Synthesis of a sucrose dimer with enone tether; A study on its functionalization

Article abstract of DOI:10.3762/bjoc.10.124

The reaction of appropriately functionalized sucrose phosphonate with sucrose aldehyde afforded a dimer composed of two sucrose units connected via their C6-positions ('the glucose ends'). The carbonyl group in this product (enone) was stereo selectively

Full text of DOI:10.3762/bjoc.10.124

Synthesis of a sucrose dimer with enone tether;
a study on its functionalization
Zbigniew Pakulski, Norbert Gajda, Magdalena Jawiczuk, Jadwiga Frelek,
Piotr Cmoch and Sławomir Jarosz*
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2014, 10, 1246–1254.
Institute of Organic Chemistry, Polish Academy of Sciences, ul.
Kasprzaka 44/52, 01-224 Warsaw, Poland
doi:10.3762/bjoc.10.124
Received: 05 March 2014
Accepted: 30 April 2014
Published: 28 May 2014
Email:
Sławomir Jarosz* - slawomir.jarosz@icho.edu.pl
* Corresponding author
This article is part of the Thematic Series "Multivalent glycosystems for
nanoscience".
Keywords:
CD-spectroscopy; Cotton effect; multivalent glycosystems;
osmylation; stereoselective synthesis; sucrose
Guest Editor: A. Casnati
© 2014 Pakulski et al; licensee Beilstein-Institut.
License and terms: see end of document.
Abstract
The reaction of appropriately functionalized sucrose phosphonate with sucrose aldehyde afforded a dimer composed of two sucrose
units connected via their C6-positions (‘the glucose ends’). The carbonyl group in this product (enone) was stereoselectively
reduced with zinc borohydride and the double bond (after protection of the allylic alcohol formed after reduction) was oxidized
with osmium tetroxide to a diol. Absolute configurations of the allylic alcohol as well as the diol were determined by circular
dichroism (CD) spectroscopy using the in situ dimolybdenum methodology.
Introduction
Molecular recognition is one of the most important phenomena During the past decade we have become engaged in the prepar-
in stereoselective processes. Chiral crown ethers (or analogs) ation of the analogs of crown and aza-crown ethers with sucrose
are particularly useful in enantioselective reactions [1,2] as well scaffold. It is based on a selective protection of 1’,2,3,3’,4,4’-
as differentiation of chiral guests [3,4]. From all of the chiral hexa-O-benzylsucrose (1) either at the glucose (C-6) [8] or fruc-
platforms designed for such receptors, sugars are the most tose (C-6’) [9] end and further transformations to a variety of
promising due to their availability and biocompatibility. Up to macrocycles (2–4; Figure 1). Such receptors exhibit interesting
date only monosaccharides have found a wide application in the complexing properties towards chiral ammonium salts including
synthesis of crown ether analogs [5,6]. The disaccharide scaf- amino acids [10-14]. More complex sucrose macrocycles, such
fold is much less pronounced [7].
as 5, are available, although in rather low yield [15].
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Beilstein J. Org. Chem. 2014, 10, 1246–1254.
methodology shown in Figure 2. The properly activated sugar is
converted into phosphorane or phosphonate which – upon reac-
tion with an aldehyde derived from another monosaccharide –
provides higher carbon sugar (HCS) enone [16-18].
Figure 2: Synthesis of higher sugar precursors by a Wittig-type
methodology.
Application of this methodology to selectively protected
2,3,3’,4,4’-penta-O-benzylsucrose allowed us to elongate the
parent disaccharide at either terminal position (1’,6’, and 6’) by
Figure 1: Examples of sucrose-based macrocycles.
In this paper we present an approach to other derivatives relatively small (C2 or C7) unit and prepare so-called higher
containing two sucrose units. This type of dimers may be even- sucroses in good yields [19,20]. A similar approach is used now
tually used for the construction of macrocycles by (simple) for a more convenient hexa-O-benzyl derivative which is easily
connecting their C-6’ (fructose) ends.
silylated at the ‘fructose end’ providing alcohol 6 [8]. This
alcohol was converted into aldehyde 7 [21] (route a in
Scheme 1) and separately into phosphonate 9 (route b). Reac-
Results and Discussion
Coupling of two sugar units can be performed by a number of tion of both synthons under the mild PTC conditions [22-24]
methods. The best one in our hands was the Wittig-type afforded the respective enone 10 in good yield (Scheme 1).
Scheme 1: Synthesis of higher sugar enone 10.
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Beilstein J. Org. Chem. 2014, 10, 1246–1254.
Functionalization of the three-carbon atom unit connecting the dichroism spectroscopy (CD) using the in situ dimolybdenum
C5-positions of both sucrose units required reduction of the car- methodology (see next chapter).
bonyl group of the enone system and oxidation of the double
bond.
Next steps of the synthesis consisted of the protection of the
C6–OH as benzyl ether (to 12) and osmylation of the double
We have already reported that reduction of higher carbon sugar bond. The cis-dihydroxylation provided, as single stereoisomer,
enones of the D series with zinc borohydride is highly selective a diol to which structure 13 could be assigned on the basis of
and provides the corresponding allylic alcohols with the R con- the Kishi rule [26] (Scheme 2). It postulates that the attack of
figuration at the newly created stereogenic center, as the only OsO4 occurs from the side opposite to hydroxy (alkoxy)
products. This can be rationalized assuming the cyclic model of substituent(s) flanking the double bond. Since in 12, both
such reduction [25] shown in Scheme 2. We expected, there- alkoxy units act in the same direction, very high diastereoselect-
fore, also very high selectivity in the reduction of 10.
ivity is not surprising. The assignment of the configuration of
this diol was further confirmed also by the CD methodology;
this is discussed in the next chapter.
