Synthesis and Pd-catalyzed coupling of1-C-stannylated glycals

Article abstract of DOI:10.1080/07328303.2018.1508590

1-Tributylstannyl glycals were applied as versatile tools in the Pd(0)-mediated synthesis of glycal phthalonitrile conjugates. Likewise, selective homo-coupling of 1-tributylstannyl glycals furnishing C1-C1’ linked glycal dimers was investigated by using Pd(II)-species. For both Stille type couplings the rate-accelerating effect of copper(I) thiophene-2-carboxylate (CuTC) was exploited. The synthesis of stannylated glycal precursors was significantly improved by establishing a one-pot two-step procedure via glycosyl sulfoxides.

Full text of DOI:10.1080/07328303.2018.1508590

Journal of Carbohydrate Chemistry
ISSN: 0732-8303 (Print) 1532-2327 (Online) Journal homepage: http://www.tandfonline.com/loi/lcar20
Synthesis and Pd-catalyzed coupling of1-C-
stannylated glycals
Marius Bayer, Felix Bächle & Thomas Ziegler
To cite this article: Marius Bayer, Felix Bächle & Thomas Ziegler (2018): Synthesis and
Pd-catalyzed coupling of1-C-stannylated glycals, Journal of Carbohydrate Chemistry, DOI:
10.1080/07328303.2018.1508590
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JOURNAL OF CARBOHYDRATE CHEMISTRY
https://doi.org/10.1080/07328303.2018.1508590
Synthesis and Pd-catalyzed coupling of
1-C-stannylated glycals
€
Marius Bayer, Felix Bachle, and Thomas Ziegler
Institute of Organic Chemistry, University of Tuebingen, Tuebingen, Germany
ABSTRACT
ARTICLE HISTORY
Received 28 May 2018
Accepted 1 August 2018
1-Tributylstannyl glycals were applied as versatile tools in the
Pd(0)-mediated synthesis of glycal phthalonitrile conjugates.
Likewise, selective homo-coupling of 1-tributylstannyl glycals
furnishing C1-C1’ linked glycal dimers was investigated by
using Pd(II)-species. For both Stille type couplings the rate-
accelerating effect of copper(I) thiophene-2-carboxylate (CuTC)
was exploited. The synthesis of stannylated glycal precursors
was significantly improved by establishing a one-pot two-step
procedure via glycosyl sulfoxides.
KEYWORDS
Stannyl glycal;
Homocoupling; Stille cross-
coupling; Phthalonitriles;
Glycosyl sulfoxides;
Palladium; Copper
GRAPHICAL ABSTRACT
Introduction
C-Aryl glycosides are structures containing an aromatic aglycon attached C-
glycosidically to the anomeric center of a sugar moiety. In nature, aryl glyco-
sides are widespread compounds especially as second metabolites of bacteria.[1]
Due to the increased stability of the exocyclic C-glycosidic bond towards
acidic, basic or enzymatic hydrolysis compared to the more labile O-glycosidic
bond C-aryl-glycosides are well suited as potential pharmaceutical agents.[2–4]
In fact, C-aryl-glycosides reveal a broad spectrum of biological activities,[2] for
instance, antitumor,[5] antibiotic[6] and antidiabetic[7–10] properties. In order to
gain access to the aryl glycosides in an efficient way, metalated glycals com-
bined with transition metal-catalyzed coupling reactions appear to be well
suited for this purpose. One of the most common C-C coupling reactions in
this sense is the so called Stille-coupling discovered by J.K. Stille in 1978.[11]
CONTACT Thomas Ziegler
thomas.ziegler@uni-tuebingen.de
Institute of Organic Chemistry, University of
Tuebingen, Auf der Morgenstelle 18, 72076 Tuebingen, Germany.
Supplemental data for this article can be accessed on the publisher’s website.
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/lcar.
ß 2018 Taylor & Francis Group, LLC

2
M. BAYER ET AL.
Scheme 1. Accomplished total synthesis of anthraquinon based antibiotics via Stille-coupling.
It requires an electrophilic organohalide, a nucleophilic organostannane and a
suitable Pd catalyst. The first examples of coupling reactions of stannylated
glucals with arylhalides under Stille-conditions were described by Friesen and
Sturino,[12] and Dubois and Beau[13] in 1990. These glycal-aryl couplings toler-
ate a wide range of different electrophiles and even give high yields with
“deactivated” aromatic systems.[14] In contrast to other metalated glycals, like
for instance glycal boronates, stannylated glycals are easily prepared and can
be stored for a long period of time.[15,16] Stille-type reactions involving stanny-
lated glycals were also previously exploited in the total synthesis of anthraqui-
non based antibiotics like vineomycinone B2 methyl ester[17] and
derhodinosylurdamycin A[18] (Scheme 1).
It was previously reported that the unwanted formation of dimeric C1–C1’
homo-coupled byproducts is often encountered in Stille couplings.[14] Dubois
and Beau have shown that such dimeric byproducts were exclusively obtained
in Stille-type couplings when the electrophilic partner was omitted.[13]
In this work we envisaged this Pd(II)-mediated side reaction (dimeriza-
tion of the metallated species) as an opportunity to selectively prepare
dimeric precursors for prospective C-linked trehalose analogues, which are
in turn promising candidates for medical application based on glycosidase
inhibition.[19–22] Furthermore, we present a straightforward synthesis of
glycal phthalonitriles conjugates. The latter are useful precursors for the
synthesis of the corresponding phthalocyanines and aza-bodipys, which are
potential agents for Photodynamic Therapy.[23]
Results and discussion
Over the last three decades the preperation of several differently protected
stannylated glycals were reported in the literature. Due to their higher sta-
bility towards harsh conditions like treatment with tert-butyllithium for the
required metalation step, MOM,[24,25] TBDPS,[26] TIPS,[14,16,25–29] TBDMS
(except for protection of position 6),[12,14,26,29–31] di-tert-butylsilylene[25,27]
and isopropylidene[16,28] protecting groups were used. In the first part of
our study, we therefore focused on the synthesis of the versatile
TBDMS-isopropylidene-protected pyranoid and furanoid stannyl glucals 5a

JOURNAL OF CARBOHYDRATE CHEMISTRY
3
and 5b (Schemes 2 and 3). The combination of the orthogonal protecting
groups TBDMS and isopropylidene groups was used because it allowed for
the regiospecific cleavage of the protecting group at position 3 in com-
pounds 5a and 5b with TBAF. Such a selective deprotection was required
since we anticipated that in following reactions the enolic double bond of
the glycals should be more accessible to a wide range of modifications. On
the other hand, bulky reagents were not hampered by the unprotected OH
group at position 3 of the glycals. Furthermore, stereoselective substrate-
controlled reactions like dihydroxylation[32–34], epoxidation[35] or cyclopro-
panation[36] were thought to be more conceivable through possible coord-
ination at the allylic hydroxyl group. Stannyl glucal 5a was first mentioned
by Dubbaka et al. in 2004[37] but was not characterized sufficiently.
Dubbaka suggested a synthetic route starting with an acid catalysed isopro-
pylidene protection of D-glucal which, however, resulted in a maximum
yield of 50% only.[38] The well-known rapid conversion of glycals into 2,3-
unsatured pseudo-glycals under acidic conditions[39] makes this reaction
nonviable and unreliable. The notorious sensitivity of glycals towards acids
can be circumvented using Jarowicki’s protocol[15] for the preparation of
stannyl glycals via phenylsulfinyl glycals. The key step in Jarowicki’s syn-
thetic strategy is the late formation of the glycal moiety whereas the protec-
tion of the hydroxyl groups is performed before the elimination step to
afford the glycal.
Synthesis of tributylstannyl glucals 5a and 5b
We started the preparation of tributylstannyl glucal 5a from known 4,6-iso-
propylidene-protected thioglycoside 1[40] the hydroxyl groups of which were
protected with tert-butyldimethylsilyl triflate (TBDMS-OTf) to furnish 2 in
98% yield (Scheme 2). Treatment of 1 with cheaper but less reactive
TBDMS chloride under similar conditions resulted in incomplete conversion
of the starting material. Oxidation of thioglucoside 2 with m-chloroperben-
zoic acid (mCPBA) afforded the sulfoxide derivative (R)-3 in 98% yield. The
oxidation was highly sensitive regarding the reaction conditions and required
low temperatures in order to suppress over-oxidation of the sulfoxide to the
corresponding sulfone derivate. Furthermore, the rate of addition proved to
be a dominating factor and by keeping it slow, (5.90 g mCPBA in 80mL
DCM added over a period of 4 h) the yield could be increased significantly.
Solely the (R)-epimer (R)-3 was obtained under these conditions. This was
proven as follows. In situ generation of LDA from n-BuLi and DIPA
followed by slow addition of a solution of (R)-3 in THF gave hex-1-enitol
(R)-4 in 96% yield. Alternatively, (R)-4 could also be prepared in a similar
fashion from known (R)-6[41] proving unambiguously the (R)-configuration

4
M. BAYER ET AL.
Scheme 2. Synthesis of 3-TBDMS-4,6-isoprpylidene-protected stannyl glucal 5a.
of the sulfoxide moiety in (R)-4 via comparison of the analytical data. It
ꢀ
should be noted that Gomez et al. prepared compound (R)-6 from the cor-
responding a-thiophenyl glycoside since they observed that the b-thiophenyl
counterpart, similar to glucoside 2, resulted in a mixture of diastereomers
upon oxidation of the thio group. Obviously, the presence of bulky TBDMS
protecting groups in 2 enabled a stereoselective formation of sulfoxide (R)-3
in our case. We deduced the (R)-configuration of the sulfoxide group in glu-
coside (R)-3 from their similarities of the analytical data in both compounds
(R)-3 and (R)-4, respectively.
Substitution of the sulfoxide group in sulfinyl-hex-1-enitols similar to
compound (R)-4 by a tributylstannyl group was previously done in two
steps by first converting enitols into an anomeric lithiated glycal through
treatment with phenyllithium followed by treatment with tributyltin chlor-
ide.[15] However, a major drawback of this strategy was the fact that small
amounts of glucal formed as a side product during the lithiation step.
These glucal side products cannot be reconverted into the corresponding
lithium species by phenyllithium or butyllithium. Therefore, we chose tert-
butyllithium for this step since all glucal which forms in the course of the
process was reversed to the lithiated glycal species. This way we were able
to convert (R)-4 into 5a in 79% yield. Furthermore, we could develop a
one-pot synthesis of stannyl glycal 5a directly from sulfoxide (R)-3 in 76%
yield by successively adding tert-butyllithium and tributylstannyl chloride
to a solution of compound (R)-3 (Scheme 2).

