From glycals to metal pyranosylidenes: Diastereoselective addition of electrophiles to metal carbene enolate intermediates

Article abstract of DOI:10.1016/S0040-4020(99)01099-6

Lithiated glucals react smoothly with Cr(CO)₅THF at the metal center to generate the corresponding vinyl chromate intermediates which represent chromium carbene enolate equivalents. Trapping by electrophiles provides an entry to novel chromium

Full text of DOI:10.1016/S0040-4020(99)01099-6

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 2167±2173
From Glycals to Metal Pyranosylidenes:
Diastereoselective Addition of Electrophiles to Metal Carbene
Enolate Intermediates
1
*
Christoph J aÈ kel and Karl Heinz D oÈ tz
Kekul e -Institut f uÈ r Organische Chemie und Biochemie der Rheinischen Friedrich-Wilhelms-Universit aÈ t, Gerhard-Domagk-Straûe 1,
D-53121 Bonn, Germany
Dedicated to Professor Sandhoff on the occasion of his 60th birthday
Accepted 7 December 1999
5
AbstractÐLithiated glucals react smoothly with Cr(CO) THF at the metal center to generate the corresponding vinyl chromate intermedi-
ates which represent chromium carbene enolate equivalents. Trapping by electrophiles provides an entry to novel chromium 2-deoxy-
pyranosylidenes. Deuteration and allylation proceed with an approximately 90% d.e. in preference of the C-2-manno complexes. q 2000
Elsevier Science Ltd. All rights reserved.
Introduction
bearing carbohydrate anion equivalents have been developed
1
1
and applied to the synthesis of C-glycosides; however, the
high-pressure conditions required for an ef®cient insertion
of alkenes and alkynes into the anomeric carbon to metal
Carbohydrates are among the three vital classes of
compounds that form the basis of life science processes.
The carbohydrate units of glycoconjugates take part in
1
2
bond have prevented wider applications. We became
interested in organometallic glycosyl donors and focused
on a metal carbene functionalization of the anomeric
2
molecular recognition at cell walls, in intracellular enzyme
3
4
5
transport, infection and cell adhesion processes. Poly-
saccharides serve as food and energy storage or construction
materials. The stereoselective formation of glycosidic
1
3
center. Over two decades, Fischer type carbene complexes
bearing an electrophilic carbene carbon atom have been
developed to valuable reagents for stereoselective carbon±
6
14
bonds which requires an appropriate activation of the
anomeric carbon atom remains a synthetic challenge
although a series of powerful glycosylation procedures
1
5
carbon bond formation. They have been applied to either
carbene ligand-centered cycloaddition reactions such as
Diels±Alder reactions which are facilitated by the
7
have been developed. Beyond the classical O-glycosides
their C-glycoside analogues have recently gained con-
1
6
electron±acceptor pentacarbonyl metal fragment
metal-centered cycloaddition reactions such as benzannula-
or
siderable attention due to their inherent stability toward
hydrolysis. The polyfunctionality of carbohydrates requires
8
17 18
tion and cyclopropanation which proceed at the metal
1
9
elaborate synthetic techniques to allow stereoselective
manipulations both within the sugar backbone and its
functional group periphery. In this respect, it is surprising
that the impact of organometallic reagents which have
revolutionalized selective organic synthesis over the past
three decades is still marginal. Beyond a few main group
metals such as lithium or tin the application of transition
metalsÐwhich are known to allow for a sensitive tuning of
carbonyl template. Moreover, they serve as precursors
for photo-generated ketene equivalents which have been
used in stereoselective syntheses of amino acids and
2
0
b-lactams. Alkylcarbene ligands undergo ready a-depro-
tonation to give enolate-type carbene complex anions which
have been exploited in diastereoselective aldol- and
2
1
Michael-type reactions.
9
the reactivity of coordinated carbon species Ðin the
The most general synthetic access to carbonyl carbene
complexes is the Fischer route which is based on the
sequential addition of an organolithium nucleophile and a
activation of the anomeric center for carbon±carbon bond
formation is mainly restricted to samarium and palladium so
far. Glycosyl manganese and iron carbonyl complexes
1
0
14
carbon electrophile across a carbonyl ligand. This
approach is limited to the synthesis of acyclic metal
carbenes; complementary routes to cyclic carbene analo-
gues are provided by the metal carbonyl template assisted
cycloisomerization of alkynols to give metal oxacyclo-
Keywords: carbenes and carbenoids; carbohydrates; chromium and
compounds; glycals.
* Corresponding author. Tel.: 149-228-73-5609, fax: 149-228-73-5813;
e-mail: doetz@uni-bonn.de
2
2
alkylidenes or by the formal substitution of an amide
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(99)01099-6

2
168
C. J aÈ kel, K. H. D oÈ tz / Tetrahedron 56 (2000) 2167±2173
Scheme 1. Alternative routes to cyclic Fischer-type carbene chromium complexes.