Determination of the absolute configuration of
11 and 13
It is widely acceptable that the circular dichroism (CD) spec-
troscopy utilizing the in situ dimolybdenum methodology offers
the hard proof of the absolute configuration of the vic-diols [27-
29]. In this methodology, dimolybdenum tetraacetate acts as
auxiliary chromophore allowing the application of electronic
circular dichroism (ECD) to (otherwise in ECD non-observable)
vic-diols. Mo2(OAc)4 when mixed with a chiral diol ligand
forms complexes active in ECD in which a transfer of ligand
chirality to the in situ-formed complex occurs in solution. Thus,
stereochemistry of vic-diols can be easily assigned based on the
helicity rule developed for this class of compounds. This rule
correlates the positive/negative signs of Cotton effects (CE)
occurring in the 300–400 nm spectral range in the ECD spectra
with the positive/negative sign of the O–C–C–O torsion angle
of the diol unit of resultant complexes with the Mo2-core. The
basic assumption leading to the assignment of the absolute con-
figuration (AC) based only on the ECD spectra with the Mo2-
core preferring the gauche conformation of the diol units with
both O–C–C–C fragments in an antiperiplanar arrangement
(Figure 3). This arrangement is favored, for steric reasons, i.e.,
to avoid any interaction with the carboxylate ligands remaining
in the stock complex. As a result of the structure–ECD spectra
relationship, it is possible to assign the AC of the diol moiety
unambiguously on the basis of the ECD spectra alone.
In the past few years, this simple but, above all, efficient and
effective method is becoming more and more recognized as evi-
denced by the steadily increasing number of reports in the
literature about its successful application in the determination of
Scheme 2: Synthesis of the diol 13 containing two sucrose units.
Indeed, treatment of enone 10 with Zn(BH4)2 under the stan- the AC of 1,2-diols [30-32].
dard conditions afforded allylic alcohol 11 as single
stereoisomer in 65% yield. Based on our model, the R-configur- Therefore, in assignment of the AC of compounds under the
ation might be safely assigned to the new stereogenic center. present study (13, 14 and 16), we decided just to take advan-
This assignment was further verified independently by circular tage of the in situ methodology.
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Figure 3: CD spectra of in situ formed chiral complexes of 13 (green line), 14 (purple line) and 16 (blue line) with dimolybdenum tetraacetate recorded
in DMSO; right: preferred gauche conformation of the diols 13, 14 and 16 in the complex with Mo2-core.
This method was used to prove indirectly the 6R configuration
at the newly created stereogenic center in allylic alcohol 11. The
double bond in 11 was cleaved with ozone and the resulting
ozonide was reduced with NaBH4; this sequence afforded
sucrose vic-diol 14 and (as a byproduct) sucrose alcohol 6
(Scheme 3).
The positive sign of the Cotton effect at around 307.0 nm
recorded for the complex of the diol 14 with Mo2(OAc)4 unam-
biguously pointed at the 6R configuration (Figure 3). However,
to exclude any errors we have also prepared 14 and epimeric
alcohol 16; its synthesis is shown in Scheme 3.
First, aldehyde 7 was converted into olefin 15 by treatment with
the simplest Wittig reagent: Ph3P=CH2. Subsequent osmylation
of the double bond in 15 provided two stereoisomeric diols in a
1:1 ratio; the first one was identical in all respects with the diol
obtained from degradation of 11.
The resultant ECD spectra of the Mo2-core with compounds 13
and 16 are shown in Figure 3. Based on the positive CE’s at
308.5 nm for 13 and negative at 310 nm for 16, respectively, the
positive (negative) sign of the O–C–C–O torsion angle has been
attributed to these diols. In the next step, based on the preferred
gauche conformation of the diol unit with both O–C–C–C frag-
ments in an antiperiplanar arrangement as shown in Figure 3,
we were able to assign unambiguously the (7R,8R) AC to diol
Scheme 3: Synthesis of model sucrose diols.
13 and (6S) to 16.
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Beilstein J. Org. Chem. 2014, 10, 1246–1254.
Conclusion
the absorption, c the molar concentration of the chiral
Coupling of two properly activated sucrose sub-units afforded ligand, assuming 100% complexation, and d the path length of
the dimer in which both glucose-rings were connected via an the cell.
enone linker. The dimer was then converted into a (partially
protected) triol via a stereoselective reduction of the carbonyl The numbering of the atoms in sucrose dimers is as followed.
group and highly selective cis-dihydroxylation of the double The bottom part (green) is marked A and the top marked as B.
bond. The configuration at each new stereogenic center was The original numbering of the sucrose skeleton in both parts is
determined by CD spectroscopy using the so-called dimolyb- retained (i.e., the glucose part is numbered C1–C6 and fructose
denum methodology which allows for fast, easy, and effective C1'–C6').
assignment of the absolute configuration of vic-diols. We have
confirmed the usefulness of this simple methodology which can
be applied even in cases when other spectroscopic methods fail.
It is worthy to point out that this methodology, which is used in
the synthesis of more simple derivatives such as higher carbon
sugars, was also applicable for the preparation of the sucrose
dimer.
Experimental
General methods
All reported NMR spectra were recorded with a Varian-Vnmrs-
600 MHz spectrometer (at 600 and 150 MHz for 1H and
13C NMR spectra, respectively) for solutions in CDCl3 at room
temperature. Chemical shifts (δ, ppm) were determined relative Synthesis of phosphonate 9. To a cooled −78 °C solution of
to TMS as the internal standard. Most of the resonances were dimethyl methylphosphonate (110 μL, 1.0 mmol) in THF
assigned by COSY (1H–1H) and gradient selected HSQC and (7 mL) a 2.5 M solution of butyllithium in hexane (0.4 mL,
HMBC correlations. Mass spectra were recorded with an ESI/ 1.0 mmol) was added and the mixture was stirred for 15 min.
MS Mariner (PerSeptive Biosystem) mass spectrometer. Then, a solution of 8 (325 mg, 0.28 mmol) in THF (5 mL) was
Elemental analyses were obtained using a Perkin-Elmer 2400 slowly added and the mixture was stirred for additional 30 min.
CHN analyzer. Optical rotations were measured with a Jasco Reaction was quenched by addition of a saturated solution of
P-2000 digital polarimeter for solutions in CHCl3 (c = 0.3) at NaCl (5 drops). The mixture was concentrated, and the residue
room temperature. Flash and column chromatographic separa- was purified by column chromatography (hexane–ethyl acetate,
tions were performed on silica gel (Merck, 230–400 mesh). 10:1 → 1:1) to afford title compound 9 (227 mg, 65%) as a
Progress of the reactions was monitored by thin-layer chroma- foam. [α]D20 16.2.; 1H NMR δ 7.64–7.61 (m, 4H, Ar),
tography (TLC) performed on aluminum plates covered with 7.35–7.18 (m, 36H, aryl-H), 6.08 (d, 1H, J1,2 = 3.6 Hz, H-1),
silica gel (60 F254, Merck).
