz, CDCl₃): δ = –0.36, –0.12, 0.08,

0.09, 0.11 and 0.12 (6 s, 6ϫ3 H, CH₃Si), 0.81, 0.93 and 0.95 [3 s,

3ϫ9 H, (CH₃)₃C], 2.92 [s, 6 H, (CH₃)₂N], 3.76 (dd, J_gem= 10.9 Hz,

J_5Јb,4Ј= 3.5 Hz, 1 H, 5Јb-H), 3.79 (dd, J_gem= 10.9 Hz, J_5Јa,4Ј

=

3.9 Hz, 1 H, 5Јa-H), 3.85 (dd, J_2Ј,1Ј= 7.2 Hz, J_2Ј,3Ј= 4.5 Hz, 1 H,

2Ј-H), 3.99 (ddd, J_4Ј,5Ј= 3.9, 3.5 Hz, J_4Ј,3Ј= 2.5 Hz, 1 H, 4Ј-H),

4.13 (dd, J_3Ј,2Ј= 4.5 Hz, J_3Ј,4Ј= 2.5 Hz, 1 H, 3Ј-H), 4.70 (d, J_1Ј,2Ј

= 7.2 Hz, 1 H, 1Ј-H), 6.68 (m, 2 H, 3,5-H), 7.25 (m, 2 H, 2,6-H)

ppm. ¹³C NMR (125.7 MHz, CDCl₃): δ = –5.49, –5.36, –5.12,

–4.51, –4.46 and –4.41 (CH₃Si), 18.00, 18.11 and 18.43 [C(CH₃)₃],

25.90, 25.94 and 26.04 [C(CH₃)₃], 40.86 [(CH₃)₂N], 63.75 (CH₂-5Ј),

73.68 (CH-3Ј), 79.22 (CH-2Ј), 83.19 (CH-1Ј), 85.16 (CH-4Ј), 112.51

(CH-3,5), 127.84 (CH-2,6), 128.61 (C-1), 150.53 (C-4) ppm. IR

5), 130.07 (CH-2), 131.08 (CH-4), 143.20 (C-1) ppm. IR (CCl ): ν

˜

4

= 3605, 3503, 3071, 2956, 2930, 2859, 1600, 1582, 1571, 1472, 1463,

1362, 1259, 1170, 1150, 1106, 1005, 962, 839 cm^–1. HRMS (FAB):

calcd. for C₂₉H₅₅BrO₅Si₃Na [M + Na] 669.2438; found 669.2434.

Compound 14: White crystals, m.p. 59–60 °C. ¹H NMR (600 MHz,

CDCl₃): δ = –0.33, –0.08, 0.09, 0.11 and 0.12 (5 s, 12 H, CH₃Si),

(CCl ): ν = 3076, 2896, 2803, 1617, 1572, 1524, 1472, 1463, 1444,

˜

4

1406, 1389, 1361, 1349, 1318, 1286, 1257, 1252, 1188, 998, 948,

941, 838 cm^–1. HRMS (FAB): calcd. for C₃₁H₆₂NO₄Si₃[M + H]

596.3987; found 596.3965.

0.86, 0.92 and 0.93 [3 s, 3 ϫ 9 H, (CH₃)₃C], 3.01 (d, J_OH,2Ј

=

1β-(4-tert-Butoxyphenyl)-1-deoxy-2,3,5-tri-O-(tert-butyldimethyl- 12.2 Hz, 1 H, OH-2Ј), 3.70 (dd, J_2Ј,OH= 12.2 Hz, J_2Ј,3Ј= 6.4 Hz, 1

silyl)-D-ribofuranose (9j): Toluene (1.8 mL) was added to a flame-

H, 2Ј-H), 3.78 (dd, J_gem= 11.0 Hz, J_5Јb,4Ј= 2.7 Hz, 1 H, 5Јb-H),

1696

www.eurjoc.org

Synthesis of 4- and 3-Substituted Benzene and Aniline C-Ribonucleosides

3.85 (dd, J_gem= 11.0 Hz, J_5Јa,4Ј= 3.1 Hz, 1 H, 5Јa-H), 4.11 (dd, J_OH,2Ј= 8.7 Hz, 1 H, OH-2Ј), 3.78 (dd, J_gem= 11.1 Hz, J_5Јb,4Ј

=

J_3Ј,2Ј= 6.4 Hz, J_3Ј,4Ј= 1.9 Hz, 1 H, 3Ј-H), 4.22 (ddd, J_4Ј,5Ј= 3.1, 3.1 Hz, 1 H, 5Јb-H), 3.82 (dd, J_gem= 11.1 Hz, J_5Јa,4Ј= 3.8 Hz, 1 H,

2.7 Hz, J_4Ј,3Ј= 1.9 Hz, 1 H, 4Ј-H), 7.16 (ddd, J_5,4= 7.9 Hz, J_5,6

7.8 Hz, J_5,2= 0.3 Hz, 1 H, 5-H), 7.39 (ddd, J_4,5= 7.9 Hz, J_4,2

2.1 Hz, J_4,6= 1.1 Hz, 1 H, 4-H), 7.52 (ddd, J_6,5= 7.8 Hz, J_6,2

1.6 Hz, J_6,4= 1.1 Hz, 1 H, 6-H), 7.75 (ddd, J_2,4= 2.1 Hz, J_2,6

=

5Јa-H), 3.83 (ddd, J_OH,2Ј= 8.7 Hz, J_2Ј,1Ј= 7.0 Hz, J_2Ј,3Ј= 5.5 Hz, 1

H, 2Ј-H), 4.00 (ddd, J_4Ј,5Ј= 3.8, 3.1 Hz, J_4Ј,3Ј= 3.0 Hz, 1 H, 4Ј-H),

4.28 (dd, J_3Ј,2Ј= 5.5 Hz, J_3Ј,4Ј= 3.0 Hz, 1 H, 3Ј-H), 4.63 (d, J_1Ј,2Ј

= 7.0 Hz, 1 H, 1Ј-H), 7.20 (t, J_5,4= J_5,6= 7.8 Hz, 1 H, 5-H), 7.37

(dddd, J_6,5= 7.8 Hz, J_6,2= 1.6 Hz, J_6,4= 1.0 Hz, J_6,1Ј= 0.6 Hz, 1

H, 6-H), 7.40 (ddd, J_4,5= 7.8 Hz, J_4,2= 2.0 Hz, J_4,6= 1.0 Hz, 1 H,

1.6 Hz, J_2,5= 0.3 Hz, 1 H, 2-H) ppm. ¹³C NMR (151 MHz,

CDCl₃): δ = –5.67, –5.43, –4.92, –4.71, –3.79 and –2.90 (CH₃Si),

18.01, 18.25 and 18.36 [C(CH₃)₃], 25.82, 25.86 and 26.06 [C- 4-H), 7.61 (dd, J_2,4= 2.0 Hz, J_2,6= 1.6 Hz, 1 H, 2-H) ppm. ¹³C

(CH₃)₃], 63.63 (CH₂-5Ј), 72.98 (CH-3Ј), 78.88 (CH-2Ј), 86.44 (CH- NMR (151 MHz, CDCl₃): δ = –5.53, –5.37, –4.89 and –4.42

4Ј), 103.63 (CH-1Ј), 121.82 (C-3), 124.50 (CH-6), 128.68 (CH-2),

(CH₃Si), 18.05 and 18.36 [C(CH₃)₃], 25.76 and 25.94 [C(CH₃)₃],

129.24 (CH-5), 130.66 (CH-4), 146.08 (C-1) ppm. IR (CCl ): ν = 62.90 (CH₂-5Ј), 72.98 (CH-3Ј), 77.75 (CH-2Ј), 83.61 (CH-1Ј), 85.17

˜

4

2955, 2930, 2896, 2858, 1609, 1508, 1473, 1463, 1389, 1364, 1257,

(CH-4Ј), 122.53 (C-3), 124.72 (CH-6), 128.85 (CH-2), 129.79 (CH-

1158, 1112, 969, 938 cm^–1. HRMS (FAB): calcd. for C₂₉H₅₅BrO₅- 5), 130.67 (CH-4), 142.82 (C-1) ppm. IR (CCl ): ν = 3541, 2956,

˜

4

Si₃Na [M + Na] 669.2438; found 669.2434. HRMS: calcd. for

C₂₉H₅₆BrO₅Si₃[M + H] 647.2619; found 647.2602.

2930, 2898, 2858, 1729, 1598, 1570, 1472, 1463, 1389, 1258, 1115,

1090, 1057, 1024, 822 cm^–1. HRMS (FAB): calcd. for C₂₃H₄₂O₄-

Si₂Br [M + H] 517.1805; found 517.1799.

1β-(3-Bromophenyl)-1-deoxy-2,3,5-tri-O-(tert-butyldimethylsilyl)-D-

ribofuranose (15): Et₃SiH (9.7 mL, 0.061 mol, 3.33 equiv.) was

added in one portion to a solution of hemiketal 13 (11.8 g,

0.018 mol) in dry CH₂Cl₂(70 mL) in an ice–brine bath (–10 °C)

under an atmosphere of argon. After 5 min, BF₃·Et₂O (2.6 mL,

0.022 mol, 1.2 equiv.) was added over 1 min by syringe, and the

solution was stirred for an additional 5 min. The mixture was then

quenched with saturated NaHCO₃and extracted with CH₂Cl₂. The

combined organic layer was washed with saturated NH₄Cl solu-

tion, dried with MgSO₄, and concentrated under reduced pressure.

The crude product was chromatographed on silica gel (gradient

hexane/toluene, 2:1 to toluene) to give 15 (9.7 g, 84%) as a colorless

1β-(3-Methylphenyl)-1-deoxy-2,3,5-tri-O-(tert-butyldimethylsilyl)-D-

ribofuranose (18a): Compound 18a was prepared according to the

procedure outlined for 9a starting from 15 (560 mg, 0.887 mmol).

1

C-nucleoside 18a was prepared in 95% yield as a colorless oil. H

NMR (600 MHz, CDCl₃): δ = –0.48, –0.14, 0.09, 0.10, 0.12 and

0.13 (6 s, 6 ϫ 3 H, CH₃Si), 0.79, 0.94 and 0.95 [3 s, 3 ϫ 9 H,

(CH₃)₃C], 2.32 (s, 3 H, CH₃), 3.78 (dd, J_gem= 10.9, J_5Јb,4Ј= 3.1 Hz,

1 H, 5Јb-H), 3.80 (dd, J_gem= 10.9 Hz, J_5Јa,4Ј= 3.9 Hz, 1 H, 5Јa-

H), 3.83 (dd, J_2Ј,1Ј= 7.9 Hz, J_2Ј,3Ј= 4.7 Hz, 1 H, 2Ј-H), 4.02 (ddd,

J_4Ј,5Ј= 3.9, 3.1 Hz, J_4Ј,3Ј= 1.7 Hz, 1 H, 4Ј-H), 4.12 (dd, J_3Ј,2Ј

=

4.7 Hz, J_3Ј,4Ј= 1.7 Hz, 1 H, 3Ј-H), 4.73 (d, J_1Ј,2Ј= 7.9 Hz, 1 H, 1Ј-

H), 7.06 (ddd, J_4,5= 7.4 Hz, J_4,2= 1.7 Hz, J_4,6= 0.8 Hz, 1 H, 4-

H), 7.18 (dd, J_5,6= 8.1 Hz, J_5,4= 7.4 Hz, 1 H, 5-H), 7.20 –7.22 (m,

2 H, 2-H and 6-H) ppm. ¹³C NMR (151 MHz, CDCl₃): δ = –5.59,

–5.53, –5.42, –4.53, –4.47 and –4.42 (CH₃Si), 17.94, 18.08 and

18.35 [C(CH₃)₃], 21.33 (CH₃), 25.82, 25.90 and 25.99 [C(CH₃)₃],

63.78 (CH₂-5Ј), 74.03 (CH-3Ј), 79.50 (CH-2Ј), 82.73 (CH-1Ј), 86.05

(CH-4Ј), 124.02 (CH-6), 127.50 (CH-2), 127.86 (CH-5), 128.33

1

oil, which crystallized on standing. H NMR (600 MHz, CDCl₃):

δ = –0.47, –0.12, 0.09, 0.10, 0.12 and 0.14 (6 s, 6ϫ3 H, CH₃Si),

0.81, 0.937 and 0.941 [3 s, 3ϫ9 H, (CH₃)₃C], 3.77 (dd, J_gem

11.0 Hz, J_5Јb,4Ј= 2.8 Hz, 1 H, 5Јb-H), 3.80 (dd, J_gem= 11.0 Hz,

J_5Јa,4Ј= 3.6 Hz, 1 H, 5Јa-H), 3.82 (dd, J_2Ј,1Ј= 8.3 Hz, J_2Ј,3Ј

=

4.4 Hz, 1 H, 2Ј-H), 4.03 (ddd, J_4Ј,5Ј= 3.6, 2.8 Hz, J_4Ј,3Ј= 1.3 Hz, 1

H, 4Ј-H), 4.11 (ddd, J_3Ј,2Ј= 4.4 Hz, J_3Ј,4Ј= 1.3 Hz, J_3Ј,1Ј= 0.5 Hz,

1 H, 3Ј-H), 4.72 (d, J_1Ј,2Ј= 8.3 Hz, 1 H, 1Ј-H), 7.16 (dd, J_5,4

7.9 Hz, J_5,6= 7.7 Hz, 1 H, 5-H), 7.34 (dddd, J_6,5= 7.7 Hz, J_6,2

1.5 Hz, J_6,4= 1.1 Hz, J_6,1Ј= 0.6 Hz, 1 H, 6-H), 7.38 (ddd, J_4,5

7.9 Hz, J_4,2= 2.1 Hz, J_4,6= 1.1 Hz, 1 H, 4-H), 7.59 (ddt, J_2,4

=

(CH-4), 137.40 (C-3), 140.38 (C-1) ppm. IR (CCl ): ν = 3107, 3029,

˜

4

2897, 1661, 1596, 1490, 1472, 1463, 1406, 1389, 1377, 1362, 1281,

1254, 1166, 1094, 1082, 939, 837 cm^–1. HRMS (FAB): calcd. for

C₃₀H₅₈O₄Si₃Na [M + Na] 589.3541; found 589.3548.

2.1 Hz, J_2,6= 1.5 Hz, J_2,5= J_2,1Ј= 0.5 Hz, 1 H, 2-H) ppm. ¹³C

NMR (151 MHz, CDCl₃): δ = –5.61, –5.55, –5.41, –4.50 and –4.38

(CH₃Si), 17.91, 18.06 and 18.34 [C(CH₃)₃], 25.81, 25.87 and 26.00

[C(CH₃)₃], 63.74 (CH₂-5Ј), 74.20 (CH-3Ј), 79.60 (CH-2Ј), 81.86

(CH-1Ј), 86.59 (CH-4Ј), 122.27 (C-3), 125.54 (CH-6), 129.52 (CH-

1β-(3-Ethylphenyl)-1-deoxy-2,3,5-tri-O-(tert-butyldimethylsilyl)-D-ri-

bofuranose (18b): Compound 18b was prepared according to the

procedure outlined for 9b starting from 15 (584 mg, 0.924 mmol).

Corresponding C-nucleoside 18b was prepared in 73 % yield

(394 mg) as a colorless oil. ¹H NMR (600 MHz, CDCl₃): δ = –0.48,

–0.15, 0.09, 0.10, 0.12 and 0.13 (6 s, 6ϫ3 H, CH₃Si), 0.78, 0.94

and 0.95 [3 s, 3 ϫ 9 H, (CH₃)₃C], 1.21 (t, J_vic= 7.6 Hz, 3 H,

5), 129.67 (CH-2), 130.68 (CH-4), 143.17 (C-1) ppm. IR (CCl ): ν

˜

4

= 3066, 2897, 1599, 1572, 1472, 1463, 1430, 1407, 1389, 1361, 1256,

1093, 1079, 997, 940 cm^–1. MS (FAB): m/z = 631 [M + H]. HRMS

(FAB): calcd. for C₂₉H₅₆O₄Si₃Br [M + H] 631.2670; found

631.2661.