2
3
oxygen atom by the isolobal pentacarbonyl fragment
which occurs along the reaction of N-alkyl lactams with
pentacarbonyl metalate dianions in the presence of TMS
focused on glycals as starting materials which are readily
available and allow an organometallic functionalization at
the anomeric center. We now report on their modi®cation to
glycosylidene complexes bearing a 2-deoxy substitution
pattern which is encountered in various biologically active
2
4
chloride (Scheme 1). However, both routes are not
attractive for the elaboration of glycosylidene complexes
either due to the tedious access to appropriately oxygenated
alkynol precursors or to the pronounced basicity of the
carbonyl metalates which results in a deprotonation at the
2
8
compounds.
2
5
2
0c
sugar skeleton rather than in metal carbonyl transfer.
more promising strategy relies on a stoichiometric ole®n
A
Results and Discussion
Protection and metalation of d-glucal
1
8b,26
metathesis reaction
of an electron-rich exo-methylene
sugar and an electron-de®cient diphenylcarbene penta-
carbonyl complex. This approach provided a straight-
2
9
Glycals can be metalated in 1-position; however, a great
excess of the strong base tert-butyllithium is required for
this process which complicates further transformations and
puri®cation. Thus, it is advantageous to purify the resulting
lithioglycal by transmetalation to the tri-n-butyl tin
2
7
forward access to chromium furanosylidenes
but
attempts to extend it to their pyranosylidene homologues
were complicated by elimination processes occurring
under the reaction and work-up conditions. Thus, we
Scheme 2. Competing addition of lithioglucals to chromium carbonyl complexes.

C. J aÈ kel, K. H. D oÈ tz / Tetrahedron 56 (2000) 2167±2173
2169
Scheme 3. Retrosynthetic concept for 2-deoxy-glycosylidene complexes.
derivatives (which can be stored for weeks without
decomposition) and regenerate the lithioglycal prior to use
chromium fragment the reaction of the lithioglucals with
(CO) CrTHF was expected to generate glucalyl
5
3
0
by a retransmetalation using n-butyl lithium. The reaction
of 1-lithioglucal 1 with group six metal carbonyl complexes
is controlled by the substitution pattern of the carbonyl
pentacarbonylchromium intermediates. These species may
be regarded as chromium enolates which are susceptible to
subsequent addition of electrophiles. Accordingly, the low-
temperature addition of lithioglucals generated from
3
1
complex (Scheme 2). Their addition to hexacarbonyl
chromium occurs at the carbonyl carbon atom as expected
for the Fischer metal carbene synthesis to giveÐafter
methylation of the acyl chromate intermediateÐthe a,b-
unsaturated carbene complex 7. However, if a single
carbonyl ligand is replaced by a ligand combining good
donor and leaving group properties such as triphenyl-
phosphine or tetrahydrofuran, the lithioglucal rather adds
at the metal to generate an enolate-type pentacarbonyl
chromium intermediate 5. Above 08C a Ferrier-type
rearrangement occurs, and elimination of trialkylsilyloxide
affords the a,b-unsaturated glucosylidene complex 8. We
anticipated that the chromium enolate intermediate 5 may
be applied to the addition of electrophiles. This approach is
expected to offer a straightforward access to 2-deoxy-
glucosylidene complexes starting from readily available
3
4
stannanes 1 and 2 to (CO) THF followed by protonation
5
with hydrogen chloride in ether afforded 2-deoxypyrano-
sylidene complexes 11 and 12 in good yields after chroma-
tography on silica gel (Scheme 5). To elucidate the
stereoselectivity of the protonation we applied deuterated
tri¯uoroacetic acid as electrophile. A .90% incorporation
of deuterium along with a .95:5 preference in favour of the
manno con®guration was observed for the tris-TIPS-
protected 2-deuteroglycosylidene complex 13. Supposed
that there is no conformational change along the formation
of the intermediate 5 from the stannane 1, the stereo-
chemical outcome may be rationalized in terms of a si-side
attack to the chromium enolate in its H conformation.We
5
4
are unable at the moment to decide whether the deuteration
occurs metal-mediated or directly at the b-carbon atom of
3
5
(
CO) CrTHF and lithioglucals (Scheme 3).
5
the enolate. Upon chromatography on silica gel the degree
of deuterium incorporation dropped to 75% while the d.e.
value of 90% remained unchanged. The diastereoselectivity
of the deuteration strongly depends on the substitution
pattern provided by the protecting groups. Substitution of
the tris-TIPS-protection for the less bulky isopropylidene
mono-TIPS-pattern results in a dramatic decrease in
selectivity, and an only slight 58:42 preference in favour
of the gluco-diastereomer 14e was observed. Moreover,
the formation of a 10% amount of 2,2-dideuterated
material suggests that the addition of the electrophile
is subject to an equilibrium process under the deuteration
conditions.