JOURNAL OF CARBOHYDRATE CHEMISTRY
5
Scheme 3. Synthesis of 3-TBDMS-5,6-isoprpylidene-protected stannylglucal 5b.
The analogous glucofuranose stannyl glucal 5b was previously prepared
by Gunn et al. from phenyl 1-thio-D-mannofuranosid 7 (Scheme 3) via the
corresponding sulfone.[42] Since furanoside 5b turned out to be instable in
contrast to its pyranose counterpart 5a, the isolation and purification of 5b
was quite difficult. Therefore we decided to examine the applicability of
Jarowicki’s protocol[15] for furanose species as well. Our synthesis started
with the oxidation of known phenyl 2,3:5,6-di-O-isopropylidene-1-thio-
b-D-mannopyranoside (7) as described below (Scheme 3). Surprizingly, an
epimeric mixture of sulfoxides (R)-8 and (S)-8 (1:2) was obtained in 91%
yield whereas in the case of (R)-3 the oxidation step proceeded diastereose-
lectively. The absolute configuration of the major epimer (S)-8 was deter-
mined by X-ray crystallography. Crystals of (S)-8 suitable for X-ray
crystallography were obtained by letting n-pentane slowly diffuse into a
saturated solution of (S)-8 in toluene (for detail see the supplementary
material). Sulfoxide (S)-8 crystallised in a triclinic space group P1 repre-
senting by one molecule in the asymmetric unit (Figure 1) and was spec-
troscopically identical to the previously obtained major epimer.[41]
Treatment of (S)-8 with LDA in THF proceeded smoothly and afforded
the furanose glycal (S)-9 in 89% yield. Next, (S)-9 was silylated with
TBDMS-OTf to give (S)-10 in 83% yield. Care had to be used during
workup of the crude reaction mixture because furanose glycals are
extremely sensitive toward acidic conditions. When we attempted to con-
vert (S)-10 into the corresponding tributylstannyl furanose glucal 5b under
the same conditions as applied for the stannylated pyranose glycal 5a (tert-
butyllithium, Bu3SnCl in THF) only extensive decomposition of the starting
material occurred. Replacing tert-butyllithium with phenyllithium as recom-
mended by Jarowicki et al.,[15] also resulted in the decomposition of (S)-10.
However, cooling down a solution of (S)-10 and Bu3SnCl in THF to

6
M. BAYER ET AL.
Figure 1. Molecular structure of (S)-8. Ellipsoids are drawn at a 50% probability level.
Yellow ¼ sulfur, red ¼ oxygen, grey ¼ carbon, white ¼ hydrogen. Disordered methyl-groups are
hidden for simplification.
Scheme 4. Synthesis of stannylated glycals 5c–e.
–78 ꢀC and adding dropwise a 1.9 M solution of phenyllithium in di-n-
butylether was successful. After the rapid sulfoxide-lithium exchange, the
C-1 lithiated intermediate was quenched directly by the presence of
Bu3SnCl, before decomposition could take place. Thus, stannylated glucal
5b was isolated in 81% yield. Additional compounds 5c-e were prepared
according to literature procedures (Scheme 4).[15,26]
Pd(II) catalysed homocoupling of stannyl glycals
For Stille-coupling reactions of stannylated glycals, the unwanted formation
of dimeric byproducts formed from the tin intermediates is an often

JOURNAL OF CARBOHYDRATE CHEMISTRY
7
Table 1. Homocoupling-reactions of stannylated glycals 5a-e.
Entry
1
Sn-glycal 5
Conditions
Dimer 11
Yield [%]
5a
Method A
83
PdCl2(CH3CN)2, CuTC, DMF, rt, 2 h
Method B
2
5a
95
PdCl2(CH3CN)2, CuTC, toluene, reflux, 3 h
3
4
5b
5b
Method A
PdCl2(CH3CN)2, CuTC, DMF, rt, 5 min
Method B
52
–
PdCl2(CH3CN)2, CuTC, toluene, reflux, 2 h
5
6
5c
5c
Method A
90
85
PdCl2(CH3CN)2, CuTC, DMF, rt, 5 min
Method C
PdCl2(CH3CN)2, DMF,60 ꢀC, 3 h
7
5d
Method A
84
PdCl2(CH3CN)2, CuTC, DMF, rt, 2 h
8
9
5e
5e
Method B
PdCl2(CH3CN)2, CuTC, toluene, reflux, 3 h
Method D
16
29
Cu(OTf)2, THF, rt, 2h
observed side reaction.[12–14,27] Stille-couplings are catalyzed by Pd(0) com-
plexes but Pd(II) species occur as well during the reaction and are respon-
sible for the dimerization of the stannylated species.[14] Indeed, Dubois and
Beau could show that the use of PdCl2(CH3CN)2 in DMF at elevated tem-
perature resulted in almost exclusive formation of dimers.[13] Thus, the
authors were able to convert tributylstannyl 3,4,6-tri-O-benzyl-D-glucal (5c)
into the corresponding dimer 11c in 85% yield (see Table 1, entry 1). Since
it is well known that addition of Cu(I) can accelerate Stille-coupling signifi-
cantly through a so called “copper effect”[43–45] we also performed the
dimerization reaction of stannylated glycals 5a-e in the presence of either
copper(I) thiophene-2-carboxylate (CuTC)[46] or copper(II) triflate
(Cu(OTf)2)[47] (see Table 1). In the case of glucal 5c we could thus shorten
the reaction time for its dimerization from 3 hours to 10 minutes and the
yield of 11c from 85% to 90% by adding 1 equivalent of CuTC (Table 1,
entries 1,2). Likewise, the stannylated pyranoses 5a and 5d[15] afforded the
corresponding dimeric glycals 11a and 11d in high yields (Table 1, entries
3–5). Using toluene instead of DMF as the solvent did not have a signifi-
cant effect on the dimerization in case of stannylated pyranose glycals. In
contrast, stannylated furanose glycal 5b only afforded the corresponding
dimer 11b (52%) in DMF as solvent. Decomposition of the starting mater-
ial occurred when toluene was used (Table 1, entries 6,7). Similarly, the

8
M. BAYER ET AL.
fully tris-isopropylsilane (TIPS) protected stannylated pyranose glucal 5e[26]
gave only a small amount (16%) of dimer 11e (Table 1, entry 8). It is
known that Stille-coupling can also be achieved with a Cu(II) catalyst alone
and without any Pd catalyst added.[47] However, performing the dimeriza-
tion of 5e with 2.2 equivalents Cu(OTf)2 in THF gave only a slightly higher
yield of 11e (29%) (Table 1, entry 9). Most likely, glucal 5e is sterically too
crowded due to the TIPS-protection for the dimerization to proceed
5
smoothly. Futhermore, 5e adopts a H4 half chair conformation due to the
steric demand of the protecting groups whereas glycals 5a,c,d rather exist
4
in a H5 half chair conformation.[16] This fact might also add to the rather
sloppy dimerization of 5e.
Pd(0) catalysed C-aryl glycosylation
In the case of transition metal mediated C-aryl glycosylation, like Stille-cou-
plings, homo-couplings of the stannyl compound (dimerization) is a
notorious problem. As outlined above, we took advantage of this usually
unwanted side reaction and used it in order to intentionally prepare
dimeric glycals. Nevertheless, our interest was also focussed on preparing
C-aryl glycosides from stannylated glycals. As part of a research project
dealing with the synthesis of glycosylated phthalocyanins for photodynamic
therapy[23,48–55] we became interested in C-aryl glycosides since C-glyco-
sides resist enzymatic cleavage in the cell.[3] Thus, we also performed some
Stille-couplings of stannylated glycals with 4,5-diiodophthalonitrile. The lat-
ter phthalonitrile was thought to be suitable for the anticipated preparation
of C-glycosylated phthalocyanins. C-glycosylated phthalonitriles are also
preferable candidates because they survive the harsh basic conditions
required for making phthalocyanins.[56] Therefore, we chose stannylated
glucals 5a and 5e for Stille-couplings with 4,5-diiodophthalonitrile. Both
4
5
glycals represent substrates with different conformation (i.e. H5 and H4
conformations, respectively). Reacting 5a and 5e with 4,5-diiodophthaloni-
trile, Pd(PPh3)4 and CuTC in toluene at 100 ꢀC gave glycosides 12a and
12e in 85% and 78% yield, respectively (Scheme 5). The almost unavoidable
formation of small amounts of dimeric byproducts could be reduced to a
minimum by carefully adjusting the conditions of the coupling reaction as
recommended in the literature for similar examples.[14] Optimal conditions
were found when using Pd(PPh3)4 as the catalyst and adding 5a and 5e
slowly with stirring to the heated solution of 4,5-diiodophthalonitrile and
the catalyst in toluene. Removal of dimeric byproducts was easily achieved
by chromatography. The good yields in both cases were somewhat surpris-
ing with regards to the fact that ortho-functionalized phthalonitriles are
considerably sterically hindered. Nevertheless, the two examples

JOURNAL OF CARBOHYDRATE CHEMISTRY
9
Scheme 5. Synthesis of C-aryl glycosides 12a and 12e via Pd(0) catalysis.
demonstrated that Stille-coupling reactions are very well suited for prepar-
ing C-glycosylated phthalonitriles as potential precursors for related C-gly-
cosylated phthalocyanins.
Conclusion
We successfully developed synthetic methods to gain access to anomerically
linked glycals, by advancing Pd(II)-catalyzed homocoupling reactions of the
corresponding 1-tributylstannyl glycals. In addition, the 1-tributylstannyl
glycals were applied as precursors in cross-coupling reactions with 4,5-diio-
dophthalonitriles, using Pd(0)-species. In both reactions, a rate-accelerating
effect was achieved by addition of copper(I) thiophene-2-carboxylate.
Preparative advices were revealed in order to improve the synthesis of 3-
TBDMS-4,6-isopropylidene-protected tributylstannyl glucal, in particular.
The oxidation of the thioglycoside to the corresponding sulfoxide was regu-
lated by a very low rate of addition of mCPBA at –78 ꢀC and resulted in
the formation of the (R)-epimer exclusively in high yield. Furthermore, a
one-pot two-step procedure, implying the elimination step from the glycal
and the attachment step for the introduction of the tributylstannyl group,
was established.
Experimental
General methods
All reactions were performed under an atmosphere of nitrogen using sol-
vents dried by standard procedures. Reaction progress was monitored by
TLC on Polygram SIL G/UV254 silicagel plates from Macherey & Nagel.
Detection of spots was effected by charring with sulphuric acid (5% in