CH₃CH₂), 2.62 (q, J_vic= 7.6 Hz, 2 H, CH₂CH₃), 3.78 (dd, J_gem

10.9 Hz, J_5Јb,4Ј= 3.2 Hz, 1 H, 5Јb-H), 3.80 (dd, J_gem= 10.9 Hz,

J_5Јa,4Ј= 3.9 Hz, 1 H, 5Јa-H), 3.85 (dd, J_2Ј,1Ј= 8.0 Hz, J_2Ј,3Ј

bofuranose (16): Et₃SiH (123 µL, 0.772 mol, 3.33 equiv.) was added 4.5 Hz, 1 H, 2Ј-H), 4.02 (ddd, J_4Ј,5Ј= 3.9, 3.2 Hz, J_4Ј,3Ј= 1.7 Hz, 1

=

1β-(3-Bromophenyl)-1-deoxy-3,5-di-O-(tert-butyldimethylsilyl)-

D

-ri-

=

in one portion to a solution of hemiketal 14 (83 mg, 0.129 mmol)

in dry CH₂Cl₂(0.5 mL) in an ice–brine bath (–10 °C) under an

atmosphere of argon. After 5 min, BF₃·Et₂O (18 µL, 0.148 mol,

1.2 equiv.) was added over 1 min by syringe, and the solution was

stirred for an additional 5 min. The mixture was then quenched

with saturated NaHCO₃and extracted with CH₂Cl₂. The combined

organic layer was washed with saturated NH₄Cl solution, dried

with MgSO₄, and concentrated under reduced pressure. The crude

product was chromatographed on silica gel (gradient hexane/tolu-

H, 4Ј-H), 4.12 (dd, J_3Ј,2Ј= 4.5 Hz, J_3Ј,4Ј= 1.7 Hz, 1 H, 3Ј-H), 4.73

(d, J_1Ј,2Ј= 8.0 Hz, 1 H, 1Ј-H), 7.09 (dt, J_4,5= 7.4 Hz, J_4,2= J_4,6

=

1.7 Hz, 1 H, 4-H), 7.19 –7.25 (m, 3 H, 2-H, 5-H and 6-H) ppm.

¹³C NMR (151 MHz, CDCl₃): δ = –5.56, –5.52, –5.42, –4.56, –4.47

and –4.41 (CH₃Si), 15.78 (CH₃CH₂), 17.95, 18.09 and 18.36

[C(CH₃)₃], 25.85, 25.90 and 25.99 [C(CH₃)₃], 28.88 (CH₂CH₃),

63.81 (CH₂-5Ј), 74.03 (CH-3Ј), 79.53 (CH-2Ј), 82.83 (CH-1Ј), 86.09

(CH-4Ј), 124.39 (CH-6), 126.56 (CH-2), 127.19 (CH-4), 127.96

(CH-5), 140.35 (C-1), 143.90 (C-3) ppm. IR (CCl ): ν = 3105, 3062,

˜

4

1

ene, 2:1 to toluene) to give 16 (67 mg, 73%) as a colorless oil. H

3031, 2896, 1610, 1592, 1487, 1472, 1463, 1406, 1389, 1374, 1362,

NMR (600 MHz, CDCl₃): δ = 0.108, 0.113, 0.15 and 0.16 (4 s, 1256, 1098, 1083, 972, 940, 837 cm^–1. HRMS (FAB): calcd. for

4ϫ3 H, CH₃Si), 0.92 and 0.95 [2 s, 2ϫ9 H, (CH₃)₃C], 2.76 (d,

C₃₁H₆₀O₄Si₃Na [M + Na] 603.3697; found 603.3686.

Eur. J. Org. Chem. 2008, 1689–1704

www.eurjoc.org

1697

ˇ

M. Stefko, R. Pohl, B. Klepetárˇová, M. Hocek

FULL PAPER

1β-(3-Benzylphenyl)-1-deoxy-2,3,5-tri-O-(tert-butyldimethylsilyl)-

D-

= 4.4 Hz, J_3Ј,4Ј= 1.6 Hz, 1 H, 3Ј-H), 4.87 (d, J_1Ј,2Ј= 8.1 Hz, 1 H,

ribofuranose) (18c): Compound 18c was prepared according to the

procedure outlined for 9c starting from 15 (652 mg, 1.03 mmol).

Corresponding C-nucleoside 18c was prepared in 67% yield as a

colorless oil. ¹H NMR (600 MHz, CDCl₃): δ = –0.50, –0.16, 0.085,

0.087, 0.10 and 0.11 (6 s, 6ϫ3 H, CH₃Si), 0.77, 0.929 and 0.931 [3

s, 3 ϫ9 H, (CH₃)₃C], 3.76 (d, J_5Ј,4Ј= 3.6 Hz, 2 H, 5Ј-H), 3.84 (dd,

J_2Ј,1Ј= 8.0 Hz, J_2Ј,3Ј= 4.5 Hz, 1 H, 2Ј-H), 3.96 (s, 2 H, CH₂Ph),

1Ј-H), 7.21 (m, 1 H, 5-py-H), 7.43 (m, 1 H, 5-H), 7.14 (ddd, J_6,5=

7.6 Hz, J_6,4= 1.3 Hz, J_6,2= 1.2 Hz, 1 H, 6-H), 7.70–7.74 (m, 2 H,

3,4-py-H), 7.95 (ddd, J_4,5= 6.4 Hz, J_4,2= 1.8 Hz, J_4,6= 1.3 Hz, 1

H, 4-H), 7.96 (dd, J_2,4= 1.8 Hz, J_2,6= 1.2 Hz, 1 H, 2-H), 8.68 (dt,

J_6,5= 4.7 Hz, J_6,4= J_6,3= 1.5 Hz, 1 H, 6-py-H) ppm. ¹³C NMR

(125.7 MHz, CDCl₃): δ = –5.51, –5.46, –5.43, –4.52, –4.47 and

–4.36 (CH₃Si), 17.92, 18.09 and 18.37 [C(CH₃)₃], 25.82, 25.91 and

4.01 (td, J_4Ј,5Ј= 3.6 Hz, J_4Ј,3Ј= 1.7 Hz, 1 H, 4Ј-H), 4.11 (dd, J_3Ј,2Ј25.99 [C(CH₃)₃], 63.86 (CH₂-5Ј), 74.11 (CH-3Ј), 79.59 (CH-2Ј),

= 4.5 Hz, J_3Ј,4Ј= 1.7 Hz, 1 H, 3Ј-H), 4.73 (d, J_1Ј,2Ј= 8.0 Hz, 1 H, 82.61 (CH-1Ј), 86.30 (CH-4Ј), 120.48 (CH-3-py), 121.94 (CH-5-py),

1Ј-H), 7.05 (ddd, J_4,5= 7.6 Hz, J_4,2= 1.7 Hz, J_4,6= 1.3 Hz, 1 H, 125.52 (CH-2), 126.37 (CH-4), 127.39 (CH-6), 128.58 (CH-5),

4-H), 7.16 (m, 2 H, o-Ph-H), 7.18 (m, 1 H, p-Ph-H), 7.21 (t, J_5,4136.54 (CH-4-py), 139.06 (C-3), 141.03 (C-1), 149.57 (CH-6-py),

J_5,3= 7.6 Hz, 1 H, 5-H), 7.23–7.29 (m, 4 H, 2-H, 6-H and m-Ph- 157.47 (C-2-py) ppm. IR (CCl ): ν = 2897, 1607, 1587, 1587, 1567,

=

˜

4

H) ppm. ¹³C NMR (151 MHz, CDCl₃): δ = –5.53, –5.47, –5.42,

–4.55, –4.47 and –4.42 (CH₃Si), 17.92, 18.08 and 18.35 [C(CH₃)₃],

25.83, 25.89 and 25.98 [C(CH₃)₃], 41.84 (CH₂Ph), 63.79 (CH₂-5Ј),

74.02 (CH-3Ј), 79.49 (CH-2Ј), 82.76 (CH-1Ј), 86.08 (CH-4Ј), 124.90

(CH-6), 125.93 (CH-p-Ph), 127.61 (CH-2), 128.14 (CH-5), 128.33

(CH-m-Ph), 128.42 (CH-4), 128.94 (CH-o-Ph), 140.63 and 140.67

1494, 1472, 1463, 1437, 1407, 1390, 1362, 1288, 1257, 1080, 1050,

994, 940, 837 cm^–1. HRMS (FAB): calcd. for C₃₄H₆₀NO₄Si₃[M +

H] 630.3830; found 630.3810.

1β-[3-(4-Fluorophenyl)phenyl]-1-deoxy-2,3,5-tri-O-(tert-butyldi-

methylsilyl)-D-ribofuranose (18f): Compound 18f was prepared ac-

cording to the procedure outlined for 9f starting from 15 (520 mg,

0.822 mmol). The reaction was carried out at 100 °C for 30 min,

which resulted in the formation of nucleoside 18f in 69% yield as

a colorless oil. ¹H NMR (600 MHz, CDCl₃): δ = –0.48, –0.14,

0.100, 0.102, 0.103 and 0.106 (6 s, 6ϫ3 H, CH₃Si), 0.77, 0.91 and

(C-1 and C-3), 141.16 (C-i-Ph) ppm. IR (CCl ): ν = 2897, 1612,

˜

4

1603, 1593, 1593, 1495, 1488, 1472, 1463, 1455, 1406, 1389, 1362,

1257, 1187, 1092, 1081, 1006, 939, 837 cm^–1. HRMS (FAB): calcd.

for C₃₆H₆₂O₄Si₃Na [M + Na] 665.3854; found 665.3845.

1β-[3-(2-Thienyl)phenyl]-1-deoxy-2,3,5-tri-O-(tert-butyldimethylsil-

0.95 [3 s, 3ϫ9 H, (CH₃)₃C], 3.79 (dd, J_gem= 10.9 Hz, J_5Јb,4Ј=

yl)-

D

-ribofuranose (18d): Compound 18d was prepared according

3.0 Hz, 1 H, 5Јb-H), 3.82 (dd, J_gem= 10.9 Hz, J_5Јa,4Ј= 3.8 Hz, 1

H, 5Јa-H), 3.89 (dd, J_2Ј,1Ј= 8.2 Hz J_2Ј,3Ј= 4.5 Hz, 1 H, 2Ј-H), 4.05

(ddd, J_4Ј,5Ј= 3.8 Hz, 3.0, J_4Ј,3Ј= 1.6 Hz, 1 H, 4Ј-H), 4.14 (ddd,

J_3Ј,2Ј= 4.5 Hz, J_3Ј,4Ј= 1.6 Hz, J_3Ј,1Ј= 0.5 Hz, 1 H, 3Ј-H), 4.82 (d,

J_1Ј,2Ј= 8.2 Hz, 1 H, 1Ј-H), 7.10 (m, 2 H, m-C₆H₄F-H), 7.36 (t, J_5,4

= J_5,6= 7.6 Hz, 1 H, 5-H), 7.41–7.44 (m, 2 H, 4,6-H), 7.53 (m, 2

H, o-C₆H₄F-H), 7.56 (tt, J_2,4= J_2,6= 1.8 Hz J_2,5= J_2,1Ј= 0.5 Hz

to procedure outlined for 9d starting from 15 (503 mg,

0.796 mmol). The reaction was carried out at 100 °C for 30 min,

which resulted in the formation of nucleoside 18d in 73% yield as

a colorless oil. ¹H NMR (600 MHz, CDCl₃): δ = –0.45, –0.13, 0.01,

0.11, 0.12 and 0.13 (6 s, 6ϫ3 H, CH₃Si), 0.79, 0.94 and 0.95 [3 s,

3ϫ9 H, (CH₃)₃C], 3.80 (dd, J_gem= 10.9 Hz, J_5Јb,4Ј= 3.4 Hz, 1 H,

5Јb-H), 3.82 (dd, J_gem= 10.9 Hz, J_5Јa,4Ј= 3.8 Hz, 1 H, 5Јa-H), 3.88 1 H, 2-H) ppm.¹³C NMR (151 MHz, CDCl₃): δ = –5.53, –5.52,

(dd, J_2Ј,1Ј= 8.0 Hz, J_2Ј,3Ј= 4.5 Hz, 1 H, 2Ј-H), 4.05 (ddd, J_4Ј,5Ј

=

–5.45, –4.52, –4.47 and –4.38 (CH₃Si), 17.93, 18.09 and 18.34

[C(CH₃)₃], 25.80, 25.90 and 25.96 [(CH₃)₃C], 63.82 (CH₂-5Ј), 74.08

(CH-3Ј, 79.65 (CH-2Ј, 82.64 (CH-1Ј), 86.36 (CH-4Ј), 115.42 (d,

J_C,F= 21 Hz, CH-m-C₆H₄F), 125.68 (CH-2), 125.97 (CH-6),

126.42 (CH-4), 128.50 (CH-5), 128.68 (d, J_C,F= 8 Hz, CH-o-

C₆H₄F), 137.47 (d, J_C,F= 3 Hz, C-i-C₆H₄F), 139.99 (C-3), 141.11

3.8, 3.4 Hz, J_4Ј,3Ј= 1.6 Hz, 1 H, 4Ј-H), 4.14 (ddd, J_3Ј,2Ј= 4.5 Hz,

J_3Ј,4Ј= 1.6 Hz, J_3Ј,1Ј= 0.5 Hz, 1 H, 3Ј-H), 4.80 (d, J_1Ј,2Ј= 8.0 Hz,

1 H, 1Ј-H), 7.02 (dd, J_4,5= 5.1 Hz, J_4,3= 3.6 Hz, 1 H, 4-thienyl-

H), 7.26 (dd, J_5,4= 5.1 Hz, J_5,3= 1.1 Hz, 1 H, 5-thienyl-H), 7.30

(dd, J_3,4= 3.6 Hz, J_3,5= 1.1 Hz, 1 H, 3-thienyl-H), 7.32 (t, J_5,4

=

J_5,6= 7.6 Hz, 1 H, 5-H), 7.14 (dddd, J_6,5= 7.6 Hz, J_6,2= 1.7 Hz,

(C-1), 162.35 (d, J_C,F= 246 Hz C-p-C H F) ppm. IR (CCl ): ν =

˜

6

4

J_6,4= 1.1 Hz, J_6,1Ј= 0.5 Hz, 1 H, 6-H), 6.90 (ddd, J_4,5= 7.6 Hz, 2956, 2930, 2897, 2858, 1610, 1515, 1472, 1389, 1362, 1256, 1236,

J_4,2= 1.9 Hz, J_4,6= 1.1 Hz, 1 H, 4-H), 7.59 (ddt, J_2,4= 1.9 Hz, J_2,6

= 1.7 Hz, J_2,5= J_2,1Ј= 0.5 Hz, 1 H, 2-H) ppm. ¹³C NMR

(151 MHz, CDCl₃): δ = –5.50, –5.48, –5.39, –4.54, –4.46 and –4.40

(CH₃Si), 17.93, 18.10 and 18.37 [C(CH₃)₃], 25.84, 25.91 and 25.99

[C(CH₃)₃], 63.81 (CH₂-5Ј), 74.05 (CH-3Ј), 79.53 (CH-2Ј), 82.53

(CH-1Ј), 86.29 (CH-4Ј), 123.01 (CH-3-thienyl), 124.58 (CH-5-thi-

enyl), 124.62 (CH-2), 125.36 (CH-4), 125.93 (CH-6), 127.83 (CH-

4-thienyl), 128.64 (CH-5), 134.02 (C-3), 141.28 (C-1), 144.54 (C-2-

1157, 1112, 1006, 966, 875, 838 cm^–1. HRMS (FAB): calcd. for

C₃₅H₆₀FO₄Si₃[M + H] 647.3783; found 647.3778.

