Sweets for catalysis - Facile optimisation of carbohydrate-based bis(oxazoline) ligands

Article abstract of DOI:10.1002/ejoc.200801035

A new type of carbohydrate-based bis(oxazoline) ligands was prepared from inexpensive D-glucosamine and tested in asymmetric cyclopropanation reactions. For optimisation, modified ligands with 3-O substituents of varying size and electronic properties were prepared as well as a 3-OH unprotected and a perpivaloylated derivative. All new ligands were tested in asymmetric cyclopropanation, revealing a strong dependence of enantioselectivity on steric demand and electronic properties of the 3-O residue. Also, a significant influence of the pyranose conformation, which is determined by the presence or absence of the cyclic acetal group, was observed. Thus, it was easily possible to tune the new carbohydrate bis(oxazoline) ligands to a given reaction.

Full text of DOI:10.1002/ejoc.200801035

FULL PAPER
DOI: 10.1002/ejoc.200801035
Sweets for Catalysis – Facile Optimisation of Carbohydrate-Based
Bis(oxazoline) Ligands
Tobias Minuth,[a] Mustafa Irmak,[a] Annika Groschner,[b] Tobias Lehnert,[a] and
Mike M. K. Boysen*[a]
Keywords: Asymmetric catalysis / Carbohydrates / Ligand design / N ligands
A new type of carbohydrate-based bis(oxazoline) ligands
was prepared from inexpensive -glucosamine and tested in
and electronic properties of the 3-O residue. Also, a signifi-
cant influence of the pyranose conformation, which is deter-
mined by the presence or absence of the cyclic acetal group,
was observed. Thus, it was easily possible to tune the new
carbohydrate bis(oxazoline) ligands to a given reaction.
D
asymmetric cyclopropanation reactions. For optimisation,
modified ligands with 3-O substituents of varying size and
electronic properties were prepared as well as a 3-OH unpro-
tected and a perpivaloylated derivative. All new ligands
were tested in asymmetric cyclopropanation, revealing a
strong dependence of enantioselectivity on steric demand
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
donor sites.[5] The first examples of carbohydrate bis(oxa-
zolines) were reported in 2005, but without any application
in asymmetric synthesis.[6]
Introduction
Carbohydrates are the most abundant compounds of the
chiral pool, but unlike amino acids, terpenes and alkaloids,
they are far less frequently employed for the preparation of
chiral ligands for metal-catalysed asymmetric synthesis.
This is mainly because they contain both stereocentres and
functional groups galore, which is often regarded rather
more of an obstacle than an advantage. In contrast, since
the first examples of efficient carbohydrate-based ligands
were reported 30 years ago,[1] many interesting structures
have emerged and application of such complexing agents
has recently met with increasing attention.[2] Bis(oxazolines)[3]
(box) and pyridylbis(oxazolines)[4] (pybox) are among the
most successful classes of chiral ligands, as they are of great
utility in a wide range of asymmetric transformations.[3,4]
They are commonly prepared from chiral β-amino alcohols
originating from mainly nonnatural sources. The inexpen-
sive amino sugar -glucosamine, whose N-acyl derivatives
easily form oxazolines, has rarely been used for the synthe-
sis of oxazoline-containing ligands. Examples are several
mono(oxazolines) containing additional phosphorus-based
Results and Discussion
We recently introduced the new ligands glucoBox[7] and
glucoPybox,[8] which are accessible from inexpensive -glu-
cosamine through four efficient steps, outlined for the box
ligand in Scheme 1.
Ligand Ac glucoBox (5) was employed in copper(I)-cata-
lysed cyclopropanations of alkenes with diazoacetates,[7]
a
reaction first reported by Evans[9a] and Masamune[9b] (cf.
Table 1). The reaction of styrene with ethyl diazoacetate,
which is a benchmark for this transformation, gave dia-
stereomeric cyclopropanation products trans-8 and cis-8 in
a 70:30 ratio, typical for this transformation using ethyl di-
azoacetate, good yields and encouraging 82%ee (Table 1,
Entry 1). Good enantioselectivities were also obtained with
4-methoxystyrene, 1,1-diphenylethylene and 2,5-dimeth-
ylhexa-2,4-diene (Table 1, Entries 3, 5 and 7). As the
trans/cis ratio can sometimes be improved by employing
bulky tert-butyl diazoacetate,[9] we repeated the reactions
with this ester. For styrene, this led to a drop in both the
yield and the enantioselectivity, as well as a complete loss
of diastereoselectivity (Table 1, Entry 2) and a slight rise in
diastereoselectivity for 4-methoxystyrene (Table 1, Entry 4).
An increase in enantioselectivity was only observed for 1,1-
diphenylethylene (Table 1, Entry 6). Because of these re-
sults, no further experiments were performed with tert-butyl
diazoacetate.
[a] Institute of Organic Chemistry, Leibniz University of Hanno-
ver,
Schneiderberg 1B, 30167 Hannover, Germany
Fax: +49-511-762-3011
E-mail: mike.boysen@web.de
URL: http://www.oci.uni-hannover.de/AK_Boysen/index.htm
[b] Institute of Organic and Biomolecular Chemistry, Georg-Au-
gust University of Göttingen,
Tammannstr. 2, 37077 Göttingen, Germany
Supporting information for this article is available on the
WWW under http://www.eurjoc.org/ or from the author.
Eur. J. Org. Chem. 2009, 997–1008
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T. Minuth, M. Irmak, A. Groschner, T. Lehnert, M. M. K. Boysen
FULL PAPER
Scheme 1. Preparation of the bidentate glucoBox ligand (5) based on -glucosamine.[7]
Table 1. Asymmetric cyclopropanations with the use of glucoBox TMS glucoBox (10) in good yield (Scheme 2). Attempts to
ligands.
prepare either the corresponding pivaloylated or the benzyl-
ated ligand were unsuccessful and led to decomposition of
unprotected ligand 9.
Employing TMS glucoBox (10) in the test reaction re-
vealed this ligand to be clearly inferior to Ac glucoBox (5)
(Table 1, Entry 8), and it was therefore not used for further
experiments.
Even more attractive than modification of all hydroxy
functions with the same residue is selective introduction of
single O-substituents. Here, the 3-position of the pyranose
ring is at the focus of interest, as it is in direct vicinity of
the oxazoline nitrogen atoms. Thus, the 3-O-substituents
should profoundly influence the steric shielding of the coor-
dinated metal centres, and in consequence, they should have
a fundamental impact on the stereoselectivity of reactions
catalysed with these complexes. Therefore, we decided to
selectively modify this position by attachment of ether and
ester groups with varying steric demands; this strategy is
[a] Results reported previously.[7] [b] Isolated yields after
illustrated in Figure 1.
chromatography. [c] Determined after separation of the isomers by
In order to address the 3-O position, introduction of cy-
chromatography. [d] Determined by GC on a chiral stationary
phase. [e] Determined by 1H NMR spectroscopy with Rh2[(R)-(+)-
MTPA]4 as chiral reagent (dirhodium method).[10] [f] TMS gluco-
Box (10) as ligand.
clic 4,6-O-benzylidene acetals into deprotected ligand 9 was
attempted, only leading to either decomposition or recovery
of the starting material. Next, unprotected bis(amide) 4 was
benzylidene-protected; cyclisation to the corresponding bis-
(oxazoline) was tried with the use of the one-pot reaction
employed for the preparation of glucoBox.[7] Because of the
acidic conditions used in the first reaction of this sequence,
only decomposition was observed.
We therefore devised a new route to 3-O-modified li-
gands with thioglycosides as key intermediates.[13] The use
of thioglycosides has several advantages, as they are easily
accessible, highly stable against all conditions necessary for
the introduction of a broad range of 3-O substituents and,
above all, can be activated for the cyclisation reaction under
mild and specific conditions. Thus, bis(amide) 16 with free
3-hydroxy groups was prepared from -glucosamine hydro-
chloride (1) as a key intermediate for the synthesis of 3-O-
modified glucoBox ligands (Scheme 3).[13]
To increase the stereoselectivity for the cyclopropana-
tions, we next set out to prepare derivatives of Ac glucoBox
(5). The new carbohydrate ligand offers plentiful options
for structural modifications and therefore optimisation. The
pyranose unit can be modified by introduction of a wide
range of residues on the hydroxy groups varying in steric
and in electronic properties. It should be noted that by this
approach the numerous polar functional groups prove to be
an advantage: rapid access to a lot of variations of a given
carbohydrate architecture is possible, something that is not
nearly as easily achieved with amino alcohols conven-
tionally employed for bis(oxazolines) synthesis.
First we studied the possibility to directly derivatise li-
gand 5. Removal of the acetate groups under mildly basic
conditions[11] yielded 9 with six free hydroxy groups. Reac-
Starting from 16, three ester- (Ac, Bz, Piv) and three
tion with TMSCl and HMDS in pyridine[12] gave ligand ether-modified (Me, Bn, TES) bis(amides) (17a–f) were pre-
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Facile Optimisation of Carbohydrate-Based Bis(oxazoline) Ligands
Scheme 2. Preparation of an O-TMS modified glucoBox ligand.
conditions originally described for the preparation of mo-
nomeric carbohydrate oxazolines from thioglycosides.[15]
With the use of this protocol, all bis(amides) could be
cyclised to the corresponding 3-O-R1-glucoBox ligands
18a–f in good to excellent yields irrespective of the 3-O sub-
stituent (Table 2).[13]
Table 2. Conditions and yields for the preparation of 3-O modified
bis(amides) 17a–f and yields of the corresponding 3-O-R1-glucoBox
ligands 18a–f in the NIS-promoted cyclisation.
Figure 1. The 3-O position of glucoBox as a starting point for
modification.
R1
Bis(amide) Yield [%]
glucoBox
3-O-Ac
Yield [%]
Ac[a]
17a
17b
17c
17d
17e
17f
97
93
93
94
84
83
18a[g]
18b
92
84
82
90
79
85
Bz[b]
3-O-Bz
3-O-Piv
3-O-Me
3-O-Bn
3-O-TES
Piv[c]
Me[d]
Bn[e]
TES[f]
18c
18d[g]
18e[g]
18f[g]
[a] Ac2O, pyridine. [b] BzCl, pyridine.[16] [c] PivCl, DMAP, pyr-
idine.[17] [d] MeI, NaH, DMF.[18] [e] BnBr, NaH, TBAI, DMF.[19]
[f] TESOTf, Et3N, CH2Cl2.[20] [g] Ligands reported previously.[13]
Additionally 3-O-acetylated ligand 18a was deacetylated
under basic conditions[11] to yield 3-OH glucoBox 19
(Scheme 4).
Scheme 3. Preparation of 3-O-modified glucoBox ligands by thio-
glucosylbis(amide) 16.[13]
pared in good to excellent yield by using the conditions
given in Table 2. Cyclisation was first attempted with acety-
lated bis(amide) 17a by addition of elemental bromine to
form anomeric bromides,[14] followed by treatment with
Scheme 4. Preparation of a 3-OH-unsubstituted glucoBox ligand.
Next, a fully pivaloylated ligand was prepared from thio-
Et4NCl and NaHCO3, previously described for the synthe- ethyl glucoside 13. Phthaloyl deprotection[19] followed by
sis of Ac glucoBox (5).[7] By this method, the target bis(oxa- O-TMS protection[12] and coupling with dimethylmalonyl
zoline) was obtained in only 20% yield, which made us look dichloride[7] yielded bis(amide) 22. After desilylation and
for an alternative cyclisation sequence. Next, we tried a pivaloylation, resulting bis(amide) 23 was treated first with
cyclisation mediated by N-iodosuccinimide (NIS) and a elemental bromine[14] and subsequently with Et4NCl under
catalytic amount of trifluoromethanesulfonic acid (TfOH), basic conditions[7] to yield Piv glucoBox (24) (Scheme 5).
Eur. J. Org. Chem. 2009, 997–1008
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T. Minuth, M. Irmak, A. Groschner, T. Lehnert, M. M. K. Boysen
FULL PAPER
Scheme 5. Preparation of a perpivaloylated ligand Piv glucoBox (24).