10
M. BAYER ET AL.
EtOH), staining by spraying the plates with an alkaline aqueous solution of
potassium permanganate or by inspection of the TLC plates under UV light
(254 nm). Preparative flash chromatography was performed on silica gel
(0.032–0.063 mm) from Macherey-Nagel, using plastic cartridges from
€
Gotec. The flowrate was regulated by a Sykam S1122 solvent delivery sys-
tem. NMR spectra were recorded with a Bruker Avance 400 spectrometer
and calibrated for the solvent signal (1H: CDCl3: d ¼ 7.26 ppm; C6D6:
d ¼ 7.16 ppm;13C: CDCl3: d ¼77.16 ppm; C6D6: d ¼ 128.36 ppm). All NMR-
assignments were proven by 2D-experiments to be correct. ESI-TOF-HRM
spectrometry was performed on a Bruker MAXIS 4G spectrometer.
Elemental analyses were obtained from a HEKAtech Euro EA 3000 appar-
atus. Optical rotations were determined with a Perkin-Elmer Polarimeter
341 in a 10 cm cuvette at 20 ꢀC with a wavelength of 589 nm (Na-lamp).
Melting points were measured with a Bu€chi Melting Point M-560 appar-
atus. In all oxidation reactions, the purity grade of the deployed mCPBA
is <77%.
Phenyl-2,3-di-O-(tert-butyldimethylsilyl)-4,6-O-isopropylidene-1-thio-b-D-gluco-
pyranoside (2)
To a solution of 1 (5.90 g, 18.9 mmol) and 2,6-lutidine (6.60 mL,
56.6 mmol) in dry CH2Cl2 (75 mL) was added TBDMSOTf (13.0 mL,
56.6 mmol) dropwise at 0 ꢀC. The reaction mixture was stirred at rt for
22 h. After complete consumption of the starting material the reaction was
quenched by addition of water (60 mL) and extracted with CH2Cl2 (3 ꢁ
20 mL). The combined organic layers were washed with brine (30 mL),
dried with Na2SO4 and evaporated. Purification of the crude product by
column chromatography (petroleum ether/ethyl acetate 20:1) afforded 2
(10.2 g, 18.8 mmol, 99%) as a colourless, highly viscous oil. Rf ¼ 0.75 (pet-
20
1
roleum ether/ethyl acetate 5:1). ½aꢂD ¼ –64.2 (c ¼ 1.0, CHCl3). H-NMR
(400 MHz, in CDCl3): d (ppm) ¼ 7.44 ꢃ 7.46 (m, 2H, Ph), 7.24 ꢃ 7.29 (m,
3H, Ph), 4.71 ꢃ 4.79 (m, 1H, H-1), 3.89 (dd, J6a,6b ¼ 10.8 Hz, J6a,5 ¼ 5.4 Hz,
1H, H-6a), 3.74 (dd, J ¼ 10.6 Hz, 1H, H-6b), 3.63 ꢃ 3.69 (m, 3H, H-2, H-3,
H-4), 3.33 ꢃ 3.42 (m, 1H, H-5), 1.47, 1.40 (2s, 6H, C(CH3)2), 0.94, 0.92 (2s,
18H, SiC(CH3)3), 0.23, 0.14, 0.12, 0.10 (4s, 12H, SiCH3). 13C-NMR
(101 MHz, in CDCl3): d (ppm) ¼ 135.4, 131.1, 129.0, 127.3 (Ph), 99.5
(C(CH3)2), 90.2 (C-1), 77.7, 75.8, 73.8 (C-2, C-3, C-4), 70.4 (C-5), 62.5 (C-
6), 29.1 (C(CH3)2), 26.6, 26.5 (SiC(CH3)3), 18.9 (C(CH3)2), 18.7, 18.4
(SiC(CH3)3), ꢃ2.1, ꢃ2.4, ꢃ2.9, ꢃ3.0 (SiCH3). HRESIMS m/z 563.26532
(calcd for C27H48O5SSi2Na, 563.26556); anal. C 59.97, H 9.18, S 5.47, calcd
for C27H48O5SSi2, C 59.95, H 8.94, S 5.93.

JOURNAL OF CARBOHYDRATE CHEMISTRY
11
2,3-Di-O-(tert-butyldimethylsilyl)-4,6-O-isopropylidene-[(SR)-phenylsulfinyl]-b-D-
glucopyranoside ((R)-3)
A suspension of 2 (10.2 g, 18.8 mmol) and NaHCO3 (19.0 g, 225 mmol) in
dry CH2Cl2 (250 mL) was stirred at –78 ꢀC. Subsequently a solution of
mCPBA (5.90 g, 26.4 mmol) in CH2Cl2 (80 mL) was added slowly by using
a programmable syringe pump over 4 h. After the addition is complete, the
reaction mixture was stirred at the same temperature for 20 h until TLC
showed complete conversion of the starting material. Saturated aq.
Na2S2O3-solution (100 mL) was added dropwise and the suspension was
warmed to ambient temperature. For dissolving the excess of NaHCO3,
water was added and the aqueous phase was extracted with CH2Cl2 (3 ꢁ
50 mL). The combined organic phases were dried with Na2SO4 and the
solvent was removed. Purification by column chromatography (ethyl acet-
ate/petroleum ether 1:3) gave (R)-3 (10.3 g, 18.5 mmol, 98%) as an amorph-
20
ous, white solid. Rf ¼ 0.19 (petroleum ether/ethyl acetate, 5:1). ½aꢂD ¼
1
–120.8 (c ¼ 1.0, CHCl3). M.p. 137 ꢀC (n-hexane). H-NMR (400 MHz, in
CDCl3): d (ppm) ¼ 7.63–7.64 (m, 2H, Ph), 7.48–7.50 (m, 3H, Ph),
3.93–3.94 (m, 2H, H-1, H-2), 3.76 (dd, J ¼ 10.5 Hz, 1H, H-6a), 3.65–3.73
(m, 3H, H-3, H-4, H-6b), 3.28–3.37 (m, 1H, H-5), 1.45, 1.36 (2s, 6H,
C(CH3)2), 0.93, 0.91 (2s, 18H, SiC(CH3)3), 0.17, 0.12, 0.11, 0.08 (4s, 12H,
SiCH3). 13C-NMR (101 MHz, in CDCl3): d (ppm) ¼ 141.2, 131.3, 129.0,
125.4 (Ph), 99.6 (C(CH3)2), 97.1 (C-1), 77.6 (C-4), 73.7 (C-3), 72.0 (C-2),
70.1 (C-5), 62.0 (C-6), 29.0 (C(CH3)2), 26.5, 26.2 (SiC(CH3)3), 19.0
(C(CH3)2), 18.6, 18.3 (SiC(CH3)3), –2.5, –2.8, –3.1, –4.2 (SiCH3). HRESIMS
m/z 579.26014 (calcd for C27H48O6SSi2Na, 579.26023); anal. C 58.09, H
8.78, S 5.56, calcd for C27H48O6SSi2, C 58.23, H 8.69, S 5.76.
1,5-Anhydro-2-deoxy-3-O-tert-butyldimethylsilyl-4,6-O-isopropylidene-1-[(SR)-
phenylsulfinyl]-D-arabino-hex-1-enitol ((R)-4)
From sulfoxid (R)-3: To a solution of DIPA (3.80 mL, 26.9 mmol) in dry
THF (20 mL) at ꢃ30 ꢀC was added dropwise n-butyllithium (2.5 M in n-
hexane, 7.10 mL, 17.8 mmol). After 15 min the mixture was cooled to
ꢃ78 ꢀC and a solution of (R)-3 (3.95 g, 7.10 mmol) in dry THF (30 mL)
was added slowly over a period of 30 min. The reaction mixture was stirred
for 2 h until TLC showed complete consumption of the starting material.
Subsequently a sat. aq. NaHCO3-solution (30 mL) was added and the mix-
ture allowed to warm to ambient temperature. The product was extracted
with CH2Cl2 (3 ꢁ 20 mL), the combined organic layers were dried with
Na2SO4 and the solvent was evaporated. The residue was purified by col-
umn chromatography (petroleum ether/ethyl acetate 6:1) to give (R)-4
(2.90 g, 6.85 mmol, 96%) as a colourless, viscous oil.

12
M. BAYER ET AL.
Additionally, the configuration at the sulfur (R,S) of (R)-4 was determined
by a comparison with the R-Isomer 6, which was prepared in accordance to
literature.[41]
From glucal 6: A solution of 6 (100 mg, 0.322 mmol) and 2,6-lutidine
(75 mL, 0.644 mmol) in dry CH2Cl2 (3 mL) was stirred at 0 ꢀC and
TBDMSOTf (111 mL, 0.483 mmol) was added dropwise. After 3 h of stirring
at ambient temperature the reaction was quenched with water (10 mL) and
the aqueous phase was extracted with CH2Cl2 (3 ꢁ 10 mL). The combined
organic phases were washed with brine (10 mL), dried with Na2SO4 and
the solvent was evaporated. Purification of the crude residue by column
chromatography (petroleum ether/ethyl acetate 6:1) yielded (R)-4 (130 mg,
0.306 mmol, 96%) as a colourless, viscous oil. Rf ¼ 0.45 (petroleum ether/
20
1
ethyl acetate 3:1). ½aꢂD ¼ –127.1 (c ¼ 1.0, CHCl3). H-NMR (400 MHz, in
CDCl3): d (ppm) ¼ 7.67–7.69 (m, 2H, Ph), 7.48–7.53 (m, 3H, Ph), 5.57 (d,
J2,3 ¼ 2.3 Hz, 1H, H-2), 4.42 (dd, J3,4 ¼ 7.2 Hz, J3,2 ¼ 2.3 Hz, 1H, H-3),
3.68–3.88 (m, 4H, H-4, H-5, H-6a, H-6b), 1.42, 1.37 (2s, 6H, C(CH3)2),
0.89 (s, 9H, SiC(CH3)3), 0.10, 0.08 (2s, 6H, SiCH3). 13C-NMR (101 MHz, in
CDCl3): d (ppm) ¼ 155.6 (C-1), 141.6, 131.7, 129.3, 125.5 (Ph), 107.5 (C-2),
99.9 (C(CH3)2), 73.0 (C-4), 72.8 (C-5), 68.3 (C-3), 61.4 (C-6), 28.9
(C(CH3)2), 25.9 (SiC(CH3)3), 19.1 (C(CH3)2), 18.4 (SiC(CH3)3), –4.4, –4.7
(SiCH3). HRESIMS m/z 447.16373 (calcd for C21H32O5SSiNa, 447.16319).
1,5-Anhydro-2-deoxy-3-O-tert-butyldimethylsilyl-4,6-O-isopropylidene-1-C-tribu-
tylstannyl-D-arabino-hex-1-enitol (5a)
From glucal (R)-4: A stirred solution of (R)-4 (239 mg, 0.563 mmol) in dry
THF (2 mL) was cooled to ꢃ78 ꢀC and tert-butyllithium (1.9 M in n-pent-
ane, 1.18 mL, 2.25 mmol) was added dropwise. The mixture allowed to
warm to 0 ꢀC for 1 h and cooled again to 278 ꢀC. Bu3SnCl (458 mL,
1.69 mmol) was added during a period of 5 min to the dark-yellow solution.
After 2 h the cooling bath was removed and the reaction was quenched by
addition of sat. aq. NH4Cl-solution (4 mL). The aqueous layer was extracted
with CH2Cl2 (3 ꢁ 2 mL), the combined organic layers were dried with
Na2SO4 and the solvent was removed. Purification of the residue by col-
umn chromatography (petroleum ether/methylene chloride 2:1 containing
0.5% triethylamine) afforded 5a (264 mg, 0.447 mmol, 79%) as a colour-
less liquid.
Two-step procedure, starting with sulfoxide (R)-3:
2,3-di-O-tert-butyl-dimethylsilyl-4,6-di-O-isopropyliden-1-[(SR)-phenylsul-
finyl]-ß-D-glucopyranosid (R)-3 (5.00 g, 8.98 mmol) was dissolved dry
THF (40mL). The reaction mixture was cooled to ꢃ78 ꢀC and a solution of

