Synthesis and Applications of Silyl 2-Methylprop-2-ene-1-sulfinates in Preparative Silylation and GC-Derivatization Reactions of Polyols and Carbohydrates

Article abstract of DOI:10.1002/chem.201504380

Trimethylsilyl, triethylsilyl, tert-butyldimethylsilyl, and triisopropylsilyl 2-methylprop-2-ene-1-sulfinates were prepared through (CuOTf)₂C₆H₆-catalyzed sila-ene reactions of the corresponding methallylsilanes with SO₂ at 50 °C. Sterically hindered, epimerizable, and base-sensitive alcohols gave the corresponding silyl ethers in high yields and purities at room temperature and under neutral conditions. As the byproducts of the silylation reaction (SO₂+isobutylene) are volatile, the workup was simplified to solvent evaporation. The developed method can be employed for the chemo- and regioselective semiprotection of polyols and glycosides and for the silylation of unstable aldols. The high reactivity of the developed reagents is shown by the synthesis of sterically hindered per-O-tert-butyldimethylsilyl-α-d-glucopyranose, the X-ray crystallographic analysis of which is the first for a per-O-silylated hexopyranose. The per-O-silylation of polyols, hydroxy carboxylic acids, and carbohydrates with trimethylsilyl 2-methylprop-2-ene-1-sulfinate was coupled with the GC analysis of nonvolatile polyhydroxy compounds both qualitatively and quantitatively. Regio- and chemoselective silylation of polyols and carbohydrates has been achieved by employing silyl sulfinates (see the picture; TBS=tert-butyldimethylsilyl, TES=triethylsilyl, TIPS=triisopropylsilyl, TMS=trimethylsilyl). The silylation reactions proceed in high yield because the reactions are mild and fast and produce only volatile byproducts. Furthermore, the silyl sulfinates are used as new derivatization reagents for the GC analysis of nonvolatile polyhydroxy compounds.

Full text of DOI:10.1002/chem.201504380

DOI: 10.1002/chem.201504380
Full Paper
&
Synthetic Methods
Synthesis and Applications of Silyl 2-Methylprop-2-ene-1-
sulfinates in Preparative Silylation and GC-Derivatization
Reactions of Polyols and Carbohydrates
[a, b, c]
´
Dean Markovic,*
Wandji Augustin Tchawou,[a] Irina Novosjolova,[d] Sylvain Laclef,[a]
Dmitrijs Stepanovs,[d, e] Maris Turks,*[d] and Pierre Vogel*[a]
¯
Abstract: Trimethylsilyl, triethylsilyl, tert-butyldimethylsilyl,
and triisopropylsilyl 2-methylprop-2-ene-1-sulfinates were
prepared through (CuOTf)2·C6H6-catalyzed sila-ene reactions
of the corresponding methallylsilanes with SO2 at 508C. Ster-
ically hindered, epimerizable, and base-sensitive alcohols
gave the corresponding silyl ethers in high yields and puri-
ties at room temperature and under neutral conditions. As
the byproducts of the silylation reaction (SO2 +isobutylene)
are volatile, the workup was simplified to solvent evapora-
tion. The developed method can be employed for the
chemo- and regioselective semiprotection of polyols and
glycosides and for the silylation of unstable aldols. The high
reactivity of the developed reagents is shown by the synthe-
sis of sterically hindered per-O-tert-butyldimethylsilyl-a-d-
glucopyranose, the X-ray crystallographic analysis of which is
the first for a per-O-silylated hexopyranose. The per-O-silyla-
tion of polyols, hydroxy carboxylic acids, and carbohydrates
with trimethylsilyl 2-methylprop-2-ene-1-sulfinate was cou-
pled with the GC analysis of nonvolatile polyhydroxy com-
pounds both qualitatively and quantitatively.
Introduction
ing group because of their stability toward basic and acidic hy-
drolysis,[2] high specificity for fluoride-mediated cleavage,[3] and
solubility in nonpolar solvents. In addition, the silylation of hy-
droxy-containing compounds is frequently used in analytical
chemistry because this reaction converts compounds with low
volatility into volatile and thermally more stable derivatives,
thus facilitating analysis by GC and MS techniques.[5] Silyl deri-
vatization is useful for the structural characterization and quan-
tification of compounds of interest.[6,7] The most common sily-
lation procedures in preparative organic synthesis react com-
pounds containing hydroxy groups with silyl halides or triflates
and a stoichiometric amount of a Lewis base in polar aprotic
solvents.[8] Approaches that deal with GC derivatization fre-
quently use N,O-bis(trimethylsilyl)acetamide (BSA), N,O-bis(tri-
methylsilyl)trifluoroacetamide (BSTFA), N-trimethylsilylimidazole
(TMSIM), N-(tert-butyldimethylsilyl)-N-methyltrifluoroacetamide
The selective semiprotection of polyols, phenols, carboxylic
acids, and other compounds containing hydroxy groups is of
great importance in modern organic synthesis.[1] Silyl ethers
and derivatives[4] are recognized as the most valuable protect-
´
[a] Prof. Dr. D. Markovic, W. A. Tchawou, Dr. S. Laclef, Prof. Dr. P. Vogel
Laboratoire de glycochimie et de synth›se asymØtrique
Swiss Federal Institute of Technology of Lausanne (EPFL)
Lausanne, 1015 (Switzerland)
Fax: (+41)21-693-93-55
E-mail: pierre.vogel@epfl.ch
´
[b] Prof. Dr. D. Markovic
Chemistry Department
University of Osijek
Osijek, Ulica cara Hadrijana 8A, (Croatia), 31000
E-mail: dmarkovic@kemija.unios.hr
2
(MTBSTFA), and others.[9] Other methods are based on the SN
substitution of SiÀO,[10] SiÀN,[11] SiÀS,[12] or SiÀC[13] compounds
or on catalyzed dehydrogenative silanolysis with R3SiH re-
agents.[14]
´
[c] Prof. Dr. D. Markovic
Department of Biotechnology
University of Rijeka
ˇ ´
Radmile Matejcic 2, 51000 Rijeka (Croatia)
Although these methods offer good reliability, they may fail
because of low reactivity, difficult removal of excess base and
byproducts, and/or their ability to epimerize or destroy base-
sensitive compounds.[15] The synthesis of complicated natural
products and analogues of biological interest often requires
the chemo- and regioselective semiprotection of polyols, an
operation that can be costly in terms of synthetic steps and re-
agents. There is a need for better semiprotection protocols
that are simpler, are less costly, and minimize waste produc-
tion.
[d] Dr. I. Novosjolova, Dr. D. Stepanovs, Prof. Dr. M. Turks
Faculty of Materials Science and Applied Chemistry
Riga Technical University
P. Valdena Str. 3, Riga, 1007 (Latvia)
E-mail: maris_turks@ktf.rtu.lv
[e] Dr. D. Stepanovs
Latvian Institute of Organic Synthesis
Aizkraukles Str. 21
Riga, 1006 (Latvia)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201504380.
Chem. Eur. J. 2016, 22, 4196 – 4205
4196
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
On the other hand, the success of GC and GC-MS analysis is
dictated by the efficiency of the procedures employed prior to
injection of the sample. Therefore, the rate of silylation may
play an important role because on many occasions only the
comparison of several empirically developed recipes leads to
an appropriate rate of silylation.[7,16] Frequently, these proce-
dures employ mixtures of reagents that include up to three
components (e.g., BSTFA+TMSCl+TMSIM).[9] In the GC analy-
sis of carbohydrates, oxime formation followed by silylation is
often required for the reliable determination of their concen-
tration.[17]
of the catalyst (up to 20%mol).[19a,20] Our efforts were first to
improve the reaction conditions and to elaborate a simpler
and more efficient route for the preparation of silyl 2-methyl-
prop-2-ene-1-sulfinates on a larger preparative scale. Therefore,
we explored the role of Lewis acids, solvent, and temperature.
tert-Butyldimethyl(2-methylprop-2-en-1-yl)silane (3a), as the
least reactive starting material, was used as a test substrate
and the reactions were carried out in sealed NMR tubes with
an excess of SO2 and toluene as an internal reference
(Scheme 2). The results of our screening are shown in Table 1.
As part of our program on the development of the organic
chemistry of sulfur dioxide,[18] we have described the use of
silyl 2-methylprop-2-ene-1-sulfinates 1 as a new and efficient
class of agent for the silylation of alcohols, phenols, and car-
boxylic acids (Scheme 1).[19] The reactions are fast, generally on
Scheme 2. Synthesis of tert-butyl-dimethylsilyl 2-methylprop-2-ene-1-sulfi-
nate (1a) by a Lewis acid (LA)-catalyzed sila-ene reaction between tert-butyl-
dimethyl-(2-methylprop-2-en-1-yl)silane (3a) and sulfur dioxide.
Table 1. Catalyst screening for the sila-ene reaction between tert-butyl-
dimethyl-(2-methylprop-2-en-1-yl)silane (3a) and sulfur dioxide according
to Scheme 2.
Scheme 1. Silylation of alcohols with silyl 2-methylprop-2-ene-1-sulfinates.
Entry
Solvent
Lewis acid
Reaction time
[h]
Conversion
[%][a]
a timescale of minutes at 208C, and the silylated products are
obtained in high yields and purities. Our conditions are neutral,
thus requiring neither acid nor base as catalysts or coreagents.
Because the byproducts are volatile (SO2 +isobutylene), the si-
lylated compounds can be purified by simple evaporation of
the solvent in many instances. This approach is particularly ad-
vantageous when temporary protection with trimethylsilyl
(TMS) groups, which are easily removed during aqueous
workup, is envisioned.