0
d-Glucal 9a was metalated after stepwise protection by 2,2 -
3
2
dimethoxypropane (to give 9b ) and triisopropylsilyl
tri¯ate (to give 10a,b) using the tert-butyllithium/tri-n-
butyl(chloro)stannane protocol (Scheme 4); under Friesen's
conditions the stannylated glucal 2 was obtained in good
yields provided that the deprotonation was limited to
30 min. Longer reaction times caused side reactions, and
the yields dropped dramatically. H NMR studies indicated
1
2
9b
that the conformation of the stannylated glucals 1 and 2 is
controlled by the protecting groups. Whereas the per-TIPS-
protected glucal 1 reveals medium and small coupling
constants J (ca. 5 Hz) and J3,4 (ca. 2 Hz) suggesting a
2
,3
5
preferred H conformation, the 4,6-diprotection by the
4
The addition of electrophiles to the chromium enolates can
be extended to C-alkylation. Allylation of intermediates 5
and 6 with allyl iodide resulted in the diastereoselective
formation of C-2-deoxypyranosylidene complexes 15 and
16 in good yields. In the TIPS-series the allylation afforded
complex 15 as a 94:6 mixture of diastereomers which could
isopropylidene group in analogue 2 shows an opposite
4
trend (J ˆ2.0 Hz, J ˆ7.4 Hz) indicative for a H confor-
2
,3
3,4
5
mation. Both stannyl glucals were readily transmetalated
upon reaction with n-butyl lithium.
2
-Deoxypyranosylidene complexes
not be separated by chromatography. A small coupling
constant J2 (1.9 Hz) was observed for the major isomer
suggesting a manno-con®guration at C-2. The isopropyl-
idene complex 16 was obtained as a single diastereomer
3
,3
3
3
Following previous reports on the addition of nucleophilic
organometallics to the solvent-stabilized pentacarbonyl-
Scheme 4. Synthesis of protected stannanes 1 and 2. Reaction conditions: (a) TIPSOTf, 2,6-lutidine, CH
8C, 30 min; (c) 3.5 eq. Bu SnCl, 2788C.
2 2
Cl , 08C to RT, 2 h; (b) 4 eq. t-BuLi, THF, 2788C to
0
3

2
170
C. J aÈ kel, K. H. D oÈ tz / Tetrahedron 56 (2000) 2167±2173
Scheme 5. Synthesis of 2-deoxy-glycosylidene complexes 11±16, axial (a) and equatorial (e) refers to the position of deuterium.
1
as indicated within the limits of H NMR spectroscopy. The
con®guration of the newly formed chiral center was char-
acterized as S-C-2 re¯ecting again the manno-con®guration
Concept 1H spectrometer. Elemental analyses were
obtained from a Heraeus CHN-O-Rapid.
3
according to the small coupling constant J (1.4 Hz).
,3
1,5-Anhydro-4,6-O-isopropylidene-3-O-triisopropylsilyl-
2-deoxy-d-arabino-hex-1-enitol (10). 3.26 ml (30.8 mmol)
2,6-Lutidine and 5.6 ml (21 mmol) TIPSOTf were added
sequentially to a solution of 2.6 g (14 mmol) 3 in 15 ml
CH Cl at 08C. The reaction mixture was allowed to warm
2
These two examples demonstrate that the allylation of the
chromium enolate intermediates occurs predominantly from
the si-side independent of the protecting group periphery.
3
6
2
2
to room temperature and stirred for 3 h. After dilution with
00 ml of water the organic layer was separated and the
1
Conclusion
aqueous layer was extracted three times with 50 ml portions
of CH Cl . The combined organic fractions were washed
with brine, dried over MgSO and evaporated to dryness.
2
2
The tandem nucleophilic alkylation/electrophilic addition
methodology provides novel functionalization of
solvent-stabilized Cr(CO) fragments to oxacycloalkylidene
4
a
Column chromatography of the residue (SiO , CH Cl )
2
2
2
5
afforded 2.86 g (8.35 mmol, 60%) of a colourless oil. R
(
f
complexes. This strategy has been applied in the synthesis
of chromium 2-deoxypyranosylidenes. The easy access to
stannyl enol ethers and their straightforward in situ C-2
functionalization render this approach a valuable alternative
to well established synthetic protocols in metal carbene
chemistry. The metal carbene moiety of the pyranosylidene
complexes enhances the a-CH acidity and allows for
metal-centered cycloaddition reactions, providing addi-
tional opportunities for the elaboration of more complex
carbohydrate skeletons.
