New methodology for the differentiation of the primary hydroxyl groups in 2,3,3′,4,4′-penta-O-benzylsucrose: Convenient approach to sucrose monophosphines

Article abstract of DOI:10.1080/07328303.2011.556286

Two new routes to derivatives of 2,3,3′,4,4′-penta-O- benzylsucrose with differently protected primary hydroxyl groups were elaborated. One of these compounds, 2,3,3′,4,4′-penta-O-benzyl- 6′-O-mesylsucrose, was used in a model synthesis of the 6′-phosphine with sucrose scaffold. Elimination of the mesyloxy-group under the reaction conditions was also noted providing the 5′,6′-unsaturated sucrose derivative. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/07328303.2011.556286

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New Methodology for the Differentiation
of the Primary Hydroxyl Groups in
2,3,3′,4,4′-Penta-O-Benzylsucrose:
Convenient Approach to Sucrose
Monophosphines
Joanna Burdyńska a , Bartosz Lewandowski a & Sławomir Jarosz a
a Institute of Organic Chemistry, Polish Academy of Sciences,
Kasprzaka 44/52, 01-224, Warszawa
Version of record first published: 15 Mar 2011
To cite this article: Joanna Burdyńska, Bartosz Lewandowski & Sławomir Jarosz (2010): New
Methodology for the Differentiation of the Primary Hydroxyl Groups in 2,3,3′,4,4′-Penta-O-
Benzylsucrose: Convenient Approach to Sucrose Monophosphines, Journal of Carbohydrate Chemistry,
29:8-9, 403-415
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Journal of Carbohydrate Chemistry, 29:403–415, 2010
ꢀ
C
Copyright Taylor & Francis Group, LLC
ISSN: 0732-8303 print / 1532-2327 online
DOI: 10.1080/07328303.2011.556286
New Methodology for the
Differentiation of the Primary
Hydroxyl Groups in 2,3,3ꢁ,4,4ꢁ-
Penta-O-Benzylsucrose:
Convenient Approach to
Sucrose Monophosphines
Joanna Burdyn´ska, Bartosz Lewandowski, and Sławomir Jarosz
Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52 01-224,
Warszawa
Two new routes to derivatives of 2,3,3ꢁ,4,4ꢁ-penta-O-benzylsucrose with differently pro-
tected primary hydroxyl groups were elaborated. One of these compounds, 2,3,3ꢁ,4,4ꢁ-
penta-O-benzyl-6ꢁ-O-mesylsucrose, was used in a model synthesis of the 6ꢁ-phosphine
with sucrose scaffold. Elimination of the mesyloxy- group under the reaction conditions
was also noted providing the 5ꢁ,6ꢁ-unsaturated sucrose derivative.
Keywords Sucrose; Sucrose monophosphines; Regioselectivity; Sucrose exo-glycal
INTRODUCTION
Although application of sucrose (α-D-fructofuranosyl β-D-glucopyranoside) as
chemically reactive organic raw material has been extensively explored,[1–3]
there is still a need for new procedures leading to fine chemicals based on
sucrose scaffold. This di-saccharide is very demanding to work with, because
of very high sensitivity of the glycosidic bond toward acids,[1,4] poor solubility
in organic solvents, and similar reactivity of eight hydroxyl groups present in
the molecule.
As part of an ongoing program on the application of sucrose as a fine chem-
ical, we have reported on the synthesis of 2,3,4,3ꢁ,4ꢁ-penta-O-benzyl-sucrose (1)
Received September 24, 2010; accepted January 17, 2011.
Address correspondence to Sławomir Jarosz, Institute of Organic Chemistry, Polish
Academy of Sciences, Kasprzaka 44/52 01-224, Warszawa. E-mail: sljar@icho.edu.pl
403

J. Burdyn´ska et al.
404
OH
X
O
O
OR
OBn
O
BnO
BnO
BnO
BnO
BnO
O
BnO
BnO
BnO
OH
Y
O
O
BnO
BnO
3. X = Y = P(O)(OEt)2
4. X = P(O)(OEt)2;Y = OH
5. X = OH;Y = P(O)(OEt)2
6. X = Y = PPh2
1. R = H
2. R = Bn
Figure 1: Phosphorus devivatives of sucrose.
and 1ꢁ,2,3,4,3ꢁ,4ꢁ-hexa-O-benzyl-sucrose[5] (2), which were used for the prepara-
tion of complex derivatives including crown and aza-crown ether analogs with
sucrose scaffold.[5,6]
The diol 2 was also recently applied by us in the model preparation of the
phosphorus derivatives of sucrose in which the terminal positions were modi-
fied by the phosphonate or phosphine functions (compounds 3–6 in Fig. 1).[7]
RESULTS AND DISCUSSION
Although we have elaborated useful methods for the differentiation of the ter-
minal positions in sucrose, we were looking for other procedures that can be
complementary to the existing ones and would allow the preparation of a wide
variety of sucrose derivatives. This will be exemplified by a model synthesis of
sucrose monophosphines that can be regarded as the analogs of bifunctional
Lewis base/Lewis acid-type ligands proposed by Shibasaki for simple mono-
sugar derivatives (Fig. 2).[8]
X
Y
O
OH
O
Ph2P
O
6
6'
O
1'
O
HO
BnO
O
R
R
OBn
OBn
BnO
OBn
HO
X = PPh2;Y = OH
or X = OH;Y = PPh2
R = H or R = F
Shibasaki's ligands
Sucrose-derived ligands
Figure 2: Sugar derived bifunctional ligands for asymmetric catalussis.