JOURNAL OF CARBOHYDRATE CHEMISTRY
13
tert-butyllithium (1.9 M in n-hexane, 23.6 mL, 44.9 mmol) was slowly added
over a period of 2 h. After the addition was complete, the yellow solution
was stirred at room temperature for 2 h. Afterwards, the reaction mixture
was cooled to 278 ꢀC again and tributyltin chloride (7.30 mL, 26.9 mmol)
was added over a period of 45 minutes. After the addition was complete,
the reaction mixture was stirred at this temperature for further 30 min,
until TLC (tlc: petroleum ether/methylene chloride 2:1) showed the com-
plete consumption of the starting material. Then, the reaction mixture was
warmed up to room temperature, diluted with a saturated NH4Cl-solution
(40mL) and extracted with CH2Cl2 (3 ꢁ 50mL). The combined organic
phases were subsequently dried with Na2SO4, filtered and concentrated
under reduced pressure. The crude product was purified by column chro-
matography on silica gel (petroleum ether/diethylether 50:1) resulting in
1,5-anhydro-2-desoxy-3-tert-butyl-dimethylsilyl-4,6-di-O-isopropyliden-1-C-
tributylstannyl-D-arabino-hex-1-enitol (5a) (4.00 g, 6.79 mmol, 76%) as a
20
colourless oil. Rf ¼ 0.75 (petroleum ether/ethyl acetate 10:1). ½aꢂD ¼ –16.9
1
(c ¼ 1.0, CHCl3). H-NMR (400 MHz, in CDCl3): d (ppm) ¼ 4.60 (ddd,
J ¼ 13.3 Hz, J ¼ 13.3 Hz, J2,3 ¼ 1.8 Hz, 1H, H-2), 4.28 (dd, J3,4 ¼ 7.5 Hz,
J3,2 ¼ 1.8 Hz, 1H, H-3), 3.88 (dd, J6a,6b ¼ 10.9 Hz, J6a,5 ¼ 5.8 Hz, 1H, H-6a),
3.71–3.79 (m, 2H, H-4, H-6b), 5.57–3.64 (m, 1H, H-5), 1.28–1.52 (m, 18H,
C(CH3)2, SnBu), 0.87–0.95 (m, 24H, C(CH3)3, SnBu), 0.09, 0.07 (2s, 6H,
SiCH3). 13C-NMR (101 MHz, in CDCl3): d (ppm) ¼ 163.1 (C-1), 116.3 (C-
2), 99.4 (C(CH3)2), 73.5 (C-4), 70.1 (C-5), 68.9 (C-3), 62.3 (C-6), 29.2
(C(CH3)2), 29.0, 27.3 (SnBu), 26.0 (SiC(CH3)3), 19.2 (C(CH3)2), 18.5
(SiC(CH3)3), 13.8, 9.8 (SnBu), –4.2, –4.6 (SiCH3). HRESIMS m/z 613.27117
(calcd for C27H54O4SiSnNa, 613.27055); anal. C 55.23, H 9.36, calcd for
C27H54O4SiSn, C 55.01, H 9.23.
2,3:5,6-Di-O-isopropylidene-1-[(SS)-phenylsulfinyl)]-b-D-mannofuranoside ((S)-8)
and
2,3:5,6-Di-O-isopropylidene-1-[(SR)-phenylsulfinyl)]-b-D-mannofuranoside
((R)-8)
To a suspension of 7 (11.6 g, 32.9 mmol) and NaHCO3 (33.2 g, 92.2 mmol)
in dry CH2Cl2 (200 mL) was added a solution of mCPBA (8.85 g,
39.5 mmol) in dry CH2Cl2 (150 mL) at –78 ꢀC over a period of 2.5 h (using
a programmable syringe pump). The reaction mixture was stirred at the
same temperature for 18 h until TLC showed complete consumption of 7.
Saturated Na2S2O3-solution (150 mL) was added dropwise and the suspen-
sion was warmed to ambient temperature. The excess of NaHCO3 was dis-
solved by addition of water, the aqueous layer was extracted with CH2Cl2
(3 ꢁ 200 mL) and the combined organic layers were dried with Na2SO4.
After removing the solvent, the crude product was purified by column
chromatography (petroleum ether/ethyl acetate 1:1) to furnish a 2:1 mixture

14
M. BAYER ET AL.
of (S)-8 and (R)-8 (11.1 g, 30.1 mmol, 91%) as white solids. Diffusion of n-
pentane in a saturated solution of (S)-8 in toluene provides crystals suitable
for X-ray structural analysis.
(S)-8 (major-epimer): Rf ¼ 0.17 (petroleum ether/ethyl acetate 1:1).
20
1
½aꢂD ¼ þ75.7 (c ¼ 1.0, CHCl3). M.p. 92 ꢀC (n-pentane/ethyl acetate). H-
NMR (400 MHz, CDCl3): d (ppm) ¼ 7.70–7.77 (m, 2H, Ph), 7.46–7.53 (m,
3H, Ph), 5.17 (dd, J2,3 ¼ 6.0 Hz, J2,1 ¼ 4.0 Hz, 1H, H-2), 4.87 (dd,
J3,2 ¼ 6.1 Hz, J3,4 ¼ 3.7 Hz, 1H, H-3), 4.41 (ddd, J5,4 ¼ 6.4 Hz, J5,6a ¼ 6.4 Hz,
J5,6b ¼ 4.6 Hz, 1H, H-5), 4.21 (d, J1,2 ¼ 4.0 Hz, 1H, H-1), 4.03 (dd,
J6a,6b ¼ 8.8 Hz, J6a,5 ¼ 6.4 Hz, 1H, H-6a), 3.90 (dd, J6b,6a ¼ 8.9 Hz,
J6b,5 ¼ 4.6 Hz, 1H, H-6b), 3.66 (dd, J4,5 ¼ 6.5 Hz, J4,3 ¼ 3.7 Hz, 1H, H-4),
1.65, 1.42 (2s, 6H, C(CH3)2), 1.34 (s, 6H, C(CH3)2). 13C-NMR (101 MHz,
CDCl3): d (ppm) ¼ 142.1, 131.4, 128.8, 125.3 (Ph), 114.6, 109.2 (C(CH3)2),
97.7 (C-1), 82.9 (C-4), 80.6 (C-2), 80.3 (C-3), 72.9 (C-5), 66.1 (C-6), 26.7,
25.6, 25.2, 24.4 (C(CH3)2).
1
(R)-8 (minor-epimer): Rf ¼ 0.26 (petroleum ether/ethyl acetate 1:1). H-
NMR (400 MHz, CDCl3): d (ppm) ¼ 7.83–7.91 (m, 2H, Ph), 7.48–7.57 (m,
3H, Ph), 4.76 (dd, J3,2 ¼ 6.0 Hz, J3,4 ¼ 3.7 Hz, 1H, H-3), 4.53 (ddd,
J5,4 ¼ 8.5 Hz, J ¼ 5.8 Hz, J ¼ 4.0 Hz, 1H, H-5), 4.45 (dd, J2,3 ¼ 6.0 Hz,
J2,1 ¼ 3.9 Hz, 1H, H-2), 4.32 (d, J1,2 ¼ 3.9 Hz, 1H, H-1), 4.12–4.23 (m, 2H,
H-6a, H-6b), 3.64 (dd, J4,5 ¼ 8.4 Hz, J4,3 ¼ 3.5 Hz, 1H, H-4), 1.62, 1.41, 1.37,
1.30 (4s, 12H, C(CH3)2). 13C-NMR (101 MHz, CDCl3): d (ppm) ¼ 140.9,
131.7, 129.1, 125.7 (Ph), 114.3, 109.4 (C(CH3)2), 100.9 (C-1), 83.3 (C-4),
80.7 (C-3), 80.5 (C-2), 72.7 (C-5), 67.1 (C-6), 27.0, 25.8, 25.1,
24.8 (C(CH3)2).
1,4-Anhydro-2-deoxy-5,6-O-isopropylidene-1-[(SS)-phenylsulfinyl)]-D-arabino-hex-
1-enitol ((S)-9)
A solution of (S)-8 (15.6 g, 42.2 mmol) in dry THF (200 mL) was stirred at
–78 ꢀC. Subsequently LDA (2.0 M in THF, 52.8 mL, 105.5 mmol) was added
dropwise over a period of 2 h. After stirring at the same temperature for
2 h, saturated NaHCO3-solution (150 mL) was added and the mixture was
warmed to ambient temperature. The aqueous phase was extracted with
CH2Cl2 (3 ꢁ 80 mL), the combined organic phases were dried with Na2SO4
and the solvent was evaporated. The residue was purified by column chro-
matography (petroleum ether/ethyl acetate 1:3 containing 0.5% triethyl-
amine) and (S)-9 (10.8 g, 34.8 mmol, 83%) was isolated as a yellow,
20
amorphous solid. Rf ¼ 0.30 (petroleum ether/ethyl acetate 1:3). ½aꢂD ¼ –17.8
1
(c ¼ 1.0, C6H6). H-NMR (400 MHz, in C6D6): d (ppm) ¼ 7.60–7.71 (m,
2H, Ph), 6.93–7.02 (m, 3H, Ph), 5.81 (d, J2,3 ¼ 2.8 Hz, 1H, H-2), 4.44 (dd,
J3,4 ¼ 6.6 Hz, J3,2 ¼ 2.7 Hz, 1H, H-3), 4.35 (dd, J5,4 ¼ 6.4 Hz, J5,6a ¼ 6.4 Hz,
J5,6b ¼ 5.9 Hz, 1H, H-5), 4.00 (dd, J4,3 ¼ 6.6 Hz, J4,5 ¼ 6.6 Hz 1H, H-4), 3.91