1
CH Cl ): 0.85; H NMR (400 MHz, CDCl ): dˆ6.21 (dd,
2
2
3
3
4
3
Jˆ6.2 Hz, Jˆ1.6 Hz, 1H, H-1), 4.63 ( Jˆ6.2 Hz,
3
2
3
3
Jˆ1.9 Hz, 1H, H-2), 4.38 (ddd, Jˆ7.2 Hz, Jˆ1.9 Hz,
2
3
Jˆ1.6 Hz, 1H, H-3), 3.88 (dd, Jˆ10.7 Hz, Jˆ5.6 Hz,
3
3
1
H, H-6 ), 3.78 (dd, Jˆ10.4 Hz, Jˆ7.2 Hz, 1H, H-4),
e
2
3
3
.76 (dd, Jˆ10.7 Hz, Jˆ10.2 Hz, 1H, H-6 ), 3.66 (ddd,
a
3
3
3
Jˆ10.4 Hz, Jˆ10.2 Hz, Jˆ5.6 Hz, 1H, H-5), 1.46 (s,
3
H, ±CH ), 1.35 (s, 3H, ±CH ), 1.07±0.99 (m, 21H, ±Si±
3 3
[
1
CH(CH ) ] ); DEPT 135 (62.8 MHz, CDCl ): dˆ143.3 (C-
3
2 3
3
), 105.9 (C-2), 73.5 (C-3), 69.9 (C-4), 67.9 (C-5), 61.9
(
C-6), 29.1 (±CH ), 19.0 (±CH ), 18.1±17.8 (±Si±
3 3
[
CH(CH ) ] ), 12.4 (±Si± [CH(CH ) ] ); EI-MS (70 eV):
3
2 3
3 2 3
1
1
Experimental
m/z (%)ˆ327.2 [M 2CH
], 299.2 [M 2C H ], 241.1
3 3 7
1
M 2C H ±C H O]; HR-MS Calcd for C H O Si
[
3
7
3
6
15 27
4
1
All transformations were performed under argon using
degassed solvents dried by standard procedures. All
reagents were used as supplied commercially; chromato-
graphy was carried out with degassed solvents on silica
gel (Merck 60 (0.063±0.200)). All H and C NMR spectra
were recorded on either the Bruker DRX-500 or AM-400
spectrometer. Chemical shifts refer to those of residual
solvent signals based on dTMSˆ0.00 ppm. Chemical ioniza-
tion mass spectra were recorded on a Kratos MS 50
spectrometer; FAB mass spectra were recorded on a Kratos
[M 2CH ]: 327.1992; Found: 327.1984.
3
1,5-Anhydro-4,6-O-isopropylidene-3-O-triisopropylsilyl-
2-deoxy-1-(tri-n-butyl)stannyl-d-arabino-hex-1-enitol
(2). 21 ml (33.4 mmol) t-BuLi (15% in hexane) were added
dropwise to a solution of 2.86 g (8.35 mmol) 10 in 30 ml
THF at 2788C. The dry ice bath was removed and stirring
was continued at 08C for 30 min. After recooling to 2788C,
6.8 ml (25.1 mmol) tri-n-butylstannyl chloride was added
dropwise and stirring was continued at this temperature
1
13

C. J aÈ kel, K. H. D oÈ tz / Tetrahedron 56 (2000) 2167±2173
2171
1
[M 2Cr(CO) ±3C H ]; Anal. Calcd for C H O Si Cr:
C, 56.54, H, 8.74; Found: C, 56.38, H, 8.87.
for 30 min. The reaction mixture was diluted with 50 ml
water, the organic layer was separated and the aqueous
phase was extracted three times with 60 ml portions of
5
3
7
38 70
9
3
Et O. The combined organic fractions were washed twice
2
Pentacarbonyl[4,6-O-isopropylidene-3-O-triisopropylsilyl-
2-deoxy-d-arabino-hexopyranosylidene]chromium(0) (12).
12 was prepared from 0.72 g (1.14 mmol) (2), 0.55 ml
(1.37 mmol) n-BuLi, 0.60 g (1.98 mmol) (CO) Cr(C H )
with 20 ml water, once with brine, dried over MgSO4
and evaporated to dryness. Column chromatography of the
residue (SiO , CH Cl /petroleum ether: 3:2) afforded 4.49 g
2
2
2
5
8
14
(
7.1 mmol, 85%) of a colourless oil. R (CH Cl /petroleum
f
and 1.37 ml (1.37 mmol) of the HCl solution to give a
71% yield (0.43 g, 0.80 mmol) of an orange oil which
solidi®ed over night at 268C. R (petroleum ether/CH Cl ,
2
2
1
ether: 3:2): 0.89; H NMR (400 MHz, CDCl ): dˆ4.66 (d,
3
3
3
3
Jˆ2.0 Hz, 1H, H-2), 4.35 (dd, Jˆ7.4 Hz, Jˆ2.0 Hz, 1H,
f
2
2
2
3
1
H-3), 3.86 (dd, Jˆ10.8 Hz, Jˆ5.7 Hz, 1H, H-6 ), 3.77 (dd,
2:3): 0.87; H NMR (400 MHz, CDCl ): dˆ4.39 (dd,
e
3
3
3
2
2
3
3
2
Jˆ10.4 Hz, Jˆ7.4 Hz, 1H, H-4), 3.74 (dd, Jˆ10.8 Hz,
Jˆ17.8 Hz, Jˆ2.2 Hz, 1H, H-2 ), 4.37 (dd, Jˆ11.0 Hz,
e
2
3
3
3
3
Jˆ10.4 Hz, 1H, H-6 ), 3.58 (ddd, Jˆ10.4 Hz, Jˆ
Jˆ5.6 Hz, 1H, H-6 ), 4.11 (dd, Jˆ11.0 Hz, Jˆ10.5 Hz,
a
e
3
3
3
1
0.4 Hz, Jˆ5.7 Hz, 1H, H-5), 1.48 (s, 3 H, ±CH ), 1.37
1H, H-6 ), 3.96 (ddd, Jˆ8.2 Hz, Jˆ6.8 Hz, Jˆ2.1 Hz, 1 H,
3
a
3
3
3
(
s, 3 H, ±CH ), 1.55±0.84 (m, 48H, ±Si[CH(CH ) ] ,
3
H-3), 3.95 (ddd, Jˆ10.5 Hz, Jˆ10.1 Hz, Jˆ5.6 Hz, 1H,
3 2 3
1
3
3
3
±
Sn(C H ) ); C NMR (100.5 MHz, CDCl ): dˆ162.7
H-5), 3.55 (dd, Jˆ10.1 Hz, Jˆ6.8 Hz, 1H, H-4), 3.28 (dd,
4
9 3
3
2
3
(
C-1), 116.4 (C-2), 99.3 (C(CH ) ), 73.6 (C-3), 69.9 (C-4),
3
Jˆ17.8 Hz, Jˆ8.2 Hz, 1H, H-2 ), 1.52 (s, 3H, ±CH ), 1.40
2
a
3
1
3
C
6
2
1
8.6 (C-5), 62.1 (C-6), 29.1 (C(CH ) ), 29.0 (±Sn(C H ) ),
2
(s, 3 H, ±CH ), 1.12±0.91 (m, 21H, ±Si[CH(CH ) ] );
3
3
4
9 3
3 2 3
7.2 (±Sn(C H ) ), 19.0 (C(CH ) ), 18.0 (±Si[CH(CH ) ] ),
3 2 3
NMR (100.5 MHz, CDCl ): dˆ355.7 (C-1), 224.0 (COtrans),
4
9 3
3 2
3
3.7
(±Sn(C H ) ),
9 3
12.3
(±Si[CH(CH3)2]3),
9.7
216.0 (CO ), 100.2 (±C(CH ) ), 76.0 (C-3), 75.0 (C-4),
3 2
4
cis
1
(
±Sn(C H ) ); EI-MS (70 eV): m/z (%)ˆ631.2 [M ],
68.7 (C-5), 64.4 (C-6), 61.4 (C-2), 28.7 (±C(CH3)2),
18.8 (±C(CH ) ), 17.8, 17.7 (±Si[CH(CH ) ] ), 12.0
4
9 3
1
1
1
89.2 [M 2C H ], 575.2 [M 2C H O], 401.1 [M 2
5
C H O±C H SiO]; Anal. Calcd for C H O SiSn: C,
5
3 6 3 6
3 2
3 2 3
1
(±Si[CH(CH ) ] ); EI-MS (70 eV): m/z (%)ˆ534.2 [M ],
3
6
9
22
30 60
4
3 2 3
1
1
1
506.2 [M 2CO], 478.1 [M 22CO], 450.0 [M 23CO],
6.93; H, 9.56; Found: C, 57.12; H, 9.66.
1
1
1
4
C
22 [M 24CO], 394 [M 25CO], 299.2 [M 2Cr(CO) ±
5
1
General procedure for the synthesis of complexes 11 and
1
H
3
7
], 241.1 [M 2Cr(CO)
5
±C
SiCr [M ]: 534.1424, Found: 534.1387; Anal.
Calcd for C H O SiCr: C, 51.67, H, 6.41; Found: C, 51.69,
3 7 3 6
H ±C H O]; HR-MS Calcd
1
2
for C23H O
34 9
2
3
34
9
1.2 equiv. n-BuLi (2.5 M in hexane) was added dropwise to
H, 6.48.
a solution of 1 equiv. stannylglucal in 10 ml of dry THF at
788C. After stirring for 1 h, a solution of 1.5 equiv. Penta-
2
General procedure for the synthesis of complexes 13 and
14
2
carbonyl(h -cis-cyclooctene)chromium(0) in 10 ml of dry
THF precooled to 2788C was added via a transfer needle.
The reaction mixture was warmed to 08C and stirred at this
temperature for 20 min. After recooling to 2788C, a solu-
tion of hydrogen chloride (1.2 equiv.) in diethyl ether (1 M)
was added dropwise. The solvent was removed in vacuo,
and the crude product was puri®ed by column
chromatography at 2108C using petroleum ether/dichloro-
methane mixtures as eluent to give the carbene complexes
as analytically pure samples.
1.2 equiv. n-BuLi (2.5 M in hexane) was added dropwise to
a solution of 1 equiv. stannylglucal in 10 ml of dry THF at
2788C. After stirring for 1 h, a solution of 1.5 equiv. Penta-
2
carbonyl(h -cis-cyclooctene)chromium(0) in 10 ml of dry
THF precooled to 2788C was added via a transfer needle.
The reaction mixture was warmed to 08C and stirred at this
temperature for 20 min. After recooling to 2788C,
1.2 equiv. of a CF COOD solution in diethyl ether (1 M)
3
was added in one portion. The solvent was removed in
vacuo, and the crude product was puri®ed by column
chromatography at 2208C using petroleum ether/dichloro-
methane mixtures as eluent to give the 2-deutero deoxy-
pyranosylidene complexes.
Pentacarbonyl[3,4,6-tri-O-triisopropylsilyl-2-deoxy-d-
arabino-hexopyranosylidene]chromium(0) (11). 11 was
prepared from 0.85 g (0.94 mmol) (1), 0.45 ml
(
1.13 mmol) n-BuLi, 0.42 g (1.38 mmol) (CO) Cr(C H )
5 8 14
and 1.13 ml (1.13 mmol) of the HCl solution to give a
0% yield (0.53 g, 0.66 mmol) of a yellow oil, R (petro-
leum ether/CH Cl , 20:1): 0.87; H NMR (500 MHz, C D ):
7
Pentacarbonyl[2-deutero-3,4,6-tri-O-triisopropylsilyl-2-
deoxy-mannosylidene]chromium(0) (13a). 1.07 g (1.18
mmol) of 1 was deuterated according to the general pro-
cedure, using 0.57 ml (1.42 mmol) n-BuLi, 0.50 g (1.66
mmol) (CO) Cr(C H ) and 1.42 ml (1.42 mmol) of the
f
1
2
3
2
6
6
3
3
dˆ5.08 (ddd, Jˆ6.5 Hz, Jˆ6.1 Hz, Jˆ1.0 Hz, 1H, H-5),
2
2
4
.51 (d, Jˆ19.5 Hz, 1H, H-2 ), 4.41 (dd, Jˆ10.8 Hz,
e
3
3
3
Jˆ6.5 Hz, 1H, H-6), 4.33 (dd, Jˆ4.4 Hz, Jˆ1.0 Hz, 1H,
5
8
14
2
3
0
1
H-4), 4.25 (dd, Jˆ10.8 Hz, Jˆ6.1 Hz, 1H, H-6 ), 3.83 (s,
D -TFA-solution. After chromatographic puri®cation
(SiO , petroleum ether, 2208C) 0.61 g (0.76 mmol, 64%)
2
3
br, 1H, H-3), 3.72 (dd, Jˆ19.5 Hz, Jˆ3.7 Hz, 1H, H-2 ),
a
2
1
3
1
of a yellow oil was obtained. Integration of the H NMR
1
.20±0.90 (m, 63 H, ±Si[CH(CH ) ] );
2 3
C
NMR
3
(
(
(
(
125.6MHz, C D ): dˆ351.5 (C-1), 224.1 (COtrans), 217.3
signals at dˆ4.51, 4.48, 3.72 and 3.68 ppm were used to
6
6
CO ), 94.6 (C-5), 67.2 (C-4), 65.3 (C-3), 64.6 (C-6), 58.1
cis
determine the degree of deuterium incorporation and the
1
C-2), 18.1, 18.0 (±Si[CH(CH ) ] ), 12.5, 12.3, 12.2
3
diastereomeric ratio. H NMR (500 MHz, C D ): dˆ4.51
2 3
6
6
2
±Si[CH(CH ) ] ); DEPT 135 (62.8 MHz, C D ): sec.- C:
6
(d, Jˆ19.7 Hz, 0.35 H, H-2 , 11), 4.48 (s, 0.75 H, H-2 ,
3
2 3
6
e
3
e
2
dˆ64.6 (C-6), 58.1 (C-2); FAB-MS (mNBA): m/z
13a), 3.72 (dd, Jˆ19.7 Hz, Jˆ4.0 Hz, 0.25H, H-2 , 11),
a
1
1
1
3
13
(
%)ˆ806.4 [M ], 752.4 [MH 22CO], 694.3 [M 24CO],
3.68 (d, Jˆ4.0 Hz, 0.025H, H-2 , 13e); C NMR
2
a
1
1
66.3 [M 25CO], 623.2 [M 25CO±C H ], 581.1
6
(125.6 MHz, C D ): dˆ58.1 (s, C-2, 11), 57.8 (t,
3
7
6
6
1
MH 25CO±2C H ], 537.1 [M 25CO±3C H ], 485.2
1
1
[
J
C,D
ˆ19 Hz, C-2, 13a).