4.86–4.38 (m, 12H, PhCH2), 4.54 (d, 1H, J5,4 = 9.9 Hz, H-5),
4.48 (d, 1H, J3,4 = 7.5 Hz, H-3'), 4.45 (dd, 1H, J4,3 = 7.5, J4,5 =
The ECD spectra were acquired at room temperature in DMSO 15.0 Hz, H-4'), 4.03 (dd, 1H, J6,5 = 3.8, J6,6’ 11.5 Hz, H-6'),
(for UV-spectroscopy, Fluka) on a Jasco J-715 spectropo- 3.94 (m, 2H, H-3, H-5'), 3.85 (dd, 1H, J6,5 = 4.1 Hz, J6,6’ = 11.5
larimeter and were collected at 0.5 nm/step with an integration Hz, H-6'), 3.71 (dd, 1H, J4,3 = 9.1 Hz, J4,5 = 9.9 Hz, H-4), 3.67
time of 0.25 s over the range 235–800 nm with 200 nm/min (d, 1H, Jgem = 10.8 Hz, H-1'), 3.62 (d, 3H, JH,P = 11.1 Hz,
scan speed, 5 scans. For the ECD standard measurements the OCH3), 3.61 (d, 3H, JH,P = 11.2 Hz, OCH3), 3.56 (d, 1H, Jgem
chiral diols (~3.6 mg, ca. 0.003 M) was mixed with stock com- = 10.8 Hz, H-1'), 3.43 (dd, 1H, J2,1 = 3.6, J2,3 = 9.7 Hz, H-2),
plex [Mo2(O2CCH3)4] (Mo1) (~0.9 mg, ca. 0.002 M) and 3.26 (dd, 1H, J7,7' = 15.7 Hz, JH,P = 20.3 Hz, H-7), 2.97 (dd,
dissolved in DMSO (1 mL) so that the molar ratio of the stock 1H, J7,7' = 15.7 Hz, JH,P = 20.8 Hz, H-7), 1.06 (s, 9H, t-Bu);
complex to ligand was about 1:1.5 in general. Quantitative 13C NMR δ 198.5 (d, J 7.4 Hz, C=O), 138.7, 138.5, 138.2,
values could not be obtained with the in situ dimolybdenum 138.1, 137.8, 137.7, 135.6, 135.4, 133.1, 132.7, 129.8, 129.8,
method since the concentration of the chiral complex formed in 128.6–127.5 (Ar), 104.5 (C-2'), 89.2 (C-1), 83.3 (C-3'), 81.5
solution and its actual structure were unknown. So the ECD (C-3), 80.8 (C-4'), 80.5 (C-5'), 79.5 (C-2), 77.9 (C-4), 75.7
data are given as the Δε' values, which are calculated in the (PhCH2), 74.9 (d, J 5.0 Hz, C-5), 74.8 (PhCH2), 73.5 (PhCH2),
usual manner by means of the equation Δε' = ΔA/c × d, A being 73.4 (PhCH2), 72.9 (PhCH2), 72.0 (PhCH2), 72.0 (C-1'), 63.5
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Beilstein J. Org. Chem. 2014, 10, 1246–1254.
(C-6'), 52.8 (d, J = 6.3 Hz, OCH3), 52.6 (d, J = 6.4 Hz, OCH3), H-5A), 4.13 (d, 1H, J = 10.9 Hz, PhCH2), 4.06–4.04 (m, 1H,
37.9 (d, J = 136.9 Hz, C-7), 26.9 (t-Bu-CH3), 19.2 (t-Bu-C); 31P H-5'), 3.99–3.95 (m, 2H, 2 × H-6'), 3.92–3.89 (m, 2H, H-5',
NMR (CDCl3) δ 23.5; anal. calcd for C73H81O14PSi (1241.51): H-6'), 3.86–3.79 (m, 3H, H-3A, H-1', H-3B), 3.65 (d, 1H, J =
C, 70.62; H, 6.58; found: C, 70.44; H, 6.79.
11.0 Hz, H-1'), 3.52 (d, 1H, J = 11.0 Hz, H-1'), 3.49 (d, 1H,
H-1'), 3.35 (dd, 1H, J = 3.5 Hz, 9.6 Hz, H-2B), 3.27–3.24 (m,
Synthesis of ketone 10. To a solution of aldehyde 7 (200 mg, 1H, H-4A), 3.21–3.16 (m, 2H, H-2A, H-4B), 1.03 (s, 9H, t-Bu),
0.18 mmol), phosphonate 9 (220 mg, 0.18 mmol), and 1.02 (s, 9H, t-Bu); 13C NMR δ 139.0, 138.9, 138.6, 138.6,
18-crown-6 (70 mg) in toluene (25 mL) potassium carbonate 138.5, 138.4, 138.3, 138.1, 138.0, 137.9, 137.8, 137.7, 135.7,
(300 mg) was added and the suspension was stirred at rt for 135.6, 135.5, 135.5, 133.5, 133.3, 133.3, 132.8, 131.3 (=CH),
4 days. The solvents were evaporated and the residue was puri- 130.4 (=CH-CHOH), 129.8, 129.7, 129.7, 129.6, 128.5–127.3
fied by column chromatography (hexane–ethyl acetate, 40:1 → (Ar), 105.0 (C-2'), 104.5 (C-2'), 90.2 (C-1B), 89.0 (C-1A), 84.5
5:1) to afford title compound 10 as a foam (287 mg; 73%). (C-3'), 83.6 (C-4'), 83.1 (C-4'), 82.3 (C-3A), 82.2 (C-4B), 81.8
[α]D20 41.8; 1H NMR δ 7.62–7.61 (m, 8H, Ar), 7.28–7.06 (m, (C-5'), 81.6 (C-3'), 81.5 (C-3B), 81.0 (C-5'), 80.4 (C-2A), 80.0
73H, Ar, =CH-CO), 6.75 (dd, 1H, J = 1.8 Hz, 15.7 Hz, =CH), (C-2B), 78.4 (C-4A), 75.5 (PhCH2), 75.4 (PhCH2), 74.6
5.90 (d, 1H, J = 3.5 Hz, H-1A), 5.82 (d, 1H, J = 3.5 Hz, H-1B), (PhCH2), 74.4 (PhCH2), 73.6 (PhCH2), 73.4 (PhCH2), 73.4
4.74–4.26 (m, 24H, 12 × PhCH2), 4.67 (d, 1H, J = 10.2 Hz, (C-5A), 73.1 (PhCH2), 73.0 (PhCH2), 72.7 (PhCH2), 72.6
H-5A), 4.58 (d, 1H, J = 12.3 Hz, H-5B), 4.37–4.26 (m, 4H, (PhCH2), 71.8 (PhCH2), 71.7 (PhCH2), 71.5 (C-6A), 71.4
furanose), 4.00–3.80 (m, 8H, H-3A, H-3B, 4 × H-6', 2 × fura- (C-1'), 70.5 (C-1'), 70.0 (C-5B), 65.8 (C-6'), 63.7 (C-6'), 27.0
nose), 3.77 (d, 1H, J = 11.0 Hz, H-1'B), 3.68 (d, 1H, J = 10.9 (t-Bu), 27.0 (t-Bu), 19.3 (CH3), 19.3 (CH3); anal. calcd for
Hz, H-1'A), 3.50 (dd, 1H, J = 9.1 Hz, 10.0 Hz, H-4A), 3.46 (d, C141H150O21Si2 (2236.92): C, 75.71; H, 6.76; found: C, 75.51;
1H, J = 10.9 Hz, H-1'A), 3.42–3.38 (m, 2H, H-1'B, H-2A), 3.25 H, 6.63.