With this set of eight new carbohydrate bis(oxazoline)
From comparison of the results obtained with 18a–f
ligands in hand, we started our evaluation studies concern- (Figure 2) a clear trend emerges for the ester- and ether-
ing their efficiency in enantioselective copper(I)-catalysed modified glucoBox ligands: in both ligand families an in-
cyclopropanation of styrene with ethyl diazoacetate crease in steric demand of the 3-O substituent has a detri-
(Table 3). All ligands 18a–f gave products trans-8a and cis- mental effect on the enantioselectivity of the cyclopropan-
8a in good to very good yields, but the ligands differed no- ation reaction (ee for 3-O-Ac Ͼ 3-O-Bz Ͼ 3-O-Piv; ee for
tably with regard to diastereoselectivity and substantially 3-O-Me Ͼ 3-O-Bn Ͼ 3-O-TES), but it also becomes clear
with regard to enantioselectivity. The best result was ob- that not only steric factors are important for ligand effi-
tained with 3-O-Ac glucoBox ligand (18a), which yielded ciency. Ligand 18a bearing a 3-O acetyl substituent yields
the products in a good trans/cis ratio of 79:21 and in 93%ee considerably better enantioselectivity than ligand 18d with
for the major trans and 82%ee for the minor cis dia- a smaller 3-O methyl residue. It appears that apart from
stereomer. The other 3-O-acyl, 3-O-alkyl and 3-O-silyl steric factors also electronic influences of the 3-O-R1 group
modified ligands 18b–f did not nearly reach comparable play an important role for the stereoselectivity of the reac-
levels of enantioselectivity. Also, ligand 3-OH glucoBox li- tion, with electron-withdrawing ester groups having a
gand (19) only gave moderate selectivity, whereas Piv gluco- favourable influence. The reason for the beneficial effect of
Box (24) yielded another good result with trans-8a in 3-O-acyl residues is as yet not fully understood.
84%ee and the minor diastereomer cis-8a in 94%ee.
Table 3. Cyclopropanations with the use of glucoBox ligands 18a–
f and 19 and 24.
glucoBox
Yield [%][a] trans/cis[b] eetrans [%][c] eecis [%][c]
1
2
3
4
5
6
7
8
3-O-Ac
3-O-Bz
3-O-Piv 18c
3-O-Me 18d
3-O-Bn
3-O-TES 18f
3-OH
Piv
18a
18b
90
74
90
87
95
71
87
86
79:21
69:31
64:36
77:23
62:38
64:36
68:32
63:37
93
64
62
73
48
33
51
84
82
36
49
39
28
7
Figure 2. Impact of 3-O substituents on the stereoselectivity of cy-
clopropanation reactions with glucoBox ligands 18a–f.
18e
19
24
44
94
Apart from the steric and electronic influences of the 3-
O substituents, the conformation of the pyranose units will
have an impact on the structure of the metal complexes
formed with the ligands. This in turn will affect the stereo-
[a] Isolated yields after chromatography. [b] Determined after sepa-
ration of the isomers by chromatography. [c] Determined by GC on
a chiral stationary phase.
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Facile Optimisation of Carbohydrate-Based Bis(oxazoline) Ligands
selectivity of any reaction catalysed by such systems. As a
result of the 1,2-cis annulated ring, oxazolines with acyclic
protective groups deviate significantly from the 4C1 confor-
mation (Figure 3, A) commonly found for glucopyranose
derivatives. Instead, they adopt a OS1 twist-like conforma-
1
tion (Figure 3, B), which was first deduced from H NMR
spectroscopic studies[21a] and later proved by X-ray struc-
3
ture analysis.[21b] The J coupling constants of ligands Ac
glucoBox (5) and Piv glucoBox (24) are in good agreement
with those reported for simple oxazolines with acyclic pro-
tecting groups[21b] and also with those reported for the first
carbohydrate bis(oxazoline).[6] Thus, we can assume with
good approximation that these two ligands adopt the iden-
tical conformation as that of simple carbohydrate oxazol-
ines. By introduction of a 4,6-O benzylidene group into a
glucopyranose derivative a conformationally rigid trans de-
caline system is formed (Figure 3, C). When this cyclic ace-
tal group is incorporated into a carbohydrate oxazoline the
trans decaline-like system partly fixes a chair-like conforma-
tion (Figure 3, D). Thus, ligands with and without benzyl-
idene groups adopt different conformations, which is also
Figure 4. Impact of the pyranose conformation on stereoselectivity
of cyclopropanation reactions with glucoBox ligands 18a, 18c, 5
and 24.
Conclusions
We developed new type of carbohydrate-based bis(oxa-
zoline) ligand based on inexpensive -glucosamine, which
as a result of the polyfunctional pyranose scaffold could
successfully be optimised for asymmetric cyclopropanation
by attaching 3-O substituents of varying steric and elec-
tronic properties in a facile manner. With benzylidene-pro-
tected ligands, considerable steric and electronic effects of
the 3-O substituent are observed, with the small acetyl
group giving far better results than those obtained with
more bulky acyl residues and ether groups irrespective of
their steric demand. Exploiting this strategy, the stereoselec-
tivity of cyclopropanations with carbohydrate bis(oxa-
zoline) ligands could be successfully increased; the major
trans diastereomer was obtained in up to 93%ee, in com-
parison to 82%ee obtained with original peracetylated li-
gand 5. Additionally, a conformational effect is in opera-
tion: ligands with a benzylidene moiety partly fixing the
pyranose ring in a chair-like conformation give best results
in combination with the rather small 3-O acetyl group. Per-
acylated ligands adopting a twist-like conformation, in con-
trast, give better results with bulky pivalate residues. The
causes for the electronic and conformational effects are, as
of yet, not fully understood and are currently under investi-
gation. To this end, a series of ligands with other acyl-based
3-O residues such as carbamates, carbonates and electron-
deficient esters will be prepared and tested. Further, the
successful optimisation strategy of varying steric, electronic
and conformational properties of the basic ligand structure
will also be applied to the corresponding glucoPybox scaf-
fold.
1
borne out by their H NMR spectroscopic data.
Figure 3. Pyranose conformations in the presence and absence of
annulated ring systems.
Figure 4 illustrates the effects of 4,6-O benzylidene ace-
tals on stereoselectivity by comparing the cyclopropanation
results obtained for ligands 3-O-Ac (18a) and 3-O-Piv glu-
coBox (18c) with those of their peracetylated and perpiva-
loylated counterparts 5 and 24. Whereas 3-O-Ac glucoBox
(18a) containing a benzylidene group led, in comparison to
Ac glucoBox (5), to substantially increased enantio-
selectivity, the reverse trend was observed for 3-O-Piv gluco-
Box (18c) and Piv glucoBox (24). Obviously, steric influ-
ences of the 3-O substituents are overlaid with a conforma-
tional effect caused by the benzylidene group. The cyclic
acetal, partly fixing a chair-like conformation, combined
with a small 3-O-acetyl group has a beneficial effect on ster-
eoselectivity, whereas larger O-pivalates give good results
when no cyclic acetal group is present and the pyranose
adopts a OS1 twist-like conformation.
Experimental Section
General Methods: Dry solvents were obtained by distillation over
appropriate drying reagents under a nitrogen atmosphere (CH2Cl2
and acetonitrile distilled from calcium hydride, THF distilled from
sodium/benzophenone ketyl) or were purchased in dry form from
commercial sources (DMF from Acros, pyridine from Fluka, abso-
lute ethanol from VWR) and used as received. All reactions involv-
ing reagents sensitive to air and moisture were carried out under a
nitrogen atmosphere (glove box and/or Schlenk techniques). Reac-
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tions were monitored by TLC on 60 F254 aluminum plates (Merck)
with detection by UV light and/or charring with 10% sulfuric acid
in ethanol or a mixture of cerium(IV) sulfate and molybdophos-
phoric acid in 8% sulfuric acid. Flash chromatography was per-
formed on Merck silica (grain size 40–63 µ). NMR spectra were
recorded with an AVS 400 instrument (Bruker) at 400 MHz (1H)
or at 100 MHz (13C). Deuterated chloroform and methanol were
used as solvents and spectra were calibrated against the residual
solvent peak (CHCl3: 7.24 ppm, CD2HOD: 3.35 ppm). Electro-
spray mass (ESI) spectra were recorded with a Micromass LCT
device (Waters), injection into the HPLC instrument (Waters) was
performed in loop modus. Optical rotations were recorded with a
Perkin–Elmer 451 instrument under the following standard condi-
tions: room temperature, wavelength 589.3 nm (sodium D line), cell
length 1 dm, solvent and sample concentration (in 10 mgmL–1) are
given with the individual experiment. Chiral GC experiments were
carried out with an HP 5890-II device (Hewlett–Packard) with a
flame ionisation detector and hydrogen as carrier gas in constant
flow modus. Starting temperature was 50 °C 1.1 °Cmin–1. A
Hydrodex-β PM capillary column (50 m, 0.25 mm, 723370, Mach-
erey–Nagel) was used for separation of the enantiomers. Determi-
nation of enantiomeric excesses by 1H NMR spectroscopy was
done with Rh2[(R)-(+)-MTPA]4 as chiral complexing reagent, di-
rhodium method.[13]
2 H, 2-H), 5.06 (d, J1,2 = 3.1 Hz, 2 H, 1-H), 7.08 (d, J2,NH = 9.2 Hz,
2 H, NH) ppm. 13C NMR (100 MHz, CDCl3): δ = –0.43, –0.27,
0.60, 0.98, (each CH3, SiCH3), 24.4 [CH3, (CH3)2C], 49.1 [C, (CH3)
2C], 54.8 (CH, C-2), 61.5 (CH2, C-6), 71.5, 73.1, 73.6 (CH, C-3, C-
4, C-5), 91.7 (CH, C-1), 173.6 (C, CONH) ppm. HRMS (ESI+):
calcd. for C41H95N2O12Si8 [M + H]+ 1031.5039; found 1031.5077.
HRMS (ESI+): calcd. for C41H94N2O12Si8Na [M + Na]+
1053.4858; found 1053.4911. [α]2D5 = +83 (c = 1.6, CHCl3).
Bis(2-amino-2-deoxy-D-glucopyranosido)dimethylmalonamide (4):
Bis(amide) 3 (9.96 g, 9.66 mmol) was treated with MeOH/TFA (9:1,
150 mL) at room temperature. TLC (MeOH/CH2Cl2, 1:9) indicated
the complete consumption of all staring material after 2 h. The
solvent was removed in vacuo, and the residue was coevaporated
with toluene until it solidified to a colourless mass. The powdery
raw product was stirred with ethyl acetate (100 mL), filtered and
washed with some more ethyl acetate to remove residual organosil-
icon byproducts. Colourless product 4 was isolated in quantitative
yield and used for the next step without further purification. As
each of the two carbohydrate moieties of bis(amide) 4 can individu-
ally occur in both anomeric forms, a total of three bis(amides) with
different anomeric configurations is obtained. The (α,α)-, (α,β)-
and (β,β)-configured compounds have all slightly different chemical
shifts in the 1H and 13C NMR spectra, complicating interpretation.
Therefore, full NMR characterisation of 4 was not attempted.
HRMS (ESI): calcd. for C17H30O12N2Na [M + Na]+ 477.1696;
found 477.1700. [α]2D5 = +41 (c = 1.02, MeOH).
2-Amino-2-deoxy-1,3,4,6-tetra-O-trimethylsilyl-α-D-glucopyranose
(2): To a suspension of glucosamine hydrochloride (1; 10.00 g,
43.36 mmol) in pyridine (500 mL) was added HMDS (90 mL,
70.00 g, 433.60 mmol) followed by TMSCl (55 mL, 47.11 g,
433.60 mmol). The resulting mixture was stirred at room tempera-
ture, and the reaction was monitored by TLC [petroleum ether
(PE)/EtOAc, 5:1]. During the reaction, a lot of salt precipitated.
After completion of the reaction (approx. 4 h), the mixture was
evaporated in vacuo with a cooling trap placed between the rotary
evaporator and the pump stand. The residue was coevaporated with
toluene (2ϫ) to remove residual pyridine. The raw material was
then submitted to short column filtration through silica gel (PE/
EtOAc, 5:1) to remove the pyridinium salts. Acid-sensitive 2 was
obtained as a colourless crystalline solid after refrigerating over-
Ac glucoBox (5): Bis(amide) 4 (1.00 g, 2.20 mmol) was taken up in
neat acetyl chloride (10 mL) (note: the acetyl chloride should not
be distilled prior to use, as a catalytic amount of hydrogen chloride
is necessary for the reaction!) and stirred for 16 h. Reaction pro-
gress was monitored by TLC (CH2Cl2/acetone, 5:1). The acetyl
chloride was then removed in vacuo, and the crude product was
coevaporated with toluene (2ϫ) to remove residual acetyl chloride
and then directly used for the next step. To a solution of the crude
product dissolved in dry acetonitrile (10 mL) was added Et4NCl
(860 mg, 5.20 mmol) and solid NaHCO3 (860 mg, 10.48 mmol),
and the resulting mixture was stirred at room temperature for 16 h.