3
7
3
7

2
172
C. J aÈ kel, K. H. D oÈ tz / Tetrahedron 56 (2000) 2167±2173
Deuteration of chromium enolate intermediate 2 with
D -TFA
Pentacarbonyl[2-allyl-4,6-O-isopropylidene-3-O-tri-
isopropylsilyl-2-deoxy-mannosylidene]chromium(0)
1
(
16). 0.60 ml (1.50 mmol) n-BuLi (2.5 M in hexane) was
0.64 g (1.02 mmol) of 2 was deuterated according to the
general procedure, using 0.70 ml (1.42 mmol) n-BuLi
added dropwise to a solution of 790 mg (1.25 mmol) of 2
in 20 ml of dry THF at 2788C. After stirring for 1 h, a
solution of 492 mg (1.63 mmol) pentacarbonyl(h -cis-
cyclooctene)chromium(0) in 10 ml of dry THF precooled
to 2788C was added via a transfer needle. The reaction
mixture was warmed to 08C and stirred at this temperature
for 20 min. After recooling to 2788C, 252 mg (1.50 mmol)
allyl iodide was added dropwise. The reaction mixture was
allowed to reach room temperature slowly overnight. The
solvent was removed in vacuo, and the crude product was
2
(
(
1.6 M), 0.34 g (1.13 mmol) (CO) Cr(C H ) and 1.13 ml
5
8
14
1
1.13 mmol) of the D -TFA-solution. After chromatographic
work-up (SiO , petroleum ether, 2208C) 0.27 g (0.50 mmol,
2
1
0%) of an orange oil was obtained. Integration of the H
5
NMR signals at dˆ4.39, 3.55, 3.28 and 3.21 ppm were used
to determine the degree of deuterium incorporation and the
1
diastereomeric ratio. H NMR (500 MHz, CDCl ): dˆ4.39
3
2
3
(
dd, Jˆ17.7 Hz, Jˆ2.2 Hz, 0.23H, H-2 , 12), 3.55 (dd,
e
3
3
Jˆ10.1 Hz, Jˆ6.8 Hz, 1.00H (reference), H-4, 12), 3.28
puri®ed by column chromatography at 268C (SiO
petroleum ether, 2:3) to afford 421 mg (0.73 mmol, 59%) of
a red-orange oil which solidi®ed overnight at 268C. R
2 2 2
, CH Cl /
2
3
(
dd, Jˆ17.8 Hz, Jˆ8.2 Hz, 0.26H, H-2 , 12), 3.21 (d,
e
3
Jˆ7.9 Hz, 0.35H, H-2 , 14e). The signal of H-2 of
f
a
e
1
compound 14a was covered by the signal of H-6 . By
e
(CH
CDCl
Cl /petroleum ether, 2:3): 0.60; H NMR (500 MHz,
2 2
3
3
subtraction, its integral was determined to correspond to
3
): dˆ5.76 (dddd, 1H, Jˆ16.8 Hz, Jˆ10.2 Hz,
3
3
0
3
0
1
.30H. The degree of 2,2-dideuteration was found to be
0% by comparison of the reference integral with the
Jˆ7.8 Hz, Jˆ6.8 Hz, H-2 ), 5.22 (ddd, 1H, Jˆ16.8 Hz,
4
4
3
4
0
3
Jˆ,2 Hz, Jˆ,1 Hz, H-3
, 5.21 (ddd, 1H, Jˆ10.2 Hz,
1
4
0
3
combined integrals of the signals at 3.28, 3.21 ppm and
H-2 of compound 14a.
Jˆ,1 Hz, Jˆ,1 Hz, H-3
2
), 4.41 (ddd, 1H, Jˆ9.4 Hz,
3
Jˆ4.0 Hz, Jˆ1.4 Hz, H-2), 4.35 (m, 1H, H-6
), 3.95±4.05
e
a
3
3
(
m, 2 H, H-5, H-6 ), 3.84 (dd, 1H, Jˆ7.4 Hz, Jˆ1.4 Hz,
a
3
3
Pentacarbonyl[2-allyl-3,4,6-tri-O-triisopropylsilyl-2-deoxy-
mannosylidene]chromium(0) (15). 0.48 ml (1.19 mmol)
n-BuLi (2.5 M in hexane) was added dropwise to a solution
of 898 mg (0.99 mmol) of 1 in 10 ml of dry THF at 2788C.