1β-[3-(4-Methoxyphenyl)phenyl]-1-deoxy-2,3,5-tri-O-(tert-butyldi-

methylsilyl)-D-ribofuranose (18g): Compound 18g was prepared ac-

cording to the procedure outlined for 9g starting from 15 (119 mg,

0.188 mmol). The reaction was carried out at 95 °C for 2 h, which

resulted in the formation of nucleoside 18g in 81% yield as a color-

less oil. ¹H NMR (500 MHz, CDCl₃): δ = –0.45, –0.14, 0.103, 0.105

and 0.109 (5 s, 18 H, CH₃Si), 0.78, 0.93 and 0.95 [3 s, 3ϫ9 H,

(CH₃)₃C], 3.79 (dd, J_gem= 10.9 Hz, J_5Јb,4Ј= 3.3 Hz, 1 H, 5Јb-H),

3.82 (dd, J_gem= 10.9 Hz, J_5Јa,4Ј= 3.8 Hz, 1 H, 5Јa-H), 3.85 (s, 3 H,

CH₃O), 3.90 (dd, J_2Ј,1Ј= 8.0 Hz, J_2Ј,3Ј= 4.5 Hz, 1 H, 2Ј-H), 4.05

thienyl) ppm. IR (CCl ): ν = 2956, 2930, 2887, 2858, 1607, 1472,

˜

4

1463, 1389, 1362, 1256, 1219, 1152, 1113, 1081, 1005, 966, 940,

873 cm^–1. HRMS (FAB): calcd. for C₃₃H₅₉O₄SSi₃[M + H]

635.3442; found 635.3447.

1β-[3-(Pyridin-2-yl)phenyl]-1-deoxy-2,3,5-tri-O-(tert-butyldimethyl- (ddd, J_4Ј,5Ј= 3.8, 3.3 Hz, J_4Ј,3Ј= 1.7 Hz, 1 H, 4Ј-H), 4.15 (dd, J_3Ј,2Ј

silyl)-

D

-ribofuranose (18e): Compound 18e was prepared according

= 4.5 Hz, J_3Ј,4Ј= 1.7 Hz, 1 H, 3Ј-H), 4.81 (d, J_1Ј,2Ј= 8.0 Hz, 1 H,

1Ј-H), 6.95 (m, 2 H, m-C₆H₄OMe-H), 7.35 (dd, J_5,6= 7.8 Hz, J_5,4

= 7.5 Hz, 1 H, 5-H), 7.39 (dt, J_6,5= 7.8 Hz, J_6,2= J_6,4= 1.7 Hz, 1

H, 6-H), 7.44 (dt, J_4,5= 7.5 Hz, J_4,2= J_4,6= 1.7 Hz, 1 H, 4-H),

to the procedure outlined for 9e starting from 15 (537 mg,

0.850 mmol). The reaction was carried out at 100 °C for 17 h,

which resulted in the formation of nucleoside 18e in 46% yield as

a colorless oil. ¹H NMR (500 MHz, CDCl₃): δ = –0.47, –0.14, 7.52 (m, 2 H, o-C₆H₄OMe-H), 7.59 (t, J_2,4= J_2,6= 1.7 Hz, 1 H, 2-

0.105, 0.107, 0.12 and 0.13 (6 s, 6ϫ3 H, CH₃Si), 0.77, 0.93 and

0.95 [3 s, 3ϫ9 H, (CH₃)₃C], 3.81 (dd, J_gem= 10.9 Hz, J_5Јb,4Ј

H) ppm. ¹³C NMR (125.7 MHz, CDCl₃): δ = –5.45, –5.41, –4.54,

–4.45 and –4.39 (CH₃Si), 17.95, 18.09 and 18.37 [C(CH₃)₃], 25.83,

=

3.2 Hz, 1 H, 5Јb-H), 3.84 (dd, J_gem= 10.9 Hz, J_5Јa,4Ј= 3.9 Hz, 1 25.91 and 25.99 [C(CH₃)₃], 55.34 (CH₃O), 63.84 (CH₂-5Ј), 74.03

H, 5Јa-H), 3.90 (dd, J_2Ј,1Ј= 8.1 Hz, J_2Ј,3Ј= 4.4 Hz, 1 H, 2Ј-H), 4.06 (CH-3Ј), 79.62 (CH-2Ј), 82.84 (CH-1Ј), 86.18 (CH-4Ј), 114.03 (CH-

(ddd, J_4Ј,5Ј= 3.9, 3.2 Hz, J_4Ј,3Ј= 1.6 Hz, 1 H, 4Ј-H), 4.15 (dd, J_3Ј,2Јm-C₆H₄OMe), 125.36 (CH-6), 125.41 (CH-2), 126.14 (CH-4),

1698

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Eur. J. Org. Chem. 2008, 1689–1704

Synthesis of 4- and 3-Substituted Benzene and Aniline C-Ribonucleosides

128.13 (CH-o-C₆H₄OMe), 128.42 (CH-5), 133.91 (C-i-C₆H₄OMe), = 1.2 Hz, 1 H, 4-H), 7.03 (dd, J_2,4= 2.5 Hz, J_2,6= 1.7 Hz, 1 H, 2-

140.50 (C-3), 140.92 (C-1), 158.99 (C-p-C₆H₄OMe) ppm. IR

H), 7.14 (ddd, J_6,5= 7.7 Hz, J_6,2= 1.7 Hz, J_6,4= 1.2 Hz, 1 H, 6-

H), 7.19 (dd, J_5,4= 7.9 Hz, J_5,6= 7.7 Hz, 1 H, 5-H) ppm. ¹³C NMR

(151 MHz, CDCl₃): δ = –5.50, –5.40, –5.32, –4.57, –4.47 and –4.43

(CH₃Si), 17.95, 18.08 and 18.40 [SiC(CH₃)₃], 25.87, 25.89 and 26.02

[(CH₃)₃CSi], 28.90 [(CH₃)₃CO], 63.81 (CH₂-5Ј), 73.89 (CH-3Ј),

78.24 [OC(CH₃)₃], 79.46 (CH-2Ј), 82.66 (CH-1Ј), 85.88 (CH-4Ј),

122.20 (CH-6), 122.59 (CH-2), 123.37 (CH-4), 128.33 (CH-5),

(CCl ): ν = 2897, 2838, 1611, 1611, 1591, 1576, 1517, 1482, 1472,

˜

4

1441, 1407, 1389, 1299, 1262, 1249, 1179, 1092, 1081, 1044, 940,

836 cm^–1. HRMS (FAB): calcd. for C₃₆H₆₃O₅Si₃[M + H] 659.3983;

found 659.3969.

1β-(3-Aminophenyl)-1-deoxy-2,3,5-tri-O-(tert-butyldimethylsilyl)-D-

ribofuranose (18h): Compound 18h was prepared according to the

procedure outlined for 9h starting from 15 (686 mg, 1.086 mmol).

Corresponding C-nucleoside 18h was prepared in 73% yield as a

yellow oil. ¹H NMR (500 MHz, CDCl₃): δ = –0.38, –0.12, 0.09,

0.11 and 0.13 (5 s, 18 H, CH₃Si), 0.82, 0.93 and 0.94 [3 s, 3ϫ9 H,

(CH₃)₃C], 3.58 (br. s, 2 H, NH₂), 3.78 (d, J_5Ј,4Ј= 3.7 Hz, 2 H, 5Ј-

H), 3.82 (dd, J_2Ј,1Ј= 7.7 Hz, J_2Ј,3Ј= 4.4 Hz, 1 H, 2Ј-H), 4.01 (td,

J_4Ј,5Ј= 3.7 Hz, J_4Ј,3Ј= 2.0 Hz, 1 H, 4Ј-H), 4.11 (dd, J_3Ј,2Ј= 4.4 Hz,

141.60 (C-1), 155.28 (C-3) ppm. IR (CCl ): ν = 3102, 3069, 3032,

˜

4

2980, 2897, 1604, 1587, 1485, 1472, 1463, 1440, 1406, 1390, 1364,

1308, 1257, 1180, 1163, 939 cm^–1. HRMS (FAB): calcd. for

C₃₃H₆₅O₅Si₃[M + H] 625.4140; found 625.4128.

General Procedure for the Deprotection of the TBDMS-Protecting

Group: Et₃N·3HF (163 µL, 1.00 mmol, 10 equiv.) was added to the

solution of compounds 6, 9a–j, 15, or 18a–j (0.10 mmol) in THF

J_3Ј,4Ј= 2.0 Hz, 1 H, 3Ј-H), 4.68 (d, J_1Ј,2Ј= 7.7 Hz, 1 H, 1Ј-H), 6.58 (1.00 mL), and the resulting mixture was stirred at 40 °C for 2 d.

(ddd, J_4,5= 7.9 Hz, J_4,2= 2.5 Hz, J_4,6= 1.1 Hz, 1 H, 4-H), 6.74 After the reaction was complete (TLC in CHCl₃/MeOH, 8:1), the

(dd, J_2,4= 2.5 Hz, J_2,6= 1.7 Hz, 1 H, 2-H), 6.82 (ddd, J_6,5= 7.6 Hz, solvents were removed under reduced pressure, and the crude prod-

J_6,2= 1.7 Hz, J_6,4= 1.1 Hz, 1 H, 6-H), 7.07 (dd, J_5,4= 7.9 Hz, J_5,6uct was dissolved in water/MeOH (8:2). Solid NaHCO₃was added

= 7.6 Hz, 1 H, 5-H) ppm. ¹³C NMR (125.7 MHz, CDCl₃): δ = until basic pH was obtained. The solvents were then evaporated

–5.48, –5.40, –5.38, –4.53, –4.45 and –4.43 (CH₃Si), 17.99, 18.08

under reduced pressure, and the crude product was dissolved in

and 18.38 [C(CH₃)₃], 25.87, 25.90 and 25.99 [C(CH₃)₃], 63.76 MeOH, adsorbed on silica gel, and chromatographed on silica gel

(CH₂-5Ј), 73.90 (CH-3Ј), 79.37 (CH-2Ј), 82.86 (CH-1Ј), 85.74 (CH- (CHCl₃/MeOH, 10:1) to obtain free C-ribonucleosides 8, 10a–j, 17,

4Ј), 113.49 (CH-2), 114.47 (CH-4), 117.40 (CH-6), 128.89 (CH-5), or 19a–j.

141.80 (C-1), 146.09 (C-3) ppm. IR (CCl ): ν = 2897, 2804, 1606,

˜

4

1β-(4-Bromophenyl)-1-deoxy-D-ribofuranose (8): Compound 8 was

1583, 1500, 1472, 1463, 1440, 1406, 1389, 1361, 1332, 1313, 1289,

1258, 1114, 1081, 997, 940, 837 cm^–1. HRMS (FAB): calcd. for

C₂₉H₅₈NO₄Si₃[M + H] 568.3674; found 568.3683.

prepared from 6 according to the general procedure in 85% yield.

Crystallization from CHCl₃yielded white needles. M.p. 97 –98 °C.

[α]²_D⁰= –12.0 (c = 3.10, MeOH). ¹H NMR (600 MHz, [D₆]DMSO):

δ = 3.52 (ddd, J_gem= 11.7 Hz, J_5Јb,OH= 5.5 Hz, J_5Јb,4Ј= 4.5 Hz, 1

1β-[3-(Dimethylamino)phenyl]-1-deoxy-2,3,5-tri-O-(tert-butyldi-

methylsilyl)-

D

-ribofuranose (18i): Compound 18i was prepared ac-

H, 5Јb-H), 3.55 (ddd, J_gem= 11.7 Hz, J_5Јa,OH= 5.6 Hz, J_5Јa,4Ј

4.4 Hz, 1 H, 5Јa-H), 3.63 (ddd, J_2Ј,1Ј= 7.3 Hz, J_2Ј,OH= 7.1 Hz,

J_2Ј,3Ј= 5.3 Hz, 1 H, 2Ј-H), 3.82 (ddd, J_4Ј,5Ј= 4.5, 4.4 Hz, J_4Ј,3Ј

3.4 Hz, 1 H, 4Ј-H), 3.88 (ddd, J_3Ј,2Ј= 5.3 Hz, J_3Ј,OH= 4.8 Hz, J_3Ј,4Ј

= 3.4 Hz, 1 H, 3Ј-H), 4.53 (d, J_1Ј,2Ј= 7.3 Hz, 1 H, 1Ј-H), 4.84 (dd,

=

cording to the procedure outlined for 9i starting from 15 (580 mg,

0.918 mmol). Corresponding C-nucleoside 18i was prepared in

77% yield as a colorless oil. ¹H NMR (500 MHz, CDCl₃): δ =

–0.38, –0.12, 0.09, 0.11 and 0.12 (5 s, 18 H, CH₃Si), 0.81, 0.937

=

and 0.938 [3 s, 3ϫ9 H, (CH₃)₃C], 2.93 (s, 6 H, CH₃N), 3.79 (d, J_OH,5Ј= 5.6, 5.5 Hz, 1 H, OH-5Ј), 4.95 (d, J_OH,3Ј= 4.8 Hz, 1 H,

J_5Ј,4Ј= 3.8 Hz, 2 H, 5Ј-H), 3.87 (dd, J_2Ј,1Ј= 7.5 Hz, J_2Ј,3Ј= 4.5 Hz, OH-3Ј), 5.02 (d, J_OH,2Ј= 7.1 Hz, 1 H, OH-2Ј), 7.35 (m, 2 H, 2,6-

1 H, 2Ј-H), 4.02 (td, J_4Ј,5Ј= 3.8 Hz, J_4Ј,3Ј= 2.2 Hz, 1 H, 4Ј-H), 4.12 H), 7.52 (m, 2 H, 3,5-H) ppm. ¹³C NMR (151 MHz, [D₆]DMSO):

(dd, J_3Ј,2Ј= 4.5 Hz, J_3Ј,4Ј= 2.2 Hz, 1 H, 3Ј-H), 4.72 (d, J_1Ј,2Ј

=

δ = 62.18 (CH₂-5Ј), 71.64 (CH-3Ј), 77.95 (CH-2Ј), 82.34 (CH-1Ј),

85.53 (CH-4Ј), 120.45 (C-4), 128.57 (CH-2,6), 131.09 (CH-3,5),

7.5 Hz, 1 H, 1Ј-H), 6.66 (br. s, 1 H, 4-H), 6.74 (br. s, 1 H, 2-H),

6.85 (br. s, 1 H, 6-H), 7.17 (br. t, J_5,4= J_5,6= 8.0 Hz, 1 H, 5-H)

ppm. ¹³C NMR (125.7 MHz, CDCl₃): δ = –5.47, –5.39, –5.32,

–4.56, –4.44 and –4.42 (CH₃Si), 17.99, 18.10 and 18.41 [SiC-

141.17 (C-1) ppm. IR (KBr): ν = 3569, 3408, 3271, 3064, 1593,

˜

1575, 1489, 1400, 1299, 1208, 1189, 1105, 1072, 1059, 1041, 1031,

967, 938 cm^–1. C₁₁H₁₃BrO₄(289.1): calcd. C 45.70, H 4.53; found

(CH₃)₃], 25.90, 25.93 and 26.02 [C(CH₃)₃], 40.84 (CH₃N), 63.82 C 45.50, H 4.52. HRMS (FAB): calcd. for C₁₁H₁₃O₄BrNa [M +

(CH₂-5Ј), 73.80 (CH-3Ј), 79.41 (CH-2Ј), 83.56 (CH-1Ј), 85.62 (CH- Na] 310.9895; found 310.9908.

4Ј), 111.78 (CH-2), 112.33 (CH-4), 115.46 (CH-6), 128.74 (CH-5),

1β-(4-Methylphenyl)-1-deoxy-D-ribofuranose (10a): Compound 10a

141.26 (C-1), 150.58 (C-3) ppm. IR (CCl ): ν = 2897, 2804, 1606,

˜

4

was prepared from 9a according to the general procedure in 95%

yield. The crude product was crystallized from CHCl₃to obtain

white needles. M.p. 102–103 °C. [α]²_D⁰= –34.5 (c = 1.19, MeOH).¹H

NMR (600 MHz, [D₆]DMSO): δ = 2.28 (s, 3 H, CH₃), 3.51 (ddd,

1583, 1500, 1472, 1463, 1440, 1406, 1389, 1361, 1332, 1313, 1289,

1258, 1114, 1081, 997, 940, 837 cm^–1. HRMS (FAB): calcd. for

C₃₁H₆₂NO₄Si₃[M + H] 596.3987; found 596.3971.