1
2
3
4
5
6
7
8
CD3CN
CD2Cl2
CD3CN
CD2Cl2
CD2Cl2
CD2Cl2
CD2Cl2
CD2Cl2
CD2Cl2
CD2Cl2
CD2Cl2
CD3CN
CD2Cl2
CD3CN
AlCl3
AlCl3
SbCl5
SbCl5
Al(OTf)3
SbCl3
Cu(OTf)2
ScCl3
Zn(OTf)2
ZnCl2
AgOTf
5
5
5
7
5
5
5
5
5
5
20
20
5
quant.
87
98
98
14[b]
17[b]
23[b]
9[b]
9
2[b]
[b]
10
11
12
13
14
–
Herein, we describe an improved and high-yielding synthetic
route for the preparation of a variety of silyl 2-methylprop-2-
ene-1-sulfinates 1 and their utilization for the protection of iso-
merizable, base-sensitive, or sterically hindered alcohols. The
chemo- and regioselective semiprotection of polyols and gly-
cosides is reported. Our neutral silylation method is demon-
strated to be especially useful for the protection of unstable
aldols and also allows a user-friendly access to fully O-silylated
hexopyranoses and their first X-ray analysis. Finally, our silyla-
tion procedure was adapted for the qualitative and quantita-
tive analysis of multicomponent mixtures by using GC-MS.
quant.
43[b]
quant.
65[b]
AgOTf
(CuOTf)2·C6H6
(CuOTf)2·C6H6
5
[a] Determined by 1H NMR spectroscopic analysis and toluene was used
as an internal reference. [b] Decomposition of the reaction mixture
occurs.
The anhydrous Lewis acids AlCl3 and SbCl5 in CD3CN or
CD2Cl2 catalyzed the sila-ene reaction efficiently (Table 1, en-
tries 1–4). Unfortunately, the purification of silyl sulfinate 1a
was unsuccessful due to the formation of stable oligomeric sul-
finic AlCl3 complexes[18c] or due to the high acidity of SbCl5
that degraded 1a during distillation. Al(OTf)3, SbCl3, Cu(OTf)2,
ScCl3, Zn(OTf)2, and ZnCl2 also catalyzed the reaction, but led
to lower conversion rates because of concurrent degradation
of the methallylsilane (Table 1, entries 4–10). Because of the
low solubility of ZnCl2, Zn(OTf)2 and ScCl3 in the reaction
media, very slow reactions were observed. High conversion
rates were obtained by applying the commercially available tri-
flates AgOTf and (CuOTf)2·C6H6 as catalysts in CD2Cl2 (Table 1,
entries 11 and 13). Lower yields were observed for both cata-
lysts in CD3CN (Table 1, entries 12 and 14), and the copper
Results and Discussion
Originally silyl sulfinates 1 were prepared by trimethylsilyl tri-
fluoromethanesulfonate (TMSOTf)-catalyzed sila-ene reactions
of the corresponding methallylsilanes 3 with sulfur dioxi-
de.[19a,20] Further development lead to the reaction between
SO2 and methallyltrimethylsilane catalyzed by N-trimethylsilyl
bis(trifluoromethanesulfonyl)imide (TMSNTf2; formed in situ
from Tf2NH and H2C=C(Me)CH2TMS) in toluene at ambient
pressure.[18i,j,19b] However, the latter advancement worked only
for the mentioned combination. The TMSOTf-catalyzed pro-
cesses lead to low yields (20–54%) and required high loading
Chem. Eur. J. 2016, 22, 4196 – 4205
www.chemeurj.org
4197
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
complex led to the fastest reaction. Optimization experiments
showed that the amount of the (CuOTf)2·C6H6 catalyst could be
decreased to 2.5% at 508C.
Table 2. User-friendly synthesis of triethylsilyl ethers from reactions be-
tween triethylsilyl 2-methylprop-2-ene-1-sulfinate 1c and selected alco-
hols in CH3CN at 208C.
We applied our optimized conditions to prepare TBS, TMS,
TES, and TIPS 2-methylprop-2-ene-1-sulfinates 1a–d. Methallyl-
silanes 3a–d were obtained by using Barbier–Calas reactions[21]
of methallyl chloride (4) with the corresponding trialkylsilyl
chlorides in the presence of magnesium (Scheme 3). These
Entry
1
Substrate
R
Product
Yield [%]
98
5a
6a
2
5b
6b
93
3
4
5c
6c
93
91
5d
6d
5
6
7
5e
5 f
5g
6e
6 f
6g
92
88
90
Scheme 3. Synthesis of silyl methallylsulfinates 1a–d on a preparative scale
(yields are given after purification by distillation). TBS=tert-butyldimethylsil-
yl, TES=triethylsilyl, TIPS=triisopropylsilyl, TMS=trimethylsilyl.
8
5h
6h
96
products were purified by distillation under reduced pressure
and obtained in yields of 68–95%. Further, a stainless-steel au-
toclave containing the catalyst (2.5 mol% of (CuOTf)2·C6H6
complex) was cooled to À788C and charged with liquid SO2
followed by the addition of a solution of the corresponding
methallyl silane 1a–d in CH2Cl2. The ene reactions were com-
pleted after 12 hours at 508C. Excess SO2 and CH2Cl2 were
evaporated under slightly reduced pressure. This solvent/re-
agent mixture can be reused in the next sila-ene reaction. The
resulting residue was collected by distillation under reduced
pressure, thus giving the pure silyl sulfinates 1 in 80–98%
yield. The process was reproducible in high yields and on
a scale of 40 gram for the methallyl silanes.
As a test of the usefulness of our reagents, we carried out
the silylation of different alcohols with triethylsilyl 2-methyl-
prop-2-ene-1-sulfinate (1c). The silylation reactions were con-
ducted in acetonitrile at 208C (the results are summarized in
Table 2). Secondary alcohols, such as cholesterol (5a) and
1,2:5,6-di-O-isopropylidene-a-d-glucofuranose (5b), were sily-
lated in a few minutes with one equivalent of 1c to give silyl
ethers 6a and 6b in 98 and 93% yield, respectively (purifica-
tion was carried out by filtration through a plug of silica gel;
Table 2, entries 1 and 2). Allylic and cis-homoallylic alcohols 5c
and 5d were protected by conversion into 6c and 6d in 93
and 91% yield, respectively (Table 2, entries 3 and 4). Silylation
of the Roche ester 5e gave the epimerizable silyl ether 6e
without loss of enantiomeric purity. The silylation of pent-4-en-
2-ol (5 f), which might be prone to water elimination,[22] was
performed under solvent-free conditions in excellent yield
(Table 2, entry 6). Similarly, sterically hindered 1,1-diethylpropa-
nol (5g) was silylated with 1c to form 6g in a high yield of
90%. Silyl sulfinate 1c was also effective for the protection of
oxime 5h by conversion into the O-silyl derivative 6h (98%).
Scheme 4. Comparison of the conventional silylation conditions used for un-
stable aldols and the use of silyl 2-methylprop-2-ene-1-sulfinate 1a. OTf=tri-
fluoromethanesulfonate.
We further tested our neutral silylation method for the pro-
tection of base-sensitive aldols (Scheme 4). Whereas all our at-
tempts to protect aldol 19 as a silyl ether by applying the clas-
sical methods failed and led exclusively to b-elimination of
water, thus giving enal 20, the use of TBS sulfinate 1a permit-
ted us to obtain b-silyloxy aldehyde 21 in 89% yield.
Next, we employed silyl sulfinates 1a–d for the regioselec-
tive protection of the primary alcohol moieties of diol 7,
methyl hexopyranosides 8–10, 12 and glucal (11) in DMF at
208C. All reactions led to high yields (Table 3, entries 1–9).
Thus, 1-phenylethane-1,2-diol (7) was selectively protected
with TMS, TES, or TIPS protecting groups to afford 13a–c in
Chem. Eur. J. 2016, 22, 4196 – 4205
www.chemeurj.org
4198
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
of the isolated product. d-Glucal (11) with one equiv-
alent of TIPS sulfinate 1d regioselectively gave 6-O-
triisopropylsilyl-d-glucal (17b) in 98% yield, whereas
the 2-O-protected glucopyranosides 18a–d were ob-
tained in high yields (83–97%) by the reaction of the
d-glucose-derived diol 12 and silyl sulfinates 1a–d.
The higher reactivity of the “super-armed” silylated
glycosyl donors was explained by an inversion of the
Table 3. Regioselective preparative silylations of 1-phenylethane-1,2-diol and mono-
saccharides by using trialkylsilyl methallylsulfinates 1a–d.
