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O-Glycoside Syntheses under Neutral Conditions in Concentrated Solutions of LiClO4 in Organic Solvents.

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COMMUNICATIONS
is the splitting of the ci1 states of two Nb, clusters (Fig. 2). The
combinations of the 2a, orbitals are shown in Scheme 1.
/
2a,
\
HOMO
Scheme I . The formation of a bonding (HOMO) and an antibonding combination
(top) from Zu, orbitals of two N b , uiii(s.
The Nb, triangles of the trigonal-prismatic unit are held together by strong Nb-S bonds, whose states. like those of N b Br bonds, are lower in energy than those metal states shown in
Figure 2. Weak N b - N b bonds strengthen this effect.
In centered clusters the interstitial atom is formally considered
either as an electron donor or an electron acceptor. Zr,CCIi,~'61
serves as an example for the former. Here the electrons of the
carbon atom are added to the cluster electrons: 6 x 4 (Zr) - 14
(CI) + 4 (C) = 14 electrons for metal-metal bonds. Centered
clusters are rare for "electron-richer" metals; an example is the
trigonal-antiprismatic Mo, unit in Mo,O(OEt),, (1 6 electrons),L'71in which the oxygen center acts as an electron acceptor. In Rb,[Nb,SBr,,] the number of electrons available to the
cluster for metal-metal bonds is fourteen (6 x 5 (Nb) + 3 x 1
(Rb) - 17 x 1 (Br) - 2 (S) = 14). Consideration of the MOs for
Rb,[Nb,SBr, ,] confirms this, since the seven highest occupied
energy states almost exclusively consist of Nb(d) states without
noteworthy contributions from sulfur. Thus, the sulfur atom in
the center of the cluster is an electron acceptor. Nevertheless, it
can be assumed that without the interstitial sulfur atom, as for
example in K4[Nb,Br,,].['41 the Nb, prism is less stable than the
competing octahedron.
is the first niobium cluster with an isolated
Rb,[Nb,SBr,
trigonal-prismatic building block. The structural principle of a
trigonal-prismatic. sulfur-centered niobium cluster was previously indicated in the structure of Nb,I,S.['81 where the sulfur
atom resides in a distorted trigonal-prismatic environment
formed by the triangular faces of two neighboring Nb, clusters.
E~xprrimentcrlProcedure
Rb,[Nb,SBr,,] was obtained by the reaction of RbBr (124 mg), niobium (74 me).
NbBr, (345 mg). and sulfur (8 mg). The starting materials were weighed under an
argon atmosphere in il glove box and placed into a niobium ampoule. which uiis
sealed and afterwards melted in an evacuated quartz g l a s ampoule. The reaction
mixture was allowed to react over a period of five days at 800'C. Rb,[Nb,SBr,,]
was obtained as the niam product (ca. 7 0 % ) in the form of black crystals The
remaining material consisted of fluffy crystals of the Cs[Nb,Br,S] type."91
Rh,[Nb,SBr,,] is relatively stable in air and is also resistant aKainst moisture for
quite some time.
Received: February 23. 1994
Revised version: May 27. 1994 [Z67061E]
German version: Aiijieir. Clirm. 1994, 106. 2022
[I] A. Simon, H. G . von Schnering. J Le5.s Coninio~~
M t , ! . 1966. 11%
31.
121 A. Broll. A. Simon, H. G. von Schnering. H . Schifer. Z . Atiorg. A/!?. Clirwi
1969, 367, 1.
[3] H. B. Yaich, J. C. Jegaden. M. Potel, M. Sergent. A. K. Rastogi. R. Tournier.
J Lc+sC'imiinrtn Me!. 1984. iO2. 9.
[4] A. Simon. H. G. von Schnering. H. Schifer. L. Anorg. A//,?. Chm7. 1967, 3.55.
295.
[5] C Perriii. M. Sergent. Eur. L Solid S t u r r Inor,y. Chcnr. 1991. 28. 933.
[6] A Simon. H. G. von Schnering. H. Wdhrle, H. Schhfer, Z. Anorg. Allg. C / i t ~ i .
196s. 339. 155.
[7] K.-J. Niehues. H. G . Nieder-Vahrenholz, H. G. von Schnering. H Schifer. L
L i w Conirrron W e t . 1965. 8. 95.
[XI A. L a c h p r . H:J. Meyer. unpublished results.
[9] A Simon. H. G . von Schnering. H. Schiifer. Z . Anor,?. Al/g (%on. 1969. 361,
235.
[lo] A. Lachgar. H.-J Meyer. J Solid Sturr Chem. 1994. 110, 15.
[ I l l S Ihmai'ne. C. Perrin. M. Sergent. .4cto CrIsrollogr.Stw. C 1989, 45, 705.
1121 H.-J. Meycr. %. Anorji. AUK. Clwrii. 1994. 620. 81.
1131 Single-crystal X-ray structure data ofRb,[Nb,SBr,-1: monoclinic. space group
C?:c(iio 15).0 =1712(1), h =1885..3(7). c = Y39.7(5)pm. /f = 90 77(4). V =
3033.4 A'. L = 4. Of 7976 measured reflections 4075 were symmetry independent, of which 1639 4, > 4,(K7h). R , ( F L ) = 0.13, R ( F ) with Fo > 4u(F0) =
0.062 Determination of the lartice parameters. of the Bravais type, and measurement of the intensities were carried out with a four-circle diffractometer
Siemens-Stoe-AED 2 (Mo,,. /t = 294cm-I. 2l7,,, = 58 ) Empirical absorption correction. structure determination with SHELXS46, structure refinement with SHELXL-93. Further details of the crystal structure investigation
may be obtained from the Fachinformationszentrum Karlsruhe, D-76344
Eggenstein-Leopoldshafen ( F R G ) on quoting the depository number CSD400496.
[14] F. Ueno. A. Simon. Aclu Crystullogr. Sect. C 1985, 41, 308.
(151 D. M. Proserpio. C. Mealli, J. Clwii. Erlnc. 1990. 67. 399.
[16] J. D. Smirh, J. D. Corbett. L A m . Clien7 Sot.. 1986, 108. 1927.
1171 J. A. Hollingshedd. R. E. McCarley, J. .4m C/it~m.Soc. 1990, It.?. 7402.
[18] H.-J. Meyer. .I.
D. Corbett. Inorg. Cliarn. 1991. 30. 963.
[lY] H.-J. Meyer. Z. ,411i)rji.Allg. C l i e i n 1994. 620. 863.
0-Glycoside Syntheses under Neutral Conditions
in Concentrated Solutions of LiCIO, in Organic
Solvents**
Herbert Waldmann,* Gerd Bohm, Uschi Schmid,
and Herbert Rottele
Glycoconjugates have crucial functions in many important
biological processes."' The development of efficient methods
for the directed syntheses of tailored complex glycosides, which
could, for example, be used to study these processes, is therefore
of great importance, in particular in medicinal chemistry."'
Reliable routes for the syntheses of glycosides are the diverse
variations of the Koenigs-Knorr reaction,[31in which glycosyl
halides must be activated by heavy metal salts. Furthermore, the
transformations with glycosyl fluoridesr4' and with trichloroacetimidates according to Schmidt et al.,[51in which in both cases
the glycosyl donor is activated by Lewis acids like BF;OEt,,
and with thioglycosides, which are transformed into reactive glycosy1 donors with alkylating agents,[4. 61 are particularly powerful
methods for the chemical synthesis of oligosaccharides.
However, numerous polyfunctional glycoconjugates that are
target compounds in complex oligosaccharide syntheses contain
many reactive functionalities as well as acid- and base-labile glycosidic bonds. For example, the recently described total synthesis of the oligosaccharide part of calicheamycin $, ['I had to take
into accout the high reactivity of nucleophilic amino and sulfide
groups, and the synthesis of benzyl-protected fucosyl glycosides
[*] Prof. Dr. H. Waldmann. DiplLChem. G. Bdhm, DiplLChem. U. Schmid.
Dr. H. Rottele
Institut fur Organische Chemie der Universitdt
Richard-WillstPtter-Allee 2. D-76128 Karlsruhe (FRG)
Telefax: Int. code + (721)608-4825
[**I This work was supported by the Deutsche Forschungsgemeinschaft and the
Fonds der Chemischen Industrie.