1β-(3-tert-Butoxyphenyl)-1-deoxy-2,3,5-tri-O-(tert-butyldimethyl- J_gem= 11.6 Hz, J_5Јb,OH= 5.5 Hz, J_5Јb,4Ј= 4.8 Hz, 1 H, 5Јb-H), 3.54

silyl)-

D

-ribofuranose (18j): Compound 18j was prepared according

(ddd, J_gem= 11.6 Hz, J_5Јa,OH= 5.7 Hz, J_5Јa,4Ј= 4.5 Hz, 1 H, 5Јa-

H), 3.64 (ddd, J_2Ј,1Ј= 7.1 Hz, J_2Ј,OH= 6.9 Hz, J_2Ј,3Ј= 5.4 Hz, 1 H,

2Ј-H), 3.78 (ddd, J_4Ј,5Ј= 4.8, 4.5 Hz, J_4Ј,3Ј= 3.7 Hz, 1 H, 4Ј-H),

to the procedure outlined for 9j starting from 15 (541 mg,

0.856 mmol). The reaction was carried out at 50 °C for 8 h, which

resulted in the formation of nucleoside 18j in 68% yield as a color-

less oil. H NMR (600 MHz, CDCl₃): δ = –0.42, –0.14, 0.09, 0.11

and 0.13 (5 s, 18 H, CH₃Si), 0.81, 0.935 and 0.943 [3 s, 3ϫ9 H,

(CH₃)₃CSi], 1.33 [s, 9 H, (CH₃)₃CO], 3.77 (dd, J_gem= 10.8 Hz,

J_5Јb,4Ј= 4.1 Hz, 1 H, 5Јb-H), 3.79 (dd, J_gem= 10.8 Hz, J_5Јa,4Ј

3.4 Hz, 1 H, 5Јa-H), 3.84 (dd, J_2Ј,1Ј= 7.8 Hz, J_2Ј,3Ј= 4.4 Hz, 1 H,

2Ј-H), 4.02 (ddd, J_4Ј,5Ј= 4.1, 3.4 Hz, J_4Ј,3Ј= 1.9 Hz, 1 H, 4Ј-H),

3.86 (dddd, J_3Ј,2Ј= 5.4 Hz, J_3Ј,OH= 4.9 Hz, J_3Ј,4Ј= 3.7 Hz, J_3Ј,1Ј

=

1

0.4 Hz, 1 H, 3Ј-H), 4.50 (d, J_1Ј,2Ј= 7.1 Hz, 1 H, 1Ј-H), 4.80 (dd,

J_OH,5Ј= 5.7, 5.5 Hz, 1 H, OH-5Ј), 4.88 (d, J_OH,3Ј= 4.9 Hz, 1 H,

OH-3Ј), 4.92 (d, J_OH,2Ј= 6.9 Hz, 1 H, OH-2Ј), 7.12 (m, 2 H, 3,5-

H), 7.26 (m, 2 H, 2,6-H) ppm. ¹³C NMR (151 MHz, [D₆]DMSO):

δ = 20.97 (CH₃), 62.30 (CH₂-5Ј), 71.62 (CH-3Ј), 77.79 (CH-2Ј),

83.17 (CH-1Ј), 85.17 (CH-4Ј), 126.44 (CH-2,6), 128.74 (CH-3,5),

=

4.12 (dd, J_3Ј,2Ј= 4.4 Hz, J_3Ј,4Ј= 1.9 Hz, 1 H, 3Ј-H), 4.73 (d, J_1Ј,2Ј136.50 (C-4), 138.59 (C-1) ppm. IR (KBr): ν = 3392, 3054, 3026,

˜

= 7.7 Hz, 1 H, 1Ј-H), 6.90 (ddd, J_4,5= 7.9 Hz, J_4,2= 2.5 Hz, J_4,63013, 2920, 1618, 1515, 1415, 1376, 1304, 1224, 1210, 1180, 1113,

Eur. J. Org. Chem. 2008, 1689–1704

www.eurjoc.org

1699

ˇ

M. Stefko, R. Pohl, B. Klepetárˇová, M. Hocek

FULL PAPER

1072, 1039, 1019, 942 cm^–1. HRMS (FAB): calcd. for C₁₂H₁₇O₄[M

+ H] 225.1127; found 225.1118.

DMSO): δ = 62.27 (CH₂-5Ј), 71.69 (CH-3Ј), 77.88 (CH-2Ј), 82.87

(CH-1Ј), 85.37 (CH-4Ј), 123.76 (CH-3-thienyl), 125.35 (CH-3,5),

125.70 (CH-5-thienyl), 127.18 (CH-2,6), 128.71 (CH-4-thienyl),

1β-(4-Ethylphenyl)-1-deoxy-D-ribofuranose (10b): Compound 10b

133.02 (C-4), 141.12 (C-1), 143.53 (C-2-thienyl) ppm. IR (KBr): ν

˜

was prepared from 9b according to the general procedure in 85%

yield. The crude product was crystallized from EtOAc/heptane to

obtain white needles. M.p. 100–101 °C. [α]²_D⁰= –31.4 (c =3.04,

= 293.0777, 3401, 3109, 3065, 3029, 1633, 1615, 1568, 1536, 1502,

1442, 1413, 1351, 1302, 1285, 1258, 1224, 1211, 1183, 1114, 1072,

1072, 1051, 1036, 1014, 902 cm^–1. C₁₅H₁₆O₄S (292.3): calcd. C

61.62, H 5.52; found C 61.23, H 5.46. HRMS (FAB): calcd. for

C₁₅H₁₇O₄S [M + H] 293.0769; found 293.0777.

MeOH). ¹H NMR (600 MHz, [D₆]DMSO): δ = 1.16 (t, J_vic

=

7.6 Hz, 3 H, CH₃CH₂), 2.57 (q, J_vic= 7.6 Hz, 2 H, CH₂CH₃), 3.51

(ddd, J_gem= 11.6 Hz, J_5Јb,OH= 5.4 Hz, J_5Јb,4Ј= 4.8 Hz, 1 H, 5Јb-

H), 3.54 (ddd, J_gem= 11.6 Hz, J_5Јa,OH= 5.6 Hz, J_5Јa,4Ј= 4.5 Hz, 1

1β-[4-(Pyridin-2-yl)phenyl]-1-deoxy-D-ribofuranose (10e): Com-

H, 5Јa-H), 3.66 (ddd, J_2Ј,1Ј= 7.1 Hz, J_2Ј,OH= 6.9 Hz, J_2Ј,3Ј

5.4 Hz, 1 H, 2Ј-H), 3.78 (ddd, J_4Ј,5Ј= 4.8, 4.5 Hz, J_4Ј,3Ј= 3.6 Hz, 1

H, 4Ј-H), 3.86 (ddd, J_3Ј,2Ј= 5.4 Hz, J_3Ј,OH= 4.8 Hz, J_3Ј,4Ј= 3.6 Hz,

=

pound 10e was prepared from 9e according to the general pro-

cedure in 86% yield as a white powder. The crude product was

crystallized from CHCl₃to obtain peel transparent crystals. M.p.

1

1 H, 3Ј-H), 4.51 (d, J_1Ј,2Ј= 7.1 Hz, 1 H, 1Ј-H), 4.82 (dd, J_OH,5Ј

=

125–129 °C. [α]²_D⁰= –26.6 (c =3.15, MeOH). H NMR (600 MHz,

5.6, 5.4 Hz, 1 H, OH-5Ј), 4.89 (d, J_OH,3Ј= 4.8 Hz, 1 H, OH-3Ј),

4.94 (d, J_OH,2Ј= 6.9 Hz, 1 H, OH-2Ј), 7.15 (m, 2 H, 3,5-H), 7.28

(m, 2 H, 2,6-H) ppm. ¹³C NMR (151 MHz, [D₆]DMSO): δ = 16.06

[D₆]DMSO): δ = 3.55 (ddd, J_gem= 11.6 Hz, J_5Јb,OH= 5.6 Hz, J_5Јb,4Ј

= 4.7 Hz, 1 H, 5Јb-H), 3.59 (ddd, J_gem= 11.6 Hz, J_5Јa,OH= 5.6 Hz,

J_5Јa,4Ј= 4.5 Hz, 1 H, 5Јa-H), 3.72 (ddd, J_2Ј,1Ј= 7.2 Hz, J_2Ј,OH

=

(CH₃CH₂), 28.19 (CH₂CH₃), 62.37 (CH₂-5Ј), 71.72 (CH-3Ј), 77.80 7.0 Hz, J_2Ј,3Ј= 5.4 Hz, 1 H, 2Ј-H), 3.84 (ddd, J_4Ј,5Ј= 4.7, 4.5 Hz,

(CH-2Ј), 83.20 (CH-1Ј), 85.23 (CH-4Ј), 126.58 (CH-2,6), 127.64 J_4Ј,3Ј= 3.6 Hz, 1 H, 4Ј-H), 3.91 (ddd, J_3Ј,2Ј= 5.4 Hz, J_3Ј,OH

=

(CH-3,5), 138.87 (C-1), 143.03 (C-4) ppm. IR (KBr): ν = 3227,

4.8 Hz, J_3Ј,4Ј= 3.6 Hz, 1 H, 3Ј-H), 4.62 (d, J_1Ј,2Ј= 7.2 Hz, 1 H, 1Ј-

˜

3414, 3084, 3060, 3024, 1603, 1586, 1514, 1494, 1452, 1433, 1415,

1342, 1333, 1309, 1205, 1181, 1114, 1073, 1052, 1039, 1012, 967,

H), 4.85 (t, J_OH,5Ј= 5.6 Hz, 1 H, OH-5Ј), 4.95 (d, J_OH,3Ј= 4.8 Hz,

1 H, OH-3Ј), 5.02 (d, J_OH,2Ј= 7.0 Hz, 1 H, OH-2Ј), 7.34 (ddd, J_5,4

789, 640, 525, 457 cm^–1. HRMS (FAB): calcd. for C₁₃H₁₈O₄Na [M = 7.4 Hz, J_5,6= 4.7 Hz, J_5,3= 1.1 Hz, 1 H, 5-py-H), 7.51 (m, 2 H,

+ Na] 261.1103; found 261.1110.

2,6-H), 7.87 (ddd, J_4,3= 8.0 Hz, J_4,5= 7.4 Hz, J_4,6= 1.8 Hz, 1 H,

4-py-H), 7.95 (ddd, J_3,4= 8.0 Hz, J_3,5= 1.1 Hz, J_3,6= 1.0 Hz, 1 H,

1β-(4-Benzylphenyl)-1-deoxy- -ribofuranose (10c): Compound 10c

D

3-py-H), 8.04 (m, 2 H, 3,5-H), 8.66 (ddd, J_6,5= 4.7 Hz, J_6,4

=

was prepared from 9c according to the general procedure in 84%

yield. The crude product was crystallized from CHCl₃to obtain

white needles. M.p. 129–130 °C. [α]²_D⁰= –16.25 (c =2.45, MeOH).

¹H NMR (500 MHz, [D₆]DMSO): δ = 3.50 (ddd, J_gem= 11.7 Hz,

1.8 Hz, J_6,3= 1.0 Hz, 1 H, 6-py-H) ppm. ¹³C NMR (151 MHz,

[D₆]DMSO): δ = 62.27 (CH₂-5Ј), 71.70 (CH-3Ј), 77.91 (CH-2Ј),

82.92 (CH-1Ј), 85.42 (CH-4Ј), 120.36 (CH-3-py), 122.70 (CH-5-py),

126.40 (CH-3,5), 126.77 (CH-2,6), 137.43 (CH-4-py), 137.94 (C-4),

J_5Јb,OH= 5.6 Hz, J_5Јb,4Ј= 4.8 Hz, 1 H, 5Јb-H), 3.53 (ddd, J_gem

=

142.63 (C-1), 149.73 (CH-6-py), 156.15 (C-2-py) ppm. IR (KBr): ν

˜

11.7 Hz, J_5Јa,OH= 5.6 Hz J_5Јa,4Ј= 4.5 Hz, 1 H, 5Јa-H), 3.65 (ddd,

J_2Ј,1Ј= 7.1 Hz J_2Ј,OH= 7.0 Hz, J_2Ј,3Ј= 5.5 Hz, 1 H, 2Ј-H), 3.78

(ddd, J_4Ј,5Ј= 4.8, 4.5 Hz, J_4Ј,3Ј= 3.6 Hz 1 H, 4Ј-H), 3.85 (ddd, J_3Ј,2Ј

= 5.5 Hz, J_3Ј,OH= 4.8 Hz, J_3Ј,4Ј= 3.6 Hz, 1 H, 3Ј-H), 3.91 (CH₂Ph),

4.50 (d, J_1Ј,2Ј= 7.1 Hz, 1 H, 1Ј-H), 4.77 (t, J_OH,5Ј= 5.6 Hz, 1 H,

= 3400, 3275, 2902, 1632, 1611, 1585, 1578, 1562, 1515, 1467, 1437,

1409, 1309, 1294, 1269 1151, 1115, 1098, 1072, 1055, 1039, 1010,

905 cm^–1. HRMS (FAB): calcd. for C₁₆H₁₈NO₄[M + H] 288.1236;

found 288.1245.

OH-5Ј), 4.85 (d, J_OH,3Ј= 4.8 Hz, 1 H, OH-3Ј), 4.92 (d, J_OH,2Ј

=

1β-[4-(4-Fluorophenyl)phenyl]-1-deoxy-D-ribofuranose (10f): Com-

7.0 Hz, 1 H, OH-2Ј), 7.17 (m, 1 H, p-Ph-H), 7 .18 (m, 2 H, H-3,5),

7.22 (m, 2 H, o-Ph-H), 7.27 (m, 2 H, m-Ph-H), 7.29 (m, 2 H, 2,6-

H) ppm.¹³C NMR (125.7 MHz, [D₆]DMSO): δ = 2.27 (CH₂-5Ј),

pound 10f was prepared from 9f according to the general procedure

in 95% yield. The crude product was crystallized from CHCl₃to

obtain a white solid. M.p. 153–157 °C. [α]²_D⁰= –13.8 (c =2.78,

71.65 (CH-3Ј), 77.66 (CH-2Ј), 83.03 (CH-1Ј), 85.20 (CH-4Ј), 126.11 MeOH).¹H NMR (600 MHz, [D₆]DMSO): δ = 3.54 (ddd, J_gem

=

(CH-p-Ph), 126.60 (CH-2,6), 128.49 (CH-3,5), 128.59 (CH-m-Ph), 11.6 Hz, J_5Јb,OH= 5.5 Hz, J_5Јb,4Ј= 4.7 Hz, 1 H, 5Јb-H), 3.57 (ddd,

128.84 (CH-o-Ph), 139.21 (C-1), 140.46 (C-4), 141.60 (C-i-Ph) ppm.

J_gem= 11.6 Hz, J_5Јa,OH= 5.6 Hz, J_5Јa,4Ј= 4.5 Hz, 1 H, 5Јa-H), 3.71

(ddd, J_2Ј,1Ј= 7.3 Hz, J_2Ј,OH= 7.0 Hz, J_2Ј,3Ј= 5.3 Hz, 1 H, 2Ј-H),

3.83 (ddd, J_4Ј,5Ј= 4.7, 4.5 Hz, J_4Ј,3Ј= 3.5 Hz, 1 H, 4Ј-H), 3.91 (ddd,

J_3Ј,2Ј= 5.3 Hz, J_3Ј,OH= 4.8 Hz, J_3Ј,4Ј= 3.5 Hz, 1 H, 3Ј-H), 4.60 (d,

J_1Ј,2Ј= 7.3 Hz, 1 H, 1Ј-H), 4.84 (dd, J_OH,5Ј= 5.6, 5.5 Hz, 1 H, OH-

5Ј), 4.93 (d, J_OH,3Ј= 4.8 Hz, 1 H, OH-3Ј), 5.01 (d, J_OH,2Ј= 7.0 Hz,

1 H, OH-2Ј), 7.29 (m, 2 H, m-C₆H₄F-H), 7.47 (m, 2 H, 2,6-H),

7.60 (m, 2 H, 3,5-H), 7.69 (m, 2 H, o-C₆H₄F-H) ppm. ¹³C NMR

(151 MHz, [D₆]DMSO): δ = 62.29 (CH₂-5Ј), 71.73 (CH-3Ј), 77.93

(CH-2Ј), 82.83 (CH-1Ј), 85.39 (CH-4Ј), 115.92 (d, J_C,F= 21 Hz,

CH-m-C₆H₄F), 126.53 (CH-3,5), 127.04 (CH-2,6), 128.80 (d, J_C,F

= 8, CH-o-C₆H₄F), 136.79 (d, J_C,F= 3, C-i-C₆H₄F), 138.37 (C-4),

140.91 (C-1), 162.02 (d, J_C,F= 244, C-p-C₆H₄F) ppm. ¹⁹F NMR

IR (KBr): ν = 3414, 3084, 3060, 3024, 1627, 1603, 1586, 1514, 1494,

˜

1452, 1433, 1415, 1342, 1333, 1309, 1205, 1205, 1181, 1181, 1114,

1073, 1052, 1039, 1012, 967, 900, 842 cm^–1. HRMS (FAB): calcd.

for C₁₈H₂₀O₄Na [M + Na] 323.1259; found 323.1258.