Entry Substrate
1
Silyl sulfonate Product
Yield [%]
95
1c
13a
13b
13c
4
1
chair conformations from C1 to C4 and by a simulta-
neous change of the positions of the substituents
from the equatorial to axial or pseudoaxial posi-
tions.[23] This concept has found important applica-
tions in sequential chemoselective oligosaccharide
synthesis. Gervay-Hague and co-workers reported the
use of per-O-trimethylsilylated monosaccharides in
the synthesis of the corresponding glycosyl iodides,
which were further applied in a one-pot stereoselec-
tive glycosylation protocol.[24] Other applications in-
clude protecting-group manipulations that start from
per-O-silylated carbohydrates,[26] such as the regiose-
lective silyl/acetate exchange of either per-O-silylated
monosaccharides[24f] or disaccharides, thus providing
advanced glycosyl donor and acceptor precursors.[26]
In addition, the per-O-silylation of saccharides has
been established as one of the most popular derivati-
zation techniques in GC and GC-MS analysis.[29] The
important limitations of the currently used silylation
reactions of carbohydrates imply the formation of
complex mixtures due to the different tautomeric
forms of glycosides or the necessity for rigorous
sample drying because of the high moisture sensitivi-
ty of the silylation reagents.[27]
2
3
1a
1d
80
98
4
5
1a
1d
14a
14b
97
98
6
7
1d
1d
15
16
99
86
8
9
1a[a]
1d
17a
17b
96
98
10
11
12
13
1a
1b
1c
1d
18a
18b
18c
18d
96
83
97
95
The efficiency of silyl sulfinates 1 as derivatization
agents for the formation of “super-armed” persilylat-
ed glycosyl donors and their conformational analysis
is further demonstrated. By applying our new silyla-
tion method, persilylated glycosides 23, 25, and 27
were obtained in one-step and with excellent conver-
sions, as analyzed by using GC-MS, NMR spectrosco-
py, and X-ray studies (Scheme 5). For example, the re-
action of d-glucose (22) with silylating reagent 1a
showed quantitative conversion (GC-MS analysis) into
[a] Two equivalents of 1a were used.
per-O-silylated a-glucopyranoside 23a (3JH1ÀH2
=
3.2 Hz), which was isolated in 70% yield.
95, 80, and 98% yield, respectively. Methyl a-d-glucopyrano-
side (8) was treated with one equivalent of sulfinates 1a and
1d, thus selectively giving the corresponding 6-O-silylated
monosaccharides 14a and 14b in excellent yields of 97 and
98%, respectively. Similarly, methyl a-d-mannopyranoside (9)
and methyl a-d-galactopyranoside (10) were converted into
monosilyl ethers 15 and 16 (99 and 86%, respectively), in
which only their primary alcohol moiety is protected as a TIPS
ether group. d-Glucal (11) with one equivalent of TBS sulfinate
1a gave a mixture of products due to the competitive silyla-
tion of the 6-O- and 3-O centers. However, 11 reacted with
two equivalents of 1a to chemo- and regioselectively give the
3,6-O-bis[(tert-butyl)dimethylsilyl] derivative 17a in 96% yield
The molecular structure and conformation of product 23a
was unambiguously established by X-ray structural analysis of
monocrystals obtained from a mixture of CD3CN/CDCl3 at
room temperature. This single-crystal X-ray analysis was the
first that has ever been carried out on any per-O-silylated hex-
opyranose. The crystals of persilylated a-d-glucopyranoside
23a form the asymmetric unit, which contains two independ-
ent conformers 23a-1 and 23a-2 (Figure 1). Conformers 23a-
1 and 23a-2 differ only by rotation of the TBSO substituents.
Atoms C2 and C5 deviate from the least-squares plane calcu-
lated for the other four atoms of the pyranose ring (i.e., O, C1,
C3, C4) by 0.64 and 0.60 Š, respectively, in conformer 23a-1.
The pyranose cycle of conformer 23a-2 is virtually superimpos-
Chem. Eur. J. 2016, 22, 4196 – 4205
www.chemeurj.org
4199
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
hand, the truncated Fourier formalism introduced by Haas-
noot[29] provides a description of six-membered-ring conforma-
tions in terms of three ring-puckering coordinates derived
from the endocyclic torsion angles. Most surprisingly, the
calculated ring-puckering parameters P2 ꢀ343, qꢀ88, and
Qꢀ648 for monosaccharide 23a define its pyranose-ring con-
0
formation as a transition between the S2 (skew-boat) and B2,5
(boat) conformations. The related thioglucosides were pro-
1
posed to adopt twisted-boat or C4 chair conformations in so-
0
lution.[24] The observed S2 (skew-boat)/B2,5 (boat) conformation
of 23a orients the silylated C2 and C3 hydroxy groups in pseu-
doaxial positions and the C4 and C5 substituents into pseu-
doequatorial positions. The lengths the of SiÀO bonds in 23a
vary from 1.622(6) to 1.705(7) Š. It is interesting to note that
the glycosidic substituents in both conformers possess the lon-
gest SiÀO bonds of 1.705(7) and 1.670(8) Š, respectively.
The reaction mixtures obtained in the silylation experiments
of monosaccharides 22, 24, and 25 with reagent 1b were ana-
1
lyzed in parallel by using H NMR spectroscopy and GC-MS to
double check each analytical method. The derivatization of
glucose (22) by using silyl sulfinates 1b and 1c also exclusively
provided a anomers of per-O-trimethylsilyl 23b (JH1ÀH2 =3.2 Hz,
99% conv.; ref. [24a]: 3JH1ÀH2 =3.0 Hz (CD2Cl2)) and per-O-trie-
thylsilyl 23c (3JH1ÀH2 =3.0 Hz, 97% yield of the isolated product;
Scheme 5). It is interesting to note that an alternative GC deri-
vatization of glucose with hexamethyldisilazane (HMDS) and
catalytic amounts of TMSOTf gave an a/b ratio of 3.5:1,[25a]
whereas BSTFA provided a mixture of a and b anomers.[27c] d-
Galactose (24) gave also only a anomer 25 (3JH1ÀH2 =2.8 Hz
(CD3CN); ref. [24a]: JH1ÀH2 =2.2 Hz (CD2Cl2)) upon treatment
with 1b, whereas alternative methods have given a mixture of
anomers.[25a] Per-O-silylation of d-mannose (26) with 1b in
CH3CN (GC-MS analysis) and CD3CN (NMR spectroscopy) result-
ed in a mixture of a and b anomers of a-27 (3JH1ÀH2 =2.1 Hz)
Scheme 5. Synthesis and analysis by using GC-MS and NMR spectroscopy of
per-O-silylated monosaccharides.
3
within the ratio of 2:1 (ref. [24f]: JH1ÀH2 =2.4 and 0.8 Hz for a-
3
27 and b-27 (CDCl3), respectively; ref. [24g]: JH1ÀH2!0 Hz for
b-27 (CDCl3)).
We further used our simple, mild, and fast silylation method
for the qualitative analysis of complex mixtures of compounds
by means of GC-MS analysis. For example, after the treatment
of a mixture of d-glucose (22), d-galactose (24), and d-man-
nose (26) with TMS sulfinate 1b for 4 hours in CH3CN at 708C,
a straightforward GC-MS analysis was performed and a clean
mixture of per-O-silylated glucopyranose (23b: tR =10.78 min),
galactopyranose (25: tR =10.61 min), and mannopyranose (a-
27: tR =10.33; b-27: tR =10.86 min) was obtained (see the GC-
MS traces presented in Figure 2). Furthermore, we performed
the GC separation of the nine-component mixture of 28–36
obtained after treatment of the corresponding alcohols with
trimethylsilyl sulfinate 1b in MeCN (Figure 3). The subsequent
submission of the mixture of 28–36 to GC provided a clean GC
trace, with a good baseline separation of peaks.
Figure 1. Superposition of two conformations of pentasilylated a-glucopyra-
noside 23a-1 and 23a-2 obtained by X-ray studies. The hydrogen atoms
have been omitted for clarity. Selected bond lengths [Š] and angles [8] for
23a-1: C1-O1 1.39(1), C2-O2 1.41(1), C3-O3 1.42(1), C4-O4 1.42(1), C6-O5
1.39(1), C1-O1-Si1 120.3(6), C2-O2- Si2 125.7(6), C3-O3- Si3 127.4(6), C4-O4-
Si4 126.5(5), C6-O5-Si5 125.3(6), Si1-O1 1.705(7), Si2-O2 1.639(7), Si3-O3
1.658(6), Si4-O4 1.645(7), Si5-O5 1.632(6).
Finally, we used our silylation technique for the purpose of
quantitative GC-MS analysis of thermally unstable hydroxy
compounds with low volatility. Calibration curves (i.e., concen-
tration c [mgmLÀ1] vs. GC mass-selective-detector correlation
area) were constructed for trimethylsilylated glycerol (30), tar-
able with the pyranose ring of conformer 23a-1, in which
atoms C2 and C5 deviate from the least-squares plane of the
other atoms by 0.69 and 0.61 Š, respectively. On the other
Chem. Eur. J. 2016, 22, 4196 – 4205
www.chemeurj.org
4200
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
Figure 2. GC-MS traces of a mixture of per-O-silylated glucopyranose (23),
galactopyranose (25), and mannopyranose (a-27 and b-27; tR =10.78, 10.61,
10.33, 10.86 min, respectively). Capillary column: HP-5MS (5% phenylmethyl-
siloxane) 30 m”0.25 mm; injector temperature=2508C; eluent=He; flow
rate=0.8 mLminÀ1; split injection=600:1; injection volume=0.2 mL; temper-
ature regime=708C for 2 min, 208CminÀ1 until 3108C; MS detector (ESI,
70 eV): MS Quad 1508C; MS source=2308C.
&
Figure 4. GC-MS calibration curves for trimethylsilylated d-mannose (27, ),
~
*
glycerol (30, ), and tartaric acid (36, ) after their derivatization in situ with
1b. Data were fitted by using a linear-fitting model y=a+bx: 27:
a=À1.07Æ0.08, b=3.89Æ0.05; 30: a=4.86Æ0.03, b=5.05Æ0.02; 36:
a=À0.006Æ0.001, b=0.19Æ0.01 (standard error values are given).
mated to be 0.7, 0.5, and 1.0% for 30, 36, and 27 by compar-
ing with the measurements and the control samples. In addi-
tion to their applications for the silylation of polyols and glyco-
sides, silyl sulfinates 1a–d can be thus used as new derivatiza-
tion reagents for qualitative and quantitative GC analysis.