(dd, 1H, J = 3.5 Hz, 9.6 Hz, H-2A), 2.97 (dd, 1H, J = 9.1 Hz,
9.9 Hz, H-4B), 1.03 (s, 9H, t-Bu), 1.02 (s, 9H, t-Bu); 13C NMR Benzylation of 11. To a solution of alcohol 11 (82 mg,
δ 195.2 (C=O), 144.7 (=CH-CO), 138.9, 138.8, 138.4, 138.3, 0.037 mmol) in DMF (1 mL), sodium hydride (60% suspension
138.2, 138.1, 138.1, 138.0, 137.9, 137.9, 137.8, 137.7, 135.6, in mineral oil, 7 mg) was added and the mixture was stirred for
135.6, 135.5, 133.4, 133.3, 133.2, 133.1, 129.7, 129.7, 129.7, 30 min at rt. Benzyl bromide (11 μL, 0.092 mmol) was added,
129.6, 128.4–127.4 (Ar), 124.8 (=CH) 105.1 (C-2'A), 104.8 and stirring was continued overnight. Excess of sodium hydride
(C-2'B), 90.3 (C-1A), 90.2 (C-1B), 84.4, 83.9, 83.3, 83.2, 81.8 was decomposed with methanol (0.5 mL). The product was
(C-4B), 81.7, 81.7, 81.5 (C-3A), 81.4 (C-3B), 79.8 (C-2A, isolated by column chromatography (hexane–ethyl acetate, 10:1
C-2B), 79.6 (C-4A), 75.7 (PhCH2), 75.4 (PhCH2), 74.9 (C-5A, → 5:1) to afford 12 (34 mg, 40%) as a foam. [α]D20 21.8 (c 0.9,
PhCH2), 74.4 (PhCH2), 73.5 (PhCH2), 73.4 (PhCH2), 73.1 CH2Cl2); 1H NMR δ 7.67–7.63 (m, 8H, Ar), 7.28–7.00 (m,
(PhCH2), 73.0 (PhCH2), 72.6 (PhCH2), 72.4 (PhCH2), 72.1 77H, Ar), 5.93–5.89 (m, 2H, H-1B, =CH-CHOH), 5.63–5.59
(PhCH2),71.8 (PhCH2), 70.6 (C-1'), 70.4 (C-1'), 69.8 (C-5B), (m, 2H, H-1A, =CH), 4.79–4.50 (m, 13H, H-5B, PhCH2),
65.3 (C-6'), 65.0 (C-6'), 27.0 (t-Bu), 27.0 (t-Bu), 19.3 (CH3), 4.47–4.16 (m, 18H, H-5A, PhCH2), 4.10–3.75 (m, 12H, H-6A,
19.3 (CH3); anal. calcd for C141H148O21Si2 (2234.91): C, 4 × H-6', H-3B, 2 × H-1', H-3A, 2 × furanose, PhCH),
75.78; H, 6.68; found: C, 75.59; H, 6.80.
3.56–3.52 (m, 2H, 2 × H-1'), 3.41 (dd, 1H, J = 3.6, 9.7 Hz,
H-2B), 3.19–3.14 (m, 2H, H-4A, H-4B), 2.92 (dd, 1H, J = 3.5,
Stereoselective reduction of ketone 10. To an ice-cooled solu- 9.6 Hz, H-2A), 1.03 (s, 9H, t-Bu), 1.03 (s, 9H, t-Bu); 13C NMR
tion of ketone 10 (270 mg, 0.12 mmol) in Et2O (15 mL), an δ: 139.0, 138.8, 138.7, 138.6, 138.5, 138.4, 138.3, 138.3, 138.3,
etheral solution of zinc borohydride (0.6 mmol) was added and 138.3, 138.2, 138.0, 137.8, 135.6, 135.5, 135.5, 135.5, 134.4
the mixture was stirred at 0 °C for 1 h. Water (10 drops) was (=CH), 133.7, 133.6, 133.4, 133.2, 129.7, 129.6, 129.6, 129.6,
added to decompose excess of hydride, the solvents were evap- 128.3–127.0 (Ar), 104.4 (C-2'), 104.4 (C-2'), 90.1 (C-1A), 89.9
orated, and the residue was purified by column chromatog- (C-1B), 84.5, 84.1, 83.2, 82.2, 82.0 (C-3A), 82.0 (C-4B), 81.6
raphy (hexane–ethyl acetate, 10:1 → 5:1) to afford title com- (C-3B, C-6A), 80.4 (C-2A), 79.9 (C-2B), 78.6, 78.2 (C-4A),
pound 11 (176 mg, 65%) as a foam. [α]D20 40.4; 1H NMR δ 75.6 (PhCH2), 75.2 (PhCH2), 74.6 (PhCH2), 74.2 (PhCH2),
7.63–7.61 (m, 8H, Ar), 7.30–7.05 (m, 72H, Ar), 5.97 (dd, 1H, J 73.6 (PhCH2), 73.2 (PhCH2), 73.1 (PhCH2), 73.0 (PhCH2),
= 7.9 Hz, 15.6 Hz, =CH-CHOH), 5.83 (d, 2H, J = 3.6 Hz, 72.7 (PhCH2), 72.6 (C-5A), 72.5 (PhCH2), 71.9 (PhCH2), 71.8
H-1A, H-1B), 5.76 (dd, 1H, J = 5.5 Hz, 15.6 Hz, =CH), (PhCH2), 71.0 (C-1'), 70.3, 70.2 (C-1'), 69.9, 66.7 (C-6'), 65.6
4.80–4.73 (m, 5H, PhCH2), 4.63–4.41 (m, 17H, PhCH2, H-3', (C-6'), 27.0 (t-Bu), 26.9 (t-Bu), 19.3 (CH3), 19.3 (CH3); anal.