Reaction progress can be monitored by TLC (CH2Cl2/acetone, 3:1).
The solvent was removed in vacuo, and the residue taken up in
CH2Cl2 (20 mL) and washed with water (20 mL). The organic
phase was dried with Na2SO4, filtered and concentrated. The resi-
due was purified by flash chromatography on silica gel (PE/EtOAc,
1:1) to afford 5 as a yellow foam (1.40 g, 2.12 mmol, 94%). 1H
NMR (400 MHz, CDCl3): δ = 1.58 [s, 6 H, (CH3)2C], 1.98, 2.16,
1
night (19.53 g, 41.72 mmol, 90%). H NMR (400 MHz, CDCl3): δ
= 0.08, 0.17, 0.15, 0.20, (each s, each 9 H, SiCH3), 1.38 (br. s, 2 H,
NH2), 2.52 (dd, J1,2 = 3.3 Hz, J2,3 = 9.7 Hz, 1 H, 2-H), 3.44 (dd,
J3,4 = 8.7 Hz, J4,5 = 9.4 Hz, 1 H, 4-H), 3.52 (dd, J2,3 = 9.7 Hz, J3,4
= 8.7 Hz, 1 H, 3-H), 3.61 (ddd, J4,5 = 9.4 Hz, J5,6 = 4.3 Hz, J5,6Ј
2.5 Hz, 1 H, 5-H), 3.64–3.75 (m, 2 H, 6-H, 6Ј-H), 5.12 (d, J1,2
=
=
3.3 Hz, 1 H, 1-H) ppm. 13C NMR (100 MHz, CDCl3): δ = 0.2, 0.4,
0.9, 1.4, (each CH3, SiCH3), 57.7 (CH, C-2), 62.0 (CH2, C-6), 78.2,
72.9, 72.0, (CH, C-3, C-4, C-5), 95.8 (CH3, C-1) ppm. HRMS
(ESI+): calcd. for C18H46O5NSi4 [M + H]+ 468.2453; found
468.2456. [α]2D5 = +87 (c = 3.4, CHCl3).
2.05 (each s, each 6 H, CH3CO), 3.86 (ddd, J4,5 = 9.2 Hz, J5,6
4.8 Hz, J5,6Ј = 2.9 Hz, 2 H, 5-H), 4.13 (dd, J5,6Ј = 2.7 Hz, J6,6Ј
12.3 Hz, 2 H, 6Ј-H), 4.18 (ddd, J1,2 = 7.5 Hz, J2,3 = 2.4 Hz, J2,4
=
=
=
1.3 Hz, 2 H, 2-H), 4.22 (dd, J5,6 = 4.8 Hz, J6,6Ј = 12.3 Hz, 2 H, 6-
H), 4.94 (ddd, J3,4 = 2.4 Hz, J2,4 = 1.3 Hz, J4,5 = 9.2 Hz, 2 H, 4-
N,NЈ-Bis(2-deoxy-1,3,4,6-tetra-O-trimethylsilyl-α-D-glucopyranosid-
H), 5.31 (dd ≈ t, J2,3 = J3,4 = 2.4 Hz, 2 H, 3-H), 6.05 (d, J1,2
=
2-yl)dimethylmalonamide (3): Under a nitrogen atmosphere, sugar
2 (18.52 g, 39.58 mmol) was dissolved in dry CH2Cl2 (250 mL), and
the resulting solution was cooled to 0 °C. Then, triethylamine
(11 mL, 8.02 g, 79.17 mmol) followed by dimethylmalonoyl dichlo-
ride (2.6 mL, 3.35 g, 19.79 mmol) was added. Progress of the reac-
tion was monitored by TLC (PE/EtOAc, 2:1). After approx. 2 h,
the solvent was evaporated in vacuo, and the raw product was sub-
jected to short column filtration through silica gel (PE/EtOAc, 3:1).
7.5 Hz, 2 H, 1-H) ppm. 13C NMR (100 MHz, CDCl3): δ = 20.7,
20.8, 20.9 (CH3, CH3CO), 23.8 [CH3, (CH3)2C], 39.2 [C, (CH3)2C],
62.8 (CH2, C-6), 64.8 (CH, C-2), 67.8 (CH, C-5), 68.3, (CH, C-4),
70.1, (CH, C-3), 100.0 (CH, C-1), 169.2, 169.5, 170.2, 170.6 (C,
CH3CO, O-C=N) ppm. HRMS (ESI+): calcd. for C29H39O16N2 [M
+ H]+ 671.2300; found 671.2298. [α]2D5 = +53 (c = 1.9, CHCl3).
OH glucoBox (9): To a solution of 5 (100 mg, 150 µmol) dissolved
Bis(amide) 3 was isolated as a colourless foam (19.60 g, in MeOH/H2O (5:2, 20 mL) was added potassium carbonate
19.00 mmol, 96%). 1H NMR (400 MHz, CDCl3): δ = 0.10, 0.17,
(40 mg, 29 µmol), and the resulting suspension was stirred at room
0.19, 0.21, (each s, each 18 H, SiCH3), 1.48 [s, 6 H, (CH3)2C], 3.61 temperature (TLC: PE/EtOAc, 1:3). After completion of the reac-
(dd ≈ t, J3,4 ≈ J4,5 = 8.4 Hz, 2 H, 4-H), 3.65–3.81 (m, 8 H, 3-H, 5-
H, 6-H, 6Ј-H), 3.99 (ddd ≈ td, J1,2 = 3.1 Hz, J2,3 ≈ J2,NH = 9.2 Hz,
tion, the solvent was evaporated in vacuo. The residue was coevap-
orated with MeOH to yield 9 (62 mg, 150 µmol, quant.) as a yellow
1002
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© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 997–1008

Facile Optimisation of Carbohydrate-Based Bis(oxazoline) Ligands
foam, which was employed in the next step without further purifi-
(1.70 g, 2.03 mL, 27.30 mmol) were dissolved in dry CH2Cl2
cation. 1H NMR (400 MHz, D2O): δ = 1.45 [s, 6 H, (CH3)2C], (20 mL). The mixture was cooled to 0 °C and borontrifluoride di-
3.34–3.42 (m, 2 H, 5-H), 3.51–3.62 (m, 4 H, 6-H, 4-H), 3.70–3.74 ethyl ether complex (970 µL, 930 mg, 7.50 mmol) was added by sy-
(m, 2 H, 6Ј-H), 3.90–3.93 (m, 2 H, 3-H), 4.08–4.12 (m, 2 H, 2-H), ringe. The mixture was stirred for 1 h at 0 °C and then 16 h at room
6.08 (d, J1,2 = 7.2 Hz, 2 H, 1-H) ppm. 13C NMR (100 MHz, D2O): temperature (TLC: PE/EtOAc, 3:1). The reaction was quenched by
δ = 23.0 [CH3, (CH3)2C], 39.1 [C, (CH3)2C], 61.5 (CH2, C-6), 66.0
(CH, C-2), 68.7 (CH, C-4), 71.8 (CH, C-5), 73.1 (CH, C-3), 101.1
(CH, C-1), 170.2 (C, O-C=N) ppm. HRMS (ESI+): calcd. for
C17H26N2O10Na [M + Na]+ 441.1485; found 441.1808. [α]2D0 = +88
(c = 1.8, H2O).
the addition of a saturated solution of NaHCO3 in water. The or-
ganic layer was separated, dried with Na2SO4, concentrated and
purified by flash chromatography on silica gel (PE/EtOAc, 3:1) to
yield 12 (3.71 g, 7.74 mmol, 74 %) as colourless crystals. M.p.
118 °C. 1H NMR (400 MHz, CDCl3): δ = 1.18 (t, J = 7.5 Hz, 3 H,
SCH2CH3), 1.82, 1.99, 2.06 (each s, each 3 H, CH3CO), 2.58–2.70
(m, 2 H, SCH2CH3), 3.86 (ddd ≈ td, J4,5 = 10.2 Hz, J5,6 = 5.1 Hz,
J5,6Ј = 2.0 Hz, 1 H, 5-H), 4.13 (dd, J5,6Ј = 2.0 Hz, J6,6Ј = 12.2 Hz,
1 H, 6Ј-H), 4.27 (dd, J5,6 = 5.1 Hz, J6,6Ј = 12.2 Hz, 1 H, 6-H), 4.36
(dd ≈ t, J1,2 = 10.5 Hz, J2,3 = 10.2 Hz, 1 H, 2-H), 5.14 (dd ≈ t, J3,4
= 9.2 Hz, J4,5 = 10.2 Hz, 1 H, 4-H), 5.45 (d, J1,2 = 10.5 Hz, 1 H,
1-H), 5.79 (dd, J2,3 = 10.2 Hz, J3,4 = 9.2 Hz, 1 H, 3-H), 7.70–7.73
(m, 2 H, Phth), 7.81–7.83 (m, 2 H, Phth) ppm. 13C NMR
(100 MHz, CDCl3): δ = 14.8 (CH3, SCH2CH3), 20.4, 20.5, 20.7
(CH3, CH3CO), 24.3 (CH2, SCH2CH3), 53.6 (CH, C-2), 62.2 (CH2,
C-6), 68.8 (CH, C-4), 71.5 (CH, C-3), 75.8 (CH, C-5), 81.4 (CH,
C-1), 123.6 (CH, Phth), 131.1 (C, Phth), 134.2 (CH, Phth), 167.1,
167.7 (C, NCO), 169.4, 170.0, 170.6 (C, CH3CO) ppm. HRMS
(ESI+): calcd. for C22H26NO9S [M + H]+ 480.1323; found
480.1319. [α]2D0 = +44 (c = 1.0, CHCl3).
TMS glucoBox (10): To a suspension of unprotected bis(oxazoline)
9 (100 mg, 240 µmol) in dry pyridine (5 mL) was added HMDS
(550 µL, 4.78 mmol) followed by the addition of TMSCl (610 µL,
4.78 mmol). The resulting mixture was stirred at room temperature
(TLC: PE/EtOAc, 5:1). After completion of the reaction (approx.
2 h), the mixture was evaporated in vacuo. The residue was coevap-
orated with toluene. The crude product was then purified by col-
umn filtration through silica gel (PE/EtOAc, 5:1) to yield com-
pound 10 as a white solid (150 mg, 170 µmol, 74 %). 1H NMR
(400 MHz, CDCl3): δ = 0.08–0.21 (18 H, SiCH3), 1.53 [s, 6 H,
(CH3)2C], 3.40–3.45 (m, 2 H, 5-H), 3.66–3.78 (m, 8 H, 3-H, 4-H,
6-H, 6Ј-H), 3.85–3.89 (m, 2 H, 2-H), 6.02 (d, J1,2 = 7.5 Hz, 2 H, 1-
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 0.2, 0.5, 1.3 (CH3,
SiCH3), 24.2 [CH3, (CH3)2C], 39.5 [C, (CH3)2C], 62.2 (CH2, C-6),
68.1 (CH, C-2), 70.0 (CH, C-4), 74.2 (CH, C-5), 76.5 (CH, C-3),
102.8 (CH, C-1), 168.4 (C, O-C=N) ppm. HRMS (ESI+): calcd.
Ethyl-2-Deoxy-2-phthalimido-1-thio-β-D-glucopyranoside (13): To a
for C35H74N2O11Si6 [M + H]+ 851.3959; found 851.3556. [α]2D0
+88 (c = 1.8, CHCl3).
=
solution of 12 (18.00 g, 37.53 mmol) dissolved in dry methanol
(380 mL) was dropwise added freshly prepared sodium methoxide
solution (170 mg of Na in 10 mL of dry methanol, 7.51 mmol).