JOURNAL OF CARBOHYDRATE CHEMISTRY
15
(dd, J6a,6b ¼ 8.7 Hz, J6a,5 ¼ 6.5 Hz, 1H, H-6a), 3.84 (dd, J6b,6a ¼ 8.6 Hz,
J6b,5 ¼ 5.6 Hz, 1H, H-6b), 2.36 (br. s., 1H, OH), 1.29, 1.20 (2s, 6H,
C(CH3)2). 13C-NMR (101 MHz, in C6D6): d (ppm) ¼ 164.3 (C-1), 142.6,
131.6, 129.6, 125.3 (Ph), 109.4 (C(CH3)2), 107.2 (C-2), 89.0 (C-4), 73.3 (C-
5), 72.6 (C-3), 66.7 (C-6), 27.1, 25.7 (C(CH3)2). HRESIMS m/z 333.07679
(calcd for C15H18O5SNa, 333.07672).
1,4-Anhydro-3-O-(tert-butyldimethylsilyl)-2-deoxy-5,6-O-isopropylidene-1-[(SS)-
phenylsulfinyl)]-D-arabino-hex-1-enitol ((S)-10)
To a solution of (S)-9 (81 mg, 0.261 mmol) and 2,6-lutidine (61 lL,
0.522 mmol) in dry CH2Cl2 (3 mL) was added slowly TBDMSOTf (90 lL,
0.391 mmol) at 0 ꢀC. The reaction mixture was stirred at rt for 2 h until
TLC showed complete conversion of the starting material. Subsequently
water (10 mL) was added and the aqueous layer was extracted with CH2Cl2
(3 ꢁ 5 mL). The combined organic layers were washed with brine (10 mL),
dried with Na2SO4 and the solvent was removed. Purification of the crude
product by column chromatography (petroleum ether/ethyl acetate 10:1
containing 0.5% triethylamine) afforded (S)-10 (99 mg, 0.233 mmol, 89%)
as a colourless, viscous oil. Rf ¼ 0.78 (petroleum ether/ethyl acetate 1:1).
20
½aꢂD ¼ þ32.4 (c ¼ 1.0, CHCl3). 1H-NMR (400 MHz, in CDCl3): d
(ppm) ¼ 7.65–7.72 (m, 2H, Ph), 7.47–7.53 (m, 3H, Ph), 5.79 (d,
J2,3 ¼ 2.7 Hz, 1H, H-2), 4.96 (dd, J3,4 ¼ 6.5 Hz, J3,2 ¼ 2.7 Hz, 1H, H-3),
4.35–4.43 (m, 2H, H-4, H-5), 3.99 (dd, J6a,6b ¼ 8.7 Hz, J6a,5 ¼ 6.3 Hz, 1H, H-
6a), 3.77 (dd, J6b,6a ¼ 8.7 Hz, J6b,5 ¼ 5.7 Hz, 1H, H-6b), 1.33, 1.31 (2s, 6H,
C(CH3)2), 0.87 (s, 9H, SiC(CH3)3), 0.08, 0.07 (2s, 6H, SiCH3). 13C-NMR
(101 MHz, in CDCl3): d (ppm) ¼ 162.6 (C-1), 141.3, 131.7, 129.4, 125.0
(Ph), 109.0 (C(CH3)2), 107.2 (C-2), 88.3 (C-4), 72.8 (C-3), 72.7 (C-5), 65.9
(C-6), 26.5 (C(CH3)2), 25.8 (SiC(CH3)3), 25.4 (C(CH3)2), 18.2 (SiC(CH3)3),
–4.5,
–5.0
(SiCH3).
HRESIMS
m/z
447.16368
(calcd
for
C21H32O5SSiNa, 447.16319).
1,4-Anhydro-3-O-(tert-butyldimethylsilyl)-2-deoxy-5,6-O-isopropylidene-1-tribu-
tylstannyl-D-arabino-hex-1-enitol (5b)
(S)-10 (6.86 g, 16.2 mmol) and Bu3SnCl (5.26 mL, 19.4 mmol) were dis-
solved in dry THF (120 mL). The reaction mixture was cooled to –78 ꢀC
and PhLi (1.9 M in Bu2O, 9.36 mL, 17.8 mmol) was added over a period of
45 min. After the addition was complete, the solution was stirred for fur-
ther 90 min at this temperature until TLC showed complete consumption
of the starting material. Afterwards, the reaction was quenched by addition
of saturated NH4Cl-solution (100 mL) and the temperature was raised to rt.
The aqueous phase was extracted with CH2Cl2 (3 ꢁ 50 mL) and the

16
M. BAYER ET AL.
combined organic phases were dried with Na2SO4. The solvent was evapo-
rated and the residue was purified by column chromatography (Al2O3
deactivated with 5% H2O; petroleum ether containing 0.5% triethylamine)
to give 5b (7.74 g, 13.1 mmol, 81%) as a colourless liquid. Rf ¼ 0.88 (petrol-
1
eum ether/ethyl acetate 5:1). H-NMR (400 MHz, in C6D6): d (ppm) ¼ 5.36
(d, J2,3 ¼ 2.6 Hz, 1H, H-2), 4.76 (dd, J3,4 ¼ 6.7 Hz, J3,2 ¼ 2.4 Hz, 1H, H-3),
4.67 (ddd, J5,4 ¼ 6.3 Hz, J ¼ 6.3 Hz, J ¼ 6.0 Hz, 1H, H-5), 4.32 (dd,
J4,3 ¼ 6.2 Hz, J4,5 ¼ 6.2 Hz, 1H, H-4), 4.25 (d, J ¼ 6.5 Hz, 2H, H-6a, H-6b),
1.55–1.72 (m, 6H, SnBu), 1.53 (s, 3H, C(CH3)2), 1.34–1.42 (m, 9H,
C(CH3)2, SnBu), 1.01–1.14 (m, 6H, SnBu), 0.92–0.97 (m, 18H, SiC(CH3)3,
SnBu), 0.07, 0.07 (2s, 6H, SiCH3). 13C-NMR (101 MHz, in C6D6): d
(ppm) ¼ 168.6 (C-1), 117.3 (C-2), 109.2 (C(CH3)2), 86.5 (C-4), 74.5 (C-3),
74.1 (C-5), 67.3 (C-6), 29.7, 27.9 (SnBu), 27.4 (C(CH3)2), 26.4 (SiC(CH3)3),
26.1 (C(CH3)2), 18.3 (C(CH3)3), 14.3, 10.4 (SnBu), –3.9, –4.4 (SiCH3).
General Procedure for homocoupling of stannyl glycals 5a-e
To a solution of stannylated glycal 5a–e in DMF (Method A) or toluene
(Method B) (0.1 M) was added PdCl2(CH3CN)2 (0.1 eq) and copper-1-thio-
phene-2-carboxylate (CuTC) (1 eq). The dark suspension was stirred at
suggested temperatures. After complete consumption of the starting mater-
ial (TLC) silicagel in case of 5a and 5c–e or Al2O3 in case of 5b (500 wt%)
was added and the solvent was evaporated. The residue was purified by col-
umn chromatography. For Method C, no CuTC was added. For Method D,
Cu(OTf)2 in THF was used.
2,6:7,11-Dianhydro-5,8-dideoxy-4,9-di-O-(tert-butyldimethylsilyl)-1,3:10,12-di-O-
isopropylidene-D-erythro-L-gulo-dodeco-5,7-dienitol (11a)
Dimer 11a was obtained as a white solid and was prepared from 5a in 95%
yield by stirring the reaction mixture in dry toluene under reflux for
10 min (Method B). A mixture of petroleum ether/methylene chloride 2:1
containing 0.5% triethylamine was used as the eluent for column chroma-
20
tography. Rf ¼ 0.60 (petroleum ether/ethyl acetate 10:1). ½aꢂD ¼ –25.6
1
(c ¼ 1.0, CHCl3). M.p. 153 ꢀC (ethanol). H-NMR (400 MHz, in CDCl3): d
(ppm) ¼ 5.03 (d, J5,4 ¼ J8,9 ¼ 2.0 Hz, 2H, H-5, H-8), 4.35 (dd,
J4,3 ¼ J9,10 ¼ 7.0 Hz, J4,5 ¼ J9,8 ¼ 1.8 Hz, 2H, H-4, H-9), 3.99 (dd,
J1a,1b ¼ J12a,12b ¼ 10.9 Hz, J1a,2 ¼ J12a,11 ¼ 5.2 Hz, 2H, H-1a, H-12a), 3.84–3.92
(m, 2H, H-1b, H-12b), 3.67–3.77 (m, 4H, H-2, H-3, H-10, H-11), 1.49, 1.41
(2s, 12H, C(CH3)2), 0.89 (s, 18H, SiC(CH3)3), 0.09, 0.07 (2s, 12H, SiCH3).
13C-NMR (101 MHz, in CDCl3): d (ppm) ¼ 145.9 (C-6, C-7), 103.0 (C-5,
C-8), 99.6 (C(CH3)2), 73.0 (C-3, C-10), 69.9 (C-2, C-11), 68.4 (C-4, C-9),
61.9 (C-1, C-12), 29.1 (C(CH3)2), 26.0 (SiC(CH3)3), 19.1 (C(CH3)2), 18.4