H-5B), 4.39–4.34 (m, 6H, PhCH2, H-3', H-3', H-4', H-6A), calcd for C148H156O21Si2 (2327.05): C, 76.39; H, 6.76; found:
4.32–4.28 (m, 1H, H-4'), 4.25 (dd, 1H, J = 2.2 Hz, 10.3 Hz, C, 76.44; H, 6.73.
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Beilstein J. Org. Chem. 2014, 10, 1246–1254.
Dihydroxylation of the double bond of 12. Olefin 12 (60 mg, 129.6, 129.6, 128.3–127.5 (Ar), 117.0 (C-7), 104.3 (C-2'), 89.2
0.026 mmol) and OsO4 (30 mg, 0.120 mmol) were dissolved in (C-1), 83.8 (C-3'), 82.5 (C-4), 82.3 (C-4'), 81.6 (C-3), 81.2
pyridine (4 mL), and stirred for 48 h. The solvent was evapo- (C-5'), 80.0 (C-2), 75.6 (PhCH2), 74.8 (PhCH2), 73.4 (PhCH2),
rated, the residue was dissolved in ethyl acetate (10 mL), to 72.9 (PhCH2), 72.6 (PhCH2), 72.3 (PhCH2), 71.4 (C-1',5), 64.9
which sat. aq Na2S2O3 (1 mL) was added, and the suspension (C-6'), 26.9 (t-Bu-CH3), 19.3 (t-Bu-C); anal. calcd for
was stirred for 2 days. The organic layer was separated, solvents C71H76O10Si (1117.47): C, 76.31; H, 6.86; found: C, 76.42; H,
were evaporated to dryness and the residue was purified by 6.99.
column chromatography (hexane–ethyl acetate, 5:1) to afford
13 (44 mg, 73%) as colorless glass. [α]D20 22.8; 1H NMR δ Ozonolytic cleavage of the double bond in sucrose dimer 11.
7.64–7.59 (m, 8H, Ar), 7.27–6.98 (m, 77H, Ar), 5.83 (bs, 1H, Determination of the configuration at the carbinol center.
H-1A), 5.80 (d, 1H, J1,2 = 3.5 Hz, H-1B), 4.82–4.69 (m, 5H, Ozone was passed through a cooled solution of 11 (51 mg,
PhCH2), 4.65–4.49 (m, 11H, PhCH2, sugar-H), 4.45–4.34 (m, 0.023 mmol) in CH2Cl2 (10 mL) until the blue color persisted
10H, PhCH2, 2 × sugar-H), 4.29–4.23 (m, 7H, PhCH2, 5 × (10 min). Dimethyl disulfide (210 μL) was added, the mixture
sugar-H), 4.08–4.05 (m, 2H, PhCH2, sugar-H), 4.01–3.95 (m, was stirred for 10 min, concentrated, and the residue was
6H, 3 × H-6', 3 × sugar-H), 3.89–3.78 (m, 4H, H-1', H-3A, dissolved in methanol (10 mL). Sodium borohydride (40 mg)
H-3B, H-6'), 3.67 (d, 1H, J = 11.1 Hz, H-1'), 3.58–3.55 (m, 2H, was added, the mixture was stirred for 1 h, concentrated, and
H-1', H-1'), 3.37 (dd, 1H, J = 3.6 Hz, 9.6 Hz, H-2B), 3.36–3.32 the crude product was purified by column chromatography
(m, 2H, H-2A, sugar-H), 1.02 (s, 9H, t-Bu), 1.01 (s, 9H, t-Bu); (hexane–ethyl acetate, 7:3) to afford sucrose 6 (16 mg, 63%)
13C NMR δ 139.1, 139.0, 138.9, 138.8, 138.6, 138.3, 138.2, and diol 14 (18 mg, 69%), both as foam.
138.2, 138.0, 137.9, 137.7, 137.6, 135.6, 135.6, 135.5, 135.5,
133.6, 133.4, 133.3, 132.9, 129.7, 129.7, 129.6, 129.5, 128.4- Synthesis of diols 14 and 16. To a solution of 15 (145 mg,
127.1 (Ar), 105.1 (C-2'), 104.7 (C-2'), 90.7 (C-1B), 89.4 0.13 mmol) in THF (10 mL), tert-butyl alcohol (500 μL), water
(C-1A), 84.4, 83.5, 82.5 (C-3B), 82.0, 81.9, 81.6 (C-3A), 81.2, (50 μL), NMO (80 mg, 0.68 mmol), and OsO4 (8 wt % in
80.4 (C-2B), 79.7 (C-2A), 79.3, 78.6, 75.5 (PhCH2), 75.3 t-BuOH, 150 μL, 0.035 mmol) were added, and the mixture was
(PhCH2), 74.6 (PhCH2), 74.3, 74.3 (PhCH2), 73.5 (PhCH2), stirred at rt for 18 h. Saturated aq Na2S2O3 (0.2 mL) was added,
73.2 (PhCH2), 73.1 (PhCH2), 73.1 (PhCH2), 72.7 (PhCH2), the mixture was stirred for 1 h at rt, concentrated, and the prod-
72.5 (PhCH2), 71.9 (PhCH2), 71.8 (PhCH2), 70.9 (C-1'), 70.7, ucts were isolated by column chromatography (hexane–ethyl
70.1 (C-1'), 69.7, 68.2, 66.4 (C-6'), 64.2 (C-6'), 27.0 (t-Bu), 19.3 acetate, 5:1 → 3:1) to afford of 14 (60 mg; 40%) and 16 (58 mg
(CH3), 19.2 (CH3); MS (ESI): 2383.08 [M + Na]+; anal. calcd 39%), both as foam.
for C148H158O23Si2 (2361.06): C, 75.29; H, 6.75; found: C,
75.29; H, 6.79.