After stirring for 1 h, a solution of 450 mg (1.49 mmol)
H-3), 3.51 (dd, 1H, Jˆ9.8 Hz, Jˆ7.4 Hz, H-4), 2.54
2
3
3
(ddddd, 1H4,
Jˆ14.1 Hz,
Jˆ6.8 Hz,
Jˆ4.0 Hz,
4
0
2
Jˆ,2 Hz, Jˆ,1 Hz, H-1
), 2.26 (ddddd, 1H, Jˆ
1
3
3
4
4
14.1 Hz, Jˆ9.4 Hz, Jˆ7.8 Hz, Jˆ,1 Hz, Jˆ,1 Hz,
13
0
21H, TIPS); C NMR (125 MHz, CDCl
H-1
), 1.49 (s, 3 H, CH
2
), 1.39 (s, 3H, CH
), 1.1±1.0 (m,
3
3
2
pentacarbonyl(h -cis-cyclooctene)chromium(0) in 10 ml
3
): dˆ359.7 (C-1),
0
0
of dry THF precooled to 2788C was added via a transfer
needle. The reaction mixture was warmed to 08C and
stirred at this temperature for 20 min. After recooling to
223.8 (COtrans), 216.0 (COcis), 140.0 (C-2 ), 120.2 (C-3 ),
100.1 (C(CH
)
), 75.8 (C-4), 75.0 (C-2, C-5), 71.9 (C-3),
3
2
0
61.9 (C-6), 35.7 (C-1 ), 29.1 (C(CH
)
), 19.2 (C(CH
), 12.3±12.0 (Si[CH(CH ) ]
3 2 3
)
),
);
EI-MS (70 eV): m/z (%)ˆ574.2 [M ], 518.2 [M 22CO],
3
2
3
2
2
788C, 200 mg (1.19 mmol) allyl iodide were added
18.8±17.9 (Si[CH(CH
3
)
]
2
3
1
1
dropwise. The reaction mixture was allowed to reach
room temperature slowly overnight. The solvent was
removed in vacuo and the crude product was puri®ed
1
1
1
490.2 [M 23CO], 462.2 [M 24CO], 434.2 [M 25CO],
1
339.2 [M 2Cr(CO)
±C
C H O SiCr [M 25CO]: 434.1944, Found: 434.1954;
21 38 4
H ]; HR-MS Calcd for
3 7
5
1
by column chromatography at 268C (SiO , petroleum
2
ether) to afford 619 mg (0.73 mmol, 74%) of an orange
oil. It solidi®ed overnight at 268C, and H NMR analy-
Anal. Calcd for C26
C, 54.33; H, 6.77.
H O SiCr: C, 54,34; H, 6.67; Found:
38 9
1
sis indicated a 96:4 mixture of diastereomers in favour
of the `manno'-isomer. A separation of the diastereo-
mers by chromatography failed. R (petroleum ether):
f
Acknowledgements
1
0
.78; H NMR (500 MHz, CDCl ): dˆ5.97 (dddd, 1H,
3
3
3
3
3
0
Jˆ17.1 Hz, Jˆ10.0 Hz, Jˆ7.8 Hz, Jˆ6.4 Hz, H-2 ),
Support of this work by the Deutsche Forschungs-
gemeinschaft (Graduiertenkolleg `Spektroskopie isolierter
und kondensierter Molek uÈ le'), the Fonds der Chemischen
Industrie and the Ministry of Science and Research (NRW)
is gratefully acknowledged.
3
4
4
0
0
5
5
4
.24 (ddd, 1H, Jˆ17.1 Hz, Jˆ3.1 Hz, Jˆ1.6 Hz, H-3 ),
1
3
4
4
.17 (ddd, 1H, Jˆ10.0 Hz, Jˆ1.6 Hz, Jˆ1.6 Hz, H-3 ),
2
3
3
3
.76 (ddd, 1H, Jˆ7.1 Hz, Jˆ4.7 Hz, Jˆ1.6 Hz, H-5),
2
3
4
.15 (dd, 1H, Jˆ11.1 Hz, Jˆ7.1 Hz, H-6 ), 4.13 (dd, 1H,
1
3
3
3
Jˆ3.4 Hz, Jˆ1.6 Hz, H-4), 4.09 (ddd, 1H, Jˆ11.5 Hz,
3
3
3
3
Jˆ1.8 Hz, Jˆ1.6 Hz, H-2), 4.05 (dd, 1H, Jˆ11.1 Hz,
3
3
Jˆ4.7 Hz, H-6 ), 3.91 (dd, 1H, Jˆ3.4 Hz, Jˆ1.8 Hz,
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3
3