COMMUNICATIONS
was often substantially hampered by their high sensitivity to
acid.I8] I t is therefore desirable to develop methods for the chemical synthesis of 0-glycosides that require very mild, and preferably neutral, conditions without the use of toxic and expensive
heavy metal salts o r other promoters like alkylating agents.
The concept behind our method was that the detachment of
the leaving group X from glycosyl donors like 1-7 should be
initiated by a solvent that could stabilize any potential glycosyl
cation that might arise as intermediate (Scheme 1 ) . The results
of Grieco et al. and other research groups on the acceleration of
cycloadditions and rearrangements['] suggested that concentrated solutions of LiCIO, in organic solvents might fulfill this
criterion. We report now that these reaction media favor the
formation of glycosyl cations from various glycosyl donors and
thus are eminently suitable for 0-glycoside syntheses under very
mild conditions.
The model glycosyl donors 1-7 were used for the development of the method. Donors 1-5 have benzyl protecting groups
that cannot influence the course of the synthesis through neighboring group effects. As leaving group X at the anomeric center,
the halides Br-, C1-, and F-, trichloroacetimidate,["' and
diphenylphosphate" ' I were employed. The stability of a benzylideneacetal group under the conditions of our synthesis
method was studied with compound 7.[121
The 0-pivaloylated
glucosyl phosphate 6" *I was selected as acyl-proctected glycosyl
donor in which the acyl protecting group at 0 - 2 directs the steric
course of the glycosylation. Model glucosyl acceptors were the
simple aliphatic alcohols 8-10, the aromatic alcohol 11, the
serine derivative 12. the steroid 13, the monosaccharides 14 and
15, and the disaccharide 16. The solvents were Et,O, CH,CIZ.
CHCI,. and CH,CN.
The glycosyl donors 1-7 react with the glycosyl acceptors
8-16 in concentrated solutions of LiCIO, in the organic solvents without addition of promotors or reagents to form the
0-glycosides 17 (Scheme 1 , Table 1 ) . According to preliminary
experiments on the influence of the LiCIO, concentration on the
course of the reaction, the best results were achieved in 1 M
solutions; all further investigations were performed at this concentration.
Table 1. Results of the 0-rlvcoside svnthescs.
No.
solvent,
IM
LiCIO,
(OPG
xo
PG
PGO
O&@
molecular sieves,
PGO
PGO
1, PG = Bzl, X
2, PG = Bzl, X
3, PG = Bzl, X
4, PG = BzI, X
5, PG = Bzl, X
6, PG = Piv, X
= Br, CI
=F
= a-O-C(=NH)CC13
= BO-C(=NH)CC13
= a-O-P(=O)(OPh),
= p-O-P(=O)(OBzI),
1
2
3
4
5
6
7
8
9
10
11
12
13
14
G
.O
PGO
*
7
OR
17
20
9
10
11
12
xo@
0
xo
14
13
BBzlO
z l O q
BBzlO
Z l o q
BzlO
BzlO
OMe
15
Glycosyl
acceptor
Solvent
Yield
[%I [a]
1 (X = Br)
n
2
3
3
3
3
3
10
10
Et,O [cl
Et,O [c]
Et,O
Et,O
Et,O
Et,O
Et,O
CH,CN
CH,CI,
Et,O
CHzC12
Et,O
CH,CI,
CH,C12
CH,CI,
CHICI,
CH,CI,
CHZCI,
CHCI,
CHCI,
61
63
19
63
56
50
45
95
96
65
58
9
I1
12
14
4
4
n
n
4
11
4
4
4
7
5
12
n
5
10
14
16
1s
5
13
6
6
6
8
13
14
41
42
4x
41
36
42
bX
56
54
Anomeric ratio
( x : / ! ) [bl
1.1
2: I
1.1
1:l
1.1
1:l
I:1
1:2
1.1
I:1
4: I
2. I
2.3: 1
5.1
1:4
1.7
1::
only [i
only /I
only [i
[a] Based on chromatographically purified glycoside 17. All glycosides 17 wcre
identified in CDC1, solution by ' H N M R spectroscopy (250 or 400 MHr). [b] Determined by integration of the relevant signals in the ' H NMR spectra of the
anomeric mixtures or by HPLC. [c] 1 equiv CsF was added as scavenger for acid.