1β-[4-(2-Thienyl)phenyl]-1-deoxy-D-ribofuranose (10d): Compound

10d was prepared from 9d according to the general procedure in

95% yield. The crude product was crystallized from CHCl₃to ob-

tain 10d as white needles. M.p. 147–149 °C. [α]²_D⁰= –19.4 (c =1.95,

MeOH).¹H NMR (600 MHz, [D₆]DMSO): δ = 3.54 (ddd, J_gem

=

11.6 Hz, J_5Јb,OH= 5.5 Hz, J_5Јb,4Ј= 4.7 Hz, 1 H, 5Јb-H), 3.57 (ddd,

J_gem= 11.6 Hz, J_5Јa,OH= 5.7 Hz, J_5Јa,4Ј= 4.5 Hz, 1 H, 5Јa-H), 3.69

(ddd, J_2Ј,1Ј= 7.1 Hz, J_2Ј,OH= 6.9 Hz, J_2Ј,3Ј= 5.2 Hz, 1 H, 2Ј-H),

3.82 (ddd, J_4Ј,5Ј= 4.7, 4.5 Hz, J_4Ј,3Ј= 3.6 Hz, 1 H, 4Ј-H), 3.90 (ddd,

J_3Ј,2Ј= 5.2 Hz, J_3Ј,OH= 4.7 Hz, J_3Ј,4Ј= 3.6 Hz, 1 H, 3Ј-H), 4.57 (d,

J_1Ј,2Ј= 7.1 Hz, 1 H, 1Ј-H), 4.84 (dd, J_OH,5Ј= 5.7, 5.5 Hz, 1 H, OH-

5Ј), 4.93 (d, J_OH,3Ј= 4.7 Hz, 1 H, OH-3Ј), 5.02 (d, J_OH,2Ј= 6.9 Hz,

1 H, OH-2Ј), 7.13 (dd, J_4,5= 5.0 Hz, J_4,3= 3.6 Hz, 1 H, 4-thienyl-

H), 7.43 (m, 2 H, 2,6-H), 7.49 (dd, J_3,4= 3.6 Hz, J_3,5= 1.2 Hz, 1

H, 3-thienyl-H), 7.52 (dd, J_5,4= 5.0 Hz, J_5,3= 1.2 Hz, 1 H, 5-thi-

(470.3 MHz, [D ]DMSO): δ = –116.10 ppm. IR (KBr): ν = 3370,

˜

6

3032, 1615, 1604, 1596, 1570, 1524, 1498, 1427, 1395, 1305, 1284,

1240, 1226, 1186, 1161, 1115, 1099, 1070, 1055, 1021, 1007,

941 cm^–1. C₁₇H₁₇FO₄(304.3): calcd. C 67.10, H 5.63, F 6.26; found

C 66.60, H 5.61, F 6.53. HRMS (FAB): calcd. for C₁₇H₁₇FO₄Na

[M + Na] 327.1008; found 327.1003.

1β-[4-(4-Methoxyphenyl)phenyl]-1-deoxy-D-ribofuranose (10g):

enyl-H), 7.61 (m, 2 H, 3,5-H) ppm. ¹³C NMR (151 MHz, [D₆]- Compound 10g was prepared from 9g according to the general

1700

www.eurjoc.org

Eur. J. Org. Chem. 2008, 1689–1704

Synthesis of 4- and 3-Substituted Benzene and Aniline C-Ribonucleosides

procedure in 95% yield. The crude product was crystallized from

EtOAc/heptane to obtain a white solid. M.p. 176 °C. [α]²_D⁰= –8.1

(c =2.60, MeOH).¹H NMR (600 MHz, [D₆]DMSO): δ = 3.54 (ddd,

J_gem= 11.6 Hz, J_5Јb,OH= 5.4 Hz, J_5Јb,4Ј= 4.7 Hz, 1 H, 5Јb-H), 3.57

(ddd, J_gem= 11.6 Hz, J_5Јa,OH= 5.6 Hz, J_5Јa,4Ј= 4.5 Hz, 1 H, 5Јa-

H), 3.71 (ddd, J_2Ј,1Ј= 7.1 Hz, J_2Ј,OH= 7.0 Hz, J_2Ј,3Ј= 5.3 Hz, 1 H,

H, (CH₃)₃C], 3.51 (ddd, J_gem= 11.6 Hz, J_5Јb,OH= 5.5 Hz, J_5Јb,4Ј

4.7 Hz, 1 H, 5Јb-H), 3.54 (ddd, J_gem= 11.6 Hz, J_5Јa,OH= 5.7 Hz,

J_5Јa,4Ј= 4.6 Hz, 1 H, 5Јa-H), 3.68 (ddd, J_2Ј,1Ј= 7.3 Hz, J_2Ј,OH

7.0 Hz, J_2Ј,3Ј= 5.4 Hz, 1 H, 2Ј-H), 3.78 (ddd, J_4Ј,5Ј= 4.7, 4.6 Hz,

J_4Ј,3Ј= 3.5 Hz, 1 H, 4Ј-H), 3.88 (dddd, J_3Ј,2Ј= 5.4 Hz, J_3Ј,OH

4.8 Hz, J_3Ј,4Ј= 3.5 Hz, J_3Ј,1Ј= 0.3 Hz, 1 H, 3Ј-H), 4.50 (d, J_1Ј,2Ј

=

2Ј-H), 3.79 (s, 3 H, CH₃O), 3.82 (ddd, J_4Ј,5Ј= 4.7, 4.5 Hz, J_4Ј,3Ј

3.5 Hz, 1 H, 4Ј-H), 3.90 (ddd, J_3Ј,2Ј= 5.3 Hz, J_3Ј,OH= 4.8 Hz, J_3Ј,4Ј

= 3.5 Hz, 1 H, 3Ј-H), 4.58 (d, J_1Ј,2Ј= 7.1 Hz, 1 H, 1Ј-H), 4.83 (dd,

=

7.3 Hz, 1 H, 1Ј-H), 4.80 (dd, J_OH,5Ј= 5.7, 5.5 Hz, 1 H, OH-5Ј),

4.89 (d, J_OH,3Ј= 4.8 Hz, 1 H, OH-3Ј), 4.93 (d, J_OH,2Ј= 7.0 Hz, 1

H, OH-2Ј), 6.92 (m, 2 H, 3,5-H), 7.29 (m, 2 H, 2,6-H) ppm. ¹³C

J_OH,5Ј= 5.6, 5.4 Hz, 1 H, OH-5Ј), 4.92 (d, J_OH,3Ј= 4.8 Hz, 1 H, NMR (151 MHz, [D₆]DMSO): δ = 28.77 [C(CH₃)₃], 62.32 (CH₂-

OH-3Ј), 5.00 (d, J_OH,2Ј= 7.0 Hz, 1 H, OH-2Ј), 7.02 (m, 2 H, m- 5Ј), 71.69 (CH-3Ј), 77.60 (CH-2Ј), 78.00 [C(CH₃)₃], 82.90 (CH-1Ј),

C₆H₄OMe-H), 7.44 (m, 2 H, 2,6-H), 7.56 (m, 2 H, 3,5-H), 7.59 (m,

85.28 (CH-4Ј), 123.48 (CH-3,5), 127.30 (CH-2,6), 136.08 (C-1),

2 H, o-C₆H₄OMe-H) ppm. ¹³C NMR (151 MHz, [D₆]DMSO): δ = 154.46 (C-4) ppm. IR (KBr): ν = 3355, 3305, 3234, 3071, 3039,

˜

55.38 (CH₃O), 62.31 (CH₂-5Ј), 71.72 (CH-3Ј), 77.88 (CH-2Ј), 82.93 2977, 1608, 1576, 1509, 1492, 1478, 1447, 1418, 1390, 1369, 1295,

(CH-1Ј), 85.33 (CH-4Ј), 114.55 (CH-m-C₆H₄OMe), 126.03 (CH- 1238, 1209, 1174, 1163, 1126, 1115, 1099, 1074, 1059, 1018,

3,5), 126.99 (CH-2,6), 127.89 (CH-o-C₆H₄OMe), 132.67 (C-i- 952 cm^–1. HRMS (FAB): calcd. for C₁₅H₂₃O₄[M + H] 283.1545;

C₆H₄OMe), 139.08 (C-1), 140.11 (C-4), 159.02 (C-p-C₆H₄OMe)

found 283.1553.

ppm. IR (KBr): ν = 3485, 3413, 3282, 3065, 3032, 3005, 2844, 1605,

˜

1β-(3-Bromophenyl)-1-deoxy-D-ribofuranose (17): Compound 17

1585, 1566, 1532, 1517, 1442, 1433, 1414, 1322, 1308, 1288, 1277,

1217, 1200, 1187, 1170, 1126, 1102, 1102, 1078, 1061, 1032, 1018,

1011, 1008, 951, 827 cm^–1. HRMS (FAB): calcd. for C₁₈H₂₀O₅[M

+ H] 316.1311; found 316.1321.

was prepared from 15 according to the general procedure in 88%

yield. Crystallization from CHCl₃yielded white needles. M.p. 79–

81 °C. [α]²_D⁰= –13.8 (c =2.54, MeOH). H NMR (600 MHz, [D₆]-

1

DMSO): δ = 3.52 (ddd, J_gem= 11.6 Hz, J_5Јb,OH= 5.6 Hz, J_5Јb,4Ј

4.4 Hz, 1 H, 5Јb-H), 3.56 (ddd, J_gem= 11.6 Hz, J_5Јa,OH= 5.6 Hz,

J_5Јa,4Ј= 4.3 Hz, 1 H, 5Јa-H), 3.65 (ddd, J_2Ј,1Ј= 7.4 Hz, J_2Ј,OH

7.3 Hz, J_2Ј,3Ј= 5.4 Hz, 1 H, 2Ј-H), 3.82 (ddd, J_4Ј,5Ј= 4.4, 4.3 Hz,

J_4Ј,3Ј= 3.3 Hz, 1 H, 4Ј-H), 3.89 (ddd, J_3Ј,2Ј= 5.4 Hz, J_3Ј,OH

4.7 Hz, J_3Ј,4Ј= 3.3 Hz, 1 H, 3Ј-H), 4.54 (d, J_1Ј,2Ј= 7.4 Hz, 1 H, 1Ј-

H), 4.88 (t, J_OH,5Ј= 5.6 Hz, 1 H, OH-5Ј), 4.97 (d, J_OH,3Ј= 4.7 Hz,

1 H, OH-3Ј), 5.06 (d, J_OH,2Ј= 7.3 Hz, 1 H, OH-2Ј), 7.29 (dd, J_5,4

= 7.9 Hz, J_5,6= 7.7 Hz, 1 H, 5-H), 7.39 (dddd, J_6,5= 7.7 Hz, J_6,2

=

1β-(4-Aminophenyl)-1-deoxy-D

-ribofuranose (10h):^[6b]Compound

10h was prepared from 9h according to the general procedure in

68% yield as a white solid. M.p. 99–100 °C. [α]²_D⁰= –22.1 (c =2.22,

DMSO). ¹H NMR (500 MHz, [D₆]DMSO): δ = 3.48 and 3.51 (2

br. dt, J_gem= 11.6 Hz, J_5Ј,4Ј= J_5Ј,OH= 5.1 Hz, 1 H, 5Ј-H), 3.65 (br.

m, 1 H, 2Ј-H), 3.71 (td, J_4Ј,5Ј= 5.1 Hz, J_4Ј,3Ј= 3.1 Hz, 1 H, 4Ј-H),

3.83 (br. m, 1 H, 3Ј-H), 4.35 (d, J_1Ј,2Ј= 7.0 Hz, 1 H, 1Ј-H), 4.72

(br. t, J_OH,5Ј= 5.1 Hz, 1 H, OH-5Ј), 4.76 (br. s, 2 H, OH-2Ј,3Ј),

4.94 (br. s, 2 H, NH₂), 6.50 (m, 2 H, 3,5-H), 7.00 (m, 2 H, 2,6-H)

ppm. ¹³C NMR (125.7 MHz, [D₆]DMSO): δ = 62.42 (CH₂-5Ј),

71.58 (CH-3Ј), 77.14 (CH-2Ј), 83.73 (CH-1Ј), 84.77 (CH-4Ј), 113.63

(CH-3,5), 127.57 (CH-2,6), 128.21 (C-1), 148.13 (C-4) ppm. IR

=

= 1.6 Hz, J_6,4= 1.1 Hz, J_6,1Ј= 0.6 Hz, 1 H, 6-H), 7.46 (ddd, J_4,5

7.9 Hz, J_4,2= 2.1 Hz, J_4,6= 1.1 Hz, 1 H, 4-H), 7.58 (ddt, J_2,4

=

2.1 Hz, J_2,6= 1.6 Hz, J_2,5= J_2,1Ј= 0.5 Hz, 1 H, 2-H) ppm. ¹³C

NMR (151 MHz, [D₆]DMSO): δ = 62.12 (CH₂-5Ј), 71.62 (CH-3Ј),

78.01 (CH-2Ј), 82.22 (CH-1Ј), 85.64 (CH-4Ј), 121.74 (C-3), 125.50

(CH-6), 128.88 (CH-2), 130.32 (CH-4), 130.49 (CH-5), 144.61 (C-

(KBr): ν = 3408, 3385, 3371, 3300, 1631, 1615, 1587, 1519, 1325,

˜

1291, 1218, 1179, 1107, 1078, 1054, 1020, 832 cm^–1. HRMS (FAB):

calcd. for C₁₁H₁₆NO₄[M + H] 226.1079; found 226.1073.

1) ppm. IR (KBr): ν = 3448, 3337, 3203, 3060, 1594, 1566, 1474,

˜

1414, 1305, 1266, 1193, 1113, 1092, 1081, 1071, 1054, 845 cm^–1.

HRMS (FAB): calcd. for C₁₁H₁₃O₄BrNa [M + Na] 310.9895;

found 310.9882.