The reaction mixture was stirred for 6 h (TLC: EtOAc) and then
neutralized with Dowex® HCR-W2 ion-exchange resin. The resin
was filtered off, and the solution was concentrated. The residue was
purified by flash chromatography on silica gel (EtOAc) to yield 13
(12.40 g, 35.10 mmol, 94 %) as colourless crystals. 1H NMR
(400 MHz, CDCl3): δ = 1.11 (t, J = 7.5 Hz, 3 H, SCH2CH3), 2.61–
2.70 (m, 2 H, SCH2CH3), 3.41 (m, 1 H, 5-H), 3.47 (br. s, 1 H, OH),
3.62 (dd ≈ t, J3,4 = 9.2 Hz, 1 H, 4-H), 3.77–3.85 (m, 2 H, 6-H, 6Ј-
H), 4.09 (dd ≈ t, J1,2 ≈ J2,3 = 10.2 Hz, 1 H, 2-H), 4.27 (dd ≈ t, J2,3
≈ J3,4 = 9.2 Hz, 1 H, 3-H), 4.43 (br. s, 1 H, OH), 4.75 (br. s, 1 H,
OH), 5.26 (d, J1,2 = 10.2 Hz, 1 H, 1-H), 7.64–7.69 (m, 2 H, Phth),
7.75–7.80 (m, 2 H, Phth) ppm. 13C NMR (100 MHz, CDCl3): δ =
14.8 (CH3, SCH2CH3), 24.3 (CH2, SCH2CH3), 55.7 (CH, C-2), 61.7
(CH2, C-6), 70.9 (CH, C-4), 72.4 (CH, C-3), 79.6 (CH, C-5), 81.1
(CH, C-1), 123.6, 123.7 (CH, Phth), 131.5, 131.6 (C, Phth), 134.0
(CH, Phth), 168.0, 168.2 (C, NCO) ppm. HRMS (ESI+): calcd. for
C16H20NO6S [M + H]+ 354.1006; found 354.1012. [α]2D0 = +6 (c =
0.9, CHCl3).
1,3,4,6-Tetra-O-acetyl-2-deoxy-2-phthalimido-D-glucopyranoside
(11): To a stirred solution of -glucosamine hydrochloride (1;
50.00 g, 231.88 mmol) in methanol (100 mL) and water (200 mL)
was added NaOH (12.05 g, 301.44 mmol) at 0 °C. Then, phthalic
anhydride (49.76 g, 336.23 mmol) dissolved in acetone (400 mL)
was added while maintaining the temperature below 15 °C. More
phthalic anhydride (20.59 g, 139.13 mmol) and NaHCO3 (49.86 g,
593.61 mmol) were added, and the solution was subsequently
stirred at room temperature overnight (TLC: EtOAc/HOAc/
MeOH/H2O, 12:3:3:2). The mixture was then brought to pH 1 with
concentrated hydrochloric acid, concentrated in vacuo and left at
2 °C in the refrigerator overnight. The resulting precipitate was fil-
tered off, washed with cold water and dried under vacuum. The
crude product was dissolved in pyridine (700 mL) and treated with
acetic anhydride (568.14 g, 525 mL, 5.57 mol), and the mixture was
stirred at room temperature overnight (TLC: toluene/EtOAc, 3:2).
The solvents were evaporated, and the product was coevaporated
with toluene (2ϫ). The residue was dried under reduced pressure
to yield compound 11 as a colourless solid (108.42 g, 227.24 mmol,
98%). 1H NMR (400 MHz, CDCl3): δ = 1.83, 2.02, 2.05, 2.08 (each
s, each 3 H, CH3CO), 4.10 (dd, J5,6Ј = 2.0 Hz, J6,6Ј = 12.2 Hz, 1 H,
6Ј-H), 4.28 (ddd ≈ td, J4,5 = 10.2 Hz, J5,6 = 3.7 Hz, J5,6Ј = 2.0 Hz, 1
H, 5-H), 4.33 (dd, J5,6 = 3.7 Hz, J6,6Ј = 12.2 Hz, 1 H, 6-H), 4.68
Ethyl-4,6-O-Benzylidene-2-deoxy-2-phthalimido-1-thio-β-D-glucopyr-
anoside (14): Compound 13 (11.00 g, 31.13 mmol) and finely pow-
dered anhydrous zinc chloride (4.67 g, 34.24 mmol) were suspended
in freshly distilled benzaldehyde (30 mL). The solution was stirred
for 16 h at room temperature (TLC: PE/EtOAc, 1:1). After adding
water (300 mL) the semi-crystalline reaction mixture was cooled to
0 °C for 2 h. The precipitate was filtered off, washed with water
and petroleum ether and dried in vacuo. Flash chromatography on
silica gel (PE/EtOAc, 1:1) yielded 14 (13.13 g, 29.74 mmol, 96%)
(dd, J1,2 = 3.4 Hz, J2,3 = 11.6 Hz, 1 H, 2-H), 5.13 (dd ≈ t, J3,4
=
9.2 Hz, J4,5 = 10.2 Hz, 1 H, 4-H), 6.24 (d, J1,2 = 3.4 Hz, 1 H, 1-
H), 6.53 (dd, J2,3 = 11.6 Hz, J3,4 = 9.2 Hz, 1 H, 3-H), 7.70–7.73
(m, 2 H, Phth), 7.79–7.83 (m, 2 H, Phth) ppm. 13C NMR
(100 MHz, CDCl3): δ = 20.5, 20.6, 20.9 (CH3, CH3CO), 52.7 (CH,
C-2), 61.4 (CH2, C-6), 66.9 (CH, C-3), 69.3 (CH, C-4), 70.1 (CH,
C-5), 90.4 (CH, C-1), 132.6 (CH, Phth), 131.0 (C, Phth), 134.4
(CH, Phth), 167.3, 168.5 (C, NCO), 169.2, 169.4, 169.7, 170.5 (C,
CH3CO) ppm. HRMS (ESI+): calcd. for C22H24NO11 [M + H]+
478.1344; found 478.1354. [α]2D0 = +112 (c = 0.9, CHCl3).
1
as colourless crystals. H NMR (400 MHz, CDCl3): δ = 1.17 (t, J
= 7.5 Hz, 3 H, SCH2CH3), 2.59–2.70 (m, 2 H, SCH2CH3), 2.76 (br.
s, 1 H, OH), 3.56 (dd ≈ t, J3,4 = 9.2 Hz, J4,5 = 9.9 Hz, 1 H, 4-H),
3.65 (ddd ≈ td, J4,5 ≈ J5.6Ј = 9.9 Hz, J5,6 = 4.7 Hz, 1 H, 5-H), 3.77
(dd ≈ t, J5.6Ј ≈ J6,6Ј = 10.2 Hz, 1 H, 6Ј-H), 4.28 (t ≈ dd, J1,2
-glucopyr- 10.2 Hz, J2,3 = 8.8 Hz, 1 H, 2-H), 4.36 (dd, J5,6 = 4.7 Hz, J6,6Ј
anoside (12): Compound 11 (5.00 g, 10.50 mmol) and ethane thiol
=
=
Ethyl-3,4,6-Tri-O-acetyl-2-deoxy-2-phthalimido-1-thio-β-
D
10.2 Hz, 1 H, 6-H), 4.62 (dd, J2,3 = 8.8 Hz, J3,4 = 9.2 Hz, 1 H, 3-
Eur. J. Org. Chem. 2009, 997–1008
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1003

T. Minuth, M. Irmak, A. Groschner, T. Lehnert, M. M. K. Boysen
FULL PAPER
H), 5.37 (d, J1,2 = 10.2 Hz, 1 H, 1-H), 5.54 (s, 1 H, CHPh), 7.33–
7.35 (m, 3 H, Ph), 7.45–7.48 (m, 2 H, Ph), 7.67–7.71 (m, 2 H, Phth),
EtOAc, 1:1). The solvent was evaporated, and the product was co-
evaporated with toluene (2ϫ). Flash chromatography on silica gel
7.80–7.85 (m, 2 H, Phth) ppm. 13C NMR (100 MHz, CDCl3): δ = (PE/EtOAc, 1:1) yielded 17a (2.17 g, 2.70 mmol, 97%) as a white
1
14.8 (CH3, SCH2CH3), 24.1 (CH2, SCH2CH3), 55.4 (CH, C-2), 68.5 foam. H NMR (400 MHz, CDCl3): δ = 1.24 (t, J = 7.5 Hz, 6 H,
(CH2, C-6), 69.4 (CH, C-3), 70.5 (CH, C-5), 81.8 (CH, C-1), 82.0 SCH2CH3), 1.35 [s, 6 H, (CH3)2C], 2.07 (s, 6 H, CH3CO), 2.61–
(CH, C-4), 101.8 (CH, PhCH), 123.2, 123.8, 126.2, 128.3, 129.3
2.74 (m, 4 H, SCH2CH3), 3.58 (ddd ≈ td, J4,5 ≈ J5,6Ј = 9.5 Hz, J5,6
(CH, arom.), 131.4, 131.6 (C, arom.), 134.1 (CH, arom.), 136.8 = 4.7 Hz, 2 H, 5-H), 3.74 (dd, J5,6Ј ≈ J6,6Ј = 10.5 Hz, 2 H, 6Ј-H),
(C, arom.), 167.2, 168.2 (C, NCO) ppm. HRMS (ESI+): calcd. for
C23H23NO6SNa [M + Na]+ 464.1138; found 464.1139. [α]2D0 = –7
(c = 1.0, CHCl3).
3.77 (dd ≈ t, J3,4 = 9.2 Hz, J4,5 = 9.5 Hz, 2 H, 4-H), 4.21 (ddd ≈
td, J1,2 = 10.5 Hz, J2,3 = 10.5 Hz, J2,NH = 9.2 Hz, 2 H, 2-H), 4.33
(dd, J5,6 = 4.7 Hz, J6,6Ј = 10.5 Hz, 2 H, 6-H), 4.79 (d, J1,2
=
10.5 Hz, 2 H, 1-H), 5.29 (dd, J2,3 = 10.5 Hz, J3,4 = 9.2 Hz, 2 H, 3-
H), 5.51 (s, 2 H, CHPh), 6.61 (d, J2,NH = 9.2 Hz, 2 H, NH), 7.32–
7.37 (m, 6 H, Ph), 7.43–7.46 (m, 4 H, Ph) ppm. 13C NMR
(100 MHz, CDCl3): δ = 14.8 (CH3, SCH2CH3), 21.2 (CH3,
CH3CO), 23.8 (CH2, SCH2CH3), 24.3 [CH3, (CH3)2C], 51.1 [C,
(CH3)2C], 53.4 (CH, C-2), 68.5 (CH2, C-6), 70.4 (CH, C-5), 74.3
(CH, C-3), 78.3 (CH, C-4), 84.0 (CH, C-1), 101.5 (CH, PhCH),
126.1, 128.2, 129.1 (CH, Ph), 136.8 (C, Ph), 172.5 (C, CH3CO),
173.0 (C, CONH) ppm. HRMS (ESI+): calcd. for C39H51N2O12S2
[M + H]+ 803.2883; found 803.2883. [α]2D0 = –107 (c = 1.0, CHCl3).
Ethyl-2-Amino-4,6-O-benzylidene-2-deoxy-1-thio-β-D-glucopyrano-
side (15): Compound 14 (5.00 g, 11.32 mmol) and ethylene diamine
(28.00 mL, 25.17 g, 679.8 mmol) were dissolved in absolute ethanol
(400 mL). The mixture was heated at reflux for 16 h (TLC: EtOAc).
The solvent was evaporated, and the product was coevaporated
with toluene (2ϫ). Flash chromatography on silica gel (EtOAc)
yielded 15 (13.13 g, 29.74 mmol, 88%) as a colourless solid. 1H
NMR (400 MHz, CDCl3): δ = 1.26 (t, J = 7.5 Hz, 3 H, SCH2CH3),
2.35 (br. s, 1 H, OH), 2.61–2.70 (m, 2 H, SCH2CH3), 2.74 (dd, J1,2
= 9.9 Hz, J2,3 = 8.8 Hz, 1 H, 2-H), 3.39 (ddd ≈ td, J4,5 ≈ J5,6Ј
9.9 Hz, J5,6 = 4.7 Hz, 1 H, 5-H), 3.48 (dd ≈ t, J2,3 = 8.8 Hz, J3,4
=
=
N,NЈ-Bis(ethyl-3-O-benzoyl-4,6-O-benzylidene-2-deoxy-1-thio-β-D-
glucopyranosid-2-yl)dimethylmalonamide (17b): Bis(amide) 16
(500 mg, 700 µmol) was dissolved in pyridine (10 mL), and the mix-
ture was cooled to 0 °C. Benzoyl chloride (250 µL, 300 mg,
2.10 mmol) was added dropwise, and the mixture was stirred for ca.