R-OH =
0
15
16
17
18
19
Glycosyl
donor
16
OMe
BzI = Ph-CH2; PIV = (H3C)3C-CO: Z = Ph-CH20-CO
Scheme 1 . Synthesis of 0-glycosides in 1 M solutions of LiCIO, in organic solvents
Considering that under these mild conditions the glycosyl
donors are not additionally activated, for example through the
formation of better leaving groups at the anomeric center. and
that the two reactants are always employed in equimolar
amounts, the yields of 17 are satisfactory to high. The halogenoses 1 can for instance be employed as benzyl-protected
donors (Table 1, no. I ) , but higher yields are recorded if the
trichloroacetimidates 3 and 4 are used. Particularly surprising is
the finding that the glycosyl fluoride 2, which usually can be
activated only by strong Lewis acids like BF;OEt,,
and the
alcohol 10 react to form the 0-glycoside in high yield (Table 1 ,
no. 2). With the a-configurated trichloroacetimidate 3, the desired glycosides are obtained as 1 :1 mixtures of the two anoniers
(Table 1, nos. 3 -7), and with the /I-imidate 4 as well as with the
p-configurated glycosyl donor 7, the r-glycosides are in general
formed predominantly (Table 1, nos. 9- 14). Distinct excesses
of /1-17 were achieved with the benzyl-protected 1-diphenyl-
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phosphate 5 (Table 1, nos. 15-17). The solvents Et,O, CH2CI,,
and CHCI, influence neither the magnitude nor the kind of the
anomeric ratio. However, if the fi-tnchioroacetimidate4 is treated
with 8 in the solvent CH,CN,[''] which stabilizes the glycosyl
cation. the [I anomer is in excess in contrast to the situation in
CH,CI, (Table I . nos. 8 and 9). Thus with the trichloroacetimidate or diphenyl phosphate residue as leaving group at the
anomeric center of the glycosyl donor and in the presence of
benzyl protecting groups that are not capable of exerting neighboring group effects, the stereoselection in the synthesis of 0glycosides 17 can be deliberately steered to either direction. On
the other hand, the pivalic acid ester in 6 participates anchimerically in the glycosylation. with the result that, as expected, the
/I-glycosides are formed with this glycosyl phosphate (Table 1,
nos. 18-20).
The examples in Scheme 1 and Table 1 indicate that not only
glycosides of simple aliphatic and aromatic alcohols can be
formed under mild conditions and without additional promoters by our method reported here, but hydroxyamino acids
and steroids can also be glycosylated and disaccharides synthesized successfully. Moreover the method is suitable for the construction of larger glycoconjugates, as the coupling of 4 with the
disaccharide 16, which yields the desired trisaccharide with satisfactory results, shows (Table 1 , no. 13).
Doubly Bridged vac-Metallocenes
of Zirconium and Hafnium**
Wolfgang A. Herrmann," Marcus J. A. Morawietz,
and Thomas Priermeier
Dedicated to Prqfessor Wolfgang Hilger
on the occasion q f h i s 65th birthday
Since the discovery of stereospecific Ziegler-Natta polymerization with metallocene catalystsl['] interest has concentrated
on the optimization of the catalytic properties by variation of
substituents.[" Only recently was attention also turned to the
rac/meso problem in the synthesis of ~insa-metallocenes;[~]
nevertheless, all concepts cling to the classical route [Eq. (a)].
Disadvantages of this pathway are the required removal of
the salt and the mostly moderate yields. Moreover, mixtures of
raclmeso diastereomers are produced, which can often be separated only by several crystallization steps.
r
1
Received: May 11, 1994 [Z6923IE]
German version: Angeii. Chrrir. 1994. 106. 2024
- 2 M'CI
[ l ] ReLiews: a ) L. A Lasky. Sciencr 1992, 258. 964: h) S Hakomori. A d v . C u m w
Res. 1989. 52. 257: c) T. Feizi. Nurure 1985. 314, 53: d ) J. C. Paulson in The
K c c c p ~ o r . ~Ibi
. I (Eds.: M. Conn). Academic Press. New York. 1985. p.
131
[2] Reiiew: J. H . Musser. Arrnu. Re/>.,Wed Chern. 1992, 27, 301.
[ 3 ] H. Paulsen. Aiigi'it. ('Iwnr. 1982, 94. 184: Anpit'. Clri~rn.Inr. Ed. Engl. 1982. 21,
J
L
155.