1β-[4-(Dimethylamino)phenyl]-1-deoxy-D-ribofuranose (10i): Com-

pound 10i was prepared from 9i according to the general procedure

in 86% yield. The crude product was crystallized from EtOAc/hep-

tane to obtain white crystals. M.p. 101–103 °C. [α]²_D⁰= –33.5 (c

=2.99, MeOH). ¹H NMR (600 MHz, [D₆]DMSO): δ = 2.86 [s, 6

H, (CH₃)₂N], 3.49 (br. dd, J_gem= 11.5 Hz, J_5Јb,4Ј= 4.9 Hz, 1 H,

5Јb-H), 3.53 (br. dd, J_gem= 11.6 Hz, J_5Јa,4Ј= 4.6 Hz, 1 H, 5Јa-H),

3.66 (br. dd, J_2Ј,1Ј= 7.0 Hz, J_2Ј,3Ј= 5.3 Hz, 1 H, 2Ј-H), 3.74 (ddd,

1β-(3-Methylphenyl)-1-deoxy-D-ribofuranose (19a): Compound 19a

was prepared from 18a (476 mg, 0.840 mmol) according to the ge-

neral procedure in 72% yield as a colorless heavy oil, which after

coevaporation with dry toluene and Et₂O furnished a white pow-

der. M.p. 70–73 °C. [α]²_D⁰= –23.2 (c =3.10, MeOH). ¹H NMR

J_4Ј,5Ј= 4.9, 4.6 Hz, J_4Ј,3Ј= 3.8 Hz, 1 H, 4Ј-H), 3.85 (br. dd, J_3Ј,2Ј

=

(600 MHz, [D₆]DMSO): δ = 2.29 (s, 3 H, CH₃), 3.52 (ddd, J_gem

=

5.3 Hz, J_3Ј,4Ј= 3.8 Hz, 1 H, 3Ј-H), 4.43 (d, J_1Ј,2Ј= 7.0 Hz, 1 H, 1Ј-

H), 4.74 (br. s, 1 H, OH-5Ј), 4.82 (br. s, 2 H, OH-2Ј,3Ј), 6.68 (m, 2

H, 3,5-H), 7.17 (m, 2 H, 2,6-H) ppm. ¹³C NMR (151 MHz, [D₆]-

DMSO): δ = 40.53 [(CH₃)₂N], 62.41 (CH₂-5Ј), 71.64 (CH-3Ј), 77.41

(CH-2Ј), 83.39 (CH-1Ј), 84.90 (CH-4Ј), 112.30 (CH-3,5), 127.51

11.6 Hz, J_5Јb,OH= 5.5 Hz, J_5Јb,4Ј= 4.8 Hz, 1 H, 5Јb-H), 3.56 (ddd,

J_gem= 11.6 Hz, J_5Јa,OH= 5.7 Hz, J_5Јa,4Ј= 4.4 Hz, 1 H, 5Јa-H), 3.66

(ddd, J_2Ј,1Ј= 7.1 Hz, J_2Ј,OH= 7.0 Hz, J_2Ј,3Ј= 5.5 Hz, 1 H, 2Ј-H),

3.79 (ddd, J_4Ј,5Ј= 4.8, 4.4 Hz, J_4Ј,3Ј= 3.8 Hz, 1 H, 4Ј-H), 3.87 (ddd,

J_3Ј,2Ј= 5.5 Hz, J_3Ј,OH= 4.9 Hz, J_3Ј,4Ј= 3.8 Hz, 1 H, 3Ј-H), 4.51 (d,

J_1Ј,2Ј= 7.1 Hz, 1 H, 1Ј-H), 4.81 (dd, J_OH,5Ј= 5.7, 5.5 Hz, 1 H, OH-

5Ј), 4.89 (d, J_OH,3Ј= 4.9 Hz, 1 H, OH-3Ј), 4.95 (d, J_OH,2Ј= 7.0 Hz,

1 H, OH-2Ј), 7.39 (dddd, J_6,5= 7.1 Hz, J_6,2= 2.5 Hz, J_6,4= 1.7 Hz,

J_6,1Ј= 0.5 Hz, 1 H, 6-H), 7.16–7.19 (m, 2 H, 2,4-H), 7.20 (dd, J_5,4

= 7.6 Hz, J_5,6= 7.1 Hz, 1 H, 5-H) ppm. ¹³C NMR (151 MHz, [D₆]

DMSO): δ = 21.33 (CH₃), 62.29 (CH₂-5Ј), 71.62 (CH-3Ј), 77.76

(CH-2Ј), 83.31 (CH-1Ј), 85.24 (CH-4Ј), 123.62 (CH-4), 127.10 (CH-

2), 128.09 (CH-6), 128.11 (CH-5), 137.19 (C-3), 141.55 (C-1) ppm.

(CH-2,6), 128.87 (C-1), 150.19 (C-4) ppm. IR (KBr): ν = 3401,

˜

2803, 1617, 1568, 1525, 1444, 1413, 1355, 1315, 1298, 1233, 1188,

1164, 1115, 1072, 1051, 1035, 950, 811 cm^–1. C₁₃H₁₉NO₄(253.3):

calcd. C 61.64, H 7.56, N 5.53; found C 61.60, H 7.56, N 5.39.

HRMS (FAB): calcd. for C₁₃H₂₀NO₄[M + H] 254.1392; found

254.1397.

1β-[(4-tert-Butoxy)phenyl]-1-deoxy-D-ribofuranose (10j): Com-

pound 10j was prepared from 9j according to the general procedure

in 95% yield. The crude product was crystallized from CHCl₃to

obtain peel transparent crystals. M.p. 108–109 °C. [α]²_D⁰= –33.6 (c

IR (KBr): ν = 3392, 3272, 3064, 3026, 1611, 1592, 1490, 1465,

˜

1382, 1284, 1263, 1237, 1163, 1091 cm^–1. HRMS (FAB): calcd. for

=2.60, DMSO). ¹H NMR (600 MHz, [D₆]DMSO): δ = 1.28 [s, 9 C₁₂H₁₆O₄Na [M + Na] 247.0946; found 247.0943.

Eur. J. Org. Chem. 2008, 1689–1704

www.eurjoc.org

1701

ˇ

M. Stefko, R. Pohl, B. Klepetárˇová, M. Hocek

FULL PAPER

1β-(3-Ethylphenyl)-1-deoxy-

D

-ribofuranose (19b): Compound 19b

4-H), 7.67 (tt, J_2,4= J_2,6= 1.5 Hz, J_2,5= J_2,1Ј= 0.5 Hz, 1 H, 2-H)

ppm. ¹³C NMR (151 MHz, [D₆]DMSO): δ = 62.18 (CH₂-5Ј), 71.59

(CH-3Ј), 77.89 (CH-2Ј), 82.99 (CH-1Ј), 85.34 (CH-4Ј), 123.47 (CH-

2), 123.89 (CH-3-thienyl), 124.61 (CH-5-thienyl), 125.65 (CH-6),

125.87 (CH-4), 128.69 (CH-4-thienyl), 129.08 (CH-5), 133.70 (C-

was prepared from 18b (394 mg, 0.679 mmol) according to the

general procedure in 77% yield as a colorless oil, which after co-

evaporation with dry toluene and Et₂O furnished a white solid.

M.p. 61–62 °C. [α]²_D⁰

=

–23.2 (c =3.10, MeOH). ¹H NMR

(600 MHz, [D₆]DMSO): δ = 1.17 (t, J_vic= 7.6 Hz, 3 H, CH₃CH₂), 3), 142.69 (C-1), 143.69 (C-2-thienyl) ppm. IR (KBr): ν = 3340,

˜

2.59 (q, J_vic= 7.6 Hz, 2 H, CH₂CH₃), 3.52 (ddd, J_gem= 11.7 Hz,

J_5Јb,OH= 5.5 Hz, J_5Јb,4Ј= 4.8 Hz, 1 H, 5Јb-H), 3.56 (ddd, J_gem

3306, 3240, 1632, 1604, 1585, 1537, 1481, 1446, 1386, 1341, 1277,

1177, 1123, 1092, 1073, 1057, 999, 868, 858, 852, 790, 695, 562,

=

11.7 Hz, J_5Јa,OH= 5.7 Hz, J_5Јa,4Ј= 4.5 Hz, 1 H, 5Јa-H), 3.67 (ddd, 521, 451 cm^–1. HRMS (FAB): calcd. for C₁₅H₁₆O₄SNa [M + Na]

J_2Ј,1Ј= 7.0 Hz, J_2Ј,OH= 6.9 Hz, J_2Ј,3Ј= 5.4 Hz, 1 H, 2Ј-H), 3.79 315.0667; found 315.0652.

(ddd, J_4Ј,5Ј= 4.8, 4.5 Hz, J_4Ј,3Ј= 3.7 Hz, 1 H, 4Ј-H), 3.87 (ddd,

1β-[3-(Pyridin-2-yl)phenyl]-1-deoxy-D-ribofuranose (19e): Com-

J_3Ј,2Ј= 5.4 Hz, J_3Ј,OH= 4.9 Hz, J_3Ј,4Ј= 3.7 Hz, 1 H, 3Ј-H), 4.52 (d,

J_1Ј,2Ј= 7.0 Hz, 1 H, 1Ј-H), 4.82 (dd, J_OH,5Ј= 5.7, 5.5 Hz, 1 H, OH-

5Ј), 4.89 (d, J_OH,3Ј= 4.9 Hz, 1 H, OH-3Ј), 4.95 (d, J_OH,2Ј= 6.9 Hz,

pound 19e was prepared from 18e (517 mg, 0.821 mmol) according

to the general procedure in 68% yield as a colorless oil, which after

coevaporation with dry toluene and Et₂O furnished a white solid.

M.p. 137–139 °C. [α]²_D⁰= –6.3 (c =3.19, MeOH). ¹H NMR

1 H, OH-2Ј), 7.10 (m, 1 H, 4-H), 7.39 (dtd, J_6,5= 7.5 Hz, J_6,2

=

J_6,4= 1.7 Hz, J_6,1Ј= 0.5 Hz, 1 H, 6-H), 7.22 (m, 1 H, 2-H), 7.23

(td, J_5,4= J_5,6= 7.5 Hz, J_5,2= 0.4 Hz, 1 H, 5-H) ppm. ¹³C NMR

(151 MHz, [D₆]DMSO): δ = 15.91 (CH₃CH₂), 28.44 (CH₂CH₃),

62.28 (CH₂-5Ј), 71.60 (CH-3Ј), 77.74 (CH-2Ј), 83.42 (CH-1Ј), 85.20

(CH-4Ј), 123.89 (CH-6), 125.92 (CH-2), 126.89 (CH-4), 128.18

(600 MHz, [D₆]DMSO): δ = 3.57 (ddd, J_gem= 11.6 Hz, J_5Јb,OH

5.4 Hz, J_5Јb,4Ј= 4.7 Hz, 1 H, 5Јb-H), 3.61 (ddd, J_gem= 11.6 Hz,

J_5Јa,OH= 5.7 Hz, J_5Јa,4Ј= 4.4 Hz, 1 H, 5Јa-H), 3.75 (ddd, J_2Ј,1Ј

=

7.1 Hz, J_2Ј,OH= 6.9 Hz, J_2Ј,3Ј= 5.4 Hz, 1 H, 2Ј-H), 3.85 (ddd, J_4Ј,5Ј

= 4.7, 4.4 Hz, J_4Ј,3Ј= 3.7 Hz, 1 H, 4Ј-H), 3.92 (ddd, J_3Ј,2Ј= 5.4 Hz,

J_3Ј,OH= 4.9 Hz, J_3Ј,4Ј= 3.7 Hz, 1 H, 3Ј-H), 4.66 (d, J_1Ј,2Ј= 7.1 Hz,

1 H, 1Ј-H), 4.87 (dd, J_OH,5Ј= 5.7, 5.4 Hz, 1 H, OH-5Ј), 4.94 (d,

J_OH,3Ј= 4.9 Hz, 1 H, OH-3Ј), 5.05 (d, J_OH,2Ј= 6.9 Hz, 1 H, OH-

2Ј), 7.35 (ddd, J_5,4= 7.4 Hz, J_5,6= 4.7 Hz, J_5,3= 1.1 Hz, 1 H, 5-

(CH-5), 141.58 (C-1), 143.59 (C-3) ppm. IR (KBr): ν = 3413, 3275,

˜

3061, 3032, 1608, 1591, 1485, 1465, 1380, 1289, 1263, 1236, 1160,

1118, 1072, 1049 cm^–1. HRMS (FAB): calcd. for C₁₃H₁₈O₄[M +

H] 238.1205; found 238.1194.

1β-(3-Benzylphenyl)-1-deoxy-D-ribofuranose (19c): Compound 19c

py-H), 7.45 (t, J_5,4= J_5,6= 7.6 Hz, 1 H, 5-H), 7.48 (dtd, J_6,5=

was prepared from 18c (442 mg, 0.700 mmol) according to the ge-

neral procedure in 80% yield as a colorless oil, which after coevap-

oration with dry toluene and Et₂O furnished a white solid. M.p.

71–72 °C. [α]²_D⁰= –22.7 (c =2.51, MeOH).¹H NMR (600 MHz,

[D₆]DMSO): δ = 3.51 (dd, J_gem= 11.6 Hz, J_5Јb,4Ј= 4.8 Hz, 1 H,

7.6 Hz, J_6,2= J_6,4= 1.6 Hz, J_6,1Ј= 0.5 Hz, 1 H, 6-H), 7.88 (ddd,

J_4,3= 8.0 Hz, J_4,5= 7.4 Hz, J_4,6= 1.7 Hz, 1 H, 4-py-H), 7.94 (ddd,

J_3,4= 8.0 Hz, J_3,5= 1.1 Hz, J_3,6= 1.0 Hz, 1 H, 3-py-H), 7.97 (dt,

J_4,5= 7.6 Hz, J_4,2= J_4,6= 1.6 Hz, 1 H, 4-H), 8.09 (tt, J_2,4= J_2,6

=

1.6 Hz, J_2,5= J_2,1Ј= 0.6 Hz, 1 H, 2-H), 8.67 (ddd, J_6,5= 4.7 Hz,

5Јb-H), 3.55 (dd, J_gem= 11.6 Hz, J_5Јa,4Ј= 4.5 Hz, 1 H, 5Јa-H), 3.67 J_6,4= 1.7 Hz, J_6,3= 1.0 Hz, 1 H, 6-py-H) ppm. ¹³C NMR

(dd, J_2Ј,1Ј= 7.0 Hz, J_2Ј,3Ј= 5.5 Hz, 1 H, 2Ј-H), 3.78 (ddd, J_4Ј,5Ј

4.8, 4.5 Hz, J_4Ј,3Ј= 3.8 Hz, 1 H, 4Ј-H), 3.86 (dd, J_3Ј,2Ј= 5.5 Hz,

J_3Ј,4Ј= 3.8 Hz, 1 H, 3Ј-H), 3.92 (s, 2 H, CH₂Ph), 4.51 (d, J_1Ј,2Ј

=

(151 MHz, [D₆]DMSO): δ = 62.24 (CH₂-5Ј), 71.57 (CH-3Ј), 77.85

(CH-2Ј), 83.27 (CH-1Ј), 85.38 (CH-4Ј), 120.52 (CH-3-py), 122.81

(CH-5-py), 124.63 (CH-2), 125.72 (CH-4), 127.12 (CH-6), 128.72

=

7.0 Hz, 1 H, 1Ј-H), 4.82 (br. s, 1 H, OH-5Ј), 4.94 (br. s, 2 H, OH- (CH-5), 137.45 (CH-4-py), 138.66 (C-3), 142.21 (C-1), 149.74 (CH-

2Ј,3Ј), 7.10 (dt, J_4,5= 6.8 Hz, J_4,2= J_4,6= 1.9 Hz, 1 H, 4-H), 7.18

(m, 1 H, p-Ph-H), 7.20-7.25 (m, 4 H, 5,6-H and o-Ph-H), 7.26–7.30

6-py), 156.31 (C-2-py) ppm. IR (KBr): ν = 3355, 3240, 3064, 2763,

1680, 1632, 1589, 1589, 1567, 1567, 1492, 1467, 1435, 1278, 1155,

˜

(m, 3 H, 2-H and m-Ph-H) ppm. ¹³C NMR (151 MHz, [D₆]- 1127, 1096, 1073, 1056, 1044, 1001 cm^–1. HRMS (FAB): calcd. for

DMSO): δ = 41.37 (CH₂Ph), 62.26 (CH₂-5Ј), 71.59 (CH-3Ј), 77.72 C₁₆H₁₈NO₄[M + H] 288.1236; found 288.1244.

(CH-2Ј), 83.34 (CH-1Ј), 85.21 (CH-4Ј), 124.20 (CH-6), 126.18 (CH-

1β-[3-(4-Fluorophenyl)phenyl]-1-deoxy-D-ribofuranose (19f): Com-

p-Ph), 126.89 (CH-2), 127.88 (CH-4), 128.33 (CH-5), 128.65 (CH-

m-Ph), 128.90 (CH-o-Ph), 141.11 (C-3), 141.51 (C-i-Ph), 141.77 (C-

pound 19f was prepared from 18f (369 mg, 0.619 mmol) according

to the general procedure in 77% yield as a colorless oil, which after

coevaporation with dry toluene and Et₂O furnished a white solid.