2 h (TLC: PE/EtOAc, 1:1). The solution was diluted with CH2Cl2,
washed with water and concentrated. The crude product was dis-
solved in CH2Cl2 and washed with hydrochloric acid (1 ), satu-
rated aqueous solution of NaHCO3, dried, filtered and concen-
trated. Flash chromatography on silica gel (PE/EtOAc, 1:1) gave
17b (600 mg, 650 µmol, 93 %) as a white foam. 1 H NMR
(400 MHz, CDCl3): δ = 1.07 [s, 6 H, (CH3)2C], 1.23 (t, J = 7.5 Hz,
6 H, SCH2CH3), 2.66–2.74 (m, 4 H, SCH2CH3), 3.63 (ddd ≈ td,
9.2 Hz, 1 H, 3-H), 3.62 (dd, J3,4 = 9.2 Hz, J4,5 = 9.9 Hz, 1 H, 4-
H), 3.70 (dd ≈ t, J5,6 ≈ J6,6Ј = 10.2 Hz, 1 H, 6Ј-H), 4.26 (dd, J5,6
=
4.7 Hz, J6,6Ј = 10.2 Hz, 1 H, 6-H), 5.28 (d, J1,2 = 9.9 Hz, 1 H, 1-
H), 5.49 (s, 1 H, CHPh), 7.33–7.36 (m, 3 H, Ph), 7.44–7.47 (m, 2
H, Ph) ppm. 13C NMR (100 MHz, CDCl3): δ = 15.1 (CH3,
SCH2CH3), 24.5 (CH2, SCH2CH3), 56.9 (CH, C-2), 68.5 (CH2, C-
6), 70.4 (CH, C-3), 74.4 (CH, C-5), 81.0 (CH, C-4), 87.6 (CH, C-
1), 101.8 (CH, PhCH), 126.2, 128.2, 129.2 (CH, Ph), 137.0 (C, Ph)
ppm. HRMS (ESI+): calcd. for C15H21NO4SNa [M + Na]+
334.1083; found 334.1056. [α]2D0 = –65 (c = 1.0, CHCl3).
N,NЈ-Bis(ethyl-2-amino-4,6-O-benzylidene-2-deoxy-1-thio-β-D-gluco-
pyranosid-2-yl)dimethylmalonamide (16): Under a nitrogen atmo-
sphere, compound 15 (2.60 g, 8.25 mmol) was dissolved in dry
CH2Cl2 (40 mL), and the resulting solution was cooled to 0 °C.
Then, Et3N (2.30 mL, 1.70 g, 16.70 mmol) followed by dimeth-
ylmalonyl dichloride (560 µL, 710 mg, 4.18 mmol) was added
(TLC: EtOAc). After approximately 2 h, the solvent was evapo-
rated in vacuo, and the product was purified by flash chromatog-
raphy on silica gel (EtOAc) to yield bis(amide) 16 (3.00 g,
4.18 mmol, quant.) as a colourless solid. 1H NMR (400 MHz,
CDCl3): δ = 1.17 (J = 7.5 Hz, 6 H, SCH2CH3), 1.47 [s, 6 H,
(CH3)2C], 2.61–2.70 (m, 4 H, SCH2CH3), 3.44 (ddd ≈ td, J4,5 ≈ J5,6Ј
= 9.7 Hz, J5,6 = 4.9 Hz, 2 H, 5-H), 3.55 (dd ≈ t, J3,4 = 9.2 Hz, J4,5
= 9.7 Hz, 2 H, 4-H), 3.64 (dd ≈ t, J5,6Ј ≈ J6,6Ј = 10.2 Hz, 2 H, 6Ј-
H), 3.88 (ddd ≈ td, J1,2 = 10.4 Hz, J2,3 = 9.5 Hz, J2,NH = 9.0 Hz, 2
H, 2-H), 4.11 (dd ≈ t, J2,3 = 9.5 Hz, J3,4 = 9.2 Hz, 2 H, 3-H), 4.20
J4,5 ≈ J5,6Ј = 9.5 Hz, J5,6 = 4.7 Hz, 2 H, 5-H), 3.81 (dd ≈ t, J5,6Ј
≈
J6,6Ј = 10.5 Hz, 2 H, 6Ј-H), 3.90 (dd ≈ t, J3,4 = J4,5 = 9.5 Hz, 2 H,
4-H), 4.32 (dd, J1,2 = 10.5 Hz, J2,3 = 9.5 Hz, 2 H, 2-H), 4.38 (dd,
J5,6 = 4.7 Hz, J6,6Ј = 10.5 Hz, 2 H, 6-H), 4.82 (d, J1,2 = 10.5 Hz, 2
H, 1-H), 5.55 (s, 2 H, CHPh), 5.68 (dd ≈ t, J2,3 = J3,4 = 9.5 Hz, 2
H, 3-H), 6.71 (d, J2,NH = 9.2 Hz, 2 H, NH), 7.28–7.31 (m, 6 H,
Ph), 7.40–7.45 (m, 8 H, Ph), 7.53–7.58 (m, 2 H, Ph), 8.00–8.34
(m, 4 H, Ph) ppm. 13C NMR (100 MHz, CDCl3): δ = 14.8 (CH3,
SCH2CH3), 23.8 (CH2, SCH2CH3), 23.9 [CH3, (CH3)2C], 50.7 [C,
(CH3)2C], 53.7 (CH, C-2), 68.5 (CH2, C-6), 70.6 (CH, C-5), 74.1
(CH, C-3), 78.7 (CH, C-4), 84.2 (CH, C-1), 101.4 (CH, PhCH),
126.1, 128.1, 128.5, 128.8, 129.2, 129.8, 130.5 (CH, Ph), 134.4,
136.7 (C, Ph), 167.5 (C, PhCO), 173.1 (C, CONH) ppm. HRMS
(ESI+): calcd. for C49H54N2O12S2Na [M + Na]+ 949.3016; found
949.3016. [α]2D0 = –97 (c = 1.0, CHCl3).
(dd, J5,6 = 4.9 Hz, J6,6Ј = 10.2 Hz, 2 H, 6-H), 4.81 (d, J1,2
=
N,NЈ-Bis(ethyl-4,6-O-benzylidene-2-deoxy-3-O-pivaloyl-1-thio-β-D-
10.4 Hz, 2 H, 1-H), 5.39 (s, 2 H, CHPh), 7.21–7.25 (m, 6 H, Ph),
7.35–7.40 (m, 4 H, Ph), 7.45 (d, J2,NH = 9.0 Hz, 2 H, NH) ppm.
13C NMR (100 MHz, CDCl3): δ = 15.0 (CH3, SCH2CH3), 23.8
[CH3, (CH3)2C], 24.2 (CH2, SCH2CH3), 50.4 [C, (CH3)2C], 55.7
(CH, C-3), 68.2 (CH2, C-6), 70.5 (CH, C-5), 73.0 (CH, C-2), 80.6
(CH, C-4), 84.5 (CH, C-1), 101.0 (CH, PhCH), 126.2, 128.1, 128.9
(CH, Ph), 137.2 (C, Ph), 173.0 (C, CONH) ppm. HRMS (ESI+):
calcd. for C35H47N2O10S2 [M + H]+ 719.2667; found 719.2689.
[α]2D0 = –106 (c = 1.0, CHCl3).
glucopyranosid-2-yl)dimethylmalonamide (17c): To a solution of 16
(500 mg, 700 µmol) in dry pyridine (45 mL) was added pivaloyl
chloride (35 µL, 340 mg, 2.80 mmol) and DMAP (100 mg). The re-
action mixture was heated at 80 °C for 5 h (TLC: PE/EtOAc, 3:1).
After evaporation of the pyridine, the residue was purified by flash
column chromatography on silica gel (PE/EtOAc, 3:1) to give 17c
(580 mg, 650 µmol, 93%) as a white foam. 1H NMR (400 MHz,
CDCl3): δ = 1.20 [s, 18 H, (CH3)3CCO], 1.22 (t, J = 7.5 Hz, 6 H,
SCH2CH3), 1.35 [s, 6 H, (CH3)2C], 2.61–2.73 (m, 4 H, SCH2CH3),
N,NЈ-Bis(ethyl-3-O-acetyl-4,6-O-benzylidene-2-deoxy-1-thio-β-D-glu- 3.61 (ddd ≈ td, J4,5 ≈ J5,6Ј = 9.5 Hz, J5,6 = 4.7 Hz, 2 H, 5-H), 3.78
copyranosid-2-yl)dimethylmalonamide (17a): To a solution of 16
(2.00 g, 2.78 mmol) dissolved in pyridine (100 mL) was slowly
added acetic anhydride (2.63 mL, 2.84 g, 27.80 mmol), and the
solution was stirred at room temperature for 16 h (TLC: PE/
(dd ≈ t, J5,6Ј ≈ J6,6Ј = 10.2 Hz, 2 H, 6Ј-H), 3.81 (dd, J3,4 = J4,5
=
9.5 Hz, 2 H, 4-H), 4.33 (dd ≈ t, J1,2 = 10.2 Hz, J2,3 = 9.5 Hz, 2 H,
2-H), 4.39 (dd, J5,6 = 4.7 Hz, J6,6Ј = 10.2 Hz, 2 H, 6-H), 4.85 (d,
J1,2 = 10.2 Hz, 2 H, 1-H), 5.33 (dd ≈ t, J2,3 = 9.5 Hz, J3,4 = 9.2 Hz,
1004
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© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 997–1008

Facile Optimisation of Carbohydrate-Based Bis(oxazoline) Ligands
2 H, 3-H), 5.56 (s, 2 H, CHPh), 6.57 (d, J2,NH = 9.5 Hz, 2 H, NH),
7.29–7.35 (m, 6 H, Ph), 7.39–7.45 (m, 4 H, Ph) ppm. 13C NMR
(100 MHz, CDCl3): δ = 14.6 (CH3, SCH2CH3), 23.0 (CH2,
SCH2CH3), 24.6 [CH3, (CH3)2C], 27.1 [CH3, (CH3)3CCO], 39.1 [C,
(CH3)3CCO], 51.5 [C, (CH3)2C], 52.8 (CH, C-2), 68.5 (CH2, C-6),
70.2 (CH, C-5), 74.9 (CH, C-3), 78.6 (CH, C-4), 83.9 (CH, C-1),
101.1 (CH, PhCH), 125.8, 128.1, 128.9 (CH, Ph), 136.8 (C, Ph),
172.6 [C, (CH3)3CCO], 180.5 (C, CONH) ppm. HRMS (ESI+):
calcd. for C45H62N2O12NaS2 [M + Na]+ 909.3642; found 909.3628.
[α]2D0 = –98 (c = 1.0, CHCl3).
C49H58N2O10NaS2 [M + Na]+ 921.3431; found 921.3432. [α]2D0
–25 (c = 1.0, CHCl3).
=
N,NЈ-Bis(ethyl-4,6-O-benzylidene-2-deoxy-1-thio-β-3-O-triethylsi-
lyl- -glucopyranosid-2-yl)dimethylmalonamide (17f): To a stirred
D
solution of 16 (250 mg, 350 µmol) in dry CH2Cl2 (25 mL) at –78 °C
was dropwise added Et3N (500 µL, 350 mg, 3.50 mmol) by syringe.