Conclusion
We have found a new catalytic system for the sila-ene reaction
of allylsilanes 3a–d with SO2. The utilization of (CuOTf)2·C6H6 as
a catalyst (2.5% mol) permitted the preparation of powerful si-
lylation reagents, namely, silyl sulfinates 1a–d, on a multigram
scale. By employing 1a–d, the silylation of sterically hindered
systems, such as tertiary alcohols and unstable aldols that
readily eliminate water, was performed in high yields on
a minute timescale. In most cases, the purification of the sily-
lated products could simply be carried out by solvent evapora-
tion because the byproducts (SO2 +isobutylene) of the reac-
tion are volatile. The regioselective semiprotection of polyols,
including carbohydrate derivatives, and the direct one-step
per-O-silylation of monosaccharides has also been developed.
To the best of our knowledge, this report has also given the
first fully described synthesis and analysis of the molecular
structure and pyranose conformation of per-O-tert-butyldime-
thylsilyl-a-d-glucopyranose,[25d] which was possible due to high
reactivity of tert-butyldimethylsilyl-2-methylprop-2-ene-1-sulfi-
nate (1a). Silyl sulfinates were also used for silyl derivatization
prior to the qualitative and quantitative GC analysis of polyhy-
droxyated compounds. Thus, silyl sufinates 1a–d are new sily-
lation reagents that should find wide applications in the syn-
thesis of complicated natural products, as analogues of biolog-
ical interest, and in analytical derivatization prior to GC analy-
sis. Further studies will be directed toward the synthesis and
conformational analysis of variously silylated glycosides by
means of NMR spectroscopic analysis and X-ray crystal diffrac-
tion studies and will be coupled to computational methods.
Figure 3. GC-MS traces of a mixture of O-silylated polyhydroxy compounds
and their retention times given in parenthesis [min]. Capillary column HP-
5MS (5% phenylmethylsiloxane) 30 m”0.25 mm”0.25 mm; injector tempera-
ture=2508C; eluent=He, flow rate=0.8 mLminÀ1; split injection=100:1; in-
jection volume=0.2 mL; temperature regime=508C for 2 min, 108CminÀ1
until 3108C; MS detector (ESI, 70 eV): MS Quad 1508C; MS source=2308C.
taric acid (36), and d-mannose (27) obtained in situ (Figure 4).
The experimental error of the developed technique was esti-
Chem. Eur. J. 2016, 22, 4196 – 4205
www.chemeurj.org
4201
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
3H; Me-C(2)), 1.57 (s, 2H-C(1)), 0.91 (s, 9H; H-C(1’)), 0.01 ppm (s,
6H; H-C(3’)).
Experimental Section
General
General procedure for the preparation of trialkylsilyl-2-methyl-
prop-2-ene-1-sulfinates 1a–d: (CuOTf)2PhH (1.07 g, 2.14 mmol,
2.5 mol%) in dry dichloromethane (15 mL) was placed in an auto-
clave. SO2, dried over a column of P2O5 and alumina oxide, was
poured to the solution at À788C, and the solution was stirred for
30 min. (2-Methylallyl)silane 3a–d (85.30 mmol) was added by sy-
ringe in the autoclave, which was heated at 508C for 12 h. The
excess of SO2 and CH2Cl2 were evaporated under reduced pressure
(30 Torr) at À208C. The resulting solution was transferred into
a flask and distilled under reduced pressure to give pure silyl meth-
allylsulfinate. The spectral data for 1a–c are in agreement with
those data previously reported for these compounds.[19a]
Commercial reagents (Fluka, Aldrich) were used without purifica-
tion, if not noted differently. Solvents were distilled prior to use:
THF, dioxane, and toluene from Na and benzophenone; MeOH
from Mg and I2; acetonitrile, DMF, DMSO, 1,1,3,3-tetramethylurea
(TMU), N-methylpyrrolidone (NMP), and CH2Cl2 from CaH2. Deuter-
ated solvents were distilled prior to use: CD2Cl2 and CDCl3 from
CaH2. SO2 was dried by passing through a column filled with P2O5
(Fluka 06400) and Al2O3 for drying (Al2O3 basic activated type
5016A Brockman I; Aldrich 19,944-3). The solutions after the reac-
tions and extractions were evaporated on a rotatory evaporator
under reduced pressure. Liquid/solid flash chromatography (FC)
was carried out on columns of silica gel (0.040–0.63 mm, Merck
no. 9385, silica gel 60, 240–400 mesh). The eluent was a mixture of
light petroleum ether (PE) and ethyl acetate (EtOAc), if not stated
otherwise. TLC analysis for reaction monitoring was carried out on
Merck silica gel 60 F254 plates with detection by UV light, the Pan-
caldi reagent ((NH4)6MoO4, Ce(SO4)2, H2SO4, and H2O) or KMnO4. IR
tert-Butyldimethylsilyl-2-methylprop-2-ene-1-sulfinate
(1a)[19a]
Colorless oil, 95% yield (19.02 g, 81.14 mmol); b.p. 648C at 0.4 Torr;
1H NMR (CDCl3, 400 MHz): d=5.09 (brs, 1H; H-C(3)), 4.99 (brs, 1H;
H-C(3)), 3.39 (s, 2H; C(1)), 1.89 (s, 3H; Me-C(2)), 0.96 (s, 9H; H-C(1’)),
0.27 (brs, 3H; Me-Si), 0.29 ppm (brs, 3H; Me-Si).
General procedure for the silylation of alcohols 5a–h: Triethylsil-
yl-2-methylprop-2-ene-1-sulfinate (1c; 91 mg, 0.388 mmol, 1 equiv)
was added to a stirred solution of alcohol 5a–h (0.388 mmol) in
CH3CN (1 mL) in an argon atmosphere at RT. After the full conver-
sion was confirmed by TLC analysis, the reaction mixture was con-
centrated under reduced pressure and filtrated though a plug of
silica gel.
1
spectra were recorded on a Varian 800 FTIR spectrometer. H NMR
spectra were recorded on Bruker ARX-300 or ARX-400 spectrome-
ters (300 or 400 MHz) and the d(H) signals are given in ppm rela-
tive to the residual solvent signals as an internal reference (CDCl3:
d(H)=7.27, CD2Cl2: d(H)=5.30, [D6]DMSO: d(H)=2.50, [D7]DMF:
d(H)=2.90 ppm). 13C NMR spectra were recorded on the same in-
1
strument as for the H NMR spectra (75.5 or 100.6 MHz), and d(C)
3-O-(Triethylsilyl)cholesterol (6a): White solid, 98% yield (191 mg,
0.38 mmol); Rf =0.37 (EP/diethyl ether=10:1); 1H NMR (400 MHz,
CDCl3): d=5.36 (d, J=5.0 Hz, 1H; H-C(6)), 3.48 (sept, J=11.0,
4.5 Hz, 1H; H-C(3)), 2.30 (dd, J=4.5, 13.0 Hz, 1H; H-C(4a)), 2.24
(ddd, J=13.0, 2.0 Hz, 1H; H-C(4b)), 2.05–1.92 (m, 2H; H-7a, H-
C(12a)), 1.89–1.83 (m, 2H; H-1a, H-C(16)), 1.72 (m, 1H; H-2b), 1.62–
1.1 (22H; all residual protons, except methyl groups), 1.02 (s, 3H;
H-C(19)), 0.90 (d, J=6.5 Hz, 3H; H-C(21)), 0.96 (t, J=8.0 Hz, 9H; H-
C(2’)), 0.7 (s, 3H; H-C(18)), 0.56 and 0.53 ppm (q, J=8.0 Hz, 6H; H-
C(1’)); the spectroscopic data for 6a are in agreement with those
data previously reported for this compound.[28b]
signals are given in ppm relative to the signal of the solvent as an
internal reference (CDCl3: d(C)=77.1, CD2Cl2: d(C)=53.5,
[D6]DMSO: d(C)=39.4, [D7]DMF: d(C)=31.0 ppm). The J(H,H) cou-
pling constants were obtained by means of selective irradiation ex-
periments. HRMS was performed on Jeol AX-505 spectrometer. GC-
MS analysis of the TMS derivatives, their mixtures, and standards
for calibration were carried out on a Hewlett–Packard Agilent 6890
system, equipped with a mass-selective detector system. The capil-
lary column was an Agilent 19091 J-433 HP-5 5% phenyl methyl si-
loxane, 30 m”0.25 mm i.d. with a film thickness of 0.25 mm. The in-
jector temperature was maintained at 2508C. The maximum tem-
perature of the capillary column was 3258C. The carrier gas was
helium at a constant flow rate of 0.8 mLminÀ1. Data were fitted by
using OriginPro 9.0 SR 2 (OriginLab Corporation). CCDC contains
the supplementary crystallographic data for this paper. These data
are provided free of charge by The Cambridge Crystallographic
Data Centre.
General procedure for the silylation of 1-phenylethanediol (7):
Trialkylsilyl-2-methylprop-2-ene-1-sulfinate 1a, 1c, or 1d
(0.29 mmol, 1 equiv) was added in an argon atmosphere at RT to
a stirred solution of 1-phenylethanediol (7; 40 mg, 0.29 mmol) in
[D7]DMF (0.7 mL) containing toluene as an internal reference. After
full conversion was confirmed by 1H NMR spectroscopic analysis,
the reaction mixture was concentrated under reduced pressure
and filtrated though a plug of silica gel.