M.p. 119–122 °C. [α]²_D⁰= –20.3 (c =2.66, MeOH). ¹H NMR

1) ppm. IR (CCl ): ν = 3392, 1632, 1609, 1602, 1590, 1590, 1494,

˜

4

1488, 1465, 1453, 1237, 1156, 1119, 1090, 1072, 1047 cm^–1. HRMS

(FAB): calcd. for C₁₈H₂₁O₄[M + H] 301.1440; found 301.1431.

(600 MHz, [D₆]DMSO): δ = 3.55 (ddd, J_gem= 11.6 Hz, J_5Јb,OH

5.5 Hz, J_5Јb,4Ј= 4.6 Hz, 1 H, 5Јb-H), 3.59 (ddd, J_gem= 11.6 Hz,

J_5Јa,OH= 5.7 Hz, J_5Јa,4Ј= 4.4 Hz, 1 H, 5Јa-H), 3.74 (ddd, J_2Ј,1Ј

=

1β-[3-(2-Thienyl)phenyl]-1-deoxy-D-ribofuranose (19d): Compound

19d was prepared from 18d (367 mg, 0.580 mmol) according to the

general procedure in 72% yield as a colorless heavy oil, which after

coevaporation with dry toluene and Et₂O furnished a white solid.

M.p. 111 °C. [α]²_D⁰= –49.7 (c =2.75, DMSO). ¹H NMR (600 MHz,

=

7.1 Hz, J_2Ј,OH= 6.9 Hz, J_2Ј,3Ј= 5.3 Hz, 1 H, 2Ј-H), 3.84 (ddd, J_4Ј,5Ј

= 4.6, 4.4 Hz, J_4Ј,3Ј= 3.6 Hz, 1 H, 4Ј-H), 3.92 (ddd, J_3Ј,2Ј= 5.3 Hz,

J_3Ј,OH= 4.8 Hz, J_3Ј,4Ј= 3.6 Hz, 1 H, 3Ј-H), 4.64 (d, J_1Ј,2Ј= 7.1 Hz,

[D₆]DMSO): δ = 3.56 (ddd, J_gem= 11.6 Hz, J_5Јb,OH= 5.4 Hz, J_5Јb,4Ј1 H, 1Ј-H), 4.86 (dd, J_OH,5Ј= 5.7, 5.5 Hz, 1 H, OH-5Ј), 4.93 (d,

= 4.5 Hz, 1 H, 5Јb-H), 3.59 (ddd, J_gem= 11.6 Hz, J_5Јa,OH= 5.6 Hz,

J_OH,3Ј= 4.8 Hz, 1 H, OH-3Ј), 5.03 (d, J_OH,2Ј= 6.9 Hz, 1 H, OH-

2Ј), 7.29 (m, 2 H, m-C₆H₄F-H), 7.39 (dtd, J_6,5= 7.6 Hz, J_6,2= J_6,4

J_5Јa,4Ј= 4.5 Hz, 1 H, 5Јa-H), 3.72 (ddd, J_2Ј,1Ј= 7.0 Hz, J_2Ј,OH

6.9 Hz, J_2Ј,3Ј= 5.3 Hz, 1 H, 2Ј-H), 3.84 (td, J_4Ј,5Ј= 4.5 Hz, J_4Ј,3Ј

=

= 1.6 Hz, J_6,1Ј= 0.5 Hz, 1 H, 6-H), 7.42 (ddd, J_5,6= 7.6 Hz, J_5,4

7.3 Hz, J_5,2= 0.6 Hz, 1 H, 5-H), 7.53 (dt, J_4,5= 7.3 Hz, J_4,2= J_4,6

= 1.6 Hz, 1 H, 4-H), 7.65 (tt, J_2,4= J_2,6= 1.6 Hz, J_2,5= J_2,1Ј

=

3.5 Hz, 1 H, 4Ј-H), 3.92 (ddd, J_3Ј,2Ј= 5.3 Hz, J_3Ј,OH= 4.9 Hz, J_3Ј,4Ј

= 3.5 Hz, 1 H, 3Ј-H), 4.61 (d, J_1Ј,2Ј= 7.0 Hz, 1 H, 1Ј-H), 4.87 (dd,

=

J_OH,5Ј= 5.6, 5.4 Hz, 1 H, OH-5Ј), 4.94 (d, J_OH,3Ј= 4.9 Hz, 1 H, 0.6 Hz, 1 H, 2-H), 7.69 (m, 2 H, o-C₆H₄F-H) ppm. ¹³C NMR

OH-3Ј), 5.05 (d, J_OH,2Ј= 6.9 Hz, 1 H, OH-2Ј), 7.14 (dd, J_4,5

5.1 Hz, J_4,3= 3.6 Hz, 1 H, 4-thienyl-H), 7.34 (dtd, J_6,5= 7.6 Hz,

J_6,2= J_6,4= 1.5 Hz, J_6,1Ј= 0.5 Hz, 1 H, 6-H), 7.37 (td, J_5,4= J_5,6

= 7.6 Hz, J_5,2= 0.5 Hz, 1 H, 5-H), 7.49 (dd, J_3,4= 3.6 Hz, J_3,5

1.2 Hz, 1 H, 3-thienyl-H), 7.54 (dd, J_5,4= 5.1 Hz, J_5,3= 1.2 Hz, 1

H, 5-thienyl-H), 7.55 (dt, J_4,5= 7.6 Hz, J_4,2= J_4,6= 1.5 Hz, 1 H,

=

(151 MHz, [D₆]DMSO): δ = 62.18 (CH₂-5Ј), 71.59 (CH-3Ј), 77.91

(CH-2Ј), 83.14 (CH-1Ј), 85.33 (CH-4Ј), 115.94 (d, J_C,F

21 Hz,CH-m-C₆H₄F), 124.69 (CH-2), 125.52 (CH-6), 125.82 (CH-

4), 128.91 (d, J_C,F= 8 Hz,CH-o-C₆H₄F), 128.92 (CH-5), 137.00 (d,

J_C,F= 3 Hz,C-i-C₆H₄F), 139.11 (C-3), 142.48 (C-1), 162.07 (d, J_C,F

= 244 Hz, C-p-C₆H₄F) ppm. ¹⁹F NMR (MHz, [D₆]DMSO): δ =

=

1702

www.eurjoc.org

Eur. J. Org. Chem. 2008, 1689–1704

Synthesis of 4- and 3-Substituted Benzene and Aniline C-Ribonucleosides

–116.01 ppm. IR (KBr): ν = 3467, 3415, 3237, 1632, 1607, 1597, 11.7 Hz, J_5Јb,OH= J_5Јb,4Ј= 5.1 Hz, 1 H, 5Јb-H), 3.57 (ddd, J_gem

=

˜

1585, 1560, 1515, 1485, 1397, 1315, 1232, 1175, 1160, 1128, 1100,

1056, 1070, 1000, 877 cm^{– 1}. HRMS (FAB): calcd. for J_2Ј,OH= 6.6 Hz, J_2Ј,1Ј= 6.5 Hz, J_2Ј,3Ј= 5.0 Hz, 1 H, 2Ј-H), 3.78

C₁₇H₁₇O₄FNa [M + Na] 327.1009; found 327.1018. (ddd, J_4Ј,5Ј= 5.1, 4.5 Hz, J_4Ј,3Ј= 3.7 Hz, 1 H, 4Ј-H), 3.87 (td, J_3Ј,2Ј

11.7 Hz, J_5Јa,OH= 5.7 Hz, J_5Јa,4Ј= 4.5 Hz, 1 H, 5Јa-H), 3.66 (ddd,

=

J_3Ј,OH= 5.0 Hz, J_3Ј,4Ј= 3.7 Hz, 1 H, 3Ј-H), 4.50 (d, J_1Ј,2Ј= 6.5 Hz, 1

H, 1Ј-H), 4.82 (dd, J_OH,5Ј= 5.7, 5.1 Hz, 1 H, OH-5Ј), 4.85 (d, J_OH,3Ј

= 5.0 Hz, 1 H, OH-3Ј), 4.95 (d, J_OH,2Ј= 6.6 Hz, 1 H, OH-2Ј), 6.60

(ddd, J_4,5= 8.3 Hz, J_4,2= 2.7 Hz, J_4,6= 0.8 Hz, 1 H, 4-H), 6.67

1β-[3-(4-Methoxyphenyl)phenyl]-1-deoxy- -ribofuranose (19g):

D

Compound 19g was prepared from 18g (479 mg, 0.727 mmol) ac-

cording to the general procedure in 73% yield as a colorless oil,

which after coevaporation with dry toluene and Et₂O furnished a

(br. d, J_6,5= 7.6 Hz, 1 H, 6-H), 6.77 (dd, J_2,4= 2.7 Hz, J_2,6

=

1

white solid. M.p. 127–128 °C. [α]²_D⁰= –17.7 (c =3.29, MeOH). H

1.3 Hz, 1 H, 2-H), 7.11 (dd, J_5,4= 8.3 Hz, J_5,6= 7.6 Hz, 1 H, 5-H)

ppm. ¹³C NMR (151 MHz, [D₆]DMSO): δ = 40.46 (CH₃N), 62.22

(CH₂-5Ј), 71.49 (CH-3Ј), 77.76 (CH-2Ј), 84.12 (CH-1Ј), 84.80 (CH-

4Ј), 110.70 (CH-2), 111.67 (CH-4), 114.45 (CH-6), 128.78 (CH-5),

NMR (500 MHz, [D₆]DMSO): δ = 3.55 (ddd, J_gem= 11.6 Hz,

J_5Јb,OH= 5.5 Hz, J_5Јb,4Ј= 4.6 Hz, 1 H, 5Јb-H), 3.59 (ddd, J_gem

=

11.6 Hz, J_5Јa,OH= 5.7 Hz, J_5Јa,4Ј= 4.4 Hz, 1 H, 5Јa-H), 3.74 (td,

J_2Ј,1Ј= J_2Ј,OH= 7.0 Hz, J_2Ј,3Ј= 5.3 Hz, 1 H, 2Ј-H), 3.79 (s, 3 H,

CH₃O), 3.83 (ddd, J_4Ј,5Ј= 4.6, 4.4 Hz, J_4Ј,3Ј= 3.7 Hz, 1 H, 4Ј-H),

3.92 (ddd, J_3Ј,2Ј= 5.3 Hz, J_3Ј,OH= 4.8 Hz, J_3Ј,4Ј= 3.7 Hz, 1 H, 3Ј-

H), 4.63 (d, J_1Ј,2Ј= 7.0 Hz, 1 H, 1Ј-H), 4.84 (dd, J_OH,5Ј= 5.7,

5.5 Hz, 1 H, OH-5Ј), 4.90 (d, J_OH,3Ј= 4.8 Hz, 1 H, OH-3Ј), 5.01

142.35 (C-1), 150.57 (C-3) ppm. IR (KBr): ν = 2800, 1609, 1585,

˜

1501, 1456, 1440, 1317, 1286, 1100, 1047, 996 cm^–1. HRMS (FAB):

calcd. for C₁₃H₂₀NO₄[M + H] 254.1392; found 254.1402.

1β-[(3-tert-Butoxy)phenyl]-1-deoxy-D-ribofuranose (19j): Com-

(d, J_OH,2Ј= 7.0 Hz, 1 H, OH-2Ј), 7.03 (m, 2 H, m-C₆H₄OMe-H), pound 19j was prepared from 18j (318 mg, 0.503 mmol) according

7.33 (dddd, J_6,5= 7.6 Hz, J_6,2= 1.9 Hz, J_6,4= 1.3 Hz, J_6,1Ј

0.6 Hz, 1 H, 6-H), 7.38 (dd, J_5,6= 7.6 Hz, J_5,4= 7.5 Hz, 1 H, 5- (c =4.27, DMSO). H NMR (600 MHz, [D₆]DMSO): δ = 1.28 (s,

=

to the general procedure in 78% yield as yellowish oil. [α]²_D⁰= –36.2

1

H), 7.50 (ddd, J_4,5= 7.5 Hz, J_4,2= 1.9 Hz, J_4,6= 1.3 Hz, 1 H, 4-

H), 7.59 (m, 2 H, o-C₆H₄OMe-H), 7.62 (tt, J_2,4= J_2,6= 1.9 Hz, = 4.7 Hz, 1 H, 5Јb-H), 3.54 (ddd, J_gem= 11.6 Hz, J_5Јa,OH= 5.6 Hz,

J_2,5= J_2,1Ј= 0.5 Hz, 1 H, 2-H) ppm. ¹³C NMR (125.7 MHz, [D₆]-

J_5Јa,4Ј= 4.5 Hz, 1 H, 5Јa-H), 3.66 (ddd, J_2Ј,1Ј= 7.0 Hz, J_2Ј,OH

DMSO): δ = 55.37 (CH₃O), 62.20 (CH₂-5Ј), 71.58 (CH-3Ј), 77.84 6.9 Hz, J_2Ј,3Ј= 5.3 Hz, 1 H, 2Ј-H), 3.80 (ddd, J_4Ј,5Ј= 4.7, 4.5 Hz,

9 H, (CH₃)₃C), 3.51 (ddd, J_gem= 11.6 Hz, J_5Јb,OH= 5.5 Hz, J_5Јb,4Ј

=

(CH-2Ј), 83.24 (CH-1Ј), 85.27 (CH-4Ј), 114.54 (CH-m-C₆H₄OMe), J_4Ј,3Ј= 3.6 Hz, 1 H, 4Ј-H), 3.87 (dddd, J_3Ј,2Ј= 5.3 Hz, J_3Ј,OH

124.24 (CH-2), 124.80 (CH-6), 125.31 (CH-4), 127.97 (CH-o- 4.9 Hz, J_3Ј,4Ј= 3.6 Hz, J_3Ј,1Ј= 0.4 Hz, 1 H, 3Ј-H), 4.52 (d, J_1Ј,2Ј

=

C₆H₄OMe), 128.76 (CH-5), 132.85 (C-i-C₆H₄OMe), 139.76 (C-3), 7.0 Hz, 1 H, 1Ј-H), 4.81 (dd, J_OH,5Ј= 5.6, 5.5 Hz, 1 H, OH-5Ј),

142.27 (C-1), 159.06 (C-p-C H OMe) ppm. IR (KBr): ν = 2837,

1607, 1607, 1589, 1573, 1517, 1482, 1453, 1439, 1302, 1265, 1247,

4.89 (d, J_OH,3Ј= 4.9 Hz, 1 H, OH-3Ј), 4.98 (d, J_OH,2Ј= 6.9 Hz, 1

H, OH-2Ј), 6.85 (ddd, J_4,5= 8.0 Hz, J_4,2= 2.5 Hz, J_4,6= 1.1 Hz, 1

˜

6

4

1180, 1116, 1103, 1085, 1065, 1053, 1035, 1022, 1003, 876, H, 4-H), 7.00 (ddt, J_2,4= 2.5 Hz, J_2,6= 1.5 Hz, J_2,5= J_2,1Ј= 0.5 Hz,

839 cm^–1. HRMS (FAB): calcd. for C₁₈H₂₀O₅Na [M + Na]

339.1208; found 339.1221.

1 H, 2-H), 7.07 (dddd, J_6,5= 7.6 Hz, J_6,2= 1.5 Hz, J_6,4= 1.1 Hz,

J_6,1Ј= 0.7 Hz, 1 H, 6-H), 7.21 (dd, J_5,4= 8.0 Hz, J_5,6= 7.6 Hz, 1 H,

5-H) ppm. ¹³C NMR (151 MHz, [D₆]DMSO): δ = 28.99 [C(CH₃)₃],

62.44 (CH₂-5Ј), 71.82 (CH-3Ј), 78.09 (CH-2Ј), 78.12 [C(CH₃)₃],

83.16 (CH-1Ј), 85.35 (CH-4Ј), 121.25 (CH-6), 121.64 (CH-2),

122.64 (CH-4), 128.89 (CH-5), 143.06 (C-1), 155.27 (C-3) ppm. IR

1β-(3-Aminophenyl)-1-deoxy-D-ribofuranose (19h): Compound 19h

was prepared from 18h (452 mg, 0.715 mmol) according to the ge-

neral procedure in 84% yield as a colorless oil, which after coevap-

oration with dry toluene and Et₂O furnished a white solid. M.p.