Then, TESOTf (460 µL, 560 mg, 2.10 mmol) was added. The mix-
ture was stirred for 2 h at –78 °C (TLC: PE/EtOAc, 2:1) and then
brought to room temperature, and the solvent was removed under
reduced pressure. Flash chromatography on silica gel (PE/EtOAc,
1
2:1) gave 17f (270 mg, 290 µmol, 83%) as a white foam. H NMR
N,NЈ-Bis(ethyl-4,6-O-benzylidene-2-deoxy-3-O-methyl-1-thio-β-D-
(400 MHz, CDCl3): δ = 0.51 (q, J = 7.8 Hz, 12 H, SiCH2CH3),
0.82 (t, J = 7.8 Hz, 18 H, SiCH2CH3), 1.25 (t, J = 7.5 Hz, 6 H,
SCH2CH3), 1.46 [s, 6 H, (CH3)2C], 2.68–2.78 (m, 4 H, SCH2CH3),
3.42–3.52 (m, 4 H, 4-H, 5-H), 3.70–3.85 (m, 4 H, 2-H, 6Ј-H), 4.06
(dd ≈ t, J2,3 ≈ J3,4 = 8.8 Hz, 2 H, 3-H), 4.31 (dd, J5,6 = 4.7 Hz, J6,6Ј
= 10.5 Hz, 2 H, 6-H), 4.83 (d, J1,2 = 10.2 Hz, 2 H, 1-H), 5.46 (s, 2
H, CHPh), 6.63 (d, J2,NH = 7.2 Hz, 2 H, NH), 7.32–7.45 (m, 10 H,
Ph) ppm. 13C NMR (100 MHz, CDCl3): δ = 5.1 (CH2, SiCH2CH3),
6.8 (CH3, SiCH3CH2), 14.8 (CH3, SCH2CH3), 23.9 (CH2,
SCH2CH3), 24.5 [CH3, (CH3)2C], 50.5 [C, (CH3)2C], 57.0 (CH, C-
2), 68.6 (CH2, C-6), 70.7 (CH, C-5), 73.0 (CH, C-3), 82.3 (CH, C-
4), 83.9 (CH, C-1), 102.1, 126.2, 128.1, 129.1 (CH, Ph), 137.0 (C,
Ph), 173.9 (C, CONH) ppm. HRMS (ESI+): calcd. for
glucopyranosid-2-yl)dimethylmalonamide (17d): To a solution of 16
(500 mg, 700 µmol) dissolved in dry THF (5 mL) was first added
sodium hydride (60% dispersion in paraffin oil, 170 mg, equalling
4.20 mmol of NaH) and second methyl iodide (400 mg, 175 µL,
2.80 mmol), and the resulting mixture was heated at reflux for 6 h
(TLC: PE/EtOAc, 1:1). The mixture was diluted with CH2Cl2
(10 mL) and washed with hydrochloric acid (3 , 2ϫ5 mL) and
saturated aqueous NaHCO3 solution (2ϫ5 mL). The organic layer
was dried with Na2SO4, concentrated and purified by flash
chromatography on silica gel (PE/EtOAc, 1:1) to yield 17d (490 g,
1
660 µmol, 94%) as a white solid. H NMR (400 MHz, CDCl3): δ
= 1.24 (t, J = 7.5 Hz, 6 H, SCH2CH3), 1.49 [s, 6 H, (CH3)2C], 2.65–
2.75 (m, 4 H, SCH2CH3), 3.49 (ddd ≈ td, J4,5 ≈ J5,6Ј = 9.9 Hz, J5,6
C47H74N2O10NaSi2S2 [M + Na]+ 969.4221; found 969.4230. [α]2D0
–35 (c = 1.0, CHCl3).
=
= 5.1 Hz, 2 H, 5-H), 3.53 (s, 6 H, OCH3), 3.62 (dd ≈ t, J2,3
9.2 Hz, J3,4 = 8.8 Hz, 2 H, 3-H), 3.68 (m, 6 H, 2-H, 4-H, 6Ј-H),
4.33 (dd, J5,6 = 5.1 Hz, J6,6Ј = 10.2 Hz, 2 H, 6-H), 4.88 (d, J1,2
=
=
Representative Procedure for the Cyclisation of Thioglucoside Bis-
9.9 Hz, 2 H, 1-H), 5.52 (s, 2 H, CHPh), 6.81 (d, J2,NH = 8.1 Hz, 2 (amides) to Bis(oxazolines): A mixture of 17a–f (1 equiv.) and 4 Å
H, NH), 7.32–7.37 (m, 6 H, Ph), 7.43–7.46 (m, 4 H, Ph) ppm. 13C
NMR (100 MHz, CDCl3): δ = 15.0 (CH3, SCH2CH3), 24.2 (CH2,
MS (approx. 1 mg per mg 17a–f) in dry CH2Cl2 (5 mL for 400 µmol
17a–f) was stirred for 1 h under a nitrogen atmosphere in a flame-
SCH2CH3), 24.3 [CH3, (CH3)2C], 50.1 [C, (CH3)2C], 55.5 (CH, C- dried flask. To this was added NIS (2.5 equiv.), and the mixture
2), 60.7 (CH3, OCH3), 68.6 (CH2, C-6), 70.6 (CH, C-5), 80.5 (CH, was cooled to –30 °C. Then, TfOH (5 µL for 400 µmol 17a–f) was
C-4), 82.0 (CH, C-3), 84.1 (CH, C-1), 101.1 (CH, PhCH), 126.0,
128.2, 129.0 (CH, Ph), 137.1 (C, Ph), 173.8 (C, CONH) ppm.
HRMS (ESI+): calcd. for C37H50N2O10NaS2 [M + Na]+ 769.2805;
found 769.2797. [α]2D0 = –38 (c = 1.0, CHCl3).
added, and the mixture was stirred for 1 h at –30 °C. The reaction
was quenched with Et3N (100 µL for 400 µmol 17a–f), and the mix-
ture was filtered through Celite, diluted with CH2Cl2, washed with
saturated aqueous NaHCO3 solution, aqueous sodium thiosulfate
solution (3 ) and dried with Na2SO4. The solvent was removed
under reduced pressure, and the residue was purified by flash
chromatography on silica gel (eluants for TLC and column given
with the respective compound) to yield the desired product.
N,NЈ-Bis(ethyl-3-O-benzyl-4,6-O-benzylidene-2-deoxy-1-thio-β-D-
glucopyranosid-2-yl)dimethylmalonamide (17e): To a mixture of 16
(250 mg, 350 µmol) and tetrabutylammonium iodide (30 mg,
70 µmol) in dry DMF (5 mL) was added sodium hydride (60% dis-
persion in paraffin oil, 50 mg, equalling 1.19 mmol NaH) at 0 °C.
The mixture was stirred for 30 min and benzyl bromide (250 µL,
360 mg, 2.10 mmol) was added by syringe (TLC: PE/EtOAc, 2:1).
After 2 h, the reaction was quenched by the addition of acetic acid
and filtered. Et2O (20 mL) was added to the filtrate, which was
extracted with saturated aqueous NH4Cl solution (20 mL) and sat-
urated aqueous NaHCO3 solution (20 mL). The organic layer was
separated and dried with Na2SO4. Flash chromatography on silica
gel (PE/EtOAc, 2:1) gave 17e (260 mg, 290 µmol, 84%) as a white
3-O-Ac glucoBox (18a): Starting from 17a (1.25 g, 1.56 mmol),
1
yielding ligand 18a (970 mg, 1.43 mmol, 92%). Eluant: EtOAc. H
NMR (400 MHz, CDCl3): δ = 1.52 [s, 6 H, (CH3)2C], 2.10 (s, 6 H,
CH3CO), 3.61 (dd ≈ t, J5,6Ј ≈ J6,6Ј = 9.9 Hz, 2 H, 6Ј-H), 3.75 (ddd
≈ td, J4,5 = J5,6Ј = 9.9 Hz, J5,6 = 5.1 Hz, 2 H, 5-H), 3.81 (dd, J3,4
= 7.5 Hz, J4,5 = 9.9 Hz, 2 H, 4-H), 4.14 (dd, J1,2 = 7.1 Hz, J2,3
=
2.7 Hz, 2 H, 2-H), 4.39 (dd, J5,6 = 5.1 Hz, J6,6Ј = 10.2 Hz, 2 H, 6-
H), 5.28 (dd, J2,3 = 2.7 Hz, J3,4 = 7.5 Hz, 2 H, 3-H), 5.51 (s, 2 H,
CHPh), 5.98 (d, J1,2 = 7.1 Hz, 2 H, 1-H), 7.32–7.37 (m, 6 H, Ph),
7.44–7.46 (m, 4 H, Ph) ppm. 13C NMR (100 MHz, CDCl3): δ =
21.1 (CH3, CH3CO), 23.4 [CH3, (CH3)2C], 38.9 [C, (CH3)2C], 62.9
(CH, C-5), 67.8 (CH2, C-6), 68.2 (CH, C-2), 73.5 (CH, C-3), 78.4
(CH, C-4), 101.4 (CH, PhCH), 101.4 (CH, C-1), 126.1, 128.2, 129.0
(CH, Ph), 136.8 (C, Ph), 169.6 (C, O–C=N), 169.8 (C, CH3CO)
ppm. HRMS (ESI+): calcd. for C35H39N2O12 [M + H]+ 679.2503;
found 679.2511. [α]2D0 = +106 (c = 1.0, CHCl3).
1
foam. H NMR (400 MHz, CDCl3): δ = 1.20 (t, J = 7.5 Hz, 6 H,
SCH2CH3), 1.39 [s, 6 H, (CH3)2C], 2.61–2.70 (m, 4 H, SCH2CH3),
3.39 (ddd ≈ td, J4,5 ≈ J5,6Ј = 9.5 Hz, J5,6 = 5.1 Hz, 2 H, 5-H), 3.68–
3.89 (m, 8 H, 2-H, 3-H, 4-H, 6Ј-H), 4.32 (dd, J5,6 = 5.1 Hz, J6,6Ј
=
10.2 Hz, 2 H, 6-H), 4.54 (d, J1,2 = 9.5 Hz, 2 H, 1-H), 4.62 (d, J =
11.2 Hz, 2 H, CH2Ph), 4.87 (d, J = 11.2 Hz, 2 H, CH2Ph), 5.55 (s,
2 H, CHPh), 6.40 (d, J2,NH = 7.8 Hz, 2 H, NH), 7.22–7.47 (m, 20
H, Ph) ppm. 13C NMR (100 MHz, CDCl3): δ = 14.9 (CH3,
3-O-Bz glucoBox (18b): Starting from 17b (400 mg, 430 µmol),
SCH2CH3), 24.0 (CH2, SCH2CH3), 24.2 [CH3, (CH3)2C], 50.4 [C, yielding ligand 18b (290 mg, 360 µmol, 84%). Eluant: PE/EtOAc
(CH3)2C], 54.7 (CH, C-2), 68.6 (CH2, C-6), 70.4 (CH, C-5), 73.7 (2:1). 1H NMR (400 MHz, CDCl3): δ = 1.57 [s, 6 H, (CH3)2C],
(CH2, PhCH2), 78.5 (CH, C-3), 82.0 (CH, C-4), 83.9 (CH, C-1), 3.66 (dd ≈ t, J5,6Ј ≈ J6,6Ј = 10.2 Hz, 2 H, 6Ј-H), 3.84 (ddd ≈ td, J4,5
101.1 (CH, PhCH), 125.9, 127.8, 127.8, 128.2, 128.4, 129.0, 137.1,
138.3 (C, Ph), 173.68 (C, CONH) ppm. HRMS (ESI+): calcd. for
≈ J5,6Ј = 9.9 Hz, J5,6 = 5.4 Hz, 2 H, 5-H), 4.06 (dd ≈ t, J3,4 = 7.1 Hz,
J4,5 = 9.9 Hz, 2 H, 4-H), 4.34 (dd ≈ t, J1,2 = 7.1 Hz, J2,3 = 2.0 Hz,
Eur. J. Org. Chem. 2009, 997–1008
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1005

T. Minuth, M. Irmak, A. Groschner, T. Lehnert, M. M. K. Boysen
FULL PAPER
2 H, 2-H), 4.47 (dd, J5,6 = 5.4 Hz, J6,6Ј = 10.2 Hz, 2 H, 6-H), 5.54 (CH3)2C], 3.55–3.66 (m, 6 H, 4-H, 5-H, 6Ј-H), 3.93 (dd, J2,3
(dd, J2,3 = 2.0 Hz, J3,4 = 7.1 Hz, 2 H, 3-H), 5.55 (s, 2 H, CHPh), 3.8 Hz, J3,4 = 7.2 Hz, 2 H, 3-H), 3.98 (dd, J1,2 = 7.2 Hz, J2,3
=
=
6.08 (d, J1,2 = 7.1 Hz, 2 H, 1-H), 7.31–7.35 (m, 6 H, Ph), 7.42–7.48 3.8 Hz, 2 H, 2-H), 4.36 (dd, J5,6 = 3.1 Hz, J6,6Ј = 8.9 Hz, 2 H, 6-
(m, 8 H, Ph), 7.55–7.58 (m, 2 H, Ph), 8.07–8.09 (m, 4 H, Ph) ppm. H), 5.53 (s, 2 H, CHPh), 5.95 (d, J1,2 = 7.2 Hz, 2 H, 1-H), 7.32–
13C NMR (100 MHz, CDCl3): δ = 23.4 [CH3, (CH3)2C], 38.8 [C, 7.37 (m, 6 H, Ph), 7.45–7.49 (m, 4 H, Ph) ppm. 13C NMR
(CH3)2C], 62.8 (CH, C-5), 68.2 (CH, C-2), 68.6 (CH2, C-6), 74.2 (100 MHz, CDCl3): δ = 4.7 (CH2, SiCH2CH3), 6.7 (CH3,
(CH, C-3), 78.7 (CH, C-4), 101.2 (CH, C-1), 101.4 (CH, PhCH), SiCH2CH3), 23.4 [CH3, (CH3)2C], 39.0 [C, (CH3)2C], 63.2 (CH, C-
126.1, 128.2, 128.3, 129.0, 129.6, 129.8 (2 CH, Ph), 133.2, 136.8 (C,
Ph), 165.6 (C, PhCO), 169.8 (C, O-C=N) ppm. HRMS (ESI+):
calcd. for C45H43N2O12 [M + H]+ 803.2816; found 803.2817. [α]2D0
= +94 (c = 0.9, CHCl3).