General procedure for the synthesis of trialkylyl(2-methylallyl)si-
lane reagents 3a–d: A few drops of iodine were added to a mix-
ture of magnesium (7 g, 0.29 mol) in anhydrous THF (20 mL) to ini-
tiate the reaction. A solution of 3-chloro-2-methylpropene (18.11 g,
0.20 mol) and trialkylsilyl chloride (0.15 mol) in THF (130 mL) was
dropwise added over 5 h to the reaction mixture at reflux in an
argon atmosphere. The reaction mixture was heated to reflux for
an additional 12 h when the addition was complete. The precipi-
tate was filtrated and the residue was extracted with petroleum
ether. The combined filtrate and extracts were distilled in a Vigreux
column under atmospheric pressure to remove the excess of or-
ganic solvents. Trialkylyl(2-methylallyl)silanes were obtained by dis-
tillation under reduced pressure. The spectral data for 3a–d are in
agreement with those data previously reported for these com-
pounds.[19a]
1-Phenyl-2-[(triethylsilyl)oxy]ethanol (13a):[19a] Colorless oil, 93%
yield, (68 mg, 0.27 mmol); Rf =0.29 (EP/diethyl ether=10:3);
1H NMR (CDCl3, 400 MHz): d=7.49–7.27 (m, 5H; aromatic), 4.80
(dd, J=8.9, J=3.9 Hz, 1H; H-C(1)), 3.78 (dd, J=10.2, 3.9 Hz, 1H; H-
C(2)), 3.57 (dd, J=10.2, 8.9 Hz, 1H; H-C(2)), 3.09 (s, 1H; H-O), 0.99
(t, J=8.3 Hz, 9H; SiCH2CH3), 0.66 ppm (q, J=8.3 Hz, 6H; SiCH2CH3).
General procedure for the silylation of methyl-a-d-pyranosides
8–10: Trialkylsilyl-2-methylprop-2-ene-1-sulfinate 1a or 1d
(0.515 mmol, 1 equiv) was added to a NMR tube containing a solu-
tion of a methyl-a-d-pyranoside (100 mg, 0.515 mmol) in [D7]DMF
(1.5 mL) containing toluene as an internal reference. The reaction
1
was followed by H NMR spectroscopic analysis at RT. The reaction
was finished after 15 min and the obtained reaction mixture was
quenched with buffer (pH 7), extracted with CH2Cl2, dried over
Na2SO4, and evaporated under reduced pressure. The resulting oil
was purified by filtration though a plug of silica gel.
tert-Butyldimethyl(2-methylallyl)silane (3a):[19a] Colorless oil, 92%
yield (23.51 g, 0.137 mol); b.p. 1408C at 1 atm; 1H NMR (CDCl3,
400 MHz): d=4.62 (brs, 1H; H-C(3)), 4.51 (brs, 1H; H-C(3)), 1.74 (s,
Chem. Eur. J. 2016, 22, 4196 – 4205
www.chemeurj.org
4202
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
Methyl-6-O-(tert-butyldimethylsilyl)-a-d-glucopyranoside (14a):
White powder, 97% yield (154 mg, 0.50 mmol); 1H NMR ([D7]DMF,
400 MHz): d=5.17 (d, J=4.8 Hz, 1H; OH-C(4)), 5.08 (d, J=4.5 Hz,
1H; OH-C(3)), 4.85 (d, J=6.5 Hz, 1H; OH-C(2)), 4.80 (d, J=3.4 Hz,
1H; H-C(1)), 4.12 (dd, J=11.0, 2.1 Hz, 1H; H-C(6a)), 3.95 (dd, J=
11.0, J=6.2 Hz, 1H; H-C(6b)), 3.78 (ddd, J=4.5, 8.5, 3.8 Hz, 1H; H-
C(3)) 3.67 (m, J=3.8, 2.1, 4.8 Hz, 1H; H-(5)), 3.52 (s, 3H; OCH3), 3.50
(t, J=3.8 Hz, 1H; H-C(2)), 3.44–3.38 (ddd, J=4.5, 8.5, 5.1 Hz, 1H; H-
C(4)), 1.08 (s, 9H; H-tBuSi), 0.26 ppm (s, 6H; H-MeSi); the spectro-
scopic data for 14a are in agreement with those data previously
reported for this compound.[28h]
layer with aqueous NaCl, drying, evaporation, and purification by
flash chromatography (petroleum ether/ethyl acetate=9:1) afford-
ed the pure elimination product 20. Colorless oil, quant. yield
(20 mg, 0.05 mmol); Rf =0.75 (petroleum ether/ethyl acetate=9:1);
1
[a]2D5 =À22 (c=0.3 in CHCl3); H NMR (CDCl3, 400 MHz): d=8.98 (s,
1H; CHO), 7.32–7.28 (m, 5H; arom), 5.99 (d, J=10.1 Hz, 1H; H-
C(5)), 5.13 (q, J=6.8 Hz, 1H; H-C(1’)), 4.39 (q, J=6.5 Hz, 1H; H-
C(1’’)), 3.25 (t, J=5.9 Hz, 1H; H-C(3)), 2.75 (2 m, 2H; H-C(4), H-C(2)),
2.59 (sept, J=7.0 Hz, 1H; (CH3)2CHCOO-C(1)), 1.55 (s, 3H; H3C-C(6)),
1.39 (d, J=7.0 Hz, 3H; H-C(2’’)), 1.37 (d, J=6.8 Hz, 3H; H-C(2’)),
1.18–1.16 (2 d, J=7.0 Hz, 6H; (CH3)2CHCOO-C(1)), 1.03 (d, 3H; J=
7.1 Hz, CH3-C(2)), 0.91 ppm (d, J=6.8 Hz, 3H; CH3-C(4)); 13C NMR
(CDCl3, 100.6 MHz): d=195.6, 174.3, 149.5, 143.2, 128.4, 128.0,
127.1, 112.4, 79.2, 77.1, 40.1, 34.8, 34.2, 29.7, 23.6, 19.2, 19.1, 14.9,
12.6, 10.8 ppm; IR (film): n˜ =2964, 2924, 2851, 1750, 1690, 1639,
1454, 1414, 1386, 1264, 1096, 1020, 865, 797, 702 cmÀ1; MS (CI;
NH3): m/z (%) 404(21) [M+18]+, 307(31), 283(38), 265(34), 212(37),
195(90), 105(100); HRMS (MALDI): m/z calcd for C24H34O4Na:
409.2354; found: 409.2349 [M+Na]+.
General procedure for the silylation of a-d-glucal (11): Trialkylsil-
yl-2-methylprop-2-ene-1-sulfinate 1a (1.36 mmol, 2 equiv) or 1d
(0.68 mmol, 1 equiv) was added to a NMR tube containing a solu-
tion of d-glucal (11; 100 mg, 0.68 mmol) in [D7]DMF (0.6 mL) con-
taining toluene as an internal reference. The reaction was followed
1
by H NMR spectroscopic analysis. The obtained reaction mixtures
were quenched with water buffer (pH 7), extracted with CH2Cl2,
dried over Na2SO4, and evaporated under reduced pressure. The re-
sulting oil was purified by filtration though a plug of silica gel.
(+)-(1Z,2S,3S,4S,5S,6S)-5-{[(tert-Butyl(dimethyl)silyl]oxy}-1-ethyli-
3,6-Bis-O-(tert-butyldimethylsilyl)-d-Glucal (17a): White powder,
96% yield (243 mg, 0.65 mmol); [a]2D5 =À30.2 (c=0.75 in CHCl3);
1H NMR (CDCl3, 400 MHz): d=6.31 (dd, J=1.7, 6.1 Hz, 1H; H-C(1)),
4.65 (dd, J=2.4, 6.1 Hz, 1H; H-C(2)), 4.24 (dt, J=6.1, 1.7 Hz, 1H; H-
C(3)), 4.00 (dd, J=4.8, 11.1 Hz, 1H; H-C(6a)), 3.92 (dd, J=3.7,
11.1 Hz, 1H; H-C(6b)), 3.88–3.84 (ddd, J=3.7, 4.8 Hz, J=8.5 Hz, 1H;
H-C(5)), 3.80 (dd, J=6.5, 8.5 Hz, 1H; H-C(4)), 2.55 (brs, 1H; C(4)-
OH), 0.94 (d, J=1.7 Hz, 18H; H-C(1’)), 0.15 (d, J=1.0 Hz, 6H; H-
C(3’)), 0.12 ppm (d, J=1.0 Hz, 6H; H-C(3’)); the spectroscopic data
for 17a are in agreement with those data previously reported for
this compound.[28i]
dene-2,4,6-trimethyl-7-oxo-3-[(1S)-1-phenylethoxy)heptyl
2-
methylpropanoate (21): tert-Butyldimethylsilyl methallylsulfinate
(11.3 mg, 0.148 mmol, 1.2 equiv) was added to a solution of alcohol
19 (50 mg, 0.123 mmol, 1 equiv) in CH3CN (1 mL). The reaction mix-
ture was stirred until total conversion, as monitored by TLC analy-
sis. Evaporation of the solvent gave the pure product 21. Colorless
oil, 89% yield, (68 mg, 0.11 mmol); Rf =0.52 (petroleum ether/ethyl
acetate=9:1); [a]D25 = +7 (c=0.25 in CHCl3); 1H NMR (CDCl3,
400 MHz): d=9.72 (d, J=2.5 Hz, 1H; CHO), 7.37–7.28 (m, 5H;
arom), 5.21 (q, J=7.0 Hz, 1H; H-C(1’)), 4.43 (q, J=6.8 Hz, 1H; H-
C(1’’)), 3.47 (d, 1H; H-C(5)), 3.25 (dd, J=4.6, 2.7 Hz, 1H; H-C(3)),
2.93 (quint, J=5.5 Hz, 1H; H-C(2)), 2.55 (sept, J=7.1 Hz, 1H;
(CH3)2CHCOO-C(1)), 2.26 (q, J=6.9 Hz, 1H; H-C(4)), 1.88 (dquint, J=
7.2, 2.6 Hz, 1H; H-C(6)), 1.47 (d, J=6.6 Hz, 3H; H-C(2’)), 1.41 (d, J=
6.8 Hz, 3H; H-C(2’’)) 1.19–1.16 (2 d, J=7.1 Hz, 6H; (CH3)2CHCOO-
C(1)), 1.09 (d, J=7.3 Hz, 3H; CH3-C(2)), 0.93 (d, J=7.2 Hz, 3H; CH3-
C(6)), 0.82 (s, 9H; TBS), 0.79 (d, J=6.9 Hz, 3H; CH3-C(4)), À0.07 (s,
3H; TBS), À0.08 ppm (s, 3H; TBS); 13C NMR (CDCl3, 100.6 MHz): d=
205.2, 174.2, 150.4, 143.1, 128.4, 127.8, 127.1, 111.8, 78.3, 75.6, 75.2,
48.2, 40.0, 39.4, 41.2, 25.7, 23.9, 19.2, 19.1, 13.2, 11.5, 10.8, 10.4,
À4.3, À5.1 ppm; IR (film): n˜ =2964, 2930, 2857, 2360, 2342, 1748,
1728, 1716, 1471, 1456, 1386, 1258, 1113, 1081, 1024, 912,
836 cmÀ1; MS (CI; NH3): m/z (%): 518(8) [M]+, 391(52), 253(100),
251(67), 235(20), 207(32), 104(10); HRMS (MALDI): m/z calcd for
C30H50O5SiNa: 542.3358; found: 542.33592 [M+Na]+.