(KBr): ν = 3414, 3070, 3032, 2977, 1604, 1586, 1486, 1440, 1391,

˜

113–115 °C. [α]²_D⁰= –26.6 (c =2.16, DMSO). H NMR (600 MHz,

1

1367, 1314, 1262, 1177, 1165, 1112, 1075, 1049, 909, 862 cm^–1

.

[D₆]DMSO): δ = 3.51 (dt, J_gem= 11.6 Hz, J_5Јb,OH= J_5Јb,4Ј= 5.4 Hz,

HRMS (FAB): calcd. for C₁₅H₂₂O₅Na [M + Na] 305.1368; found

305.1372.

1 H, 5Јb-H), 3.53 (ddd, J_gem= 11.6 Hz, J_5Јa,OH= 5.7 Hz, J_5Јa,4Ј

4.8 Hz, 1 H, 5Јa-H), 3.64 (td, J_2Ј,1Ј= J_2Ј,OH= 6.8 Hz, J_2Ј,3Ј

=

5.2 Hz, 1 H, 2Ј-H), 3.75 (ddd, J_4Ј,5Ј= 5.4, 4.8 Hz, J_4Ј,3Ј= 3.6 Hz, 1

H, 4Ј-H), 3.82 (ddd, J_3Ј,2Ј= 5.2 Hz, J_3Ј,OH= 5.1 Hz, J_3Ј,4Ј= 3.6 Hz,

Single Crystal X-ray Diffraction Analysis of 5 and 10i: X-ray diffrac-

tion analysis of single crystals of 5 (colorless, 0.21ϫ0.31ϫ0.63 mm)

and 10i (colorless, 0.08ϫ0.27ϫ0.60 mm) was performed with an

Xcalibur X-ray diffractometer with Cu-K_α(λ = 1.54180 Å), data

collected at 150 K (5) and at 295 K (10i). Both structures were

solved by direct methods with SIR92^[27]and refined by full-matrix

least-squares on F with CRYSTALS.^[28]All non-hydrogen atoms

were refined anisotropically. The hydrogen atoms were located in

1 H, 3Ј-H), 4.33 (d, J_1Ј,2Ј= 6.8 Hz, 1 H, 1Ј-H), 4.76 (dd, J_OH,5Ј

=

5.7, 5.4 Hz, 1 H, OH-5Ј), 4.84 (d, J_OH,3Ј= 5.1 Hz, 1 H, OH-3Ј),

4.91 (d, J_OH,2Ј= 6.8 Hz, 1 H, OH-2Ј), 4.97 (br. s, 2 H, NH₂), 6.44

(ddd, J_4,5= 7.9 Hz, J_4,2= 2.3 Hz, J_4,6= 1.0 Hz, 1 H, 4-H), 6.53

(ddd, J_6,5= 7.6 Hz, J_6,2= 1.6 Hz, J_6,4= 1.0 Hz, 1 H, 6-H), 6.57

(dd, J_2,4= 2.3 Hz, J_2,6= 1.6 Hz, 1 H, 2-H), 6.94 (dd, J_5,4= 7.9 Hz,

J_5,6= 7.6 Hz, 1 H, 5-H) ppm. ¹³C NMR (151 MHz, [D₆]DMSO): the difference map, but those attached to carbon atoms were repo-

δ = 62.46 (CH₂-5Ј), 71.65 (CH-3Ј), 77.47 (CH-2Ј), 83.88 (CH-1Ј),

84.89 (CH-4Ј), 112.03 (CH-2), 113.11 (CH-4), 114.08 (CH-6),

sitioned geometrically and then refined with riding constraints.

Crystal data for 5: C₂₉H₅₅BrO₅Si₃, orthorhombic, space group

128.64 (CH-5), 142.15 (C-1), 148.53 (C-3) ppm. IR (KBr): ν = P2₁2₁2₁, a = 8.4121(1) Å, b = 12.0094(1) Å, c = 35.3997(3) Å, V =

˜

3412, 3374, 3306, 3223, 3052, 3041, 3028, 1631, 1631, 1609, 1609,

1599, 1494, 1463, 1305, 1168, 1121, 1113, 1072, 1050, 1032, 1001,

948 cm^–1. HRMS (FAB): calcd. for C₁₁H₁₆NO₄[M + H] 226.1079;

found 226.1071.

3576.23(6) Å³, Z = 4, M = 647.90, 61159 reflections measured,

5970 independent reflections. Final R = 0.0275, wR = 0.0305, GoF

= 1.0315 for 5397 reflections with IϾ2σ(I) and 344 parameters.

Crystal data for 10i: C₁₃H₁₉NO₄, orthorhombic, space group

P2₁2₁2₁, a = 6.5896(1) Å, b = 7.0174(1) Å, c = 26.9375(2) Å, V =

1245.64(3) Å³, Z = 4, M = 253.29, 19514 reflections measured,

2560 independent reflections. Final R = 0.0308, wR = 0.0392, GoF

= 1.0508 for 2152 reflections with IϾ2σ(I) and 165 parameters.

1β-[3-(Dimethylamino)phenyl]-1-deoxy-D-ribofuranose (19i): Com-

pound 19i was prepared from 18i (579 mg, 0.971 mmol) according

to the general procedure in 77% yield as a colorless oil, which after

coevaporation with dry toluene and Et₂O furnished a white solid.

M.p. 72–76 °C. [α]²_D⁰

=

–25.5 (c =3.15, MeOH). ¹H NMR

CCDC-670179 (5) and -670180 (10i) contain the supplementary

(600 MHz, [D₆]DMSO): δ = 2.86 (s, 6 H, CH₃N), 3.52 (dt, J_gem

=

crystallographic data for this paper. These data can be obtained

Eur. J. Org. Chem. 2008, 1689–1704

www.eurjoc.org

1703

ˇ

M. Stefko, R. Pohl, B. Klepetárˇová, M. Hocek

FULL PAPER

ann, Chem. Eur. J. 2005, 11, 1911–1923; c) A. Zahn, C. Brots-

chi, C. J. Leumann, Chem. Eur. J. 2005, 11, 2125–2129.

D. Reha, M. Hocek, P. Hobza, Chem. Eur. J. 2006, 12, 3587–

3595.

free of charge from The Cambridge Crystallographic Data Centre

via www.ccdc.cam.ac.uk/data_request/cif.

ˇ

[10]

[11]

[12]

Z. Johar, A. Zahn, C. J. Leumann, B. Jaun, Chem. Eur. J. 2008,

14, 1080–1086.

a) I. Singh, W. Hecker, A. K. Prasad, V. S. Parmar, O. Seitz,

Chem. Commun. 2002, 500–501; b) C. Beuck, I. Singh, A. Bhat-

tacharya, W. Hecker, V. S. Parmar, O. Seitz, E. Weinhold, An-

gew. Chem. Int. Ed. 2003, 42, 3958–3960.

A. Zahn, C. J. Leumann, Chem. Eur. J. 2008, 14, 1087–1094.

a) J. Gao, C. Strässler, D. Tahmassebi, E. T. Kool, J. Am.

Chem. Soc. 2002, 124, 11590–11591; b) J. Gao, S. Watanabe,

E. T. Kool, J. Am. Chem. Soc. 2004, 126, 12748–12749; c) J. N.

Wilson, Y. N. Teo, E. T. Kool, J. Am. Chem. Soc. 2007, 129,

15426–15427.

a) S. Matsuda, F. E. Romesberg, J. Am. Chem. Soc. 2004, 126,

14419–14427; b) G. Mathis, J. Hunziker, Angew. Chem. Int. Ed.

2002, 41, 3203–3205; c) C. B. Reese, Q. Wu, Org. Biomol.

Chem. 2003, 1, 3160–3172.

a) N. C. Chaudhuri, E. T. Kool, Tetrahedron Lett. 1995, 36,

1795–1798; b) R. X.-F. Ren, N. C. Chaudhuri, P. L. Paris, S.

Rumney IV, E. T. Kool, J. Am. Chem. Soc. 1996, 118, 7671–

7678; c) N. Griesang, C. Richert, Tetrahedron Lett. 2002, 43,

8755–8758; d) S. Aketani, K. Tanaka, K. Yamamoto, A. Ishih-

ama, H. Cao, A. Tengeiji, S. Hiraoka, M. Shiro, M. Shinoya,

J. Med. Chem. 2002, 45, 5594–5603; e) S. Hainke, I. Singh, J.

Hemmings, O. Seitz, J. Org. Chem. 2007, 72, 881–8819.

a) M. Yokoyama, M. Nomura, H. Togo, H. Seki, J. Chem.

Soc. Perkin Trans. 1 1996, 2145–2149; b) W. He, H. Togo, M.

Yokoyama, Tetrahedron Lett. 1997, 38, 5541–5544; c) S.

Hainke, S. Arndt, O. Seitz, Org. Biomol. Chem. 2005, 3, 4233–

4238.

a) Y. X. Wang, L. I. Wiebe, E. De Clercq, J. Balzarini, E. E.

Knaus, Can. J. Chem. 2000, 78, 1081–1088; b) A. Häberli, C. J.

Leumann, Org. Lett. 2001, 3, 489–492; c) Y. Sun, S. Ahmed,

L. W. McLaughlin, J. Org. Chem. 2006, 71, 2922–2926.

M. Hocek, R. Pohl, B. Klepetárˇová, Eur. J. Org. Chem. 2005,

4525–4528.

Acknowledgments

This work was supported by the Centre of Biomolecules and Com-

plex Molecular Systems (LC 512), by NIH, Fogarty International

Center (Grant 1R03TW007372-01), and by Gilead Sciences Inc. as

part of the research project Z04 055 905. Antiviral activity was

studied by E. Mabery and Drs. I. Shih and R. Mackman (Gilead).

The contribution of these scientists is gratefully acknowledged.

[13]

[14]

[1] Reviews: a) L. Wang, P. G. Schultz, Chem. Commun. 2002, 1–

11; b) A. A. Henry, F. E. Romesberg, Curr. Opin. Chem. Biol.

2003, 7, 727–733; c) E. T. Kool, J. C. Morales, K. M. Guckian,

Angew. Chem. Int. Ed. 2000, 39, 990–1009; d) E. T. Kool, Acc.

Chem. Res. 2002, 35, 936–943.

[2] a) A. K. Ogawa, O. K. Abou-Zied, V. Tsui, R. Jimenez, D. A.

Case, F. E. Romesberg, J. Am. Chem. Soc. 2000, 122, 9917–

9920; b) K. M. Guckian, T. R. Krugh, E. T. Kool, J. Am.

Chem. Soc. 2000, 122, 6841–6847; c) J. S. Lai, J. Qu, E. T. Kool,

Angew. Chem. Int. Ed. 2003, 42, 5973–5977; d) J. S. Lai, E. T.

Kool, J. Am. Chem. Soc. 2004, 126, 3040–3041.

[3] a) A. A. Henry, A. G. Olsen, S. Matsuda, C. Yu, B. H. Geier-

stanger, F. E. Romesberg, J. Am. Chem. Soc. 2004, 126, 6923–

6931; b) A. A. Henry, C. Z. Yu, F. E. Romesberg, J. Am. Chem.

Soc. 2003, 125, 9638–9646; c) G. T. Hwang, F. E. Romesberg,

Nucleic Acids Res. 2006, 34, 2037–2045; d) S. Matsuda, A. A.

Henry, F. E. Romesberg, J. Am. Chem. Soc. 2006, 128, 6369–

6375; e) Y. Kim, A. M. Leconte, Y. Hari, F. E. Romesberg, An-

gew. Chem. Int. Ed. 2006, 45, 7809–7812; f) S. Matsuda, J. D.

Fillo, A. A. Henry, P. Rai, S. J. Wilkens, T. J. Dwyer, B. H. Gei-

erstanger, D. E. Wemmer, P. G. Schultz, G. Spraggon, F. E. Ro-

mesberg, J. Am. Chem. Soc. 2007, 129, 10466–10473; g) S. Mat-

suda, A. M. Leconte, F. E. Romesberg, J. Am. Chem. Soc.

2007, 129, 5551–5557.

[4] a) J. Parsch, J. W. Engels, Helv. Chim. Acta 2000, 83, 1791–

1808; b) A. Zivkovic, J. W. Engels, Nucleosides Nucleotides Nu-

cleic Acids 2005, 24, 1023–1027.

[5] A. Somoza, J. Chelliserrykattil, E. T. Kool, Angew. Chem. Int.

Ed. 2006, 45, 4994–4997.

[6] a) J. Matulic-Adamic, L. Beigelman, S. Portman, M. Egli, N.

Usman, J. Org. Chem. 1996, 61, 3909–3911; b) J. Matulic-Ad-

amic, L. Beigelman, Tetrahedron Lett. 1996, 37, 6973–6976; c)

G. Minasov, J. Matulic-Adamic, C. J. Wilds, P. Haeberli, N.

Usman, L. Beigelman, M. Egli, RNA 2000, 5, 1510–1528; d)

K. F. Blount, N. L. Grover, V. Mokler, L. Beigelman, O. C.

Uhlenbeck, Chem. Biol. 2002, 9, 1009–1016.

[7] Examples: a) P. Franchetti, L. Cappellacci, M. Griffantini, A.

Barzi, G. Nocentini, H. Y. Yang, A. O’Connor, H. N. Jayaram,

C. Carrell, B. M. Goldstein, J. Med. Chem. 1995, 38, 3829–

3837; b) J. A. Walker, W. Liu, D. S. Wise, J. C. Drach, L. B.

Townsend, J. Med. Chem. 1998, 41, 1236–1241.

[15]

[16]

[17]

[18]

[19]

[20]

[21]

[22]

[23]

[24]

M. Urban, R. Pohl, B. Klepetárová, M. Hocek, J. Org. Chem.

ˇ

2006, 71, 7322–7328.

N. Joubert, R. Pohl, B. Klepetárˇová, M. Hocek, J. Org. Chem.

2007, 72, 6797–6805.

A. Zahn, C. J. Leumann, Bioorg. Med. Chem. 2006, 14, 6174–

6188.

S. V. Attwood, A. G. M. Barrett, J. Chem. Soc. Perkin Trans. 1

1984, 1315–1322.

a) S. Lee, M. Jørgensen, J. F. Hartwig, Org. Lett. 2001, 3, 2729–

2732; b) D.-Y. Lee, J. F. Hartwig, Org. Lett. 2005, 7, 1169–1172;

c) J. P. Wolfe, H. Tomori, J. P. Sadighi, J. Yin, S. L. Buchwald,

J. Org. Chem. 2000, 65, 1158–1174.

[25]

[26]

X. Huang, S. L. Buchwald, Org. Lett. 2001, 3, 3417–3419.

ˇ

P. C apek, R. Pohl, M. Hocek, J. Org. Chem. 2005, 70, 8001–

8008.

[27]

[28]

A. Altomare, G. Cascarano, G. Giacovazzo, A. Guagliardi,

M. C. Burla, G. Polidori, M. J. Camalli, J. Appl. Crystallogr.

1994, 27, 435–435.

P. W. Betteridge, J. R. Carruthers, R. I. Cooper, K. Prout, D. J.

Watkin, J. Appl. Crystallogr. 2003, 36, 1487–1487.

Received: December 10, 2007

[8] a) K. Krohn, H. Heins, K. Wielckens, J. Med. Chem. 1992, 35,

511–517; b) K. W. Pankiewicz, Pharmacol. Therapeut. 1997, 76,

89–100; c) T. Szekeres, J. Sedlak, L. Novotny, Curr. Med. Chem.

2002, 9, 759–764; d) K. Krohn, H. Dorner, M. Zukowski, Curr.

Med. Chem. 2002, 9, 727–731.

[9] a) C. Brotschi, A. Häberli, C. J. Leumann, Angew. Chem. Int.

Ed. 2001, 40, 3012–3014; b) C. Brotschi, G. Mathis, C. J. Leum-

Published Online: February 12, 2008

1704

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Article Doi

A modular methodology for the synthesis of 4- and 3-substituted benzene and aniline C-ribonucleosides

DOI: 10.1002/ejoc.200701168

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