Data for 14: [α]D20 32.6; 1H NMR δ 7.64–7.62 (m, 4H, aryl-H),
7.36–7.14 (m, 36H, Ar), 6.04 (d, 1H, J1,2 = 3.8 Hz, H-1),
Synthesis of olefin 15. To a suspension of methyltriph- 4.95–4.39 (m, 10H, PhCH2), 4.47–4.45 (m, 4H, H-3',4',PhCH2),
enylphosphonium bromide (895 mg, 2.50 mmol) in benzene 4.14 (dd, 1H, J5,4 = 10.2, J5,6 = 4.1 Hz, H-5), 4.03 (dd, 1H, J6,5
(20 mL) a 2.5 M solution of BuLi in hexane (0.95 mL, = 3.4, J6,6’ = 11.6 Hz, H-6'), 3.93–3.89 (m, 2H, H-3,5'),
2.30 mmol) was added and the mixture was stirred at rt for 3.84–3.79 (m, 2H, H-6,6'), 3.65–3.62 (m, 2H, H-1',7), 3.55 (d,
90 min. A solution of aldehyde 7 (298 mg, 0.27 mmol) in 1H, Jgem = 10.8 Hz, H-1'), 3.49–3.43 (m, 3H, H-2,4,7), 1.07 (s,
benzene (5 mL) was added, the mixture was stirred for another 9H, t-Bu); 13C NMR δ 138.6, 138.2, 138.0, 137.9, 137.8, 137.3,
45 min, quenched with water (100 μL), concentrated, and the 135.7, 135.4, 133.0, 132.6, 129.8, 129.7, 128.7–127.6 (Ar),
residue was purified by column chromatography (hexane–ethyl 104.3 (C-2'), 88.2 (C-1), 82.9 (C-3'), 82.0 (C-3), 80.3 (C-5'),
acetate, 15:1 → 10:1) to afford 15 (172 mg, 58%) as a foam. 80.1 (C-2,4'), 79.0 (C-4), 75.5 (PhCH2), 74.7 (PhCH2),73.4
[α]D20 24.0; 1H NMR δ 7.67–7.64 (m, 4H, Ar), 7.35–7.18 (m, (PhCH2), 73.1 (PhCH2), 72.8 (PhCH2), 72.3 (C-1'), 72.2 (C-6),
36H, Ar), 5.77–5.72 (m, 2H, H-1,6), 5.12–5.09 (m, 1H, H-7), 71.9 (PhCH2), 71.3 (C-5), 63.0 (C-6'), 62.9 (C-7), 26.9 (t-Bu-
5.02–5.00 (m, 1H, H-7), 4.82–4.50 (m, 11H, PhCH2), 4.45–4.43 CH3), 19.2 (t-Bu-C); anal. calcd for C71H78O12Si (1151.49): C,
(m, 3H, H-3',5,PhCH), 4.30 (t, 1H, J4,3 = J4,5 = 7.4 Hz, H-4'), 74.06; H, 6.83; found: C, 74.00; H, 6.79.
4.05–4.02 (m, 1H, H-5'), 3.94 (dd, 1H, J6,5 = 4.8 Hz, J6,6’ =
11.1 Hz, H-6'), 3.90–3.87 (m, 2H, H-3,6'), 3.69 (d, 1H, Jgem = Data for 16: [α]D20 21.6; 1H NMR δ 7.64–7.62 (m, 4H, Ar),
11.0 Hz, H-1'), 3.50 (d, 1H, Jgem = 11.0 Hz, H-1'), 3.44 (dd, 1H, 7.37–7.16 (m, 36H, aryl-H), 6.04 (d, 1H, J1,2 = 3.6 Hz, H-1),
J2,1 = 3.7 Hz, J2,3 = 9.7 Hz, H-2), 3.16 (dd, 1H, J4,3 = 9.4 Hz, 4.93–4.40 (m, 12H, PhCH2), 4.40 (d, 1H, J = 6.5 Hz, H-3'),
J4,5 = 9.5 Hz, H-4), 1.06 (s, 9H, t-Bu); 13C NMR δ 138.9, 4.32 (t, 1H, J4,3 = J4,5 = 6.7 Hz, H-4'), 4.03–3.99 (m, 2H,
138.6, 138.4, 138.3, 138.0, 135.7, 135.6, 135.6, 133.5, 133.3, H-5,6'), 3.95 (t, 1H, J3,2 = J3,4 = 9.4 Hz, H-3), 3.92–3.91 (m,
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Beilstein J. Org. Chem. 2014, 10, 1246–1254.
1H, H-5'), 3.81 (dd, 1H, J6,5 = 4.0 Hz, J6,6’ = 11.4 Hz, H-6'), 129.6, 128.5–127.5 (Ar), 104.6 (C-2'), 89.1 (C-1), 83.7 (C-3'),
3.74–3.72 (m, 1H, H-6), 3.70–3.66 (m, 2H, H-1',4), 3.55 (d, 1H, 81.6 (C-3), 81.3 (C-4'), 80.8 (C-5'), 79.8 (C-2), 76.9 (C-4), 75.6
Jgem = 10.9 Hz, H-1'), 3.48–3.42 (m, 3H, H-2,7,7), 1.07 (s, 9H, (PhCH2), 75.0 (PhCH2), 73.5 (PhCH2), 73.3 (PhCH2), 72.8
t-Bu); 13C NMR δ 138.8, 138.5, 138.3, 137.9, 137.7, 137.5, (PhCH2), 71.8 (PhCH2), 71.4 (C-1'), 70.2 (C-5), 69.0 (C-6),
135.7, 135.5, 132.9, 132.7, 129.8, 129.8, 128.4–127.5 (Ar), 64.8 (C-7), 63.7 (C-6'), 26.9, 21.0, 20.8, 19.2; anal. calcd for
104.8 (C-2'), 89.3 (C-1), 83.2 (C-3'), 81.4 (C-3), 81.1 (C-4'), C75H82O14Si × ½H2O (1253.57): C, 72.38; H, 6.72; found: C,
80.8 (C-5'), 79.9 (C-2), 77.3 (C-4), 75.5 (PhCH2), 75.1 72.34; H, 6.29. HRMS (ESI) calc. for C75H86NO14Si [M +
(PhCH2), 73.5 (PhCH2), 73.2 (PhCH2), 72.5 (PhCH2), 72.0 NH4]+: 1252.5818; found: 1252.5819.