Convenient Approach to Sucrose Monophosphines
405
OH
OC(O)Ar
6
O
OBOM
O
BnO
6
O
BnO
BnO
OH
O
BnO
1'
BnO
BnO
1'
6'
BnO
6'
OH
BnO
O
OC(O)Ar
O
8
BnO
7
1
BnO
selective
silylation
selective
TPSO
HO
6
OTPS
OTPS
6'
6'
6
TPSO
OH
6'
6
de-silylation
11
10
9
Figure 3: Differentiation of the primary hydrocyl groups in 2,3,34,4-penta-O-benzyls scrose
(ref. 2).
Our standard strategy for differentiation of the primary hydroxyl groups
in the triol 1 allows for the preparation of selectively protected sucrose deriva-
tives, 8, 9, and 11,[2] the drawback being, however, the fact that the 1ꢁ-OH is
blocked as BOM ether (Fig. 3).
Removal of this block in the presence of benzyl groups protecting the re-
maining secondary hydroxyls might be troublesome. This forced us to elaborate
a complementary strategy toward sucrose alcohols.
The high affinity of the 6ꢁ-OH (fructose part) toward silylating agents is
well known in free sucrose,[9] as well as the benzylated derivatives 2 and 8.[2,10]
We have observed similar selectivity in silylation of the triol 1, which, upon re-
action with 1 equiv. of TPSCl, provided the diol 12 (with only 6ꢁ-OH protected)
in good yield. The position of the silyl group was proven by chemical and spec-
tral correlations. Thus, both free hydroxyl groups in the diol 12 were protected
as acetates (13) and the silyl block was removed. The resulting alcohol 14 was
then oxidized to an aldehyde under the Swern conditions[11] and further trans-
formed into the α,β-unsaturated ester 15 by reaction with Ph3P = CH-CO2Me.
In the 1H NMR spectrum of this compound the olefinic signals (at δ = 6.99 and
6.08 ppm) correlated to the H5ꢁ proton (δ = 4.45 ppm), which fully confirmed
the position of the ester at the “fructose end” and, hence, the position of the
silyl block in (Sch. 1) 12 .
Readily available di-chlorosucrose[12] (16) served as the starting material
for the synthesis of another target molecule. Protection of the 1ꢁ-OH group
in 16 as a trityl ether afforded the compound 17, which was then benzylated
under standard conditions to 18. Replacement of the chlorine atoms with ac-
etates provided the di-acetate 19, which was converted into the diol 20 with
the 6- and 6ꢁ-hydroxyl groups free. It was also possible to protect the 6ꢁ-OH as
a silyl ether giving rise to another sucrose-derived mono alcohol (21; Sch. 2).

J. Burdyn´ska et al.
406
OR
OAc
6
O
OR
1'
i.
O
BnO
BnO
iii.
OTPS
1'
BnO
O
BnO
1
OH
O
6'
BnO
O
6'
BnO
12. R = H
13. R = Ac
ii.
BnO
14
OAc
1'
5'
O
BnO
7'
iv.
selected data for 15
O
CO2Me
H5' = 4.45,
H6' = 6.99 (Jolef. 15.7 Hz),
6'
BnO
15
H7' = 6.08 ppm
Scheme 1: i. TPSCI, CH2Cl2 DIPEA, DMAP, 24 h, 8.99; ii py. DMAP, Ac2O; iii Bn4NF, THF, 24 h,
9596; iv 1. Swern acid. 2. Ph3P Ch CO2Me, CH2Cl2.
Cl
OR1
6
O
OR1
O
R2O
R2O
OTr
iii.
BnO
BnO
1'
O
HO
O
6'
R2O
from 18
Cl
BnO
BnO
O
OR2
O
R2O
BnO
19. R1 = Ac; R2 = Ac
20. R1 = H; R2 = H
21. R1 = H; R2 = TPS
iv.
v.
16. R1 = H; R2 = H
17. R1 = Tr; R 2 = H
18. R1 = Tr; R 2 = Bn
i.
ii.
Scheme 2: i. TrCl, py. DMAP, rt. 72 h; ii DMF, NaH, BnBr, 24 h, rt; iii. DMF, AcONa, 120◦C, 10 days;
iv. THF/MeOH, MeONa, 3 h, rt; v. CH2Cl2, DIPEA, DMAP, TPSCl, 48 h, rt.
Both sucrose-derived alcohols 14 and 21 seemed to be convenient synthons
for the preparation of sucrose monophosphines. Activation of the unprotected
hydroxyl groups should allow introduction of the PPh2 group at the fructose
(in 14) and glucose (21) “ends.”
In the model reaction the hydroxyl group in alcohol 14 was activated as
mesylate (22), which was treated with KPPh2. No desired product (23) was,
however, formed; only removal of one or two acetate groups protecting the hy-
droxyls at the C-1ꢁ and C-6 positions was noted (24a–c; Sch. 3).
Therefore, we changed our strategy and used the deprotected mesylate 24c
as a starting material (Sch. 4). It was converted into the iodide 25 and then
treated with KPPh2 under the conditions described by Shibasaki.[8]
This reaction provided two products. The first one resulted from elimina-
tion of HI [as confirmed by MS: m/z = 797; (M-HI)+Na] to which structure 26
was assigned on the basis of the NMR data. Thus, both vinylic (H6ꢁ) protons