General procedure for the silylation of methyl-4,6-O-benzyli-
dene-a-d-glucopyranoside (12): Trialkylsilyl-2-methylprop-2-ene-1-
sulfinate 1a–d (0.354 mmol, 1 equiv) was added to a stirred solu-
tion of methyl-4,6-O-benzylidene-a-d-glucopyranoside (100 mg,
0.354 mmol) in DMF (1.5 mL) in an argon atmosphere at RT. The re-
action was followed by TLC analysis (petroleum ether/ethyl ace-
tate=10:2). At the end of the reaction, the reaction mix was
quenched with water buffer (pH 7), extracted with CH2Cl2, and
dried over Na2SO4. The obtained solution was evaporated under re-
duced pressure and purified by filtration though a plug of silica gel
(petroleum ether/ethyl acetate=10:2).
(+)-Methyl-4,6-O-benzylidene-2-O-(tert-butyldimethylsilyl)-a-d-
glucopyranoside (18a): White powder, 96% yield (134 mg,
0.34 mmol); Rf =0.57; [a]2D5 = +57.8 (c=1.1 in CHCl3); 1H NMR
(CDCl3, 400 MHz): d=5.56 (s, 1H; PhCH), 4.68 (d, J=3.5 Hz, 1H; H-
C(1), 4.33 (dd, J=10.0, 5.0 Hz, 1H; H-C(6a)), 4.03 (t, J=9.5 Hz, 1H;
H-C(3)), 3.90–3.84 (ddd, J=9.0, 5.0, 3.5 Hz, 1H,H-C(5)), 3.76 (t, J=
10.0 Hz, 1H; H-C(6b)), 3.72 (dd, J=3.5, 9.5 Hz, 1H; H-C(2)), 3.52 (t,
J=9.0 Hz, 1H; H-C(4)), 3.46 (s, 3H; MeO), 0.95 (s, 9H; H-tBuSi),
0.16 ppm (d, J=1.5 Hz, 6H; MeSi); the spectroscopic data for 18a
are in agreement with those data previously reported for this com-
pound.[28i]
1,2,3,4,6-Penta-O-tert-butyldimethylsilyl-a-d-glucopyranose
(23a): tert-Butyldimethylsilyl-2-methylprop-2-ene-1-sulfinate (1b;
122.0 mg, 0.52 mmol, 15 equiv) was added to a stirred suspension
of d-glucose (22; 6.3 mg, 0.035 mmol, 1 equiv) in a mixture of
CD3CN (0.6 mL) and CDCl3 (0.6 mL) at ambient temperature. The re-
sulting reaction mixture was heated at 608C for 24 h (monitored
by NMR and GC-MS). The conversion of 99% was established by
1H NMR spectroscopic analysis by using toluene as an internal ref-
erence. MeOH (0.5 mL) was added and the volatiles were evaporat-
ed under reduced pressure. The oily residue was purified by prepa-
rative TLC (hexane/dichloromethane=4:1). Crystals were isolated
from a mixture of CD3CN (0.6 mL) and CDCl3 (0.2 mL). Yield=70%
(À)-(1Z,2S,3S,4R,5E)-1-Ethylidene-2,4,6-trimethyl-7-oxo-3-[(1S)-1-
phenylethoxy]hept-5-en-1-yl 2-methylpropanoate (20): This
product resulted from the silylation of 19 in basic media. Proce-
dure with triethylamine as the base: Triethylamine (21 mL,
0.15 mmol, 2.2 equiv) was added to a solution of aldehyde 19
(21 mg, 0.05 mmol, 1 equiv) in dichloromethane (2 mL). The reac-
tion mixture was cooled to À158C, treated with TBSOTf (14 mL,
0.06 mmol, 1.2 equiv), and allowed to reach RT over 5 h. The mix-
ture was poured into saturated aqueous NaHCO3 solution (1 mL).
Extraction with dichloromethane, washing the combined organic
1
(18.3 mg, 0.025 mmol); H NMR (CD3CN+CDCl3, 300 MHz): d=5.16
(d, J=3.2 Hz, 1H; H-C(1)), 4.02–3.95 (m, 1H; H-C(5)), 3.85 (bd, J=
3.8 Hz, 1H; H-C(4)), 3.83–3.68 (m, 4H; H-C(2), H-C(3), H-C(6)), 0.91,
0.90, 0.88 (3 s, 45H; 15”CH3), 0.11–0.04 ppm (m, 30H; 10”CH3);
13C NMR (CD3CN+CDCl3, 75.5 MHz,): d=91.6, 77.3, 76.7, 73.4, 72.7,
63.5, 26.5, 26.4, 26.3, 26.2, 26.0, 0.06 (2C), À0.04 (2C), À0.1 ppm;
Chem. Eur. J. 2016, 22, 4196 – 4205
www.chemeurj.org
4203
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
crystal data for 23a (C36H82O6Si5): Mr =751.47, monoclinic, P21, a=
12.1077(1), b=36.4878(5), c=12.1834(3) Š, b=112.7115(8)8, V=
4965.07(15) Š3, T=173(2) K, Z=4, m(MoKa)=0.178 mmÀ1, 21172 re-
flections measured, 21172 independent reflections, R1(obs) =0.093,
wR1(obs) =0.191, R1(all) =0.233, wR1(all) =0.244, S=1.01.
(2.22 mgmLÀ1),
(2.29 mgmLÀ1).
22,63 mg
(2.26 mgmLÀ1),
and
22.87 mg
Calibration curve for tris-O-trimethylsilyl glycerol (30) generated
in situ: The following samples of glycerol were weighted into
a volumetric flask (20 mL), derivatized, and analyzed as described
above: 12.25 mg (0.61 mgmLÀ1), 17.17 mg (0.86 mgmLÀ1),
22.27 mg (1.11 mgmLÀ1), 33.69 mg (1.68 mgmLÀ1), 36.14 mg
(1.81 mgmLÀ1), 41.84 mg (2.09 mgmLÀ1).
Monosaccharides 23b, 25, and 27: CD3CN (1 mL) and silyl sulfi-
nate 1b (10 equiv) were added to monosaccharides 22, 24, or 26
measured in a GC vial, and the resulting mixture was stirred in an
argon atmosphere for 18 h at 608C. The GC-MS and NMR spectro-
scopic analyses were performed and revealed full conversion into
the corresponding products 23b, 25, or 27, respectively. The sam-
ples of silylated monosaccharides were injected into the gas chro-
matograph in the split mode (100:1; injection volume=1.00 mL).
The oven temperature was held at 708C for 2 min, increased to
3108C at 208CminÀ1, and held at 3108C for 2 min.
Calibration curve for per-O-trimethylsilylated tartaric acid (36)
generated in situ: The following aliquots of l-(+)-tartaric acid
were measured into a volumetric flask (10 mL), derivatized, and an-
alyzed as described above: 7.50 mg (0.75 mgmLÀ1), 9.21 mg
(0.92 mgmLÀ1), 9.73 mg (0.97 mgmLÀ1), 13.51 mg (1.35 mgmLÀ1),
18.83 mg (1.88 mgmLÀ1), 21.06 mg (2.11 mgmLÀ1), 21.80 mg
(2.18 mgmLÀ1),
(2.77 mgmLÀ1).
24.61 mg
(2.46 mgmLÀ1),
and
27.70 mg
Silylation of a mixture of monosaccharides: CH3CN (1 mL) and
silyl sulfinate 1b (255 mg, 227 mL, 10 equiv) were added to mono-
saccharides d-(+)-glucose (22; 13.46 mg, 0.075 mmol), d-(+)-galac-
tose (24; 4.45 mg, 0.025 mmol), and d-(+)-mannose (26; 5.99 mg,
0.033 mmol) measured into a GC vial. The resulting mixture was
stirred in an argon atmosphere for 4 h at 708C and GC-MS analysis
was then carried out. The mixture of silylated monosaccharides
were injected into the gas chromatograph in the split mode
(600:1; injection volume=0.20 mL). The oven temperature was held
at 708C for 2 min, increased to 3108C at 208CminÀ1, and held at
3108C for 2 min (the GC-MS traces are depicted in Figure 2).