(PhCH2), 71.9 (C-5), 71.6 (C-1'), 68.9 (C-6), 64.5 (C-7), 63.1
(C-6'), 26.9 (t-Bu-CH3), 19.2 (t-Bu-C); anal. calcd for
Supporting Information
C71H78O12Si (1151.49): C, 74.06; H, 6.83; found: C, 73.94; H,
6.66.
Supporting Information File 1
The 1H and 13C NMR spectra of all new compounds
Both compounds were further characterized as diacetates:
(9–16Ac).
14-Ac and 16-Ac.
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-10-124-S1.pdf]
Data for 14-Ac: [α]D20 33.3; 1H NMR δ 7.66–7.64 (m, 4H, Ar),
7.34–7.21 (m, 36H, aryl-H), 5.82 (d, 1H, J1,2 = 3.6 Hz, H-1),
5.48 (m, 1H, H-6), 4.93–4.55 (m, 10H, PhCH2), 4.46–4.42 (m,
3H, H-3', PhCH2), 4.15 (dd, 1H, J5,4 = 10.3 Hz, J5,6 = 1.4 Hz,
H-5), 4.03–3.96 (m, 3H, H-5', H-6', H-7), 3.91 (dd, 1H, J6,5 =
4.7, J6,6’ = 10.9 Hz, H-6'), 3.88 (t, 1H, J3,2 = J3,4 = 9.2 Hz,
H-3), 3.67 (d, 1H, J1,1 = 11.0 Hz, H-1'), 3.51 (d, 1H, J1,1 = 11.0
Hz, H-1'), 3.49 (dd, 1H, J4,3 = 9.2 Hz, J4,5 = 10.3 Hz, H-4),
3.39 (dd, 1H, J2,1 = 3.6 Hz, J2,3 = 9.7 Hz, H-2), 1.96 (s, 3H,
CH3), 1.84 (s, 3H, CH3), 1.05 (s, 9H, t-Bu); 13C NMR δ 170.5
(C=O), 169.8 (C=O), 138.6, 138.4, 138.2, 138.1, 138.0, 137.9,
135.7, 135.5, 133.3, 133.0, 129.7, 129.6, 128.3-127.5 (Ar),
104.2 (C-2'), 89.0 (C-1), 83.7 (C-3'), 82.0 (C-3), 81.9 (C-4'),
81.0 (C-5'), 79.8 (C-2), 77.6 (C-4), 75.6 (PhCH2), 74.6
(PhCH2), 73.3 (PhCH2), 73.1 (PhCH2), 72.8 (PhCH2), 72.1
(PhCH2), 71.4 (C-1'), 71.1 (C-6), 70.9 (C-5), 64.6 (C-6'), 63.2
(C-7), 26.9, 20.9, 20.8, 19.2; anal. calcd for C75H82O14Si ×
½H2O (1253.57): C, 72.38; H, 6.72; found: C, 72.51; H, 6.36.
HRMS (ESI) calc. for C75H86NO14Si [M + NH4]+: 1252.5818;
found: 1252.5825.
Acknowledgements
The support from Grant: POIG.01.01.02-14-102/09 (part-
financed by the European Union within the European Regional
Development Fund) and N N204 187439 (from the Ministry of
Science and Higher Education) is acknowledged.
References
1. Ooi, T.; Maruoka, K. Angew. Chem., Int. Ed. 2007, 46, 4222–4266.
doi:10.1002/anie.200601737
2. Rapi, Z.; Démuth, B.; Keglevich, G.; Grün, A.; Drahos, L.; Sóti, P. L.;
Bakó, P. Tetrahedron: Asymmetry 2014, 25, 141–147.
doi:10.1016/j.tetasy.2013.12.007
3. Zhang, X. X.; Bradshaw, J. S.; Izatt, R. M. Chem. Rev. 1997, 97,
3313–3362. doi:10.1021/cr960144p
4. Cheng, C.; Cai, Z.; Peng, X.-S.; Wong, H. N. C. J. Org. Chem. 2013,
78, 8562–8573. doi:10.1021/jo401240k
5. Jarosz, S.; Listkowski, A. Curr. Org. Chem. 2006, 10, 643–662.
doi:10.2174/138527206776359702
6. Bako, P.; Keglevich, G.; Rapi, Z.; Toke, L. Curr. Org. Chem. 2012, 16,
297–304. doi:10.2174/138527212799499877
7. Jarosz, S.; Potopnyk, M. A.; Kowalski, M. Sucrose as chiral platform in
the synthesis of macrocyclic receptors. In Carbohydrate
Chemistry-Chemical and Biological Approaches; Rauter, A. P.;
Lindhorst, T.; Queneau, Y., Eds.; RSC Publishing, 2014; Vol. 40,
pp 236–256. doi:10.1039/9781849739986-00236
See for a recent review.