JOURNAL OF CARBOHYDRATE CHEMISTRY
17
(SiC(CH3)3), –4.2, –4.5 (SiCH3). HRESIMS m/z 621.32512 (calcd for
C30H54O8Si2Na, 621.32494); anal. C 60.18, H 9.36, calcd for C30H54O8Si2, C
60.16, H 9.09. Treatment of 5a according to Method A for 3 h gave 11a in
83% yield.
3,6:7,10-Dianhydro-4,9-di-O-(tert-butyldimethylsilyl)-5,8-dideoxy-1,2:11,12-di-O-
isopropylidene-D-erythro-L-gulo-dodeco-5,7dienitol (11b)
Dimer 11b was obtained as a colourless oil and was prepared in 52% yield
by stirring the reaction mixture in dry DMF for 5 min at ambient tempera-
ture (Method A). Petroleum ether containing 0.5% triethylamine was used
as the eluent for the column chromatography (Al2O3 deactivated with 5%
20
H2O). Rf ¼ 0.67 (petroleum ether/ethyl acetate 5:1). ½aꢂD ¼ –9.9 (c ¼ 1.0,
CHCl3). 1H-NMR (400 MHz, in CDCl3):
d
(ppm) ¼ 5.34 (d,
J5,4 ¼ J8,9 ¼ 2.7 Hz, 2H, H-5, H-8), 4.99 (dd, J4,3 ¼ J9,10 ¼ 6.7 Hz,
J4,5 ¼ J9,8 ¼ 2.6 Hz, 2H, H-4, H-9), 4.41–4.49 (m, 4H, H-2, H-3, H-10, H-
11), 4.13 (dd, J1a,1b ¼ J12a,12b ¼ 8.6 Hz, J1a,2 ¼ J12a,11 ¼ 6.4 Hz, 2H, H-1a, H-
12a), 3.99 (dd, J1b,1a ¼ J12b,12a ¼ 8.6 Hz, J1b,2 ¼ J12b,11 ¼ 6.6 Hz, 2H, H-1b, H-
12b), 1.44, 1.38 (2s, 12H, C(CH3)2), 0.88 (s, 18H, SiC(CH3)3), 0.08, 0.07
(2s, 12H, SiCH3). 13C-NMR (101 MHz, in CDCl3): d (ppm) ¼ 150.9 (C-6,
C-7), 108.8 (C(CH3)2), 103.9 (C-5, C-8), 85.2 (C-3, C-10), 73.9 (C-4, C-9),
73.4 (C-2, C11), 66.2 (C-1, C-12), 26.5 (C(CH3)2), 26.0 (SiC(CH3)3), 25.7
(C(CH3)2), 18.4 (SiC(CH3)3), –4.5, –4.8 (SiCH3). HRESIMS m/z 621.32480
(calcd for C30H54O8Si2Na, 621.32494); anal. C 59.97, H 9.21, calcd for
C30H54O8Si2, C 60.16, H 9.09. Treatment of 5b according to Method B for
2 h resulted in complete decomposition of the starting material.
2,6:7,11-Dianhydro-5,8-dideoxy-1,3,4,9,10,12-hexakis-O-benzyl-D-erythro-L-gulo-
dodeco-5,7-dienitol (11c)
Dimer 11c was obtained as a white solid and was synthesised in 90% yield
by stirring the reaction mixture in dry DMF at ambient temperatures for
10 min (Method A). A mixture of petroleum ether/ethyl acetate 7:1 con-
taining 0.5% Et3N was used as the eluent for column chromatography.
20
Rf ¼ 0.60 (petroleum ether/ethyl acetate 2:1). ½aꢂD ¼ –39.5 (c ¼ 1.0, CHCl3).
1
M.p. 114 ꢀC (acetone). H-NMR (400 MHz, in CDCl3): d (ppm) ¼ 7.28–7.37
(m, 30H, Ph), 5.55 (d, J5,4 ¼ J8,9 ¼ 2.9 Hz, 2H, H-5, H-8), 4.85 (d,
J ¼ 11.4 Hz, 2H, PhCH2), 4.55–4.71 (m, 10H, PhCH2), 4.31 (dd,
J4,3 ¼ J9,10 ¼ 5.9 Hz, J4,5 ¼ J9,8 ¼ 3.0 Hz, 2H, H-4, H-9), 4.15 (ddd,
J2,3 ¼ J11,10 ¼ 8.3 Hz, J ¼ 3.9 Hz, J ¼ 3.9 Hz, 2H, H-2, H-11), 3.91 (dd,
J3,2 ¼ J10,11 ¼ 8.4 Hz, J3,4 ¼ J10,9 ¼ 6.1 Hz, 2H, H-3, H-10), 3.80–3.88 (m, 4H,
H-1a, H-1b, H-12a, H-12b). 13C-NMR (101 MHz, in CDCl3): d
(ppm) ¼ 147.3 (C-6, C-7), 138.5, 138.4, 138.3, 128.5, 128.1, 127.9, 127.7,

18
M. BAYER ET AL.
127.7 (Ph), 98.0 (C-5, C-8), 77.6 (C-2, C-11), 76.1 (C-4, C-9), 74.4 (C-3, C-
10), 73.7, 73.5, 70.5 (PhCH2), 68.7 (C-1, C-12). HRESIMS m/z 853.37109
(calcd for C54H54O8Na, 853.37109); anal. C 78.19, H 6.55, calcd for
C54H54O8, C 78.05, H 6.55. Method C gave 11c in 85% yield. Treatment of
5c according to Method C for 3 h gave 11c in 85% yield.
2,6:7,11-Dianhydro-5,8-dideoxy-1,3,4,9,10,12-hexakis-O-benzyl-D-threo-L-galo-
dodeco-5,7-dienitol (11d)
Dimer 11d was obtained as a yellow, viscous oil and was synthesised in
84% yield by stirring the reaction mixture in dry DMF at ambient tempera-
tures for 2 h (Method A). A mixture of petroleum ether/ethyl acetate 5:1
containing 0.5% triethylamine was used as the eluent for column chroma-
20
tography. Rf ¼ 0.46 (petroleum ether/ethyl acetate 3:1). ½aꢂD ¼ –44.4
1
(c ¼ 1.0, CHCl3). H-NMR (400 MHz, in CDCl3): d (ppm) ¼ 7.26 ꢃ 7.33 (m,
30H, Ph), 5.49 (d, J5,4 ¼ J8,9 ¼ 3.2 Hz, 2H, H-5, H-8), 4.85 (d, J ¼ 11.9 Hz,
2H, PhCH2), 4.57–4.70 (m, 6H, PhCH2), 4.45–4.53 (m, 4H, PhCH2),
4.22–4.29 (m, 4H, H-2, H-4, H-9, H-11), 3.94 (dd, J3,2 ¼ J10,11 ¼ 3.1 Hz,
J3,4 ¼ J10,9 ¼ 3.1 Hz, 2H, H-3, H-10), 3.75 ꢃ 3.84 (m, 4H, H-1a, H-1b, H-
12a, H-12b). 13C-NMR (101 MHz, in CDCl3): d (ppm) ¼ 146.6 (C-6, C-7),
138.7, 138.6, 138.3, 128.5, 128.5, 128.4, 128.2, 127.9, 127.7, 127.6 (Ph), 97.7
(C-5, C-8), 76.5 (C-2, C-11), 73.5, 73.2 (PhCH2), 71.5 (C-3, C-10), 71.1 (C-
4, C-9), 71.0 (PhCH2), 68.4 (C-1, C-12). HRESIMS m/z 853.37132 (calcd
for C54H54O8Na, 853.37109); anal. C 77.95, H 6.76, calcd for C54H54O8, C
78.05, H 6.55.
2,6:7,11-Dianhydro-5,8-dideoxy-1,3,4,9,10,12-hexakis-O-triisopropylsilyl-D-
erythro-L-gulo-dodeco-5,7-dienitol (11e)
To a solution of 5e (760 mg, 0.840 mmol) in dry THF (3 mL) was added
Cu(OTf)2 (655 mg, 1.81 mmol) and the reaction mixture was stirred for 2 h
at ambient temperature (Method D). Subsequently water (20 mL) was
added and the aqueous layer was extracted with CH2Cl2 (3 ꢁ 10 mL). The
combined organic layers were washed with brine (2 ꢁ 10 mL), dried with
Na2SO4 and the solvent was removed. The residue was purified by column
chromatography (petroleum ether/methylene chloride 20:1 containing 0.5%
triethylamine) to give 11e (149 mg, 0.121 mmol, 29%) as a white solid.
20
Rf ¼ 0.71 petroleum ether/CH2Cl2 5:1). ½aꢂD ¼ –25.4 (c ¼ 1.0, CHCl3). M.p.
184 ꢀC (acetone). 1H-NMR (400 MHz, in CDCl3): d (ppm) ¼ 5.39 (dd,
J5,4 ¼ J8,9 ¼ 5.0 Hz, J5,3 ¼ J8,10 ¼ 1.8 Hz, 2H, H-5, H-8), 4.27–4.32 (m, 2H, H-
2, H-11), 4.12 (m, 4H, H-3, H-4, H-9, H-10), 3.95 (dd, JH1a, H1b ¼ JH12a,
¼ 10.9 Hz, J1a,2 ¼ J12a,11 ¼ 5.1 Hz, 2H, H-1a, H-12a), 3.88 (dd,
H12b
J1b,1a ¼ J12b,12a ¼ 10.9 Hz, J1b,2 ¼ J12b,11 ¼ 6.9 Hz, 2H, H-1b, H-12b),