[4] Short Revieu: H. Waldmann. Nu<lrr.C/wrii. 7i.eh. Luh. 1991, 39, 675
15) Reviex: R. R Schmidt. Argrw. Chon. 1986. 98. 213: A n g e i ~Chrni. I n r . Ed
EngI. 1986, 25. 212.
[6] a ) P. Fiigedi. P. .I.
Garegg. H . Lonn. T. Norberg. G/vtacon;rrgure J! 1987. 4. 97:
b) review on more recent methods of glycoside synthesis: K. Toshima, K.
Tatsuta. Chon. Rev. 1993. Y3. 1503.
[7] R. D. Groneherg. T. Miyazaki. N. A. Stylianides. T. J. Schulze. W. Stahl, E. P.
Schreiner, T. Suruki. Y. Iwahuchi. A. L. Smith. K . C Nicolaou. J. A m . Chrm.
So<..1993. 115. 7593.
(81 See H. K u n i . C. Unverzngt. A i r g w . Chern. 1988. 100. 1763: Angew. Climr. Inr.
Ed. En,q/. 1988. 77. 1697.
[Y] Reviews: a ) P. A. Grieco. Aldrichinricu Acru 1991. 24. 59; b) H. Waldmann,
An,qrii,. CIwnf. 1991. 103, 1335: A n g w . Clrrm. Iril. Ed. Engl. 1991. 30.
1306.
[I01 a ) R R. Schmidt. J. Michel. M. Roos. Liehrgs Ann. Cliern. 1984, 1343: b) R. R.
Schmidt. M Stumpp. ihid. 1983. 1249.
[ l l ] R. R. Schmidt, M . Stumpp. Lich~.\Ann. Chenr. 1984. 680.
[12] C o m p o u n d 7 u a s synthesiredanalogously to4[10] byreactionoftheappropriate carbohydrate deblocked in the 1-position with trichlorodcetonitrile in the
presence of KICO,: colorless oil: [l]iO= -7 ( c =1.5 in CHCI,): ' H N M R
(250 MHL. CDCI,. 25 C, TMS): d = 5.93 (d. 'J(l-H, 2-H) =7.7 Hz, 1H: 1H ) . Compound 6 was obtained analogously to the diphenylphosphate 5 [l I ] by
reaction of the appropriate 2-configurdted trichloroacetimidate with diben= - 8.1 (( = I
in CHCI,): ' H N M R
zylphosph:ite: n1.p. 74 C: [1]3
(250 MHr. CDCI,. 25 C. TMS): 6 = 5.38 (dd, "(1-H. 2-H) =7.Y Hz. 'JJ(1H.
P) = 6.7 H / ; 1H: 1-H).
1131 R. R. Schmidt. M. Behrend. A. Toepfer. Synirtf 1990, 694
rac
meso
M =Ti,Zr, Hf
X = SIR2, CR'&Rp
M' = Li, Na
R,R' = alkyl, aryl
In this communication we describe a salt-free synthesis in
which the raclmesu isomer problem does not arise, and new
metallocenes of the constitution of type A can be simply
and universally prepared as
potential catalysts. The conA
cept is based on the treatment
of homoleptic metal amides
[M(NR,),] with functionalized cyclopentadienes.
If zirconium and hafnium tetraamides 1 and 2 are treated with
one equivalent of cyclopentadienyldimethyl(N-pheny1amino)silane (3)[41or bis(cyclopentadienyl)dimethylsilane (4)[5d1in toluene, two amide ligands are substituted (yields > 9 8 % ,
Scheme 1 ) .
e
&
[*I
["*I
Prof. Dr. W. A. Herrmann. M. J. A. Morawietz. T. Priermeier
Anorganisch-chemisches lnstitut der Technischen Universitit Miinchrn
Lichtenbergstrasse 4, D-85747 Garching (FRG)
Telefax: Int. code + (89)3209-3473
This work was supported by the Fonds der Chemischen Industrie (scholarship
for M. J A. M.) and Hoechat AG (Zentralforschung).
0570-0833!9411919-/946 $ 1(1.00+ .259
Angriv. Chon. Inr. Ed. En,$. 1994, 33. N o . I Y
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