5), 68.6 (CH2, C-6), 70.8 (CH, C-2), 74.4 (CH, C-3), 81.1 (CH, C-
4), 101.4 (CH, PhCH), 102.7 (CH, C-1), 126.0, 128.0 (CH, Ph),
128.8, 137.3 (C, Ph), 168.5 (C, O-C=N) ppm. HRMS (ESI+): calcd.
for C43H63N2O10Si2 [M + H]+ 823.4021; found 823.4003. [α]2D0
+106 (c = 0.9, CHCl3).
=
3-O-Piv glucoBox (18c): Starting from 17c (250 mg, 280 µmol),
yielding ligand 18c (170 mg, 230 µmol, 82%). Eluant: PE/EtOAc
(2:1). 1H NMR (400 MHz, CDCl3): δ = 1.22 [s, 18 H, (CH3)3CCO],
1.52 [s, 6 H, (CH3)2C], 3.61 (dd ≈ t, J5,6Ј = 9.9 Hz, J6,6Ј = 10.2 Hz,
2 H, 6Ј-H), 3.74 (ddd ≈ td, J4,5 = J5,6Ј = 9.9 Hz, J5,6 = 5.1 Hz, 2
H, 5-H), 3.85 (dd, J3,4 = 7.1 Hz, J4,5 = 9.9 Hz, 2 H, 4-H), 4.12 (dd,
J1,2 = 7.1 Hz, J2,3 = 2.0 Hz, 2 H, 2-H), 4.41 (dd, J5,6 = 5.1 Hz, J6,6Ј
= 10.2 Hz, 2 H, 6-H), 5.24 (dd, J2,3 = 2.0 Hz, J3,4 = 7.1 Hz, 2 H,
3-H), 5.52 (s, 2 H, CHPh), 5.60 (d, J1,2 = 7.1 Hz, 2 H, 1-H), 7.31–
7.37 (m, 6 H, Ph), 7.44–7.47 (m, 4 H, Ph) ppm. 13C NMR
(100 MHz, CDCl3): δ = 23.4 [CH3, (CH3)2C], 27.0 [CH3, (CH3)3-
CCO], 38.7 [C, (CH3)3CCO], 38.8 [C, (CH3)2C], 62.7 (CH, C-5),
68.1 (CH, C-2), 68.6 (CH2, C-6), 73.5 (CH, C-3), 78.7 (CH, C-4),
101.2 (CH, C-1), 101.2 (CH, PhCH), 126.0, 128.2, 128.9 (CH, Ph),
136.9 (C, Ph), 169.7 (C, O-C=N), 177.4 [C, (CH3)3CCO] ppm.
HRMS (ESI+): calcd. for C41H50N2O12Na [M + Na]+ 785.3261;
found 785.3262. [α]2D0 = +102 (c = 1.0, CHCl3).
3-OH glucoBox (19): A mixture of compound 18a (500 mg,
740 µmol) and potassium carbonate (200 mg, 1.48 mmol) in
MeOH/H2O (5:2, 42 mL) was stirred for 1 h at room temperature
(TLC: EtOAc). The reaction mixture was neutralized by the ad-
dition of a saturated solution of hydrogen chloride in MeOH. After
concentration under vacuum, the product was purified by flash
chromatography on silica gel (EtOAc) to yield 19 (350 mg, 59 µmol,
1
80%) as a white solid. H NMR (400 MHz, CDCl3): δ = 1.41 [s, 6
H, (CH3)2C], 3.53–3.67 (m, 6 H, 4-H, 5-H, 6Ј-H), 3.72 (dd, J2,3
5.4 Hz, J3,4 = 8.5 Hz, 2 H, 3-H), 3.95 (dd, J1,2 = 7.8 Hz, J2,3
=
=
5.4 Hz, 2 H, 2-H), 4.31 (dd, J5,6 = 3.4 Hz, J6,6Ј = 8.8 Hz, 2 H, 6-
H), 4.81 (br. s, 2 H, OH), 5.52 (s, 2 H, CHPh), 5.89 (d, J1,2
=
7.8 Hz, 2 H, 1-H), 7.30–7.35 (m, 6 H, Ph), 7.44–7.48 (m, 4 H, Ph)
ppm. 13C NMR (100 MHz, CDCl3): δ = 23.2 [CH3, (CH3)2C], 39.4
[C, (CH3)2C], 63.5 (CH, C-5), 68.3 (CH2, C-6), 68.9 (CH, C-2),
73.9 (CH, C-3), 79.0 (CH, C-4), 101.7 (CH, PhCH), 103.6 (CH, C-
1), 126.2, 128.2, 129.1 (CH, Ph), 136.9 (C, Ph), 169.3 (C, CONH)
ppm. HRMS (ESI+): calcd. for C31H35N2O10 [M + H]+ 595.2292;
found 595.2294. [α]2D0 = +167 (c = 1.0, CHCl3).
3-O-Me glucoBox (18d): Starting from 17d (280 mg, 380 µmol),
yielding ligand 18d (210 mg, 340 µmol, 90%). Eluant: PE/EtOAc
(1:2). 1H NMR (400 MHz, CDCl3): δ = 1.53 [s, 6 H, (CH3)2C],
3.54 (s, 6 H, OCH3), 3.60–3.71 (m, 8 H, 3-H, 4-H, 5-H, 6Ј-H), 4.11
(dd, J1,2 = 7.5 Hz, J2,3 = 2.4 Hz, 2 H, 2-H), 4.33–4.41 (m, 2 H, 6-
H), 5.56 (s, 2 H, CHPh), 5.97 (d, J1,2 = 7.5 Hz, 2 H, 1-H), 7.32–
7.37 (m, 6 H, Ph), 7.44–7.47 (m, 4 H, Ph) ppm. 13C NMR
(100 MHz, CDCl3): δ = 23.4 [CH3, (CH3)2C], 39.0 [C, (CH3)2C],
58.5 (CH3, OCH3), 62.6 (CH, C-5), 67.8 (CH, C-2), 68.2 (CH2, C-
6), 80.1 (CH, C-3), 81.7 (CH, C-4), 101.3 (CH, PhCH), 102.2 (CH,
C-1), 126.1, 128.2, 129.0 (CH, Ph), 137.1 (C, Ph), 168.8 (C, O–
C=N) ppm. HRMS (ESI+): calcd. for C33H39N2O10 [M + H]+
623.2599; found 623.2521. [α]2D0 = +124 (c = 1.0, CHCl3).
Ethyl-2-Amino-2-deoxy-1-thio-β-D-glucopyranose (20): Under a ni-
trogen atmosphere, 13 (10.00 g, 28.00 mmol) was dissolved in abso-
lute ethanol (800 mL). To this solution was added ethylene diamine
(112 mL, 100.90 g, 1.70 mol), and the resulting reaction mixture
was heated at reflux for 2.5 h (TLC: CH2Cl2/MeOH, 9:1). The sol-
vent was evaporated in vacuo, and the residue was coevaporated
with toluene (2ϫ) to yield 20 (6.25 g, 28.00 mmol, quant.) as a
brownish foam, which was employed for the next step without fur-
ther purification and characterization.
Ethyl-2-Amino-2-deoxy-1-thio-3,4,6-tris-O-trimethylsilyl-β-D-gluco-
pyranose (21): Compound 20 (8.90 g, 40.00 mmol) was dissolved in
pyridine (220 mL) and then treated with HMDS (82.80 mL,
64.60 g, 400.00 mmol) and TMSCl (51.10 mL, 43.40 g,
400.00 mmol). The mixture was then stirred for 16 h at room tem-
perature (TLC: PE/EtOAc, 7:1). After completion of the reaction
the remaining TMSCl as well as the solvent were removed in vacuo
(a cooling trap was placed between the rotary evaporator and the
pump stand). The crude product was purified by column filtration
through silica gel (PE/EtOAc, 7:1) to yield 21 as a yellow oil
(14.60 g, 33.00 mmol, 83%). 1H NMR (400 MHz, CDCl3): δ =
0.08, 0.14, 0.19, (each s, each 9 H, SiCH3), 1.22 (t, J = 7.5 Hz, 3
H, SCH2CH3), 1.48 (br. s, 2 H, NH2), 2.60–2.74 (m, J2,3 = 8.5 Hz,
3 H, 2-H, SCH2CH3), 3.19 (ddd, J4,5 = 9.2 Hz, J5,6 = 4.4 Hz, J5,6Ј
= 1.7 Hz, 1 H, 5-H), 3.36 (dd ≈ t, J2,3 = 8.5 Hz, J3,4 = 8.9 Hz, 1 H,
3-H), 3.56 (dd ≈ t, J3,4 = 8.9 Hz, J4,5 = 9.2 Hz, 1 H, 4-H), 3.72 (dd,
J5,6 = 4.4 Hz, J6,6Ј = 11.6 Hz, 1 H, 6-H), 3.78 (dd, J5,6Ј = 1.7 Hz,
J6,6Ј = 11.6 Hz, 1 H, 6Ј-H), 4.23 (d, J1,2 = 9.6 Hz, 1 H, 1-H) ppm.
13C NMR (100 MHz, CDCl3): δ = 0.2, 0.7, 1.2 (CH3, SiCH3) 15.4
3-O-Bn glucoBox (18e): Starting from 17e (250 mg, 280 µmol),
yielding ligand 18e (170 mg, 220 µmol, 79%). Eluant: PE/EtOAc
(1:1). 1H NMR (400 MHz, CDCl3): δ = 1.51 [s, 6 H, (CH3)2C],
3.63 (dd ≈ t, J5,6Ј ≈ J6,6Ј = 9.6 Hz, 2 H, 6Ј-H), 3.68 (ddd ≈ td, J4,5
≈ J5,6Ј = 9.6 Hz, J5,6 = 4.1 Hz, 2 H, 5-H), 3.78 (dd, J3,4 = 7.5 Hz,
J4,5 = 9.6 Hz, 2 H, 4-H), 3.93 (dd, J2,3 = 3.0 Hz, J3,4 = 7.5 Hz, 2
H, 3-H), 4.23 (dd, J1,2 = 7.5 Hz, J2,3 = 3.0 Hz, 2 H, 2-H), 4.38 (dd,
J5,6 = 4.1 Hz, J6,6Ј = 9.6 Hz, 2 H, 6-H), 4.77 (d, J = 12.0 Hz, 2 H,
CH2Ph), 4.82 (d, J = 12.0 Hz, 2 H, CH2Ph), 5.57 (s, 2 H, CHPh),
5.98 (d, J1,2 = 7.5 Hz, 2 H, 1-H), 7.25–7.46 (m, 20 H, Ph) ppm.
13C NMR (100 MHz, CDCl3): δ = 23.4 [CH3, (CH3)2C], 38.9 [C,
(CH3)2C], 62.8 (CH, C-5), 68.4 (CH, C-2), 68.6 (CH2, C-6), 72.4
(CH2, PhCH2), 79.7 (CH, C-3), 80.1 (CH, C-4), 101.1 (CH, PhCH),
102.2 (CH, C-1), 126.0, 127.6, 127.8, 128.1, 128.2, 128.9 (CH, Ph),
137.1, 137.9 (C, Ph), 168.8 (C, O-C=N) ppm. HRMS (ESI+): calcd.
for C45H47N2O10 [M + H]+ 775.3231; found 775.3234. [α]2D0 = +82
(c = 1.0, CHCl3).
3-O-TES glucoBox (18f): Starting from 17f (250 mg, 260 µmol), (CH3, SCH2CH3), 23.8 (CH2, SCH2CH3), 56.8 (CH, C-2), 62.1
yielding ligand 18f (180 mg, 220 µmol, 85%). Eluant: PE/EtOAc (CH2, C-6), 71.3 (CH, C-4), 80.9 (CH, C-3), 80.9 (CH, C-5), 86.3
(1:1). H NMR (400 MHz, CDCl3): δ = 0.65 (q, J = 7.8 Hz, 12 H, (CH, C-1) ppm. HRMS (ESI+): calcd. for C17H41NO4SSi3Na [M
SiCH2CH3), 0.93 (t, J = 7.8 Hz, 18 H, SiCH2CH3), 1.50 [s, 6 H,
+ Na]+ 462.1962; found 462.1960. [α]2D0 = –12 (c = 1.2, CHCl3).
1
1006
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© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 997–1008

Facile Optimisation of Carbohydrate-Based Bis(oxazoline) Ligands
N,NЈ-Bis(ethyl-2-deoxy-1-thio-3,4,6-tri-O-trimethylsilyl-β- -gluco-
D
CDCl3): δ = 14.9 (CH3, SCH2CH3), 23.3 [CH3, (CH3)2C], 24.5
(CH2, SCH2CH3), 27.0, 27.1, 27.2 [CH3, (CH3)3 CCO], 38.7, 38.8,
39.0 [C, (CH3)3CCO], 51.2 (CH, C-2), 54.6 [C, (CH3)2C], 62.1
(CH2, C-6), 67.6 (CH, C-5), 74.7 (CH, C-4), 76.3 (CH, C-3), 83.2
(CH, C-1), 172.8, 176.3, 178.1 [C, (CH3)3CCO], 179.6 (C, CONH)
ppm. HRMS (ESI+): calcd. for C51H86N2O16Na [M + Na]+
1069.5316; found 1069.5306. [α]2D0 = –26 (c = 1, CHCl3).
pyranosid-2-yl)dimethylmalonamide (22): Under a nitrogen atmo-
sphere, 21 (5.00 g, 11.40 mmol) was dissolved in dry CH2Cl2
(75 mL). The solution was cooled to 0 °C and Et3N (3.2 mL,
2.30 g, 22.80 mmol) and dimethylmalonyl dichloride (800 µL,
1.00 g, 5.70 mmol.) were added. The reaction mixture was warmed
to room temperature and subsequently stirred for 72 h (TLC: PE/
EtOAc, 7:1). After completion of the reaction the solvent was evap-
orated and the raw product purified by flash chromatography on
silica gel (PE/EtOAc, 9:1Ǟ7:1). Compound 22 (3.40 g, 3.50 mmol,
60%) was isolated as a colourless solid. M.p. 118 °C. 1H NMR
(400 MHz, CDCl3): δ = 0.08, 0.09, 0.13 (each s, each 18 H, SiCH3),
1.23 (t, J = 7.5 Hz, 6 H, SCH2CH3), 1.45 [s, 6 H, C(CH3)2], 2.61–
2.71 (m, 4 H, SCH2CH3), 3.41 (dd, J5,6 = 5.1 Hz, J6,6Ј = 10.9 Hz,
2 H, 6-H), 3.60 (ddt, J2,3 ≈ J3,4 = 6.2 Hz, 2 H, 3-H), 3.68–3.73 (m,
4 H, 4-H, 5-H), 3.92 (dd, J5,6Ј = 4.8 Hz, J6,6Ј = 10.9 Hz, 2 H, 6Ј-
H), 4.04 (ddd ≈ q, J1,2 ≈ J2,3 ≈ J2,NH = 8.2 Hz, 2 H, 2-H), 4.49 (d,
J1,2 = 8.2 Hz, 2 H, 1-H), 7.35 (d, JNH = 9.6 Hz, 2 H, NH) ppm.
13C NMR (100 MHz, CDCl3): δ = 0.4, 0.4, 0.7, (each CH3, SiCH3),
14.9 (CH3, SCH2CH3), 24.5 [CH3, (CH3)2C], 24.7 (CH2,
SCH2CH3), 49.6 (CH, C-2), 54.3 [C, (CH3)2C], 62.5 (CH2, C-6),
70.6 (CH, C-4), 75.4 (CH, C-3), 81.1 (CH, C-5), 83.2 (CH, C-1),
173.7 (C, CONH) ppm. HRMS (ESI+): calcd. for C39H88N2O10S2-
Si2Na [M + Na]+ 997.4237; found 997.4249. [α]2D0 = –22 (c = 1,
CHCl3).
Piv glucoBox (24): Under a nitrogen atmosphere, 23 (500 mg,
500 µmol) was taken up in dry CH2Cl2 (5 mL) and cooled to 0 °C.
Bromine (100 µL; 229 mg; 1.40 mmol) was slowly added, and the
mixture was stirred for 1.5 h (TLC: PE/EtOAc, 4:1). After complete
conversion of the starting material, the solvent was removed in
vacuo and the raw product was coevaporated with toluene (3ϫ).
The crude product was used in the next step without further purifi-
cation. The crude product of the previous reaction was dissolved in
dry MeCN (10 mL) and treated with Et4NCl (199 mg, 1.20 mmol).
Subsequently, solid NaHCO3 (190 mg, 2.30 mmol) was added, and
the mixture was stirred for 16 h at room temperature (TLC: PE/
EtOAc, 4:1). Then, the solvent was removed in vacuo, and the resi-
due was taken up in CH2Cl2 (15 mL) and washed with water
(15 mL). The organic phase was dried with Na2SO4 and concen-
trated. The residue was purified by flash chromatography on silica
gel (PE/EtOAc, 4:1) to yield 24 (278 mg, 300 µmol, 60%) as a white
foam. 1H NMR (400 MHz, CDCl3): δ = 1.17, 1.17, 1.18 [each s,
each 18 H, (CH3)3CCO], 1.54 [s, 6 H, C(CH3)2], 3.77 (ddd, J4,5
9.2 Hz, J5,6 = 4.8 Hz, J5,6Ј = 2.4 Hz, 2 H, 5-H), 4.02 (dd, J5,6Ј
2.4 Hz, J6,6Ј = 12.6 Hz, 2 H, 6Ј-H), 4.17 (ddd, J1,2 = 7.2 Hz, J2,3
2.7 Hz, J2,4 = 1.4 Hz, 2 H, 2-H), 4.23 (dd, J5,6 = 4.8 Hz, J6,6Ј
=
=
=
=
N,NЈ-Bis(ethyl-2-deoxy-3,4,6-tri-O-pivaloyl-1-thio-β-D-glucopyrano-
sid-2-yl)dimethylmalonamide (23): Compound 22 (300 mg,
300 µmol) was dissolved in MeOH/TFA (9:1, 10 mL). The mixture
was stirred at room temperature for 45 min (TLC: CH2Cl2/MeOH,
9:1). After removal of the solvents and coevaporation with toluene,
the crude product was treated with EtOAc, filtered and washed
with more EtOAc to remove organosilicon byproducts. The crude
product was taken up in CH2Cl2 and MeOH, dried with Na2SO4,
filtered and concentrated to yield bis(ethyl-2-amino-2-deoxy-1-
thio-β--glucopyranosido)dimethylmalonamide (164 mg,
300 µmol, quant.) as a white foam which was used for the next step
12.6 Hz, 2 H, 6-H), 4.94 (ddd ≈ dt, J3,4 = 2.7 Hz, J4,5 = 9.2 Hz, J2,4
= 1.4 Hz, 2 H, 4-H), 5.22 (dd ≈ t, J2,3 ≈ J3,4 = 2.7 Hz, 2 H, 3-H),
5.95 (d, J1,2 = 7.2 Hz, 2 H, 1-H) ppm. 13C NMR (100.6 MHz,
CDCl3): δ = 26.9, 26.9, 27.1 [CH3, (CH3)3CCO, (CH3)2C] 38.6 [C,
(CH3)2C, (CH3)3CCO], 38.8, 39.1 [C, (CH3)3CCO], 62.5 (CH2, C-
6), 64.6 (CH, C-2), 67.6 (CH, C-5), 67.8 (CH, C-4), 69.8 (CH, C-
3), 100.1 (CH, C-1), 170.1 (C, O-C=N), 176.4, 176.7, 177.9 [C,
(CH3)2CCO] ppm. HRMS (ESI+): calcd. for C47H75N2O16 [M +
H]+ 923.5117; found 923.5112. [α]2D0 = +20 (c = 1, CHCl3).
1
without any further purification. H NMR (400 MHz, CD3OD): δ
= 1.29 (t, J = 7.5 Hz, 6 H, SCH2CH3), 1.47 [s, 6 H, (CH3)2C], 2.65–
2.83 (m, 4 H, SCH2CH3), 3.33–3.36 (m, 2 H, 5-H), 3.42 (dd ≈ t,
J3,4 = 8.5 Hz, J4,5 = 9.9 Hz, 2 H, 4-H), 3.57 (dd, J2,3 = 9.9 Hz, J3,4
= 8.5 Hz, 2 H, 3-H), 3.72 (dd, J5,6 = 5.5 Hz, J6,6Ј = 12.3 Hz, 2 H,
6-H), 3.85–3.90 (m, 4 H, 2-H, 6Ј-H), 4.61 (d, J1,2 = 10.2 Hz, 2 H,
1-H) ppm. 13C NMR (100MHz, CD3OD): δ = 15.6 (CH3,
SCH2CH3), 24.4 [CH3, (CH3)2C], 25.2 (CH2, SCH2CH3), 52.1 (CH,
C-2), 56.6 [C, (CH3)2C], 63.2 (CH2, C-6), 72.1 (CH, C-4), 77.6 (CH,
C-3), 82.4 (CH, C-5), 85.5 (CH, C-1), 176.3 (C, CONH) ppm.
HRMS (ESI+): calcd. for C21H38N2O10S2Na [M + Na]+ 565.1866;
found 565.1873. The deprotected bis(amide) (160 mg, 300 µmol)
was dissolved in dry pyridine (8 mL) and pivaloyl chloride (500 µL,
440 mg, 3.60 mmol) and a catalytic amount of DMAP (10 mg)
were added. The suspension was stirred for 8 h at 80 °C (TLC: PE/
EtOAc, 2:1). After completion of the reaction the solvent was evap-
orated in vacuo and the residue was purified by flash chromatog-
raphy on silica gel (PE/EtOAc, 7:1Ǟ2:1). Compound 23 (192 mg,
163 mmol, 61%) was isolated as a colourless crystalline solid. M.p.
96 °C. 1H NMR (400 MHz, CDCl3): δ = 1.12, 1.14, 1.18 [each s,
each 18 H, (CH3)3CCO], 1.24 (t, J = 7.5 Hz, 6 H, SCH2CH3), 1.30
General Procedure for CuI-Catalysed Asymmetric Cyclopropanation
of Olefins with Diazoacetates by using glucoBox Ligands: In a glove
box, CuOTf·0.5C6H6 (1.8 mg, 7.2 µmol, 1 mol-%) and the respec-
tive glucoBox ligand (8 µmol, 1.1 mol-%) were placed into a flame-
dried flask. Under a nitrogen atmosphere, dry CH2Cl2 (2 mL) was
added, and the resulting mixture was stirred for 2 h at room tem-
perature. To this preformed catalyst solution was added the alkene
component (5 mmol). The mixture was cooled to 0 °C, and the re-
spective diazoacetate (700 µmol) dissolved in dry CH2Cl2 (1 mL)
was slowly added over a period of 2.5 h with a syringe pump at the
same temperature. After stirring for another 16 h at 0 °C the sol-
vent was removed under reduced pressure, and the residue was
purified by flash chromatography on silica gel.
Supporting Information (see footnote on the first page of this arti-
cle): Determination of enantiomeric excesses for the cyclopropan-
ation products by either chiral GC or NMR spectroscopic methods
and analytical data of these cyclopropanation products.
Acknowledgments
[s, 6 H, (CH3)2C], 2.58–2.78 (m, 4 H, SCH2CH3), 3.70 (ddd, J4,5
9.9 Hz, J5,6 = 5.1 Hz, J5,6Ј = 1.7 Hz, 2 H, 5-H), 4.03 (dd, J5,6Ј
=
=
5.5 Hz, J6,6Ј = 12.3 Hz, 2 H, 6Ј-H), 4.15–4.23 (m, 4 H, 2-H, 6-H), We thank Deutsche Forschungsgemeinschaft (grant BO 1938/2-1),
4.75 (d, J1,2 = 10.6 Hz, 2 H, 1-H), 5.18 (dd ≈ t, J3,4 = 9.6 Hz, J4,5
= 9.9 Hz, 2 H, 4-H), 5.28 (dd ≈ t, J2,3 = J3,4 = 9.6 Hz, 2 H, 3-H),
6.35 (d, J2,NH = 9.2 Hz, 2 H, NH) ppm. 13C NMR (100 MHz,
VolkswagenStiftung and Fonds der Chemischen Industrie for finan-
cial support of our research and Anja Glinschert for her help with
the cover design.
Eur. J. Org. Chem. 2009, 997–1008
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1007

T. Minuth, M. Irmak, A. Groschner, T. Lehnert, M. M. K. Boysen
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Received: October 22, 2008
Published Online: January 2, 2009
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1008
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Eur. J. Org. Chem. 2009, 997–1008