JOURNAL OF CARBOHYDRATE CHEMISTRY
19
1.01–1.08 (m, 126H, SiCH(CH3)2). 13C-NMR (101 MHz, in CDCl3): d
(ppm) ¼ 145.9 (C-6, C-7), 97.4 (C-5, C-8), 81.0 (C-2, C-11), 70.3 (C-4, C-
9), 66.6 (C-3, C-10), 62.1 (C-1, C-12), 18.4, 18.3, 18.3, 18.2, 18.2, 18.2
(SiCH(CH3)2), 12.7, 12.6, 12.1 (SiCH(CH3)2). HRESIMS m/z 1249.89065
(calcd for C66H138O8Si6Na, 1249.88995); anal. C 64.29, H 11.53, calcd for
C66H138O8Si6, C 64.54, H 11.32. Treatment of 5e according to Method B
for 3 h gave 11e in 16% yield)
Coupling of the stannyl-glycals with 4,5-diiodophthalonitrile
4,5-Bis-[1,5-anhydro-2-deoxy-3-O-tert-butyl-dimethylsilyl-4,6-O-isopropyliden-D-
arabino-hex-1-enitolyl]-phthalonitrile (12a)
4,5-Diiodophthalonitrile (269 mg, 0.710 mmol), tetrakis(triphenylphospine)-
palladium(0) (82.0 g, 0.0710 mmol) and copper(I) thiophene-2-carboxylate
(324 mg, 1.70 mmol) were suspended in dry toluene (20 mL). The reaction
mixture was heated to 100 ꢀC and a solution of 1,5-anhydro-2-deoxy-3-O-
tert-butyl-dimethylsilyl-4,6-O-isopropylidene-1-C-tributylstannyl-D-arabino-
hex-1-enitol 5a (1.00 g, 1.70 mmol) in toluene (35 mL) was slowly added.
After the addition was complete, the reaction mixture was stirred 1 h at
100 ꢀC until TLC showed the complete consumption of the starting mater-
ial. The reaction mixture was cooled to room temperature and the solvent
removed under reduced pressure. Purification of the residue by column
chromatography (methylene chloride/petroleum ether 3:1 containing 0.5%
triethylamine) gave 12a (435 mg, 0.604 mmol, 85%) as a pale yellow foam.
Rf ¼ 0.15 (methylene chloride/petroleum ether 2:1 containing 1% triethyl-
20
1
amine). ½aꢂD 5 þ6.0 (c ¼ 1.0, CHCl3). H-NMR (400 MHz, in CDCl3): d
(ppm) ¼ 7.81 (s, 2H, H-aryl), 4.99 (d, J2,3 ¼ 2.2 Hz, 2H, H-2), 4.39 (dd,
J3,2 ¼ 2.2 Hz, J3,4 ¼ 7.4 Hz, 2H, H-3), 3.96–4.03 (m, 4H, H-6a, H-5),
3.79–3.89 (m, 4H, H-6b, H-4), 1.51 (s, 6H, C(CH3)2), 1.43 (s, 6H,
C(CH3)2), 0.93 (s, 18H, SiC(CH3)3), 0.11–0.12 (2s, 12H, SiCH3). 13C-NMR
(101 MHz, in CDCl3): d (ppm) ¼ d 149.4 (C-1), 138.7 (C-aryl-(C-1)), 134.5
ꢄ
ꢄ
(CH-aryl), 115.6 (C-aryl) , 115.0 (C, CN) , 107.8 (C-2), 99.8 (C(CH3)2),
81.5 (C-5), 72.7 (C-4), 71.0 (C-5), 68.3 (C-3), 28.9 (C(CH3)2), 26.1
(SiC(CH3)3), 19.1 (C(CH3)2), 18.4 (SiC(CH3)3), ꢃ4.2 (SiCH3), ꢃ4.7
(SiCH3). HRESIMS m/z 747.34655 (calcd for C38H56N2O8Si2Na, 747.34674);
anal. C 62.81, H 7.86, N 3.82, calcd for C38H56N2O8Si2, C 62.95, H 7.79, N
ꢄ
3.86. Signals can be interchanged.
4,5-Bis-[1,5-anhydro-2-deoxy-3,4,6-tri-O-triisopropylsilyl-D-arabino-hex-1-eni-
tolyl]-phthalonitrile (12e)
4,5-Diiodophthalonitrile (17.5 mg, 0.0460 mmol), tetrakis(triphenylpho-
spine)-palladium(0) (2.7 mg, 0.00230 mmol) and copper(I) thiophene-2-
carboxylate (38.6 mg, 0.184 mmol) were suspended in dry toluene (3mL).

20
M. BAYER ET AL.
The reaction mixture was heated to 100 ꢀC and a solution of 1,5-anhydro-
2-deoxy-3-O-tert-butyl-dimethylsilyl-4,6-O-isopropylidene-1-C-tributyl-
stannyl-D-arabino-hex-1-enitol 5e (100 mg, 0.110 mmol) in toluene (10 mL)
was slowly added. After the addition was complete, the reaction mixture
was stirred 1 h at 100 ꢀC until TLC showed the complete consumption of
the starting material. The reaction mixture was cooled to room temperature
and the solvent was removed under reduced pressure. Purification by col-
umn chromatography (methylene chloride/petroleum ether 2:3) gave 12e
(50.0 mg, 0.0359 mmol, 78%) as a white foam. Rf ¼ 0.65 (petroleum ether/
20
methylene chloride, 3:2) ½aꢂD ¼ þ20.0 (c ¼ 1.0, CHCl3). 1H-NMR
(400 MHz, in CDCl3): d (ppm) ¼ 8.00 (s, 2H, H-aryl), 5.15 (d, J2,3 ¼ 4.0 Hz,
2H, H-2), 4.31–4.32 (m, 2H, H-5), 4.09–4.19 (m, 6H, H-6a, H-3, H-4), 3.80
(dd, J6b,6a ¼ 11.5 Hz, J6b,5 ¼ 3.3 Hz, 2H, H-6b), 1.02–1.13 (m, 126H,
SiCH(CH3)2). 13C-NMR (101 MHz, in CDCl3): d (ppm) ¼ d 147.8 (C-1),
ꢄ
ꢄ
140.2 (C-aryl-(C-1)), 135.3 (CH-aryl), 115.2 (C-aryl) , 114.7 (CN) , 104.5
(C-2), 81.5 (C-5), 70.3 (C-4), 67.8 (C-3), 61.1 (C-6), 18.4, 18.4, 18.4, 18.3,
18.1, 18.1 (SiCH(CH3)2), 13.0, 12.8, 12.1 (SiCH(CH3)2). HRESIMS m/z
1375.91161 (calcd for C74H140N2O8Si6Na, 1375.91175); anal. C 65.56, H
ꢄ
10.63, N 1.85, calcd for C74H140N2O8Si6, C 65.62, H 10.42, N 2.07. Signals
can be interchanged.
Acknowledgments
€
We thank Petra Kruger (elemental analysis), Dr. Dorothee Wistuba, Claudia Kruse, Dr.
€
€
Peter Haiss (mass spectra), Dr. Cacilia Maichle-Mossmer (X-ray crystallography) and Marc
Halang for their contributions to this work.
Funding
This work was supported by State of Baden-Wuerttemberg.
References
[1] Hultin, P.G. Bioactive C-glycosides from bacterial secondary metabolism. Curr.
Topics Med. Chem. 2005, 5, 1299–1331.
[2] Bililign, T.; R. Griffith, B.; S. Thorson, J. Structure, activity, synthesis and biosyn-
thesis of aryl- C -glycosides. Nat. Prod. Rep. 2005, 22, 742–760.
[3] Kitamura, K.; Ando, Y.; Matsumoto, T.; Suzuki, K. Total synthesis of aryl C-glyco-
side natural products: strategies and tactics. Chem. Rev. 2018, 118, 1495–1598.
[4] Yang, Y.; Yu, B. Recent advances in the chemical synthesis of C-glycosides. Chem.
Rev. 2017, 117, 12281–12356.
~
[5] Caneque, T.; Gomes, F.; Mai, T.T.; Maestri, G.; Malacria, M.; Rodriguez, R.
Synthesis of marmycin A and investigation into its cellular activity. Nat. Chem.
2015, 7, 744–751.

JOURNAL OF CARBOHYDRATE CHEMISTRY
21
[6] Kawai, H.; Hayakawa, Y.; Nakagawa, M.; Imamura, K.; Tanabe, K.; Shimazu, A.;
Seto, H.; Otake, N. Arugomycin, a new anthracycline antibiotic. J. Antibiot. 1983,
36, 1569–1571.
[7] Wang, X.J.; Zhang, L.; Byrne, D.; Nummy, L.; Weber, D.; Krishnamurthy, D.; Yee,
N.; Senanayake, C.H. Efficient synthesis of empagliflozin, an inhibitor of SGLT-2,
utilizing an AlCl3-promoted silane reduction of a b-glycopyranoside. Org. Lett.
2014, 16, 4090–4093.
[8] Chao, E.C.; Henry, R.R. SGLT2 inhibition-a novel strategy for diabetes treatment.
Nat. Rev. Drug Discov. 2010, 9, 551–559.
[9] Guo, C.; Hu, M.; Deorazio, R.J.; Usyatinsky, A.; Fitzpatrick, K.; Zhang, Z.; Maeng,
J.H.; Kitchen, D.B.; Tom, S.; Luche, M.; et al. The design and synthesis of novel
SGLT2 inhibitors: C-glycosides with benzyltriazolopyridinone and phenylhydantoin
as the aglycone moieties. Bioorganic Med. Chem. 2014, 22, 3414–3422.
[10] Henschke, J.P.; Wu, P.-Y.; Lin, C.-W.; Chen, S.-F.; Chiang, P.-C.; Hsiao, C.-N.
b-Selective C-Arylation of silyl protected 1,6-Anhydroglucose with arylalanes: the
synthesis of SGLT2 inhibitors. J. Org. Chem. 2015, 80, 2295–2309.
[11] Milstein, D.; Stille, J.K. A general, selective, and facile method for ketone synthesis
from acid chlorides and organotin compounds catalyzed by palladium. J. Am. Chem.
Soc. 1978, 100, 3636–3638.
[12] Friesen, R.W.; Sturino, C.F. The preparation of C-Arylglycals. The palladium-cata-
lyzed coupling of 3,4,6-Tri-O-(Tert-Butyldimethylsilyl)-1-(Tributylstannyl)-D-Glucal
and Aryl Bromides. J. Org. Chem. 1990, 55, 2572–2574.
[13] Dubois, E.; Beau, J.-M. Formation of C-glycosides by a palladium-catalysed coupling
reaction of tributylstannyl glycals with organic halides. J. Chem. Soc. Chem.
Commun. 1990, 1191–1192.
[14] Friesen, R.W.; Loo, R.W.; Sturino, C.F. The Preparation of C-Aryl glucals via palla-
dium-catalyzed cross-coupling methods. Can. J. Chem. 1994, 72, 1262–1272.
[15] Jarowicki, K.; Kilner, C.; Kocienski, P.J.; Komsta, Z.; Milne, J.E.; Wojtasiewicz, A.;
Coombs, V. A Synthesis of 1-lithiated glycals and 1-Tributylstannyl Glycals from 1-
Phenylsulfinyl glycals via sulfoxide-lithium ligand exchange. Synthesis. 2008, 17,
2747–2763.
€
€
[16] Jakel, C.; Dotz, K.H. From glycals to metal pyranosylidenes: diastereoselective add-
ition of electrophiles to metal carbene enolate intermediates1. Tetrahedron. 2000, 56,
2167–2173.
[17] Tius, M.A.; Gomez-Galeno, J.; Gu, X.Q.; Zaidi, J.H. C-Glycosylanthraquinone syn-
thesis: total synthesis of vineomycinone B2 methyl ester. J. Am. Chem. Soc. 1991,
113, 5775–5783.
[18] Khatri, H.R.; Nguyen, H.; Dunaway, J.K.; Zhu, J. Total synthesis of antitumor anti-
biotic derhodinosylurdamycin A. Chem. Eur. J. 2015, 21, 13553–13557.
[19] Wei, A.; Kishi, Y. Preferred conformation of C-Glycosides. 12. Synthesis and con-
formational analysis of a,a-, ab- and b,b-C-Trehaloses. J. Org. Chem. 1994, 59,
88–96.
[20] Martin, O.R.; Lai, W. Synthesis and conformational studies of b-(1!6)- and
b,b-(1!1)-linked C-disaccharides. J. Org. Chem. 1993, 58, 176–185.
[21] Patro, B.; Schmidt, R.R. Carbon-bridged trehalose. Synthesis of Bis[C-(b-D-
Galactopyranosyl)]methanol. Synthesis. 1998, 1998, 1731–1734.
[22] Mochizuki, T.; Shiozaki, M. Synthesis of (6R,7R)-D-gluco-L-gulo-6,7-dodecodiulose-
(6,2),(7,11). Chem. Lett. 1997, 26, 801–802.