Acknowledgements
This work was supported by the Swiss National Science Foun-
dation and by the Latvian Council of Science Grant No
12.0291. D.M. would like to thank to the ERASMUS+ program
2015/16-2020/21. We also thank Mr. Martial Rey and Francisco
Sepulveda for technical help. Dr. Vitalijs Rjabovs is acknowl-
edged for helpful discussions.
Silylation of a mixture of polyhydroxy compounds and analysis
of the silylated forms 28–36: CH3CN (1 mL) and TMS sulfinate 1b
(200 mg, 180 mL, 1.041 mmol) were added to ethane-1,2-diol
(4.16 mg, 0.067 mmol), 2,2-dimethylpropane-1,3-diol (2.74 mg,
0.026 mmol), glycerol (2.38 mg, 0.026 mmol), resorcinol (5.82 mg,
0.053 mmol), 2-ethyl-2-(hydroxymethyl)propane-1,3-diol (3.73 mg,
Keywords: chemoselectivity
regioselectivity · silyl sulfinates · silylation
·
gas chromatography
·
0.0278 mmol),
(R)-2-hydroxy-2-phenylacetic
acid
(5.64 mg,
[1] a) P. J. Kocienski in Protecting Groups (Eds.: D. Enders, R. Noyori, B. M.
Trost), Thieme, Stuttgart, 2005; b) T. W. Green, P. G. M. Wuts, Greene’s
Protective Groups in Organic Synthesis, 4rd ed., Wiley, New York, 2006.
[2] J. S. Davies, L. C. L. Higginbotham, E. J. Tremeer, C. Brown, R. S. Treadg-
old, J. Chem. Soc. Perkin Trans. 1 1992, 3043.
[3] The SiÀF bond strength is about 30 kcalmolÀ1 stronger than the SiÀO
bond. See also: J. W. Gillard, R. Fortin, H. E. Morton, C. Yoakim, C. A.
Quesnell, S. Daignault, Y. Guindon, J. Org. Chem. 1988, 53, 2602.
[4] a) R. D. Crouch, Tetrahedron 2013, 69, 2383; b) R. D. Crouch, Synth.
Commun. 2013, 43, 2265; c) G. Van Look, G. Simchen, J. Heberle, Silylat-
ing Agents, 2nd ed., Fluka, Buchs, 1995.
[5] a) K. Blau, J. Halket, Handbook of Derivatives for Chromatography,
2nd ed., Wiley, Chichester, 1993; b) J. S. Splitter, F. Turecek, Applications
of Mass Spectrometry to Organic Stereochemistry, Wiley-VCH, Weinheim,
1994.
[6] J. M. Halket, V. G. Zaikin, Eur. J. Mass Spectrom. 2003, 9, 1.
[7] J. A. Bowden, D. M. Colosi, D. C. Mora-Montero, T. J. Garrett, R. A. Yost, J.
Chromatogr. B 2009, 877, 3237.
[8] E. J. Corey, A. Venkateswarlu, J. Am. Chem. Soc. 1972, 94, 6190.
[9] A. Shareef, M. J. Angove, J. D. Wells, J. Chromatogr. A 2006, 1108, 121.
[10] a) L. Birkofer, P. Sommer, J. Organomet. Chem. 1975, 99, C1; b) M. N. Gal-
braith, D. H. S. Horn, E. J. Middleton, R. J. Hackney, Chem. Commun.
1968, 466; c) S. D. Young, C. T. Buse, C. H. Heathcock, Org. Synth. 1985,
63, 79; d) Z. Lasocki, Syn. Inorg. Metal.-Org. Chem. 1973, 3, 29; e) J. R.
Hwu, D. A. Anderson, N. Wang, M. M. Buchner, P. Gani, S. C. Tsay, Chem.
Ber. 1990, 123, 1667; f) A. Iida, A. Horii, T. Misaki, Y. Tanabe, Synthesis
2005, 2677; g) R. Malherbe, G. Rist, D. Bellus, J. Org. Chem. 1983, 48,
860; h) E. J. Nanni, M. E. Lovette, R. D. Hicks, K. W. Fowler, M. F. Borgerd-
ing, J. Chromatogr. 1990, 505, 365; i) Y. Tanabe, M. Murakami, K. Kitaichi,
Y. Yoshida, Tetrahedron Lett. 1994, 35, 8409; j) E. Vedejs, N. S. Bennett,
L. M. Conn, S. T. Diver, M. Gingras, S. Lin, P. A. Oliver, M. J. Peterson, J.
Org. Chem. 1993, 58, 7286; k) A. R. Gholson, R. St. Louis, H. H. Hill, J.
Chromatogr. 1987, 408, 329; l) H. Matsunaga, M. Katano, H. Yamamoto,
M. Mori, K. Takata, M. Nishi, J. Chromatogr. 1989, 481, 368.
0.037 mmol), l-(À)-malic acid (4.30 mg, 0.032 mmol), pentaerythri-
tol (3.05 mg, 0.022 mmol), and l-(+)-tartaric acid (5.79 mg,
0.039 mmol) measured into a GC vial. The resulting mixture was
stirred in an argon atmosphere for 4 h at 508C, and GC-MS analysis
was then performed. The sample containing the silylated polyhy-
droxyates 28–36 was injected into a gas chromatograph in the
split mode (split ratio=100:1, injection volume=0.20 mL). The
oven temperature was held at 508C for 3 min, increased to 1208C
at 108CminÀ1, increased to 3108C at 1008CminÀ1, and held at
3108C for 3 min (the GC-MS traces are depicted in Figure 3).
General procedure to obtain calibration curves for 1,2,3,4,6-
penta-O-trimethylsilyl-d-mannopyranose (27), tris-O-trimethyl-
silyl glycerol (30), and per-O-trimethylsilylated tartaric acid (36)
generated in situ: The samples of d-mannose (26), glycerol or l-
(+)-tartaric acid were precisely weighed in a volumetric flask (10 or
20 mL) and diluted with anhydrous CH3CN. Trimethylsilyl sulfinate
1b (2 equiv per OH group) was added, the volumetric flask was
filled to the mark, and the resulting solution was left for 3 h. The
samples were transferred into GC vials and analyzed 3” each. The
samples were injected into the gas chromatograph in a splitless
mode (injection volume=0.20 mL). The oven temperature was held
at 508C for 2 min, increased to 3108C at 1008CminÀ1, and held at
3108C for 2 min (the calibration curves are depicted in Figure 4).
Calibration curve for 1,2,3,4,6-penta-O-trimethylsilyl-d-manno-
pyranose (27) generated in situ: The following aliquots of d-man-
nose were measured into a volumetric flask (10 mL), derivatized,
and analyzed as described above: 5.17 mg (0.52 mgmLÀ1), 6.89 mg
(0.69 mgmLÀ1), 9.31 mg (0.93 mgmLÀ1), 11.21 mg (1.12 mgmLÀ1),
12.79 mg (1.28 mgmLÀ1), 18.54 mg (1.85 mgmLÀ1), 22.23 mg
Chem. Eur. J. 2016, 22, 4196 – 4205
www.chemeurj.org
4204
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
[11] a) H. Firouzabadi, B. Karimi, Synth. Commun. 1993, 23, 1633; b) B. Karimi,
B. Golshani, J. Org. Chem. 2000, 65, 7228; c) R. Ghorbani-Vaghei, M. A.
Zolfigol, M. Chegeny, H. Veisi, Tetrahedron Lett. 2006, 47, 4505; d) D. Zar-
eyee, B. Karimi, Tetrahedron Lett. 2007, 48, 1277; e) F. Shirini, S. Akbari-
Dadamahaleh, A. Mohammad-Khah, A.-R. Aliakbar, C. R. Chim. 2013, 16,
207.
[12] a) J. R. Frost, C. M. Pearson, T. N. Snaddon, R. A. Booth, S. V. Ley, Angew.
Chem. Int. Ed. 2012, 51, 9366; Angew. Chem. 2012, 124, 9500; b) D. J.
Harrison, D. R. Edwards, R. McDonald, L. Rosenberg, Dalton Trans. 2008,
3401; c) R. J. P. Corriu, C. Guerin, J. Organomet. Chem. 1982, 225, 141;
d) I. Paterson, T. Paquet, Org. Lett. 2010, 12, 2158; e) S. Nambiar, J. F.
Daeuble, R. J. Doyle, K. G. Taylor, Tetrahedron Lett. 1989, 30, 2179.
[13] a) T. Morita, Y. Okamoto, H. Sakurai, Tetrahedron Lett. 1980, 21, 835;
b) G. A. Olah, A. Husain, B. G. B. Gupta, G. F. Salem, S. C. Narang, J. Org.
Chem. 1981, 46, 5212; c) A. Hosomi, H. Sakurai, Chem. Lett. 1981, 85;
d) G. A. Olah, A. Husain, B. P. Singh, Synthesis 1983, 892; e) T. Suzuki, T.
Watahiki, T. Oriyama, Tetrahedron Lett. 2000, 41, 8903; f) T. Shibata, K.
Kanda, Y. Ueno, R. Fujiwara, Bull. Chem. Soc. Jpn. 2006, 79, 1146; g) A.
Hosomi, A. Shirahata, Y. Araki, H. Sakurai, J. Org. Chem. 1981, 46, 4631;
h) J.-W. Park, C.-H. Jun, Org. Lett. 2007, 9, 4073.