Convenient Approach to Sucrose Monophosphines
407
OAc
OAc
ii.
O
OAc
O
BnO
O
OAc
O
BnO
BnO
BnO
BnO
BnO
i.
BnO
BnO
PPh2
O
OMs
O
22
23
14
BnO
BnO
ii.
OR1
O
OR2
24a. R1 = H, R2 = Ac
24b. R1 = Ac, R = H
24c. R1 = R1 = R2 = H
BnO
BnO
O
BnO
BnO
OMs
O
BnO
Scheme 3: i. CH2Cl2 Et3N, DMAP, MsCl, rt, 8h, 9596; ii. KPPh2, THF, 0◦C.
OH
OH
6
1'
O
OH
O
BnO
BnO
6'
1'
BnO
5'
O
BnO
6'
I
O
ii.
BnO
O
BnO
25
26
BnO
i.
+
OH
6
O
OH
BnO
1'
24c
BnO
O
O
BnO
Ph
BnO
6'
P
O
Ph
BnO
27
Scheme 4: i. 1. MeOh, MeONa, 3h, rt. 9496; 2. DMF, 120◦C, 48 h 8896; ii CH2Cl2 0◦C PPh2
30 min.
(at δ: 4.58 and 4.35 ppm) correlated to the quaternary (157.68 ppm) and sec-
ondary (85.88 ppm) carbon resonances, which fully proved the proposed struc-
ture. This compound might be interesting, since the exo-glycals are very useful
building blocks in synthetic organic chemistry.[12]
The second product isolated from this reaction turned out to be the oxi-
dized phosphine (27), which was formed during the isolation process. This is
in agreement with our recent observation that sucrose phosphines (in which
the phosphorus functionalities are located at the C6,C6ꢁ positions) are readily
oxidized to the phosphine oxides with air.[7]

J. Burdyn´ska et al.
408
CONCLUSIONS
Two synthetic routes toward sucrose derivatives selectively protected at the
terminal positions have been presented. Although the products are obtained
in moderate yields, these routes may constitute an alternative strategy to
those already described by us. One of the obtained molecules was successfully
applied in the synthesis of monophosphine-derivative, potential, bifunctional
ligand in asymmetric catalysis. Especially interesting is the formation of the
exo-glycal at the C-5ꢁ (fructose part) position of sucrose.
EXPERIMENTAL
The NMR spectra were recorded in CDCl3 at 303K with a Bruker DRX Avance
500 spectrometer equipped with a TBI 50SB H-C/BB-D-05 Z-G probehead,
1
operating at 500.133 and 125.773 MHz for H and 13C, respectively (inter-
1
nal Me4Si), unless otherwise stated. The assignment of the H and 13C NMR
1
signals was made using COSY, HSQC, and DEPT correlations. The H- and
13C-aromatic resonances occurring at the typical δ values were omitted for
1
simplicity. Only diagnostic signals in the H NMR spectra were shown. Mass
spectra were recorded with an ESI/MS Mariner (PerSeptive Biosystem) mass
spectrometer. Column chromatography was performed on silica gel (Merck,
70–230 mesh). Methylene chloride was distilled from CaH2 and THF from
potassium prior to use. Organic solutions were dried over anhydrous magne-
sium or sodium sulphate.
6ꢀ-O-(Tert-butyldiphenyl)silylo-2,3,3ꢀ,4,4ꢀ-penta-O-benzylsucrose
(12)
To a stirred solution of the triol 1 (10.4 g, 13.1 mmol) in anhydrous methy-
lene chloride (25 mL) containing DIPEA (5 mL, 29.3 mmol) and DMAP (cat.
ca. 20 mg), tert-butyldiphenylsilyl chloride (1.2 equiv. 4.0 mL, 14.1 mmol) was
added in small portions during 20 min and stirring was continued for 24 h at
rt. The mixture was then partitioned between water (50 mL) and ethyl acetate
(150 mL); the organic phase was separated, washed with water (2 × 50 mL)
and brine (50 mL), dried, and concentrated; and the product was isolated by
column chromatography (hexane–ethyl acetate: 6:1 to 1:2) to afford pure 12 as
an oil (8.5 g; 63%).
MS m/z: 1053.6 [M(C63H70O11Si) + Na+]
1H NMR δ: 5.19 (d, 1H, J1,2 = 3.6 Hz, H-1), 0.98 [s, 9H, C(CH3)3]. 13C NMR
δ: 138.46, 138.43, 138.19, 137.78, 136.94, 133.10, 132.99 (Cquat, 5 × OCH2Ph, 2
× SiPh), 106.69 (C-2ꢁ), 90.36 (C-1), 85.55, 83.72, 82.48, 81.96, 79.09, 77.24, and
71.64 (C-2,3,3ꢁ,4,4ꢁ,5,5ꢁ), 75.47, 74.74, 74.41, 73.14, 71.82 (5 × OCH2Ph), 64.49,
63.48, 60.66 (C-1ꢁ,6,6ꢁ), 26.67 [C(CH3)3], 19.12 [C(CH3)3)].

Convenient Approach to Sucrose Monophosphines
409
1ꢀ,6-Di-O-acetyl-6ꢀ-O-(tert-butyldiphenyl)silyl-2,3,3ꢀ,4,4ꢀ-penta-
O-benzylsucrose (13)
To a solution of 12 (8.5 g, 8.24 mmol) in pyridine (20 mL) containing cat-
alytic amounts of DMAP (20 mg), acetic anhydride (8.0 mL) was added and
the mixture was stirred at rt for 4 h. Pyridine was evaporated and the residue
was partitioned between water (50 mL) and ethyl acetate (150 mL). The or-
ganic phase was separated, washed with water (2 × 50 mL) and brine (50 mL),
dried, and concentrated to afford a crude product 13 (9.0 g), which was used
without purification in the next steps.
MS m/z: 1137.6 [M(C67H74O13Si) + Na+]
1H NMR δ: 5.90 (d, 1H, J1,2 = 3.7 Hz, H-1), 1.97, 1.92 (s, 6H, COCH3), 1.05
[s, 9H, C(CH3)3]. 13C NMR δ: 170.63, 170.15 (COCH3) 138.71, 138.27, 138.24,
137.99, 137.434, 133.18, 132.81 (Cquat, 5 × OCH2Ph, 2 × SiPh), 102.81 (C-2ꢁ),
89.20 (C-1), 83.78, 81.88, 81.33, 81.05, 79.89, 77.18 i 69.09 (C-2,3,3ꢁ,4,4ꢁ,5,5ꢁ),
75.65, 74.81, 73.22, 73.00, 72.25 (5 × OCH2Ph), 65.37, 64.09, 62.99 (C-1ꢁ,6,6ꢁ),
26.88 [C(CH3)3], 19.21 [C(CH3)3].
1ꢀ,6-Di-O-acetyl-2,3,3ꢀ,4,4ꢀ-penta-O-benzylsucrose (14)
To a solution of 13 (9.0 g, 8.07 mmol) in THF (30 mL), tetrabutylammonium
fluoride trihydrate (2 equiv., 4.2 g, 16.14 mmol) was added and the mixture
was stirred at rt for 24 h (TLC monitoring in hexane–ethyl acetate, 3:1). Then
it was concentrated and the product was isolated by column chromatography
(hexane–ethyl acetate, 4:1 to 2:1) to afford 14 as an oil (6.7 g, 7.67 mmol, 95%).
MS m/z: 899.6 [M(C51H56O13) + Na+]
1H NMR (600 MHz) δ: 5.52 (d, 1H, J1,2 = 3.5 Hz, H-1), 2.02, 2.00 (s,
6H, COCH3). 13C NMR (150 MHz) δ: 170.66, 170.04 (COCH3), 138.43, 137.86,
137.79, 137.78, 137.69 (Cquat, 5 × CH2Ph), 102.65 (C-2ꢁ), 91.10 (C-1), 83.57,
81.68, 81.62, 79.73, 79.01, 77.04, 69.90 (C-2,3,3ꢁ,4,4ꢁ,5,5ꢁ), 75.63, 75.07, 73.55,
73.19, 72.65 (5 × OCH2Ph), 64.71, 62.45, 61.36 (C-1ꢁ,C-6, C-6ꢁ), 20.82, 20.79
(COCH3).
Determination of the Structure of 14; Synthesis of the
α,β-Unsaturated Ester 15
To a cooled (to –78◦C) solution of oxalyl chloride (0.37 µL, 0.422 mmol) in
methylene chloride, DMSO (0.12 mL, 1.68 mmol) was added slowly. After 5 min
a solution of alcohol 14 (100 mg, 0.114 mmol) in dry methylene chloride (5 mL)
was added and the mixture was stirred at –78◦C for 30 min. Triethylamine
(0.12 mL) was added, and the mixture was allowed to reach rt and partitioned
between water (20 mL) and methylene chloride (50 mL). The organic phase was
separated, washed with water (2 × 20 mL) and brine, dried, and concentrated.
The crude aldehyde was dissolved in CH2Cl2 (10 mL) to which the ylid Ph3P

J. Burdyn´ska et al.
410
= CH−CO2Me (100 mg, 0.313 mmol) was added, the mixture was stirred for
24 h at rt and concentrated, and the product 15 was isolated by column chro-
matography (hexane–ethyl acetate, 4:1 to 2:1) as an oil (75 mg, 0.081 mmol,
71%).
MS m/z: 953.5 [M(C54H58O14) + Na+]
1H NMR (600 MHz) δ: 6.99 (dd, 1H, J6 ,7 = 15.7 Hz, J6 ,5 = 6.6 Hz, H-6ꢁ),
ꢁ
ꢁ
ꢁ
ꢁ
6.08 (dd, 1H, J6 ,7 = 15.7 Hz, J5 ,7 = 1.3 Hz, H-7ꢁ), 5.54 (d, 1H, J1,2 = 3.6 Hz, H-
1), 4.45 (m, 1H, H-5ꢁ), 4.23 (m, 1H, H-3ꢁ), 4.21 (m, 1H, H-4ꢁ), 4.19 (s, 2H, H-1ꢁ),
4.16, 4.09 (m, 2H, H−6), 4.14 (m, 1H, H−5), 4.01 (t, 1H, J2,3 = 9,3 Hz, H-3), 3.71
(s, 3H, OCH3), 3.53 (m, 1H, H-2), 3.49 (m, 1H, H−4), 2.00, 1.99 (s, 6H, COCH3).
13C NMR (150 MHz) δ: 170.68, 169.93 (COCH3), 166.18 (COOCH3) 144.85 (C-
6ꢁ), 138.64, 138.02, 137.90, 137.44, 137.39 (Cquat, 5 × OCH2Ph), 122.76 (C-7ꢁ)
102.98 (C-2ꢁ), 90.50 (C-1), 84.65 (C-4ꢁ), 83.03 (C-3ꢁ), 81.96(C-3), 79.57 (C-5ꢁ),
79.37 (C-2), 77.26 (C-4), 75.69, 74.95, 73.43, 73.00, 72.98 (5 × OCH2Ph), 69.43
(C-5), 64.33 (C-1ꢁ), 63.08 (C-6), 20.77, 20.75 (COCH3).
ꢁ
ꢁ
ꢁ
ꢁ
6,6ꢀ-Dichloro-6,6ꢀ-dideoxy-1ꢀ-O-tritylsucrose 17
To a solution of 6,6ꢁ-di-chloro-6,6ꢁ-dideoxysucrose (16)[13] (3.0 g, 7.31 mmol)
in pyridine (30 mL), trityl chloride (1.5 equiv., 3.56 g, 11.0 mmol) and cat.
amounts of DMAP (20 mg) were added, and the mixture was stirred for
72 h at rt. Pyridine was removed in vacuum and the residue partitioned
between water (30 mL) and ethyl acetate (50 mL). The organic phase was
separated, washed with water (2 × 20 mL), dried, and concentrated, and the
product was purified by column chromatography (100% ethyl acetate, then
ethyl acetate–methanol, 45:5) to afford 17 as an oil (1.61 g, 2.59 mmol, 33%).
MS m/z: 643.4 [M(C31H34Cl2O9) + Na+])
1
This product was further characterized as pentaacetate: H NMR δ: 5.88
(d, 1H, J1,2 = 5.7 Hz, H-1), 2.10, 2.06, 2.02, 1.99, 1.89 (5 × s, 15H, 5 × COCH3).
13C NMR δ: 170.11, 170.03, 169.93, 169.44, 169.42 (5 × COCH3), 143.16 (quat.,
C(Ph)3), 105.60 (C-2ꢁ), 90.25 (C-1), 87.26 (CPh3), 80.46, 76.66, 76.20, 69.94,
69.71, 69.45 i 68.96 (C-2,3,3ꢁ,4,4ꢁ,5,5ꢁ), 63.11 (C-1ꢁ), 44.32, 43.15 (C-6, C-6ꢁ),
20.80, 20.62, 20.59, 20.51, 20.44 (5 × COCH3).
6,6ꢀ-Dichloro-6,6ꢀ-dideoxy-1ꢀ-O-trityl-,3,3ꢀ,4,4ꢀ-penta-O-
benzylsucrose 18
To a solution of 17 (470 mg, 0.756 mmol) in DMF (25 mL) containing cat-
alytic amounts (20 mg) of imidazole, sodium hydride (60% suspension in min-
eral oil, 324 mg, 8.10 mmol) was added, and the mixture was stirred for 20
min at rt. Benzyl bromide (1.5 mL, 9.72 mmol) was added dropwise and the
mixture was stirred for another 24 h. It was then partitioned between water

Convenient Approach to Sucrose Monophosphines
411
(20 mL) and ether (30 mL); the organic phase was separated, washed with wa-
ter (3 × 15 mL) and brine (15 mL), dried, and concentrated; and the product
was isolated by column chromatography (hexane–ethyl acetate, 14:1 to 12:1)
to afford 18 (274 mg, 0.256 mmol, 34%) as an oil.
MS m/z: 1093.6 [M(C66H64Cl2O9) + Na+]
1H NMR δ: 5.56 (d, 1H, J1,2 = 3.7 Hz, H-1). 13C NMR δ: 138.61, 138.47,
138.36, 138.05, 137.95, 137.83 (Cquat, 5 × OCH2Ph, 2 × PPh), 104.64 (C-2ꢁ),
89.75 (C-1), 84.31, 82.40, 81.33, 79.86, 79.28, 77.93, 69.81 (C-2,3,3ꢁ,4,4ꢁ,5,5ꢁ),
75.36, 75.08, 72.95, 72.68, 72.14 (5 × OCH2Ph), 65.14 (C-1ꢁ), 45.10, 44.77 (C-
6,6ꢁ).
6,6ꢀ-Di-O-acetyl-1ꢀ-O-trityl-2,3,3ꢀ,4,4ꢀ-penta-O-benzylosucrose 19
To a solution of 18 (1.345 g, 1.25 mmol) in DMF (20 mL), sodium acetate
(3.0 g, 36 mmol) was added, the mixture was stirred at 110–120◦C for 10 days
(TLC monitoring in hexane–ethyl acetate, 4:1), and after cooling to rt, it was
partitioned between water (40 mL) and ether (40 mL). The organic phase was
separated and the aqueous one extracted with ether (2 × 20 mL). Combined or-
ganic solutions were washed with water (30 mL), dried, and concentrated, and
the product was isolated by column chromatography (hexane–ethyl acetate,
9:1 to 3:1) to afford 19 as amorphous solid (615 mg, 0.55 mmol, 44%).
MS m/z: 1141.6 [M(C70H70O13) + Na+]
1H NMR δ: 5.56 (d, 1H, J1,2 = 3.7 Hz, H-1), 1.99, 1.93 (s, 6H, COCH3). 13
C
NMR δ: 170.60, 170.54 (COCH3), 138.74, 138.17, 138.07, 138.04, 137.70 (Cquat
,
5 × OCH2Ph), 104.53 (C-2ꢁ), 89.24 (C-1), 83.95, 81.73, 80.88, 79.35, 77.81, 77.13
(C-2,3,3ꢁ,4,4ꢁ,5,5ꢁ), 75.44, 74.74, 72.81, 72.70, 72.10 (5 × OCH2Ph), 65.36, 64.59,
62.90 (C-1ꢁ,C-6, C-6ꢁ), 20.78, 20.67 (COCH3).
1ꢀ-O-Trityl-2,3,3ꢀ,4,4ꢀ-penta-O-benzylsucrose 20
To a solution of compound 19 (615 mg, 0.55 mmol) in a methanol/THF
mixture (20 + 5 mL), metallic sodium (20 mg) was added and the mixture was
stirred at rt for 3 h (TLC monitoring in hexane–ethyl acetate, 2:1). Then it
was partitioned between water (20 mL) and ethyl acetate (30 mL), the organic
phase was separated, and the aqueous one extracted with ethyl acetate (2 ×
20 mL). Combined organic solutions were washed with water (2 × 20 mL),
dried, and concentrated to afford crude 21 (550 mg, 0.53 mmol) pure enough to
be used in the next reactions.
MS m/z: 1057.4 [M(C66H66O11) + Na+]

J. Burdyn´ska et al.
412
6ꢀ-O-(tert-Butyldiphenyl)silyl-1ꢀ-O-trityl-2,3,3ꢀ,4,4ꢀ-penta-O-
benzylsucrose 21
To a solution of the diol 20 (150 mg, 0.15 mmol) in anhydrous methy-
lene chloride (3.0 mL) containing di-isopropylethyl amine (0.2 mL) and DMAP
(20 mg), tert-butyldiphenylsilyl chloride was added (1.2 equiv., 0.05 mL,
0.18 mmol) and the mixture was stirred at rt for 48 h (TLC monitoring in
hexane–ethyl acetate, 3:1). Then it was partitioned between water (20 mL) and
methylene chloride (15 mL), the organic phase was separated, and the aque-
ous one extracted with CH2Cl2 (2 × 10 mL). Combined organic solutions were
washed with water, dried, and concentrated, and the product was isolated by
column chromatography (hexane–ethyl acetate, 6:1 to 5:1) to afford 21 as an
oil (108 mg, 0.08 mmol, 55%).
MS m/z: 1295.7 [M(C82H84O11Si) + Na+]
1H NMR δ: 5.84 (d, 1H, J1,2 = 3.7 Hz, H-1), 1.08 (s, 9H). 13C NMR δ: 138.92,
138.48, 138.25, 138.23, 137.81 (Cquat, 5 × OCH2Ph), 135.74, 135.51 (2 × SiPh2),
134.79, 133.31, 132.95 (3 × CPh3), 104.20 (C-2ꢁ), 88.38 (C-1), 86.82 [C(CH)3]
83.81, 81.73, 80.43, 79.83, 79.67, 77.64, 71.03 (C-2,3,3ꢁ,4,4ꢁ,5,5ꢁ), 75.39, 74.83,
72.91, 72.59, 72.03 (5 × OCH2Ph), 66.21 (C-1ꢁ), 64.05, 61.75 (C-6, 6ꢁ), 26.88 [3 ×
C(CH3)3].
1ꢀ,6-Di-O-acetyl -6ꢀ-O-mesyl-2,3,3ꢀ,4,4ꢀ-penta-O-
benzylosucrose 22
To a solution of the alcohol 14 (6.7 g, 7.67 mmol), methylene chloride (35
mL) containing triethylamine (5 mL) and DMAP (20 mg) mesyl chloride (4.2
equiv., 2.5 mL, 32.5 mmol) was added dropwise; the mixture was stirred for
6 h at rt (TLC monitoring in hexane–ethyl acetate, 3:1) and then partitioned
between water (50 mL) and methylene chloride (30 mL). The organic phase was
separated and the aqueous one extracted with CH2Cl2 (2 × 20 mL). Combined
organic solutions were washed with water, dried, and concentrated, and the
product was isolated by column chromatography (hexane–ethyl acetate, 6:1 to
5:1) to afford 22 as an oil (6.9 g, 7.25 mmol, 95%).
MS : 977.4 [M(C52H58O15S) + Na+]
1H NMR (500 MHz) δ: 5.63 (d, 1H, J1,2 = 3.6 Hz, H-1), 2.92 (s, 3H,
OSO2CH3), 1.99 (s, 6H, COCH3). 13C NMR (125 MHz) δ: 170.64, 169.84
(COCH3), 138.56, 137.92, 137.88, 137.34, 137.23 (Cquat, 5 × OCH2Ph),
103.52 (C-2ꢁ), 90.56 (C-1), 83.61, 81.73, 81.71, 79.40, 78.48, 77.40, 69.55 (C-
2,3,3ꢁ,4,4ꢁ,5,5ꢁ), 75.62, 74.98, 73.08, 72.99 (double intensity) (5 × OCH2Ph),
69.82, 63.94, 63.05 (C-1ꢁ,C-6, C-6ꢁ), 37.32 (OSO2CH3), 20.75, 20.72 (COCH3).
6ꢀ-O-Mesyl-2,3,3ꢀ,4,4ꢀ-penta-O-benzylosucrose 24c
To a solution of the diacetate 22 in methanol (30 mL), metallic sodium
(50 mg) was added and the mixture was stirred for 3 h at rt (TLC monitoring

Convenient Approach to Sucrose Monophosphines
413
in hexane–ethyl acetate, 2:1). Then it was partitioned between water (30 mL)
and ethyl acetate (50 mL), the organic phase was separated, and the aqueous
one extracted with ethyl acetate (2 × 20 mL). Combined organic solutions were
washed with water, dried, and concentrated, and the product was isolated by
column chromatography (hexane–ethyl acetate, 3:1 to 2:1) to afford 24c as an
oil (5.9 g, 6.77 mmol, 94%).
MS m/z: 977.4 [M(C48H54O13S) + Na+]
6ꢀ-Deoxy-6ꢀ-iodo-2,3,3ꢀ,4,4ꢀ-penta-O-benzylsucrose 25
To a solution of 24c (5.9 g, 6.77 mmol) in DMF (20 mL), solid KI (12.0 g,
72.3 mmol) was added and the mixture was stirred at 120◦C for 48 h (TLC mon-
itoring in hexane–ethyl acetate, 2:1). After cooling, it was partitioned between
water (30 mL) and AcOEt (50 mL), the organic phase was separated, and the
aqueous one extracted with ethyl acetate (2 × 20 mL). Combined organic so-
lutions were washed with water, dried, and concentrated, and the product was
isolated by column chromatography (hexane–ethyl acetate, 3:1 to 2:1) to afford
25 as an oil (4.0g, 4.43 mmol, 66%).
MS m/z: 925.5 [M(C47H51O10I) + Na+]
1H NMR (600 MHz) δ: 5.25 (d, 1H, J1,2 = 3.5 Hz, H-1). 13C NMR (150 MHz)
δ: 138.29, 138.18, 138.03, 137.47, 136.72 (Cquat, 5 × OCH2Ph), 107.23 (C-2ꢁ),
91.00 (C-1), 85.98, 85.74, 82.69, 81.96, 79.06, 77.52, 71.84 (C-2,3,3ꢁ,4,4ꢁ,5,5ꢁ),
75.52, 74.93, 74.75, 73.05, 71.84 (5 × OCH2Ph), 64.00, 61.49 (C-1ꢁ,6), 5.80 (C-
6ꢁ).
Reaction of Iodide 25 with KPPh2
Iodide 25 (4.0 g, 4.43 mmol) was dried in a round-bottom flask at high vac-
uum for 3 h. Then, under an argon atmosphere, dry methylene chloride (30 mL)
was added and the clear solution was cooled to 0◦C. Potassium phosphide
(22 mL of a 0.5M solution in THF, 2.5 equiv., 11.07 mmol) was added drop-
wise and the mixture was stirred at 0◦C until all starting material was con-
sumed (30 min., TLC monitoring in hexane–ethyl acetate, 1:1). Water (30 mL)
was added, the organic phase was separated, and the aqueous one extracted
with ethyl acetate (2 × 30 mL). Combined organic solutions were washed with
water, dried, and concentrated, and the product was isolated by column chro-
matography (hexane–ethyl acetate, 3:1 to 2:1) to afford 26 as an oil (850 mg,
0.95 mmol) and 27 as an amorphous solid (930 mg, 0.95 mmol, 21%).
Compound 26
MS m/z: 797.5 [M(C47H50O10) + Na+]
1H NMR (500 MHz) δ: 5.17 (d, 1H, J1,2 = 3.7 Hz, H-1), 4.58, 4.35 (s, 2H, H-
6ꢁa, H-6ꢁb). 13C NMR (125 MHz) δ: 157.68 (Cquat, C-5ꢁ), 138.43, 138.04, 137.94,

J. Burdyn´ska et al.
414
137.94, 136.99 (Cquat, 5 × OCH2Ph), 104.42 (Cquat, C-2ꢁ), 90.90 (C-1), 85.88 (C-
6ꢁ), 85.25, 82.18, 80.86, 78.88, 77.85, 72.22 (C-2,3,3ꢁ,4,4ꢁ,5), 75.65, 75.09, 74.49,
72.92, 72.33 (5 × OCH2Ph), 63.79, 61.76 (C-1ꢁ,6)
6ꢀ-deoxy-6ꢀ-diphenylphosphinoxide-2,3,3ꢀ,4,4ꢀ-penta-O-
benzylosucrose 27
MS m/z: 977.6 [M(C59H61O11P) + Na+]
1H NMR (600 MHz) δ: 5.18 (d, 1H, J1,2 = 3.5 Hz, H-1). 13C NMR (150
MHz) δ: 138.61, 138.47, 138.36, 138.05, 137.95, 137.83 (Cquat, 5 × OCH2Ph, 2
× PPh), 97.34 (C-2ꢁ), 91.15 (C-1), 84.49, 83.23, 81.53, 80.13, 77.62 77.57, 70.98
(C-2,3,3ꢁ,4,4ꢁ,5,5ꢁ), 75.69, 75.67, 75.02, 74.78, 73.19, 61.90, 61.85 (5 × OCH2Ph,
C-1ꢁ,6,6ꢁ). 31P NMR (500Hz) δ: 31.90 (P(O)Ph2)
Anal. Calcd. for C59H61O11P + 2H2O: C, 69.95; H, 6.47; found: C, 69.88; H,
6.77%.
ACKNOWLEDGMENTS
The support from grant: POIG.01.01.02–14-102/09 (part-financed by the Eu-
ropean Union within the European Regional Development Fund) is acknowl-
edged.
REFERENCES
1. See for example: Khan, R. The chemistry of sucrose. Adv. Carbohydr. Chem.
Biochem. 1976, 33, 235–299; Khan, R. Chemistry and new uses of sucrose: how im-
portant? Pure App. Chem. 1984, 56, 833–844; Lichtenthaler, F.W. Carbohydrates as Or-
ganic Raw Materials, Vol. 1. VCH, Weinheim (1991).
2. Review: Jarosz, S.; Mach, M. Regio- and stereoselective transformations of sucrose
at the terminal positions. Eur. J. Org. Chem. 2002, 769–780.
3. Queneau, Y.; Jarosz, S.; Lewandowski, B.; Fitremann, J. Sucrose chemistry and
applications of sucrochemicals. Adv. Carbohydr. Chem. Biochem. 2007, 61, 217–292 and
references therein.
4. Purves, C.B.; Hudson, C.S. The analysis of gamma-methylfructoside mixtures by
means of invertase. IV. Behavior of sucrose in methyl alcohol containing hydrogen chlo-
ride. J. Am. Chem. Soc. 1934, 56, 1973–1977.
5. Mach, M.; Jarosz, S.; Listkowski, A. Crown ether analogs from sucrose. J. Carbo-
hydr. Chem. 2001, 20, 485–493.
6. Jarosz, S.; Listkowski, A.; Lewandowski, B.; Ciunik, Z.; Brzuszkiewicz, A. Macro-
cyclic receptors containing sucrose skeleton. Tetrahedron 2005, 61, 8485–8492; Jarosz,
S.; Lewandowski, B. Synthesis and complexation properties towards the ammonium
cation of aza-coronand analogues containing sucrose. Carbohydr. Res. 2008, 343,
965–969.
7. Gaweł, A.; Jarosz, S. Synthesis of 6-Phosphonate, 6,6ꢁ-di-Phosphonate and 6,6ꢁ-di-
Phosphine Derivatives of Sucrose. J. Carbohydr. Chem. 2010, 29, 332–347.

Convenient Approach to Sucrose Monophosphines
415
8. Kato, N.; Suzuki, M.; Kanai, M.; Shibasaki, M. General and practical catalytic
enantioselective Strecker reaction of ketoimines: significant improvement through cat-
alyst tuning by protic additives. Tetrahedron Lett. 2004, 45, 3147–3151. Shibasaki,
M.; Sasai, H.; Arai, T. Asymmetric catalysis with heterobimetallic compounds. Angew.
Chem. Int. Ed. Engl. 1997, 36, 1236–1256. Groaning, M.D.; Rowe, B.J.; Spilling, C.D.
New homochiral cyclic diol ligands for titanium alkoxide catalyzed phosphonylation
of aldehydes. Tetrahedron Lett. 1998, 39, 5485–5488. Shin, S.; RajanBabu, T.V. Water-
soluble Organometallic Catalysts from Carbohydrates. 1. Diphosphinite-Rh Complexes.
Org. Lett. 1999, 1, 1229–1232; Yonehara, K.; Hashizume, T.; Ohe, K.; Uemura, S. Syn-
thesis of novel chiral phosphines from α,α-trehalose. Tetrahedron Asymm. 1999, 10,
4029–4035. Masumoto, S.; Yabu, K.; Kanai, M.; Shibasaki, M. Practical synthesis of
chiral ligands for catalytic enantioselective cyanosilylation of ketones. Tetrahedron Lett.
2002, 43, 2919–2922.
9. Karl, H.; Lee, C.K.; Khan, R. Synthesis and reactions of tert-butyldiphenylsilyl
ethers of sucrose. Carbohydr. Res. 1982, 101, 31–38.
10. Jarosz, S.; Listkowski, A. Towards C-2 symmetrical macrocyles with incorporated
sucrose unit. Can. J. Chem. 2006, 84, 492–496.
11. Omura, K.; Swern, D. Oxidation of alcohols by “activated” dimethyl sulfoxide. A
preparative, steric and mechanistic study. Tetrahedron 1978, 34, 1651–1660.
12. See for example:Taylor, R.J.K.; McAllister, G.D.; Franck, R.W. The
Ramberg–Backlund reaction for the synthesis of C-glycosides, C-linked-disaccharides
and related compounds. Carbohydr. Res. 2006, 341, 1298–1311; Taylor, R.J.K. Recent
developments in Ramberg–Ba¨cklund and episulfone chemistry. Chem. Commun. 1999,
217–227.
13. Aissuzzaman, A.K.M.; Whistler, R.L. Selective replacement of primary hydroxyl
groups in carbohydrates: preparation of some carbohydrate derivatives containing
halomethyl groups. Carbohydr. Res. 1978, 61, 511–518.