22
M. BAYER ET AL.
€
[23] Bachle, F.; Hanack, M.; Ziegler, T. Synthesis and spectroscopic evaluation of two
novel glycosylated zinc(II)-phthalocyanines. Molecules 2015, 20, 18367–18386.
[24] Paquette, L.A.; Oplinger, J.A. Limitations in the application of anionic oxy-
cope sigmatropy to elaboration of the forskolin nucleus. Tetrahedron 1989, 45,
107–124.
[25] Steunenberg, P.; Jeanneret, V.; Zhu, Y.-H.; Vogel, P. C(1!4)-Linked disaccharides
through carbonylative stille cross-coupling. Tetrahedron: Asymmetry 2005, 16,
337–346.
[26] Friesen, R.W.; Sturino, C.F.; Daljeet, A.K.; Kolaczewska, A. Observation of alpha.-
Silyl carbanions in the metalation of 3,4,6-Tri-O-(Tert-Butyldimethylsilyl)-D-Glucal.
J. Org. Chem. 1991, 56, 1944–1947.
[27] Jeanneret, V.; Meerpoel, L.; Vogel, P. C-Glycosides and C-Disaccharide Precursors
through carbonylative stille coupling reactions. Tetrahedron Lett. 1997, 38, 543–546.
€
€
[28] Jakel, C.; Dotz, K.H. Organotransition metal modified sugars: Part 22. direct metala-
tion of glycals: short and efficient routes to diversely protected stannylated glycals. J.
Organomet. Chem. 2001, 624, 172–185.
[29] Friesen, R.W.; Loo, R.W. Preparation of C-Aryl glucals via the palladium catalyzed
coupling of metalated aromatics with 1-Iodo-3,4,6-Tri-O-(Triisopropylsilyl)-D-
Glucal. J. Org. Chem. 1991, 56, 4821–4823.
[30] Hanessian, S.; Martin, M.; Desai, R.C. Formation of C-glycosides by polarity inver-
sion at the anomeric centre. J. Chem. Soc. Chem. Commun. 1986, 926–927.
[31] Lesimple, P.; Beau, J.-M.; Jaurand, G.; Sina€y, P. Preparation and use of lithiated gly-
cals: vinylic deprotonation versus tin-lithium exchange from 1-Tributylstannyl gly-
cals. Tetrahedron Lett. 1986, 27, 6201–6204.
[32] Upreti, M.; Vishwakarma, R.A. Synthesis of the phosphodisaccharide repeat of anti-
genic lipophosphoglycan of leishmania donovani parasite. Tetrahedron Lett. 1999,
40, 2619–2622.
ꢁ
ꢀ
ꢁꢀ
[33] Bılik, V.; Kucar, S. Stereoselective hydroxylation of glycals. Carbohydr. Res. 1970, 13,
311–313.
ꢀ
ꢀ
ꢀ
[34] Marın, I.; Matheu, M.I.; Dıaz, Y.; Castillon, S. Stereoselective tandem epoxidation-
alcoholysis/hydrolysis of glycals with molybdenum catalysts. Adv. Synth. Catal.
2010, 352, 3407–3418.
[35] Bellucci, G.; Catelani, G.; Chiappe, C.; D’Andrea, F. A simple and highly diastereo-
selective preparation of glycal epoxides using the MCPBA-KF complex. Tetrahedron
Lett. 1994, 35, 8433–8436.
[36] Ganesh, V.; Kundu, T.; Chandrasekaran, S. r-ferrier rearrangement of carbohydrate
derived vinylcyclopropanes: A facile approach to oxepane analogs. Tetrahedron.
2014, 70, 7268–7282.
[37] Reddy Dubbaka, S.; Steunenberg, P.; Vogel, P. Aryl and arylmethyl-c-glycosides
through desulfitative stille and carbonylative stille cross-coupling of tinglycals and
sulfonyl chlorides. Synlett. 2004, 1235–1238.
€
[38] Dotz, K.H.; Otto, F.; Nieger, M. Organotransition-metal-modified sugars: Part 17.
Glucal-derived carbene complexes: synthesis and diastereoselective benzannulation.
J. Organomet. Chem. 2001, 621, 77–88.
[39] Fraser-Reid, B.; Walker, D.L.; Tam, S. Y.-K.; Holder, N.L. A rapid route to hex-1-
Enopyran-3-Uloses. Can. J. Chem. 1973, 51, 3950–3954.
[40] Mensah, E.; Camasso, N.; Kaplan, W.; Nagorny, P. Chiral phosphoric acid directed
regioselective acetalization of carbohydrate-derived 1,2-Diols. Angew. Chemie - Int.
Ed. 2013, 52, 12932–12936.

JOURNAL OF CARBOHYDRATE CHEMISTRY
23
ꢀ
ꢀ
[41] Gomez, A.M.; Casillas, M.; Barrio, A.; Gawel, A.; Lopez, J.C. Synthesis of pyranoid
and furanoid glycals from glycosyl sulfoxides by treatment with organolithium
reagents. European J. Org. Chem. 2008, 2008, 3933–3942.
[42] Gunn, A.; Jarowicki, K.; Kocienski, P.; Lockhart, S. The preparation of 1-
Tributylstannyl glycals from 1-Phenylsulfonyl Glycals via Ni(0)-catalysed coupling
with tributylstannylmagnesium bromide. Synthesis. 2001, 331–338.
[43] Farina, V.; Kapadia, S.; Krishnan, B.; Wang, C.; Liebeskind, L.S. On the nature of
the “copper effect” in the stille cross-coupling. J. Org. Chem. 1994, 59, 5905–5911.
[44] Casado, A.L.; Espinet, P. Quantitative evaluation of the factors contributing to the
“copper effect” in the stille reaction. Organometallics. 2003, 22, 1305–1309.
[45] Mee, S.P.H.; Lee, V.; Baldwin, J.E. Stille coupling made easier—The synergic effect
of copper(I) salts and the fluoride ion. Angew. Chemie Int. Ed. 2004, 43, 1132–1136.
[46] Allred, G.D.; Liebeskind, L.S. Copper-mediated cross-coupling of organostannanes
with organic iodides at or below room temperature. J. Am. Chem. Soc. 1996, 118,
2748–2749.
[47] Morita, H.; Oida, Y.; Ariga, T.; Fukumoto, S.; Sheikh, M.C.; Fujii, T.; Yoshimura, T.
Synthesis of ‘Thianthrene dimer’ by the coupling reaction of stannylthianthrenes in
the presence of copper catalysts. Tetrahedron. 2011, 67, 4672–4679.
ꢀ
ꢀ
[48] Alvarez-Mico, X.; Calvete, M.J.F.; Hanack, M.; Ziegler, T. A new glycosidation
method through nitrite displacement on substituted nitrobenzenes. Carbohydr. Res.
2007, 342, 440–447.
[49] Lyubimtsev, A.; Iqbal, Z.; Crucius, G.; Syrbu, S.; Taraymovich, E.S.; Ziegler, T.;
Hanack, M. Aggregation behavior and UV-Vis spectra of Tetra- and octaglycosy-
lated zinc phthalocyanines. J. Porphyr. Phthalocyanines. 2011, 15, 39–46.
[50] Iqbal, Z.; Lyubimtsev, A.; Hanack, M.; Ziegler, T. Synthesis and characterization of
1,8(11),15(18),22(25)-Tetraglycosylated Zinc(II) Phthalocyanines. J. Porphyr.
Phthalocyanines 2010, 14, 494–498.
[51] Lyubimtsev, A.; Iqbal, Z.; Crucius, G.; Syrbu, S.; Ziegler, T.; Hanack, M. Synthesis of
glycosylated metal phthalocyanines and naphthalocyanines. J. Porphyr.
Phthalocyanines. 2012, 16, 434–463.
[52] Iqbal, Z.; Masilela, N.; Nyokong, T.; Lyubimtsev, A.; Hanack, M.; Ziegler, T.
Spectral, photophysical and photochemical properties of tetra- and octaglycosylated
zinc phthalocyanines. Photochem. Photobiol. Sci. 2012, 11, 679.
ꢀ
ꢀ
[53] Alvarez-Mico, X.; Calvete, M.; Hanack, M.; Ziegler, T. Expeditious synthesis of gly-
cosylated phthalocyanines. Synthesis. 2007, 2007, 2186–2192.
[54] Iqbal, Z.; Hanack, M.; Ziegler, T. Synthesis of an octasubstituted galactose zinc(II)
phthalocyanine. Tetrahedron Lett. 2009, 50, 873–875.
[55] Alvarez-Mico, X.; Calvete, M.J.F.; Hanack, M.; Ziegler, T. The first example of
anomeric glycoconjugation to phthalocyanines. Tetrahedron Lett. 2006, 47,
3283–3286.
[56] Liao, H.; Ma, J.; Yao, H.; Liu, X.-W. Recent progress of C -glycosylation methods in
the total synthesis of natural products and pharmaceuticals. Org. Biomol. Chem.
2018, 16, 1791–1806.