Data for 16-Ac: [α]D20 13.1; 1H NMR (CDCl3) δ 7.65–7.63 (m,
4H, Ar), 7.34–7.20 (m, 36H, Ar), 6.09 (d, 1H, J1,2 = 3.5 Hz,
H-1), 5.48 (ddd, 1H, J = 1.5 Hz, 2.9 Hz, 9.2 Hz, H-6),
4.88–4.42 (m, 12H, PhCH2), 4.42–4.38 (m, 2H, H-3', H-4'),
4.28 (dd, 1H, J7,6 = 9.1 Hz, J7,7 = 12.0 Hz, H-7), 4.11 (dd, 1H,
J5,4 = 10.1 Hz, J5,6 = 1.3 Hz, H-5), 4.06 (dd, 1H, J7,6 = 3.1 Hz,
J7,7 = 12.0 Hz, H-7), 4.02 (dd, 1H, J6,5 = 4.2 Hz, J6,6’ = 11.4
Hz, H-6'), 3.97–3.93 (m, 2H, H-3, H-5'), 3.85 (dd, 1H, J6,5 = 4.1
Hz, J6,6’ = 11.4 Hz, H-6'), 3.74 (d, 1H, J1,1 = 10.8 Hz, H-1'),
3.53 (d, 1H, J1,1 = 10.8 Hz, H-1'), 3.48 (dd, 1H, J2,1 = 3.5 Hz,
J2,3 = 9.7 Hz, H-2), 3.33 (dd, 1H, J4,3 = 8.9 Hz, J4,5 = 10.1 Hz,
H-4), 2.08 (s, 3H, CH3), 1.95 (s, 3H, CH3), 1.06 (s, 9H, t-Bu);
13C NMR (CDCl3) δ 170.3 (C=O), 170.2 (C=O), 138.5, 138.3,
138.3, 138.2, 137.8, 137.7, 135.6, 135.5, 133.2, 132.7, 129.7,
8. Jarosz, S.; Listkowski, A. Can. J. Chem. 2006, 84, 492–496.
doi:10.1139/v06-035
9. Jarosz, S.; Listkowski, A.; Lewandowski, B.
Phosphorus, Sulfur Silicon Relat. Elem. 2009, 184, 1285–1295.
doi:10.1080/10426500902856370
10.Queneau, Y.; Jarosz, S.; Lewandowski, B.; Fitremann, J.
Adv. Carbohydr. Chem. Biochem. 2007, 61, 217–292.
doi:10.1016/S0065-2318(07)61005-1
11.Jarosz, S.; Lewandowski, B. Carbohydr. Res. 2008, 343, 965–969.
doi:10.1016/j.carres.2008.01.016
1253

Beilstein J. Org. Chem. 2014, 10, 1246–1254.
12.Potopnyk, M. A.; Lewandowski, B.; Jarosz, S. Tetrahedron: Asymmetry
2012, 23, 1474–1479. doi:10.1016/j.tetasy.2012.10.003
13.Lewandowski, B.; Jarosz, S. Chem. Commun. 2008, 6399–6401.
doi:10.1039/b816476b
License and Terms
This is an Open Access article under the terms of the
Creative Commons Attribution License
14.Potopnyk, M. A.; Jarosz, S. Eur. J. Org. Chem. 2013, 5117–5126.
doi:10.1002/ejoc.201300427
(http://creativecommons.org/licenses/by/2.0), which
permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
15.Lewandowski, B.; Jarosz, S. Org. Lett. 2010, 12, 2532–2535.
doi:10.1021/ol100749m
16.Jarosz, S. J. Carbohydr. Chem. 2001, 20, 93–107.
doi:10.1081/CAR-100103951
17.Jarosz, S.; Mach, M. J. Chem. Soc., Perkin Trans. 1 1998, 3943–3948.
doi:10.1039/a807190j
The license is subject to the Beilstein Journal of Organic
Chemistry terms and conditions:
18.Jarosz, S. Curr. Org. Chem. 2008, 12, 985–994.
doi:10.2174/138527208785161187
(http://www.beilstein-journals.org/bjoc)
19.Jarosz, S.; Mach, M.; Frelek, J. J. Carbohydr. Chem. 2000, 19,
693–715. doi:10.1080/07328300008544111
The definitive version of this article is the electronic one
which can be found at:
20.Mach, M.; Jarosz, S. J. Carbohydr. Chem. 2001, 20, 411–424.
doi:10.1081/CAR-100105713
doi:10.3762/bjoc.10.124
21.Synthesis of this aldehyde was already reported by us as intermediate
in the preparation of the uronate 8 (see ref. [8]).
22.Makosza, M.; Fedorynski, M. Adv. Catal. 1987, 35, 375–422.
doi:10.1016/S0360-0564(08)60097-8
23.Makosza, M. Pure Appl. Chem. 2000, 72, 1399–1403.
doi:10.1351/pac200072071399
24.Makosza, M.; Fedoryński, M. Catal. Rev.: Sci. Eng. 2003, 45, 321–367.
doi:10.1081/CR-120025537
25.Jarosz, S. Carbohydr. Res. 1988, 183, 201–207.
doi:10.1016/0008-6215(88)84074-6
26.Cha, J. K.; Christ, W. J.; Kishi, Y. Tetrahedron 1984, 40, 2247–2255.
doi:10.1016/0040-4020(84)80008-3
27.Frelek, J.; Pakulski, Z.; Zamojski, A. Tetrahedron: Asymmetry 1996, 7,
1363–1372. doi:10.1016/0957-4166(96)00153-X
28.Frelek, J.; Ikekawa, N.; Takatsuto, S.; Snatzke, G. Chirality 1997, 9,
578–582.
doi:10.1002/(SICI)1520-636X(1997)9:5/6<578::AID-CHIR27>3.0.CO;2-
K
29.Frelek, J.; Klimek, A.; Ruśkowska, P. Curr. Org. Chem. 2003, 7,
1081–1104. doi:10.2174/1385272033486576
30.Jawiczuk, M.; Górecki, M.; Suszczyńska, A.; Karchier, M.;
Jaźwiński, J.; Frelek, J. Inorg. Chem. 2013, 52, 8250–8263.
doi:10.1021/ic401170m
31.Biela, A.; Oulaïdi, F.; Gallienne, E.; Górecki, M.; Frelek, J.;
Martin, O. R. Tetrahedron 2013, 69, 3348–3354.
doi:10.1016/j.tet.2012.12.082
32.Schönemann, W.; Gallienne, E.; Ikeda-Obatake, K.; Asano, N.;
Nakagawa, S.; Kato, A.; Adachi, I.; Górecki, M.; Frelek, J.; Martin, O. R.
ChemMedChem 2013, 8, 1805–1817. doi:10.1002/cmdc.201300327
1254