[19] a) X. Huang, C. Craita, L. Awad, P. Vogel, Chem. Commun. 2005, 1297;
b) I. Novosjolova, M. Turks, Phosphorus Sulfur Silicon Relat. Elem. 2015,
190, 1251.
[20] a) L. Bouchez, P. Vogel, Synthesis 2002, 225; b) X. Huang, C. Craita, P.
Vogel, J. Org. Chem. 2004, 69, 4272.
[21] L. H. Li, D. Wang, T. H. Chan, Tetrahedron Lett. 1991, 32, 2879.
[22] C. Margot, M. Rizzolio, M. Schlosser, Tetrahedron 1990, 46, 2411.
[23] a) C. H. Marzabadi, J. E. Anderson, J. Gonzalez-Outeirino, P. R. J. Gaffney,
C. G. H. White, D. A. Tocher, L. J. Todaro, J. Am. Chem. Soc. 2003, 125,
15163; b) Y. Okada, T. Mukae, K. Okajima, M. Taira, M. Fujita, H. Yamada,
Org. Lett. 2007, 9, 1573; c) C. M. Pedersen, L. U. Nordstrøm, M. Bols, J.
Am. Chem. Soc. 2007, 129, 9222; d) H. H. Jensen, C. M. Pedersen, M.
Bols, Chem. Eur. J. 2007, 13, 7576.
[24] a) A. Bhat, J. Gervay-Hague, Org. Lett. 2001, 3, 2081; b) W. Du, J. Gervay-
Hague, Org. Lett. 2005, 7, 2063; c) W. Du, S. S. Kulkarni, J. Gervay-Hague,
Chem. Commun. 2007, 2336; d) S. S. Kulkarni, J. Gervay-Hague, Org. Lett.
2008, 10, 4739; e) M. Schombs, F. E. Park, W. Du, S. S. Kulkarni, J.
Gervay-Hague, J. Org. Chem. 2010, 75, 4891; f) M. A. Witschi, J. Gervay-
Hague, Org. Lett. 2010, 12, 4312; g) C. Y. Lee, T. E. Acree, R. S. Shallen-
berger, Carbohydr. Res. 1969, 9, 356.
[14] For recent references on the catalyzed silylation of alcohols with hydro-
silanes, see: a) A. Biffis, M. Braga, M. Basato, Adv. Synth. Catal. 2004, 346,
451; b) H. Ito, K. Takagi, T. Miyahara, M. Sawamura, Org. Lett. 2005, 7,
3001; c) S. Rendler, O. Plefka, B. Karatas, G. Auer, R. Froehlich, C. Muck-
Lichtenfeld, S. Grimme, M. Oestreich, Chem. Eur. J. 2008, 14, 11512;
d) R. A. Corbin, E. A. Ison, M. M. Abu-Omar, Dalton Trans. 2009, 2850;
e) A. Weickgenannt, M. Mewald, M. Oestreich, Org. Biomol. Chem. 2010,
8, 1497; f) A. Weickgenannt, M. Mewald, T. W. T. Muesmann, M. Oes-
treich, Angew. Chem. Int. Ed. 2010, 49, 2223; Angew. Chem. 2010, 122,
2269; g) A. Krüger, M. Albrecht, Chem. Eur. J. 2012, 18, 652; h) D. Gati-
neau, Q. Zhao, D. P. Curran, M. Malacria, E. Lacôte, L. Fensterbank, J.-P.
Goddard, Dalton Trans. 2013, 42, 7458; i) D. Gao, C. Cui, Chem. Eur. J.
2013, 19, 11143; j) A. Simonneau, J. Friebel, M. Oestreich, Eur. J. Org.
Chem. 2014, 2077.
[15] J. D. White, R. G. Carter in Science of Synthesis (Ed.: I. Fleming), Thieme,
Stuttgart, 2002, pp. 371.
[16] C. Schummer, O. Delhomme, B. M. R. Appenzeller, R. Wennig, M. Millet,
Talanta 2009, 77, 1473.
[17] E. Rojas-Escudero, A. L. Alarcón-JimØnez, P. Elizalde-Galvµn, F. Rojo-Calle-
jas, J. Chromatogr. A 2004, 1027, 117.
[18] a) P. Vogel, D. Markovic, M. Turks, in Stereoselective Synthesis of Drugs &
Natural Products, Vol. 2 (Eds.: V. Andrushko, N. Andrushko), Wiley, New
[25] a) A. A. Joseph, V. P. Verma, X.-Y. Liu, C.-H. Wu, V. M. Dhurandhare, C.-C.
Wang, Eur. J. Org. Chem. 2012, 744; b) K.-L. Chang, M. M. L. Zulueta, X.-
A. Liu, Y.-Q. Zhong, S.-C. Hung, J. Org. Chem. 2010, 75, 7424; c) T.-Y.
Huang, M. M. L. Zulueta, S.-C. Hung, Org. Lett. 2011, 13, 1506; d) J.
Prandi, Carbohydr. Res. 2012, 347, 151.
[26] H.-W. Hsieh, M. W. Schombs, M. A. Witschi, J. Gervay-Hague, J. Org.
Chem. 2013, 78, 9677.
[27] a) A. I. Ruiz-Matute, O. Hernµndez-Hernµndez, S. Rodríguez-Sµnchez,
M. L. Sanz, I. Martínez-Castro, J. Chromatogr. B 2011, 879, 1226–1240;
b) A. I. Ruiz-Matute, O. Hernµndez-Hernµndez, S. Rodríguez-Sµnchez,
M. L. Sanz, I. Martínez-Castro, J. Chromatogr. B 2011, 879, 1240; c) P. M.
Medeiros, B. R. T. Simoneit, J. Chromatogr. A 2007, 1141, 271.
[28] a) T. Ooi, K. Ohmatsu, D. Uraguchi, K. Maruoka, Tetrahedron Lett. 2004,
45, 4481; b) J. Diekman, C. Djerassi, J. Org. Chem. 1967, 32, 1005; c) E. J.
Grayson, S. J. Ward, A. L. Hall, P. M. Rendle, D. P. Gamblin, A. S. Batsanov,
B. G. Davis, J. Org. Chem. 2005, 70, 9740; d) R. Bourhis, E. Frainnet, F.
Moulines, J. Organomet. Chem. 1977, 141, 157; e) O. P. Anderson,
A. G. M. Barrett, J. J. Edmunds, S.-I. Hachiya, J. A. Hendrix, K. Horita, J. W.
Malecha, C. J. Parkinson, A. VanSickle, Can. J. Chem. 2001, 79, 1562;
f) E. A. Lukevits, M. G. Voronkov, Chem. Heterocycl. Compd. 1965, 1, 116;
g) S. A. M. Nieuwenhuis, L. B. J. Vertegaal, M. C. De Zoete, A. Van Der
Gen, Tetrahedron 1994, 50, 13207; h) A. Belaissaoui, I. M. Saez, S. J. Cowl-
ing, X. Zeng, J. W. Goodby, Chem. Eur. J. 2012, 18, 2366; i) E. I. Balmond,
D. Benito-Alifonso, D. M. Coe, R. W. Alder, E. M. McGarrigle, M. C. Galan,
Angew. Chem. Int. Ed. 2014, 53, 8190; Angew. Chem. 2014, 126, 8329;
j) T. K. Park, S. J. Danishefsky, Tetrahedron Lett. 1995, 36, 195; k) M.
Takano, S. Ohya, K. Yasuda, M. Nishikawa, A. Takeuchi, D. Sawada, T.
Sakaki, A. Kittaka, Chem. Pharm. Bull. 2014, 62, 182; l) D. G. Streefkerk,
M. J. A. de Bie, J. F. G. Vliegenthart, Carbohydr. Res. 1974, 38, 47.
[29] C. A. G. Haasnoot, J. Am. Chem. Soc. 1992, 114, 882.
´
York, 2013, pp. 623–666; b) P. Vogel, M. Turks, L. Bouchez, D. Markovic,
A. Varela-lvarez, J. A. Sordo, Acc. Chem. Res. 2007, 40, 931; c) P. Vogel,
M. Turks, L. Bouchez, C. Craita, X. Huang, M. C. Murcia, F. Fonquerne, C.
´
Didier, C. Flowers, Pure Appl. Chem. 2008, 80, 791; d) D. Markovic,
C. M. R. Volla, P. Vogel, A. Varela-lvarez, J. A. Sordo, Chem. Eur. J. 2010,
´
16, 5969; e) C. M. R. Volla, D. Markovic, S. Laclef, P. Vogel, Chem. Eur. J.
´
2010, 16, 8984; f) C. M. R. Volla, D. Markovic, S. R. Dubbaka, P. Vogel, Eur.
´
J. Org. Chem. 2009, 6281; g) D. Markovic, A. Varela-lvarez, J. A. Sordo,
P. Vogel, J. Am. Chem. Soc. 2006, 128, 7782; h) A. Varela-lvarez, D. Mar-
´
kovic, P. Vogel, J. A. Sordo, J. Am. Chem. Soc. 2009, 131, 9547; i) B. K.
´
´
Zambron, S. R. Dubbaka, D. Markovic, E. Moreno-Clavijo, P. Vogel, Org.
ˇ
Lett. 2013, 15, 2550; j) A. Stikute, V. Peipin¸s, M. Turks, Tetrahedron Lett.
Received: October 31, 2015
2015, 56, 4578; k) M. Turks, A. K. Lawrence, P. Vogel, Tetrahedron Lett.
2006, 47, 2783.
Published online on February 11, 2016
Chem. Eur. J. 2016, 22, 4196 – 4205
www.chemeurj.org
4205
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim