Simple oxidation of 3-O-silylated glycals: Application in deblocking 3-0-protected glycals

Article abstract of DOI:10.1039/a807479h

A high yielding allylic oxidation of 3-O-siIylated glycals 5-10 with the reagent system PhI(OAc)2-TMSN3 is presented. The iodine(m) species generated under these conditions is a lot more effective for generating carbohydrate-derived 3-trialkylsiloxy-2,3-d

Full text of DOI:10.1039/a807479h

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Simple oxidation of 3-O-silylated glycals: application in
deblocking 3-O-protected glycals
Andreas Kirschning,* Ulrike Hary, Claus Plumeier, Monika Ries and Lars Rose
Institut für Organische Chemie, Technische Universität Clausthal, Leibnizstraße 6,
D-38678 Clausthal-Zellerfeld, Germany
Received (in Cambridge) 25th September 1998, Accepted 4th January 1999
A high yielding allylic oxidation of 3-O-silylated glycals 5–10 with the reagent system PhI(OAc)2–TMSN3 is presented.
The iodine() species generated under these conditions is a lot more effective for generating carbohydrate-derived
3-trialkylsiloxy-2,3-dihydro-4H-pyran-4-ones 11–15 than is [hydroxy(tosyloxy)iodo]benzene, the Koser reagent. Even
disaccharide 9 containing the oxidation-labile phenylseleno group is smoothly oxidized to the corresponding enone
15. The hypervalent azido iodine reagent is complementary to the Koser reagent, because 3-O-benzylated or -acylated
glycals cannot be oxidized. When the iodine()-mediated oxidation of 3-O-silylated or -benzylated glycals is followed
by a reduction step, the formal 3-O-deblocking of glycals is achieved. In particular, the Luche reduction of enones
obtained from the oxidation of lyxo-configured glycals 24 and 26 is highly selective and exclusively affords the
corresponding lyxo-configured glycals 28 and 30. In some cases, these products can be transformed under Mitsunobu
conditions into glycals with inverted configuration at C-3 in moderate yield.
to develop a method for selectively deblocking the allylic
Introduction
position of glycals.11
Glycals are carbohydrate-based enol ethers, and numerous
examples have served as enantiopure synthetic intermediates;
e.g., the use of glycals as chiral building blocks in various
cycloaddition reactions1 and for the synthesis of C-glycosides2
are important applications. Furthermore, they have often been
employed as useful intermediates for the construction of com-
plex natural products, typical examples being the ionophores
lasalocid A3a and calcimycin3b as well as the macrolactones
rapamycin3c and avermectin A.3d Most frequently, however,
they have proven to be useful for the preparation of oligo-
saccharides4 including 2-deoxy glycosides.5 Besides the devel-
opment of efficient glycosidation methods the availability of
partially protected glycals has turned out to be another key
issue for the construction of oligosaccharide chains present
in anthracyclines, angucyclines such as landomycin A 1, the
aureolic acids and other glycosylated antibiotics.5
Although many studies have been conducted into the prepar-
ation of partially blocked glycals, and in particular 3-O-
deprotected members of 2,6-dideoxy sugars, these approaches
often lack a high degree of regioselectivity and afford mixtures
of reaction products.6 The methods employed typically rely on
the selective protection of glycals by using alkylation methods
under phase-transfer catalysis conditions,7,8 the use of bulky
silylating reagents,9 and electrophilic attack on cis-O,OЈ-dibutyl-
stannylene acetals.8 During our efforts to synthesize the
hexasaccharide chain of landomycin A 1,10 it became necessary
Results and discussion
Improved iodine(III)-promoted oxidation of glycals
In this paper an oxidation/reduction strategy is presented which
effectively deprotects fully protected glycals in the allylic pos-
ition to afford glycals 3 (Scheme 1). With our discovery of the
oxidative deblocking at O-3 of fully protected glycals 2 medi-
ated by hypervalent iodine() reagents, we were able to achieve
rapid synthetic access to carbohydrate-derived 2,3-dihydro-
4H-pyran-4-ones 4.12 In the presence of [hydroxy(tosyloxy)-
iodo]benzene [PhI(OH)OTs], the Koser reagent, almost any
O-3-protected glycal 2 can be used as a starting material.13 In
fact, the ketone functionality can be elaborated from diverse
precursors including esters, acetals and ethers in a regiospecific
process. However, in most cases, namely esters, and benzyl or
methoxymethyl ethers, yields for 2,3-dihydro-4H-pyran-4-ones
4 do not exceed 60% and additional by-products are formed.
These by-products helped to elucidate the mechanism of this
process.14 Due to the synthetic versatility of the oxidation
products as chiral building blocks,15 we pursued an improve-
ment of the allylic oxidation. In comparison with the Koser
reagent, most common hypervalent iodine reagents such as
PhI(OAc)2,16 PhI(O2CCF3)2, PhI(OCH3)OTs17 and PhI(CN)2
were ineffective oxidants, giving yields of 0–10%, as did BF3ؒ
18
J. Chem. Soc., Perkin Trans. 1, 1999, 519–528
519

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Table 1 PhI(OAc)2–TMSN3-mediated oxidation of 3-O-silylated glycals
Glycal
Methoda
Enone
Yield [%]b
5
6
A (B)
A (B)
11 95 (33)
12 92(<10c )
7
8
9
A (B)
A (B)
A
13 95 (67)
14 43 (18)
15 79
10
A
16 57d
a Method A: PhI(OAc)2–TMSN3; method B: PhI(OH)OTs. b The second value in the parentheses refers to the yield of method B. c Compound 17 is
the major product. d Inseparable mixture of 3-epimers.
electrophiles.14 Therefore, enone 14 is formed in only 18% yield
in the presence of the Koser reagent, whereas formation of a
ring-contracted tetrahydro-2-furaldehyde (35% yield) and a 2,3-
anhydropyranose (20% yield) prevails.14 When employing the
azide-based iodine() reagent, only enone 14, along with start-
ing enol ether 8, was isolated. The reagent can be employed in
Scheme 1
the presence of a variety of reactive protective groups, such as
acid-labile triethylsilyl ethers or tosyloxy groups. For studying
OEt2 or trimethyloxonium tetrafluoroborate-activated iodosyl-
benzene [(PhIO)n].19 However, we found that the reagent system
PhI(OAc)2–TMSN3 was the best oxidant for the oxidative
the full scope of this oxidation we planned to treat disaccharide
9, which contains an oxidation-labile phenylselenyl group and a
glycosidic linkage with the reagent system PhI(OAc)2–TMSN3.
For this purpose, we had to prepare glycal 9 which was
achieved by utilizing a method developed by Perez and Beau21
in the initial step. Glycal 18 was transformed into a single 1,2-
addition product, the seleno acetate 19a (Scheme 2). However,
at this stage it was not possible to clearly prove the β-gluco-
configuration of product 19a, as the coupling constants J for
20
deblocking of 3-O-silylated glycals 5–9 to afford enones 11–15
(Table 1).13 In all cases, the reaction proceeds in higher yields
compared with those obtained with PhI(OH)OTs.12,14 Due to
the more acidic reaction conditions used when employing the
Koser reagent, glycal 6 was selectively desilylated instead, yield-
ing compound 17 in 52% yield, while the desired enone 12
was inefficiently formed. The 6-O-tosylated glycal 8 adopts a
1
the ring protons in the H NMR-spectrum are not diagnostic
(J1,2 4.0 Hz, J2,3 3.6 Hz, J3,4 3.6 Hz, J4,5 not determined).
5
twist-boat or H4(D) conformation with reduced reactivity for
520
J. Chem. Soc., Perkin Trans. 1, 1999, 519–528

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studies23 it was concluded that PhI(N3)OAc is the active species
while other authors24 claim that in most cases (diazidoiodo)-
benzene PhI(N3)2 is involved. We believe that this oxidation
proceeds via similar intermediates that were found for the
analogous reaction using the Koser reagent13 as well as for the
iodine()-promoted oxidation of triisopropylsilyl enol ethers
described by Magnus et al.24
Chemical modifications of the keto group
In the next step, the crude products of the iodine()-mediated
oxidations were directly reduced to the corresponding allylic
alcohols, which terminates our allylic deprotecion strategy. As
is shown in Table 2, per-O-benzylated glycals 23–26 can effi-
ciently be deblocked with this oxidation-reduction strategy,
affording allyl alcohols 27–30. However, for these glycals it
became necessary to use PhI(OH)OTs in the primary oxidation
step. We found that in most cases Luche reduction25 proved to
be a very effective protocol for the reduction of the keto func-
tionality with yields in the range of 85–99%.26 However, this
method turned out to be ineffective in the presence of a siloxy
substituent α to the carbonyl group as shown for enone 13.27 In
this case, DIBAL-H was the reagent of choice which, starting
from compound 7, furnished glycals 31a,b. Furthermore, the
reduction is highly stereoselective for threo-configured pyran-
ones with a pseudoaxial substituent next to the carbonyl group.
Thus, lyxo-configured fully protected glycals 24 and 26 are
selectively converted into the corresponding 3-O-unprotected
glycals 28a and 30a; indeed, the corresponding xylo-configured
epimers 28b and 30b were not detected in the crude product. In
fact, this route is the shortest one to 3-O-unprotected lyxo-
configured glycals. Also, for glycals 23, 25, 7 and 9 the starting
arabino-configuration is preserved preferentially, leading to gly-
cals 27a, 29a, 31a and 32a. Nevertheless, the corresponding
ribo-configured isomers 27b, 29b, 31b and 32b are formed also.
Apparently, a pseudoequatorial substituent at C-4 is respon-
sible for the moderate stereoselectivity of this process.27 How-
ever, for all examples the epimers could be separated by column
chromatography, which is in contrast to several mixtures
obtained by the regioselective blocking of unprotected glycals.6–9
The configuration of the newly formed stereogenic center at
C-3 was confirmed by comparison of the relevant coupling con-
stants in the 1H NMR spectra (arabino: J2,3 2.0–2.4 Hz, J3,4 6.5–
7.6 Hz; ribo: J2,3 4.8–5.8 Hz, J3,4 3.6–4.0 Hz; lyxo: J2,3 3.0–4.0
Hz, J3,4 4.4–4.6 Hz) which were in accordance with literature
values6–9 as well as NMR data collected from the starting
glycals.
In order to unequivocally confirm its configuration, glycal
31a was acetylated and the resulting product 35 was com-
pared with authentic material obtained by an alternative and
new chemo-enzymic route (Scheme 3). Thus, lipase-catalyzed
irreversible transesterification28 of -rhamnal 33 afforded the
3-O-acylated glycal 34 as a single isomer, which was trans-
formed into compound 35 under standard silylating conditions.
Good yields are only achieved for this sequence if the alcohol
34 is not stored for too long, as acetyl migration to the
4-position can occur.9,29 It should be noted that this chemo-
enzymic route is restricted to a few glycals;28 e.g., we found that
the 4-epimers of 33 (-rhamnal) or di-O-acetyl--rhamnal
cannot be used for this purpose.
The oxidation/reduction sequence presented here can advan-
tageously be exploited for the specific incorporation of deuter-
ium at C-3, which became necessary for us during our ongoing
studies on the biogenesis of deoxygenated sugars.30 As depicted
in Scheme 4, di-O-benzyl--arabinal 36 was oxidized to the
corresponding enone 37, which was in turn reduced to afford
the allyl alcohol 38 or the deuterated analogue 39. Formation
of the erythro-configured 3-epimer was not observed.
Scheme 2 Reagents, conditions (and yields): (a) PhSeCl (1.3 equiv.),
AgOAc (1.5 equiv.), toluene, rt, 3 h, (72%, crude); (b) Et2O, cat. TIPS-
OTf, Ϫ80 ЊC, 10 min; then addition of 20 (1.2 equiv.), Ϫ50 ЊC, 10 min
(59%); (c) TBAF (3.0 equiv.), THF, 0 ЊC, 12 h, 21 (43%) and 22 (35%).
Unfortunately, the acetyl group in pyranosyl acetate 19a turned
out to be very sensitive and was hydrolysed upon attempted
purification on silica gel to afford pyranose 19b. Therefore,
crude alcohol 19a was glycosidated after activation with triiso-
propylsilyl triflate (TIPSOTf) in the presence of glycal 20 to
provide disaccharide 9 in 59% yield. At this stage, the configur-
ation of all stereogenic centers were assigned after fluoride-
initiated removal of the silyl protection. Thus, treatment of
compound 9 with TBAF furnished disaccharides 21 and 22.
With the large protective groups now missing, both compounds
1
adopt a C4(L)-conformation. From the ring-proton coupling
constants J of the second pyran ring (between 9.2 and 11.2 Hz)
the gluco-configuration in compounds 21 and 22 as well as 19a
was unequivocally established. Finally, iodine()-promoted
oxidation afforded the 2,3-dihydro-4H-pyran-4-one 15 in satis-
factory yield, thereby confirming the exceptional mildness of
the azide-based hypervalent iodine reagent.
Clearly, both hypervalent iodine reagents [PhI(OAc)2–
TMSN3 and PhI(OH)OTs] employed here differ in their reactiv-
ity, for which further support was obtained when other than
silyl protection was introduced in the allylic position.13 Glycals
with a 3-O-acyl or 3-O-methoxymethyl group, which are
good substrates for the Koser reagent,12 do not react with the
PhI(OAc)2–TMSN3 system or gave reduced yields, whereas
3-O-benzyl glycals showed substantial decomposition under the
reaction conditions. The two hypervalent iodine reagents are
obviously complementary. When a deoxygenation is introduced
at C-3 as in glycal 10, 3-azido glycals 16 were formed in a com-
parable yield to those obtained in the reagent system (PhIO)n–
TMSN3.22 These observations are in sharp contrast to earlier
work by Ehrenfreund and Zbiral,23 who observed oxidative
ring-cleavage of 2,3-dihydropyran with the same reagent sys-
tem, providing the corresponding formic acid 3-cyanopropyl
ester in 61% yield. However it has to be pointed out that
PhI(OAc)2–TMSN3 provides a large variety of reactions with
alkenes which for most cases may either be explained by elec-
trophilic attack of a hypervalent iodine species on the π-bond
or alternatively may be rationalized on the basis that the
reaction is initiated by a 1,3-dipolar cycloaddition of the azide
group to the double bond. At present the precise structure
of the intermediate reagent formed is still not clear. From IR
Inversion of configuration at C-3 of glycals or substitution
would increase the applicability of our oxidation/reduction
J. Chem. Soc., Perkin Trans. 1, 1999, 519–528
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Table 2 3-O-Deblocking of protected glycals by the oxidation/reduction sequence
3-O-deblocked
glycals
Yield
Glycal
R1
H
R1
Conditions
Ratioa
1.5:1
[%]b
23
OBn 1. Phl(OH)OTs
2. NaBH4, CeCl3
27a,b
38
24 OBn
H
1. Phl(OH)OTs
2. NaBH4, CeCl3
28a,b >10:1
57
25 OBn
H
1. Phl(OH)OTs
2. NaBH4, CeCl3
29a,b
1.1:1
47
59
26
7
H
OBn 1. Phl(OH)OTs
2. NaBH4, CeCl3
30a,b >10:1
1. Phl(OAc)2, TMSN3
2. DIBAL-H
31a,b
32a,b
2:1
1:1
65
67
9
1. Phl(OAc)2, TMSN3
2. NaBH4, CeCl3
a Determined from 1H NMR spectra of crude products. b Refers to separated isomers.
However, in only a few cases has the formation of the desired
substitution product with inversion of configuration at C-3
been reported.34 We found that Mitsunobu reaction of galactal
28a with benzoic acid in toluene afforded a mixture of glycal 40
and enopyranoses 41 (α:β >8:1) (Scheme 5). Interestingly,
Scheme 3 Reagents, conditions (and yields): (a) lipase PS, CH2᎐᎐
t
CHOAc, ethyl acetate, rt, 2 d, 67%; (b) BuMe2SiCl, imidazole, DMF,
rt, 12 h (89%); (c) Ac2O, pyr, rt, 10 h (92%).
Scheme 5 Reagents, conditions (and yields): (a) PPh3, BzOH, DEAD,
toluene, 20 h, 0 ЊC→rt, 58% from 28a and 63% from 30a; (b) LiN3,
PPh3, CBr4, DMF, rt, 12 h, 15% from 30a; (c) BzCl, pyr, CH2Cl2, 12 h,
rt, 30%.
fucal 30a exclusively furnished SN2-product 43 under the same
conditions.
Scheme 4 Reagents, conditions (and yields): (a) PhI(OH)OTs, mol-
ecular sieves 3 Å, CH3CN, rt, 1 h (64%); (b) CeCl3ؒ(H2O)7, NaBH4
(NaBD4), EtOH, CH2Cl2, Ϫ50 ЊC→rt, 30 min 88%.
A particularly useful application in this respect would be the
stereoselective introduction of a masked amino functionality
(the azide anion) at C-3. In fact, 3-azido glycals have served
as important glycosyl precursors for the construction of
glycosides containing 3-amino-2,3,6-trideoxyhexopyranoses.35
These are constituents of various pharmaceutically important
glycosylated antitumor agents. Treatment of glycal 30a in the
presence of lithium azide, carbon tetrabromide and triphenyl-
phosphine in DMF afforded azido glycal 44 as a single isomer.36
In principle, this reaction leads to stereochemically rare 3-azido
glycals although the yield is far from satisfactory.
sequence as O-differentiated and stereochemically rare glycals
would be accessible via a short route. We reckoned that
Mitsunobu-type reactions31 should be the transformation of
choice for this purpose. However, Guthrie et al.32 first reported
that the Ph3P/ethyl diazoacetate mediated reaction of 1,5-
anhydro-4,6-O-benzylidene-2-deoxy--arabino-hex-1-enitol
with benzoic acid gave only the SN2Ј-product. Later, Sulikowski
and Sobti employed the Mitsunobu reaction for the preparation
of unsaturated aryl glycosides starting from various glycals.33
In summary we have shown a straightforward two-step
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J. Chem. Soc., Perkin Trans. 1, 1999, 519–528

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procedure for selectively deblocking fully protected glycals at
C-3. The process is initiated by an iodine-promoted oxidation
of 3-O-benzyl- or silyl-protected glycals to afford the corre-
sponding enones, followed by chemoselective reduction of the
ketone functionality. The 3-O-unprotected glycals obtained by
this route may further be manipulated at C-3 by variants of the
Mitsunobu reaction. This short sequence provides an efficient
access to valuable, partially blocked glycals. These can serve as
monosaccharide precursors in glycosylation reactions towards
deoxygenated oligosaccharides which are constituents of
numerous important glycoconjugates from microbial sources,
including landomycin A 1.
fied by flash column chromatography (SiO2; petroleum spirit–
ethyl acetate 12:1). The title compound 19a (1.01 mg, 72%) was
sufficiently pure for the next step. For analytical purposes, a
small amount was further purified by column chromatography
(SiO2; petroleum spirit–ethyl acetate 20:1).
1st fraction: acetyl 3,4-bis-O-(tert-butyldiphenylsilyl)-6-
deoxy-2-phenylseleno-β--gluco-pyranose 19a (contaminated
with ~10% of alcohol 19b): δH(400 MHz; C6D6; TMS = 0.0
ppm) 7.7–7.1 (25H, m, Ph), 6.32 (1H, d, J 4.0, 1-H), 4.39 (1H,
dd, J 3.6 and 3.6, 3-H), 3.81 (1H, dd, J 3.6 and 4.0, 2-H), 3.64
(2H, m, 4- and 5-H), 2.12 (3H, s, OAc), 1.12 (3H, d, J 7.2, 6-H3)
and 0.97 and 0.79 (18H, 2 s, 2 × tBu); δC(100 MHz; C6D6) 169.5
(s, OAc), 132.4, 132.3, 131.9, 131.8 and 129.9 (s, Ph), 135.6,
135.4, 134.6, 134.5, 132.0, 128.8, 128.7, 128.6, 128.5, 126.6,
126.5, 126.4, 126.3 and 126.2 (d, Ph), 91.0 (d, 1-C), 72.4, 71.5
and 70.8 (d, 3-, 4- and 5-C), 44.6 (d, 2-C), 26.2 and 25.6 (q,
2 × tBu), 20.5 (q, OAc), 19.0 (q, 6-C) and 18.5 and 17.9 (s,
2 × tBu).
2nd fraction: 3,4-bis-O-(tert-butyldiphenylsilyl)-6-deoxy-2-
phenylseleno-β--gluco-pyranose 19b: mp 58 ЊC; [α]D25.2 ϩ 32.5
(c 0.925, CHCl3); δH(400 MHz; C6D6; TMS = 0.0 ppm) 7.7–7.0
(25H, m, Ph), 5.30 (1H, dd, J 13.2 and 2.0, 1-H), 4.78 (1H, dd,
J 2.0 and 2.0, 3-H), 3.96 (1H, q, J 7.2, 5-H), 3.78 (1H, d, J 13.2,
OH), 3.54 (1H, d, J 2.0, 4-H), 3.14 (1H, dd, J 2.0 and 2.0, 2-H),
1.22 (3H, d, J 7.2, 6-H3) and 1.06 and 0.95 (18H, 2 s, 2 × tBu);
δC(50 MHz; CDCl3; TMS = 0.0 ppm) 135.9, 135.8, 135.6,
132,6, 130.0, 129.9, 129.7, 129.0, 128.2, 127.8, 127.7, 127.6,
127.5 and 126.8 (d, Ph), 133.4, 132.9 and 132.3 (q, Ph), 84.9
(d, 1-C), 76.9, 75.9 and 71.2 (d, 3-, 4- and 5-C), 54.3 (d, 2-C),
27.0 and 26.9 (q, 2 × tBu), 19.1 and 18.9 (s, 2 × tBu) and 16.6
(q, 6-C) (Found: C, 67.4; H, 7.1. C44H52O4Si2Se requires C,
67.75; H, 6.72%).
Experimental
General procedures
All temperatures quoted are uncorrected. Optical rotations
were recorded on a Perkin-Elmer 141 polarimeter and are
given in 10Ϫ1 deg cm2 gϪ1. IR spectra were obtained on a PYE
1
Unicam SP3-200 as thin films on NaCl plates. H NMR, 13C
1
1
NMR, H,1H- and H,13C-COSY as well as NOESY spectra
were recorded on a Bruker ARX 400-NMR spectrometer for
solutions in CDCl3 or C6D6 using residual CHCl3 or C6H6 as
internal standards (δ 7.26 and 7.20, respectively) unless other-
wise stated. Multiplicities are described using the following
abbreviations: s = singlet, d = doublet, t = triplet, q = quartet,
sept = septet, m = multiplet, br = broad. Coupling constants (J)
are quoted in Hz. Chemical-shift values of 13C NMR spectra
are reported as values in ppm relative to residual CHCl3 (δC 77)
or C6D6 (δC 128) as internal standards. The multiplicities refer
to the resonances in the off-resonance spectra and were eluci-
dated using the distortionless enhancement by polarization
transfer (DEPT) spectral editing technique, with secondary
pulses at 90Њ and 135Њ. Multiplicities are reported using the
following abbreviations: s = singlet (due to quaternary carbon),
d = doublet (methine), t = triplet (methylene), q = quartet
(methyl). Mass spectra were obtained using a Kratos MS-
80RFA mass spectrometer (DS-55/DS-90 peak matching
option) when electron impact (EI, 70 eV) was the ionization
method of choice. Fast-atom bombardment (FAB) mass spec-
tra were obtained on a BG Analytical ZAB-2F (Ion Tech
FAB gun, 8 kV, Xe carrier gas). Ion mass (m/z) signals are
reported as values in atomic mass units followed, in paren-
theses, by the peak intensities relative to the base peak (100%).
Combustion analyses were performed by the Institut für Phar-
mazeutische Chemie, Technische Universität Braunschweig
and Institut für Chemie, Humboldt Universität zu Berlin. All
solvents used were of reagent grade and were further dried.
Petroleum spirit refers to the fraction with distillation range
50–70 ЊC. Reactions were monitored by TLC on silica gel 60 F254
(E. Merck, Darmstadt) and spots were detected either by
UV-absorption or by charring with H2SO4–4-methoxybenz-
aldehyde in methanol. Preparative column chromatography was
performed on silica gel 60 (E. Merck, Darmstadt). Lipase PS
(Pseudomonas fluorescens) was obtained from Amano Pharma-
ceutical Co. [Hydroxy(tosyloxy)iodo]benzene [PhI(OH)OTs]
was prepared according to Koser’s procedure.37 O-Silylated
glycals 5–7 and 18 were synthesized according to the liter-
ature.12 O-Benzylated glycals 23–26 and 36 were obtained as
described in ref. 38. The 6-O-tosyl glucal 814 and 3-deoxy glycal
1022 have been described before.
Preparation of 1,5-anhydro-4-O-[3,4-bis-O-(tert-butyldiphenyl-
silyl)-6-deoxy-2-phenylseleno-â-L-gluco-pyranosyl]-3-O-(tert-
butyldimethylsilyl)-2,6-dideoxy-L-arabino-hex-1-enitol 9
To a solution of monosaccharide 19a (1.45 g, 1.76 mmol) in
absolute diethyl ether (50 ml) under N2 at Ϫ80 ЊC was added
TIPSOTf (0.048 ml, 55 mg, 0.18 mmol) and the solution was
stirred for 10 min. Then, glycal 20 (0.52 g, 2.1 mmol)
was added, the temperature was raised to Ϫ50 ЊC and stirring
was continued for 10 min. For work-up, saturated aq. NaHCO3
was added, the phases were separated, and the aqueous phase
was extracted with CH2Cl2 (2×). The combined organic layers
were dried (MgSO4), and concentrated in vacuo. Flash chrom-
atography (petroleum spirit–ethyl acetate 30:1) afforded the
title compound 9 (1.06 g, 59%); mp 95 ЊC; [α]D19 ϩ63.3 (c 1.01,
CHCl3); δH(200 MHz; C6D6) 7.8–7.6 and 7.3–7.0 (25H, m,
ArH), 6.34 (1H, dd, J 0.8 and 6.0, 1-H), 5.69 (1H, d, J 6.4, 1Ј-
H), 5.13 (1H, d, J 3.2, 4Ј-H), 4.80 (1H, dd, J 3.6 and 6.0, 2-H),
4.50 (1H, ddt, J 0.8, 3.6 and 4.0, 3-H), 4.24 (1H, dq, J 6.0 and
6.4, 5-H), 3.96 (1H, dd, J 4.0 and 6.0, 4-H), 3.86 (2H, m, 2Ј- and
5Ј-H), 3.72 (1H, d, J 3.6, 3Ј-H), 1.64 (3H, d, J 6.4, 6-H3), 1.21,
1.14 and 1.08 (27H, 3 s, 3 × tBu), 1.0 (3H, d, J 6.4, 6Ј-H3) and
0.33 and 0.25 [6H, 2 s, Si(CH3)2]; δC(50 MHz; C6D6) 136.5,
136.4, 136.3, 136.2, 131.9, 130.2, 130.1, 130.0, 129.9, 129.0,
128.3, 128.1 and 126.5 (d, Ph), 133.7, 133.6, 133.5 and 133.4 (q,
Ph), 143.1 (d, 1-C), 103.8 (d, 1Ј-C), 103.1 (d, 2-C), 79.7 (d, 4-C),
78.9 and 78.8 (d, 4Ј- and 5Ј-C), 73.7 (d, 3Ј-C), 73.3 (d, 5-C), 67.1
(d, 3-C), 49.5 (d, 2Ј-C), 27.4, 27.2 and 26.2 (q, 3 × tBu), 20.2 (q,
6Ј-C), 19.3, 19.2 and 18.3 (s, 3 × tBu), 17.6 (q, 6-C) and Ϫ4.0
and Ϫ4.6 [q, Si(CH3)2] (Found: C, 66.9; H, 7.8. C56H74O6Si3Se
requires C, 66.83; H, 7.41%).
Preparation of acetyl 3,4-bis-O-(tert-butyldiphenylsilyl)-6-
deoxy-2-phenylseleno-â-L-gluco-pyranose 19a
Desilylation of disaccharide 9
To a solution of glycal 18 (1.05 g, 1.7 mmol) in absolute toluene
(50 ml) under N2 at rt were added benzeneselenenyl chloride
(422 mg, 2.2 mmol) and silver acetate (435 mg, 2.6 mmol). The
suspension was stirred at rt for 3 h, before the reaction mixture
was filtered, and concentrated in vacuo. The residue was puri-
TBAF trihydrate (800 mg) was dissolved in absolute THF (5
ml) under N2. After rapid removal of the solvent in vacuo the
compound was kept in high vacuum for 6 h. The compound
was re-dissolved in absolute THF (25 ml) under N2 to afford a
J. Chem. Soc., Perkin Trans. 1, 1999, 519–528
523

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0.1 molar solution. A portion (2.1 ml, 0.21 mmol) of this solu-
tion were added to a solution of disaccharide 9 (70 mg, 0.07
mmol) in absolute THF (3 ml) at 0 ЊC. Stirring was continued
for 12 h before the reaction mixture was treated with aq.
NaHCO3 (5 ml), and the phases were separated. The aqueous
layer was washed with methylene dichloride, and the combined
organic extracts were dried (MgSO4), and concentrated under
reduced pressure. The crude product was chromatographed on
silica gel (petroleum spirit–ethyl acetate 1.5:1) to afford two
fractions:
1st fraction: 1,5-anhydro-3-O-(tert-butyldimethylsilyl)-2,6-
dideoxy-4-O-(6-deoxy-2-phenylseleno-β--gluco-pyranosyl--
arabino-hex-1-enitol 21 (16 mg, 43%); [α]D22 Ϫ24.6 (c 0.54,
CHCl3); δH(400 MHz; CDCl3) 7.72–7.60 and 7.35–7.18 (5H, m,
Ph), 6.32 (1H, dd, J 0.6 and 6.0, 1-H), 4.72 (1H, ddd, J 0.8, 4.8
and 6.0, 2-H), 4.58 (1H, d, J 9.2, 1Ј-H), 4.28 (1H, ddq, J 1.2, 4.0
and 6.8, 5-H), 4.16 (1H, ddd, J 1.2, 3.2 and 4.8, 3-H), 3.72 (1H,
ddd, J 0.8, 3.2 and 4.0, 4-H), 3.36 (3H, m, 3Ј-, 4Ј- and 5Ј-H),
2.99 (1H, dd, J 9.2 and 10.8, 2Ј-H), 2.94 (1H, br, OH), 2.53 (1H,
br, OH), 1.45 (3H, d, J 6.8, 6-H3), 1.32 (3H, J 5.6, 6Ј-H3), 0.88
(9H, s, tBu) and 0.06 and 0.05 [6H, 2 s, Si(CH3)2].
2nd fraction: 1,5-anhydro-4-O-(6-deoxy-2-phenylseleno-β--
gluco-pyranosyl)--arabino-hex-1-enitol 22 (10 mg, 35%); [α]D22
Ϫ18.7 (c 0.525, CHCl3); δH(400 MHz; CDCl3) 7.63–7.57 and
7.37–7.24 (5H, m, Ph), 6.32 (1H, dd, J 1.6 and 6.0, 1-H), 4.76
(1H, dd, J 2.0 and 6.0, 2-H), 4.58 (1H, d, J 9.2, 1Ј-H), 4.46 (1H,
br, OH), 4.27 (1H, ddd, J 1.6, 2.0 and 7.2, 3-H), 3.86 (1H, dq,
J 6.4 and 10.0, 5-H), 3.43 (1H, dq, J 6.4 and 9.2, 5Ј-H), 3.38
(1H, dd, J 7.2 and 10.0, 4-H), 3.32 (2H, m, 3Ј- and 4Ј-H), 3.08
(1H, dd, J 9.2 and 11.2, 2Ј-H), 1.59 (3H, d, J 6.4, 6-H3) and 1.37
(3H, d, J 6.4, 6Ј-H3).
described above. Compound 12 was subjected to filtration on
silica gel (petroleum spirit–ethyl acetate 10:1) to afford an oil;
[α]D24 ϩ53.9 (c 1.95; CHCl3); δH(200 MHz; CDCl3) 7.31 (1H, d,
J 6.0, 1-H), 5.36 (1H, dd, J 1.4 and 6.0, 2-H), 4.26 (1H, ddd,
J 2.4, 6.4 and 6.4, 5-H), 4.04 (1H, dd, J 1.4 and 2.4, 4-H), 3.98–
3.92 (2H, m, 6-H2), 1.02–0.87 [18H, m, 2 × Si(CH2CH3)3] and
0.70–0.54 [12H, m, 2 × Si(CH2CH3)3]; δC(50 MHz; CDCl3)
191.1 (s, 3-C), 162.1 (d, 1-C), 104.8 (d, 2-C), 83.1 (d, 4-C), 69.5
(d, 5-C), 59.9 (t, 6-C), 6.7 and 6.6 [q, 2 × Si(CH2CH3)3] and 4.6
and 4.3 [t, 2 × Si(CH2CH3)3]; m/z 372 (Mϩ, 5%) (Found: Mϩ,
372.2151. C18H36O4Si2 requires M, 372.2152).
1,5-Anhydro-4-O-[3,4-bis-O-(tert-butyldiphenylsilyl)-6-
deoxy-2-phenylseleno-â-L-gluco-pyranosyl]-2,6-dideoxy-L-
erythro-hex-1-en-3-ulose 15. Compound 9 (50 mg, 0.05 mmol)
was used to prepare the title compound 15 (35 mg, 79%) via the
general procedure described above. Compound 15 was chrom-
atographed on silica gel (petroleum spirit–ethyl acetate 8:1),
mp 43–47 ЊC; [α]D25.2 Ϫ0.6 (c 1.05, CHCl3); δH(400 MHz; C6D6;
TMS = 0.0 ppm) 7.6–6.6 (25H, m, PhSe, PhSiO), 6.16 (1H, d,
J 6.0, 1-H), 5.41 (1H, d, J 6.4, 1Ј-H), 4.88 (1H, dd, J 0.8 and 6.0,
2-H), 4.70 (1H, dd, J 3.6 and 3.6, 3Ј-H), 3.95 (1H, dq, J 6.4 and
6.8, 5-H), 3.66 (1H, q, J 6.8, 5Ј-H), 3.61 (1H, dd, J 3.6 and 6.4,
2Ј-H), 3.57 (1H, dd, J 0.8 and 6.4, 4-H), 3.53 (1H, d, J 3.6,
4Ј-H), 0.96 and 0.78 (18H, 2 s, 2 × tBu), 0.81 (3H, d, J 6.8,
6Ј-H3) and 0.72 (3H, d, J 6.8, 6-H3); δC(100 MHz; C6D6) 188.3
(s, 3-C), 159.9 (d, 1-C), 136.6, 136.5, 136.3, 131.9, 130.3, 130.1,
130.0, 129.9, 129.0, 128.2, 127.9, 127.5, 127.4, 127.3 and 126.4
(d, Ph), 138.8, 133.7, 133.5, 133.4 and 133.3 (s, Ph), 105.3 (d,
2-C), 104.1 (d, 1Ј-C), 79.4 (d, 4-C), 78.6 (d, 5Ј-C), 78.3 (d, 5-C),
78.1 (d, 3Ј-C), 73.8 (d, 4Ј-C), 48.2 (d, 2Ј-C), 27.5 and 27.2 q
(2 × tBu), 20.3 (q, 6Ј-C), 19.4 and 19.3 (s, 2 × tBu) and 14.2 (q,
6-C) (Found: C, 67.4; H, 6.9. C59H58O6Si2Se requires C, 67.47;
H, 6.57%).
General procedure for the allylic oxidation of glycals with
PhI(OAc)2–TMSN3
A solution of (diacetoxyiodo)benzene (2 equiv.) and trimethyl-
silyl azide (4 equiv.) in absolute methylene dichloride (~20 ml
mmolϪ1) was stirred for 5 min at Ϫ5 ЊC. A solution of the glycal
(1 equiv.) in absolute methylene dichloride (~1 ml mmolϪ1) was
added dropwise and the ice-bath was removed, whereupon the
temperature rose to ambient. Note that due to the exothermic
character of the oxidation, a reaction scale of 10 mmol and
larger may lead to reflux of the solvent. After 1 h, aq. NaHCO3
(10 ml mmolϪ1) was added, and the phases were separated. The
aqueous layer was washed with methylene dichloride and the
combined organic extracts were dried (MgSO4), and concen-
trated under reduced pressure. Physical constants and spectro-
scopic data for 2,3-dihydro-4H-pyran-4-ones 13 (scale: 1.39
mmol, yield: 95%)12 and 14 (scale: 0.56 mmol; yield: 43%)14 as
well as for 3-azido glycal 16 (scale: 0.7 mmol; yield: 57%)22 have
been presented before.
General procedure for the allylic oxidation of glycals with the
Koser reagent [PhI(OH)OTs]
A suspension of the glycal (1 equiv.) and powdered molecular
sieves (3 Å; 0.25 g mmolϪ1 glycal) in absolute acetonitrile (20
ml mmolϪ1) under N2 was stirred for 5 min at 0 ЊC. [Hydroxy-
(tosyloxy)iodo]benzene (1.2 equiv.) was added in one portion
and the temperature was raised to ambient. After 75 min the
suspension was filtered through a pad of Celite and the residue
was washed with methylene dichloride (2 ×). The combined fil-
trate and washings were dried (MgSO4) and were concentrated
under reduced pressure to give a yellow oil. This crude product
was rapidly purified by gel filtration. Following this procedure,
glycals 23–26 were oxidized. Physical constants and spectro-
scopic data for the intermediate 2,3-dihydro-4H-pyran-4-ones
have been presented before.12
(؊)-(3S)-3-Benzyloxy-2,3-dihydro-4H-pyran-4-one 37. 3,4-
Di-O-benzyl--arabinal 36 (3.65 g, 12.33 mmol) was used to
prepare the title compound 37 (1.65 g, 66%) via the general
procedure described above. Compound 37 was sufficiently pure
for the next step. For collecting physical and spectroscopic data
a small amount was purified by column chromatography (pet-
roleum spirit–ethyl acetate 10:1) to give an oil; [α]D23 Ϫ94.8 (c 1.2,
CHCl3); δH(400 MHz; C6D6; TMS = 0.0 ppm) 7.39–7.28 (5H,
m, ArH), 7.31 (1H, d, J 6.0, 2-H) 5.40 (1H, dd, J 0.8 and 6.0, 3-
H), 4.83 and 4.61 (2H, 2 d, J 12.0, CH2Ph), 4.45 (1H, dd, J 6.4
and 12.4, 6-HB), 4.36 (1H, dd, J 4.0 and 12.4, 6-HA) and 3.81
(1H, ddd, J 0.8, 4.0 and 6.4, 5-H); δC(100 MHz; CDCl6) 190.8
(s, 4-C), 163.5 (d, 6-C), 128.9–128.5 (d, Ph), 105.2 (d, 5-C), 73.5
(d, 3-C), 72.5 and 71.2 (t, CH2Ph, 2-C) (Found: C, 71.0; H, 6.2.
C12H12O3 requires C, 70.57; H, 5.92%).
1,5-Anhydro-6-O-(tert-butyldimethylsilyl)-2-deoxy-4-O-tri-
ethylsilyl-D-threo-hex-1-en-3-ulose 11. Compound 5 (5.0 g, 10.2
mmol) was used to prepare the title compound 11 (3.61 g, 95%)
via the general procedure described above. Compound 11 was
subjected to filtration on silica gel (petroleum spirit–ethyl acet-
ate 10:1) to afford an oil; [α]D21 ϩ50.2 (c 1.16, CHCl3); δH(200
MHz; C6D6) 6.60 (1H, d, J 6.0, 1-H), 5.17 (1H, dd, J 1.0 and
6.0, 2-H), 4.09–3.82 (4H, m, 4-, 5-H and 6-H2), 4.04 (1H, dd,
J 1.4 and 2.4, 4-H), 1.08–0.95 [9H, m, Si(CH2CH3)3] and 0.80–
0.64 [6H, s, Si(CH2CH3)3]; δC(50 MHz; C6D6) 191.1 (s, 3-C),
162.1 (d, 1-C), 104.8 (d, 2-C), 83.1 (d, 4-C), 69.5 (d, 5-C), 59.9
(t, 6-C), 6.7 and 6.6 [q, 2 × Si(CH2CH3)3] and 4.6 and 4.3 [t, 2
Si(CH2CH3)3]; m/z 372 (Mϩ, 5%), 343 (74) (Found: Mϩ,
343.1789. C16H31O4Si2 requires M, 343.1761).
1,5-Anhydro-2-deoxy-4,6-bis-O-triethylsilyl-D-threo-hex-1-en-
3-ulose 12. Compound 6 (9.1 g, 18.7 mmol) was used to prepare
the title compound 12 (6.4 g, 92%) via the general procedure
Regioselective 3-O-deprotection of fully per-O-benzylated glycals
After CeCl3ؒ7H2O (3.54 equiv.) was dissolved in ethanol (10 ml
524
J. Chem. Soc., Perkin Trans. 1, 1999, 519–528

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mmolϪ1) at rt, methylene dichloride (10 ml mmolϪ1) was added
and the solution was cooled to Ϫ50 ЊC. Crude or partially puri-
fied (gel filtration on silica gel) 2,3-dihydro-4H-pyran-4-ones
(1 equiv.) obtained from the iodine()-promoted oxidations
described above were added, followed by NaBH4 or NaBD4 (2.4
equiv.). The temperature was slowly raised to ambient and the
reaction mixture was hydrolysed with methylene dichloride and
water (1:1). The aqueous layer was washed with methylene
dichloride (2 ×). The combined organic extracts were dried
(MgSO4), then evaporated in vacuo, and the crude product was
purified by column chromatography.
1. PhI(OH)OTs-promoted oxidation of compound 23 (1.45
g, 3.47 mmol) followed by reduction afforded 1,5-anhydro-
4,6-di-O-benzyl-2-deoxy--arabino-hex-1-enitol 27a and 1,5-
anhydro-4,6-di-O-benzyl-2-deoxy--ribo-hex-1-enitol 27b (0.43
g, 1.32 mmol; 38%; 1:1.5) after separation by column
chromatography on silica gel (petroleum spirit–ethyl acetate
10:1).
(t, CH2Ph), 70.0 (d, 5-C) and 17.6 (q, 6-C) (Found: C, 70.95;
H, 7.4. C13H16O3 requires C, 70.89; H, 7.32%).
2nd fraction: compound 29b9: mp 92 ЊC (crystals); [α]D22 Ϫ206
(c 0.89, CHCl3); δH(400 MHz; CDCl3) 7.36 (5H, m, Ph), 6.40
(1H, d, J 6.0, 1-H), 4.92 (1H, dd, J 5.2 and 6.0, 2-H), 4.70 and
4.62 (2H, 2 d, J 12.0, CH2Ph), 4.20 (1H, m, 3-H), 4.05 (1H, dq,
J 6.4 and 9.6, 5-H), 3.36 (1H, dd, J 3.6 and 9.6, 4-H), 2.46 (1H,
br, OH) and 1.36 (3H, d, J 6.4, 6-H3); δC(100 MHz; CDCl3)
146.5 (d, 1-C), 137.4 (s, Ph), 128.6, 128.2 and 128.0 (d, Ph),
100.3 (d, 2-C), 79.1 (d, 3-C), 72.1 (t, CH2Ph), 69.1 (d, 4-C), 59.7
(d, 3-C) and 17.3 (q, 6-C) (Found: C, 70.80; H, 7.81%).
4. PhI(OH)OTs-promoted oxidation of compound 26 (2.0 g,
6.45 mmol) followed by reduction afforded 1,5-anhydro-4-O-
benzyl-2,6-dideoxy--lyxo-hex-1-enitol 30a (0.84 g, 59%) after
purification by column chromatography on silica gel (petroleum
spirit–ethyl acetate 10:1). Compound 30a7: mp 73 ЊC (crystals
from hexane); [α]D20 ϩ36.2 (c 1.02, acetone); δH(400 MHz; C6D6)
7.4–7.2 (5H, m, Ph), 6.21 (1H, dd, J 1.2 and 6.4, 1-H), 4.64 (1H,
dd, J 4.0 and 6.4, 2-H), 4.42 and 4.37 (2H, 2 d, J 11.6, CH2Ph),
4.17 (2H, m, 3- and 4-H), 3.65 (1H, q, J 6.8, 5-H), 3.10 (1H, s,
OH) and 1.17 (3H, d, J 6.8, 6-H3); δC(100 MHz; C6D6) 144.5 (d,
1-C), 137.8 (s, Ph), 128.2–127.5 (d, Ph), 102.7 (d, 2-C), 75.9 and
75.3 (d, 3- and 4-C), 72.8 (d, 5-C), 71.9 (t, CH2Ph) and 16.7
(q, 6-C) (Found: C, 70.9; H, 7.2. Calc. for C13H16O3: C, 70.89;
H, 7.32%).
1st fraction: compound 27a: mp 47 ЊC (crystals); [α]D19 ϩ44.8 (c
1.0, CHCl3); δH(400 MHz; CDCl3) 7.30 (10H, m, Ph), 6.43 (1H,
dd, J 1.6 and 6.0, 1-H), 4.73 (1H, dd, J 2.4 and 6.0, 2-H), 4.79,
4.69, 4.64 and 4.58 (4H, 4 d, J 11.6, CH2Ph), 4.34 (1H, dt, J 2.4
and 6.5, 3-H), 3.99 (1H, ddd, J 3.0, 3.6 and 9.1, 5-H), 3.83
(1H, dd, J 3.6 and 10.2, 6-HA), 3.80 (1H, dd, J 3.0 and 10.2,
6-HB), 3.68 (1H, dd, J 6.5 and 9.1, 4-H) and 1.87 (1H, d, J 6.2,
OH); δC(100 MHz; CDCl3) 144.6 (d, 2-C), 138.3 and 137.8 (s,
Ph), 128.6–127.8 (d, Ph), 102.7 (d, 1-C), 77.3 and 76.3 (d, 3- and
4-C), 73.8 and 73.7 (t, 2 × CH2Ph), 69.1 (d, 5-C) and 68.9 (t, 6-
C) (Found: C, 73.6; H, 6.55. C20H22O4 requires C, 73.60; H,
6.79%).
2nd fraction: compound 27b: oil; δH(400 MHz; CDCl3) 7.30
(10H, m, Ph), 6.47 (1H, d, J 6.0, 1-H), 4.92 (1H, dd, J 5.4 and
6.0, 2-H), 4.65, 4.64, 4.60 and 4.58 (4H, 4 d, J 11.8, CH2Ph),
4.18 (1H, dd, J 4.0 and 5.4, 3-H), 4.08 (1H, dt, J 3.0 and 10.2,
5-H), 3.81 (3H, m, 4-H and 6-H2) and 3.50 (1H, s, OH); δC(100
MHz; CDCl3) 146.6 (d, 1-C), 137.9 and 137.5 (s, Ph), 128.6–
127.6 (d, Ph), 100.1 (d, 2-C), 74.1 and 70.7 (d, 3- and 4-C), 73.6
and 72.2 (t, 2 × CH2Ph), 68.6 (t, 6-C) and 59.9 (d, 5-C) (Found:
C, 73.1; H, 6.9%).
2. PhI(OH)OTs-promoted oxidation of compound 24 (2.62
g, 6.3 mmol) followed by reduction afforded 1,5-anhydro-4,6-
di-O-benzyl-2-deoxy--lyxo-hex-1-enitol 28a (1.17 g, 57%)
after purification by column chromatography on silica gel
(petroleum spirit–ethyl acetate 10:1), mp 66 ЊC (crystals); [α]D21
Ϫ15 (c 1.0, CHCl3) {lit.,39 mp 65 ЊC; [α]D ϩ12.06 (c 0.6,
CHCl3)}; δH(400 MHz; CDCl3) 7.30 (10H, m, Ph), 6.35 (1H,
dd, J 1.6 and 6.0, 1-H), 4.74 (1H, ddd, J 1.4, 3.0 and 6.0, 2-H),
4.72, 4.66, 4.75 and 4.47 (4H, 4 d, J 12.0, CH2Ph), 4.32 (1H,
dddd, J 1.6, 3.0, 4.6 and 9.2, 3-H), 4.18 (1H, ddd, J 2.6, 5.6 and
6.6, 5-H), 3.90 (1H, ddd, J 1.0, 2.6 and 4.6, 4-H), 3.78 (1H, dd,
J 6.6 and 9.8, 6-HA), 3.63 (1H, dd, J 5.6 and 9.8, 1H, 6-HB) and
2.35 (1H, d, J 9.2, OH); δC(100 MHz; CDCl3) 144.3 (d, 1-C),
137.7 (s, Ph), 128.6–127.8 (d, Ph), 102.9 (d, 2-C), 75.1, 73. 1 (d,
3- and 4-C), 74.3 and 73.5 (t, 2 × CH2Ph), 68.1 (t, 6-C) and 62.8
(d, 5-C) (Found: C, 73.4; H, 6.7. C20H22O4 requires C, 73.60; H,
6.79%).
3. PhI(OH)OTs-promoted oxidation of compound 25 (1.0
g, 3.2 mmol) followed by reduction afforded 1,5-anhydro-
4-O-benzyl-2,6-dideoxy--arabino-hex-1-enitol 29a and 1,5-
anhydro-4-O-benzyl-2,6-dideoxy--ribo-hex-1-enitol 29b (0.34
g, 47%) in a 1.1:1 ratio after separation by column chrom-
atography on silica gel (petroleum spirit–ethyl acetate 10:1).
1st fraction: compound 29a: mp 108 ЊC (crystals); [α]D22 Ϫ33.7
(c 1.29, CHCl3); δH(400 MHz; CDCl3) 7.36 (5H, m, Ph), 6.32
(1H, dd, J 1.6 and 6.0, 1-H), 4.85 and 4.79 (2H, 2 d, J 12.0,
CH2Ph), 4.70 (1H, dd, J 2.4 and 6.0, 2-H), 4.36 (1H, m, 3-H),
3.91 (1H, dq, J 6.4 and 9.6, 5-H), 3.28 (1H, dd, J 7.0 and 9.6,
4-H), 1.68 (1H, d, J 5.6, OH) and 1.41 (3H, d, J 6.4, 6-H3);
δC(100 MHz; CDCl3) 144.6 (d, 1-C), 138.3 (s, Ph), 128.6–128.0
(d, Ph), 103.1 (d, C-2), 82.4 and 74.1 (d, 3- and 4-C), 74.3
5. Preparation of 1,5-anhydro-4-O-(tert-butyldimethylsilyl)-
2,6-dideoxy-L-arabino-hex-1-enitol 31a and 1,5-anhydro-4-O-
(tert-butyldimethylsilyl)-2,6-dideoxy-L-ribo-hex-1-enitol
31b.
Glycal 7 (0.62 g, 1.74 mmol) was oxidized under the conditions
described above and iodobenzene was removed by filtration on
silica gel (petroleum spirit). (Due to the volatility of compound
13, all solvents have to be evaporated with care.) Crude enone
1312 was dissolved in diethyl ether (35 ml) under nitrogen, the
solution was cooled to Ϫ70 ЊC and was treated with DIBAL-H
in n-hexane (1M; 1.36 ml, 1.36 mmol). After 1 h, water (0.3 ml)
was added and stirring was continued for another 15 min at rt.
After filtration through a pad of Celite, the filtrate was concen-
trated under reduced pressure and finally traces of water were
removed by co-distillation with toluene. Purification by column
chromatography (petroleum spirit–ethyl acetate 15:1) afforded
the title compounds 31a and 31b (275 mg, 65%) in a 2:1 ratio.
1st fraction: compound 31b (contaminated with ~10% of
isomer 31a): oil; δH(400 MHz; C6D6) 6.42 (1H, d, J 5.8, 1-H),
5.03 (1H, t, J 5.8, 2-H), 4.21 (1H, dq, J 6.2 and 9.6, 5-H), 4.02
(1H, dd, J 4.0 and 5.8, 3-H), 3.55 (1H, dd, J 4.0 and 9.6, 4-H),
t
2.63 (1H, br, OH), 1.35 (3H, d, J 6.2, 6-H3), 0.94 (9H, s, Bu)
and 0.02 and 0.0 [6H, 2 s, Si(CH3)2]; δC(100 MHz; C6D6) 146.3
(d, 1-C), 101.6 (d, 2-C), 74.1, 70.4 and 63.1 (d, 3-, 4- and 5-C),
25.8 (q, tBu), 18.1 (s, tBu), 17.7 (q, 6-C) and Ϫ4.6 and Ϫ4.9 (q,
SiMe2).
2nd fraction: compound 31a: oil; [α]D22 Ϫ17.9 (c 2.15, CHCl3)
{lit.,8 [α]D25 Ϫ10.0 (c 1.0, CHCl3)}; δH(400 MHz; C6D6) 6.15 (1H,
dd, J 1.2 and 6.0, 1-H), 4.42 (1H, dd, J 2.4 and 6.0, 2-H), 3.99
(1H, m, 3-H), 3.69 (1H, dq, J 6.4 and 9.6, 5-H), 3.31 (1H, dd,
J 7.6 and 9.6, 4-H), 1.30 (3H, d, J 6.4, 6-H3), 0.96 (10H, s, tBu
and OH) and 0.18 and 0.06 [6H, 2 s, Si(CH3)2]; δC(100 MHz;
C6D6) 144.7 (d, 1-C), 104.2 (d, 2-C), 77.2, 75.7 and 71.2 (d,
t
3-, 4-C and 5-C), 26.0 (q, Bu), 18.5 (tBu), 17.2 (q, 6-C) and
Ϫ3.1 and Ϫ3.5 (q, SiMe2) (Found: C, 58.7; H, 10.0. Calc. for
C12H24O3Si: C, 58.97; H, 9.90%).
For further characterisation, the hydroxy group in compound
31a (0.23 mmol) was acylated under standard conditions.40
Column chromatography on silica gel (petroleum spirit–ethyl
acetate 50:1) afforded 3-O-acetyl-1,5-anhydro-4-O-(tert-butyl-
dimethylsilyl)-2,6-dideoxy--arabino-hex-1-enitol 35 (60 mg,
92%) as an oil; [α]D22 ϩ68.9 (c 2.02, CHCl3) {lit.,8 [α]D25 ϩ62 (c 1.0,
CHCl3)}; δH(400 MHz; CDCl3) 6.36 (1H, dd, J 0.8 and 6.0,
1-H), 5.19 (1H, ddd, J 0.8, 2.2 and 7.0, 3-H), 4.73 (1H, dd, J 2.2
and 6.0, 2-H), 3.88 (1H, dq, J 6.4 and 9.6, 5-H), 3.69 (1H, dd,
J. Chem. Soc., Perkin Trans. 1, 1999, 519–528
525

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J 7.0 and 9.6, 4-H), 2.09 (3H, s, OAc), 1.35 (3H, d, J 6.4, 6-H3),
0.90 (9H, s, Bu) and 0.13 and 0.10 [6H, 2 s, Si(CH3)2]; δC(100
shaken for two days (280 rpm) and filtered through a pad of
t
Celite. Concentration under reduced pressure afforded the title
compound (123 mg, 67%) which was directly used for the next
step. A small sample was purified by flash column chrom-
atography (petroleum spirit–ethyl acetate 5:1); δH(200 MHz;
C6D6) 6.42 (1H, dd, J 1.4 and 6.0, 1-H), 5.22 (1H, ddd, J 1.4, 2.6
and 6.6, 3-H), 4.68 (1H, dd, J 2.6 and 6.0, 2-H), 3.91 (1H, dq,
J 6.4 and 9.6, 5-H), 3.61 (1H, ddd, J 2.6, 6.6 and 9.6, 4-H), 3.28
(1H, br d, J 2.6, OH), 2.11 (3H, s, OAc) and 1.40 (3H, d, J 6.4,
6-H3); δC(50 MHz; C6D6) 171.9 (s, OAc), 146.3 (d, 1-C), 99.0 (d,
2-C), 74.9, 74.0 and 72.6 (d, 3-, 4- and 5-C) and 20.3 and 16.9
(q, 6-C and OAc).
MHz; CDCl3) 170.8 (s, OAc), 145.9 (d, 1-C), 99.7 (d, 2-C), 75.5,
t
t
73.8 and 72.4 (3-, 4- and 5-C), 25.8 (q, Bu), 21.4 (s, Bu), 18.1
and 17.8 (q, 6-C and OAc) and Ϫ4.1 and Ϫ4.5 (q, SiMe2).
6. Preparation of 1,5-anhydro-4-O-[3,4-bis-O-(tert-butyl-
diphenylsilyl)-6-deoxy-2-phenylseleno-â-L-gluco-pyranosyl]-L-
arabino-hex-1-enitol 32a and 1,5-anhydro-4-O-[3,4-bis-O-(tert-
butyldiphenylsilyl)-6-deoxy-2-phenylseleno-â-L-gluco-pyrano-
syl]-L-ribo-hex-1-enitol 32b. To a solution of enone 15 (130 mg,
0.145 mmol) in THF–methanol (1:1; 9 ml) at rt were added
CeCl3ؒ7 H2O (59 mg, 0.16 mmol) and NaBH4 (8 mg, 0.2 mmol).
After 10 min the reaction mixture was hydrolysed with methyl-
ene dichloride and water (1:1). The aqueous layer was washed
with methylene dichloride (2 ×). The combined organic extracts
were dried (MgSO4), then evaporated in vacuo, and the crude
product was purified by column chromatography (petroleum
spirit–ethyl acetate 20:1).
The crude product was silylated under standard conditions40
to afford 3-O-acetyl-1,5-anhydro-4-O-(tert-butyldimethylsilyl)-
2,6-dideoxy--arabino-hex-1-enitol 35 (183 mg, 89%). Physical
and spectroscopic data are given above.
General procedure for Mitsunobu reactions of 3-O-unblocked
glycals
1st fraction: compound 32a (77 mg, 60%); mp 49 ЊC (crys-
tals); [α]D22.5 ϩ24.8 (c 1.005, CHCl3); δH(400 MHz; C6D6) 7.79–
7.57 and 7.40–6.90 (25H, m, ArH), 6.22 (1H, dd, J 1.6 and 6.0,
1-H), 5.50 (1H, d, J 6.8, 1Ј-H), 5.10 (1H, d, J 4.0, 4Ј-H), 5.07
(1H, dd, J 2.0 and 6.0, 2-H), 4.77 (1H, br, OH), 4.66 (1H, ddd,
1H, J 1.6, 2.0 and 7.2, 3-H), 3.89 (1H, dq, J 6.4 and 10.0, 5-H),
3.88–3.80 (3H, m, 2Ј-, 3Ј- and 5Ј-H), 3.64 (1H, dd, J 7.2 and
10.0, 4-H), 1.48 (3H, d, J 6.4, 6-H3), 1.20 and 1.07 (18H, 2 s,
2 × tBu) and 1.00 (3H, d, J 6.8, 6Ј-H3); δC(100 MHz; C6D6)
143.3 (d, C-1), 136.4, 136.3, 136.2, 136.1, 130.9, 130.4, 130.2,
130.1, 129.1, 128.2, 127.9 and 126.4 (d, Ph), 133.6, 133.4, 133.3,
133.3 and 133.2 (s, Ph), 106.0 (d, 1Ј-C), 103.6 (d, 2-C), 85.8
(d, 4-C), 79.5 (d, 5-C), 79.0 (d, 4Ј-C), 73.7 and 73.4 (d, 3Ј- and
5Ј-C), 68.6 (d, 3-C), 48.6 (d, 2Ј-C), 27.0 and 26.9 (q, 2 × tBu),
19.8 (q, 6Ј-C), 19.3 and 19.1 (s, 2 × tBu) and 17.8 (q, 6-C).
2nd fraction: compound 32b (32 mg, 25%) (oil); [α]D22 Ϫ11.7
(c 0.535, CHCl3); δH(400 MHz; C6D6) 7.86–7.65 and 7.41–7.13
(25H, m, ArH), 6.40 (1H, d, J 6.0, 1-H), 5.62 (1H, d, J 6.8,
1Ј-H), 5.13 (1H, d, J 3.6, 4Ј-H), 5.04 (1H, dd, J 4.8 and 6.0,
2-H), 4.49 (1H, br dd, J 4.0 and 4.8, 3-H), 4.37 (1H, dq, J 6.4
and 10.0, 5-H), 3.98–3.88 (3H, m, 2Ј-, 3Ј- and 5Ј-H), 3.72 (1H,
br, OH), 3.64 (1H, dd, J 4.0 and 10.0, 4-H), 1.28 and 1.13 (18H,
2 s, 2 × tBu), 1.24 (3H, d, J 6.4, 6-H3) and 1.03 (3H, d, J 6.8,
6Ј-H3); δC(100 MHz; C6D6) 146.1 (d, 1-C), 136.5, 136.4, 136.3,
136.2, 131.5, 130.4, 130.2, 130.1, 129.2, 127.9 and 127.6 (d, Ph),
133.7, 133.5, 132.3, 133.2 and 132.7 (s, Ph), 106.3 (d, 1Ј-C),
101.3 (d, 2-C), 83.3 (d, 4-C), 79.2 and 73.9 (d, 3Ј- and 5Ј-C),
78.9 (d, 4Ј-C), 69.4 (d, 5-C), 62.3 (d, 3-C), 48.8 (d, 2Ј-C), 27.4
and 27.1 (q, 2 × tBu), 20.2 (q, 6Ј-C), 19.3 and 19.2 (s, 2 × tBu)
and 17.4 (q, 6-C) (Found: C, 67.5; H, 7.0. C50H60O6Si2Se
requires C, 67.31; H, 6.78%).
To a solution of the glycal (1 equiv.) under N2 in dry toluene (20
ml mmolϪ1) at 0 ЊC were added triphenylphosphine (2.67 equiv.)
and benzoic acid (2.67 equiv.). Diethyl azodicarboxylate
(DEAD; 2.71 equiv.) was dissolved in dry toluene (1.8 ml) and
the solution was added dropwise to the reaction mixture. The
resulting solution was allowed to warm to rt. After 20 h, a
mixture of methylene dichloride and aq. NaHCO3 (10 ml
mmolϪ1; 1:1) was added and the phases were separated.
The aqueous layer was washed with methylene dichloride (2 ×)
and the combined organic extracts were dried (MgSO4), and
concentrated under reduced pressure.
1,5-Anhydro-3-O-benzoyl-4,6-di-O-benzyl-2-deoxy-D-xylo-
hex-1-enitol 40 and 1-O-benzoyl-4,6-di-O-benzyl-2,3-dideoxy-á-
D-threo-hex-2-enopyranose 41. Compound 28a (300 mg, 0.92
mmol) was used to prepare the title compounds 40 and 41 via
the general procedure described above. The crude product was
subjected to column chromatography on silica gel (petroleum
spirit–ethyl acetate 10:1) to afford 40 (108 mg, 27.2%) and
α-pyranose 41 (122 mg, 30.8%). The β-anomer 41 was detect-
able only in the 1H NMR spectrum of the crude product.
1st fraction: compound 40, oil; δH(400 MHz; C6D6) 8.1–6.9
(15H, m, Ph), 6.50 (1H, d, J 6.0, 1-H), 5.60 (1H, dd, J 1.8 and
5.2, 3-H), 4.93 (1H, ddd, J 1.6, 5.2 and 6.0, 2-H), 4.66, 4.43, 4.27
and 4.22 (4H, 4 d, J 11.6, CH2Ph), 4.34 (1H, br t, J 6.2, 5-H),
3.87 (1H, dd, J 1.8 and 1.2, 4-H), 3.82 and 3.68 (2H, 2 dd, J 6.2
and 9.6 and J 6.2 and 9.6, 6-HA and -HB); δC(100 MHz; C6D6)
165.7 (s, OBz) 148.6 (d, C-1), 138.6, 133.1 (s, Ph), 130.8–127.8
(d, Ph), 97.1 (d, 2-C), 73.7 and 73.1 (d, 3- and 4-C), 73.5 and
72.2 (t, 2 × CH2Ph), 69.2 (t, 6-C) and 63.8 (d, 5-C) (Found: C,
75.6; H, 6.1. C27H26O5 requires C, 75.33; H, 6.09%).
7. PhI(OH)OTs-promoted oxidation of compound 36 (414
mg, 1.4 mmol) afforded enone 37 (183 mg, 64%), which gave
1,5-anhydro-4-O-benzyl-2-deoxy--erythro-pent-1-enitol 38 (162
mg, 88%) after reduction and purification by column chrom-
atography on silica gel (petroleum spirit–ethyl acetate
6:1). Under identical conditions using NaBD4 enone 37 was
reduced to 1,5-anhydro-4-O-benzyl-2-deoxy--erythro-[3-2H]-
pent-1-enitol 39.
2nd fraction: α-pyranose 41; mp 53 ЊC (crystals); [α]D20 Ϫ177.6
(c 1, CHCl3); δH(400 MHz; C6D6) 8.1–6.9 (15H, m, Ph), 6.79
(1H, d, J 3.0, 1-H), 5.89 (1H, dd, J 10.0 and 6.2, 3-H), 5.75 (1H,
dd, J 10.0 and 3.0, 2-H), 4.48 (1H, m, H-5), 4.46, 4.36, 4.34 and
4.27 (4H, 4 d, J 11.6, CH2Ph), 3.95 (1H, dd, J 9.6 and 7.2, 6-H),
3.74 (1H, dd, J 9.6 and 6.4, 6Ј-H3) and 3.65 (1H, dd, J 6.2 and
2.4, 4-H); δC(100 MHz; C6D6) 165.3 (s, OBz), 139.2, 138.9 and
133.1 (s, Ph), 130.8 and 130.1–127.6 (d, 2- and 3-C, Ph), 89.5 (d,
1-C), 73.5 and 71.0 (t, 2 × CH2Ph), 72.4 and 69.2, (d, 4- and
5-C), 67.0 (t, 6-C) (Found: C, 75.59; H, 6.13. C27H26O5 requires
C, 75.10; H, 6.19%).
Compound 38: mp 52 ЊC (crystals); [α]D20 Ϫ114.6 (c 1, CHCl3);
for compound 39; mp 53 ЊC; [α]D23 Ϫ115.9 (c 1, CHCl3); δH(400
MHz; CDCl3) 7.36 (5H, m, Ph), 6.41 (1H, d, J 6.0, 1-H), 4.88
(1H, dd, J 5.0 and 6.4, 2-H), 4.70 and 4.66 (2H, 2 d, J 12.0,
CH2Ph), 4.24 (1H, m, 3-H), 3.93 (2H, br d, J 6.4, 5-H2), 3.73
(1H, ddd, J 4.0, 6.0 and 6.8, 4-H) and 2.47 (1H, br d, J 3.0, OH)
(Found: C, 70.0; H, 6.6. C12H14O3 requires C, 69.88; H, 6.84%).
1,5-Anhydro-3-O-benzoyl-4-O-benzyl-2,6-dideoxy-L-xylo-
hex-1-enitol 43. Compound 30a (121 mg, 0.55 mmol) was used
to prepare the title compound 43 (112 mg, 63%) via the general
procedure described above. Column chromatography on silica
gel (petroleum spirit–ethyl acetate 10:1) afforded an oil; δH(400
MHz; CDCl3) 7.5–7.2 (10H, m, Ph), 6.69 (1H, d, J 6.0, 1-H),
5.46 (1H, dd, J 2.0 and 5.2, 3-H), 5.00 (1H, ddd, J 2.0, 5.2 and
1,5-Anhydro-3-O-acetyl-2,6-dideoxy-L-arabino-hex-1-enitol3d 34
A suspension of -rhamnal 33 (139 mg, 1.07 mmol) and lipase
PS (0.2 g) in vinyl acetate–ethyl actetate (10 ml; 1:1) at rt was
526
J. Chem. Soc., Perkin Trans. 1, 1999, 519–528

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D. M. Armistead, F. E. Wincott, H. G. Selnick and R. Hungate,
J. Am. Chem. Soc., 1989, 111, 2967.
4 S. J. Danishefsky and M. T. Bilodeau, Angew. Chem., 1996, 108,
1482; Angew. Chem., Int. Ed. Engl., 1996, 35, 1380.
6.0, 2-H), 4.88 and 4.67 (2H, 2 d, J 12.0, CH2Ph), 4.06 (1H, dq,
J 0.8 and 6.6, 5-H), 3.50 (1H, br s, 4-H), 1.30 (3H, d, J 6.6,
6-H3); δC(100 MHz; CDCl3) 165.8 (s, OBz), 148.8 (d, 1-C),
137.6 (s, Ph), 133.2–127.9 (d, Ph), 96.5 (d, 2-C), 72.0 (t, CH2Ph),
74.6 and 70.3 (d, 3- and 4-C), 64.1 (d, 5-C) and 16.3 (q, 6-C)
(Found: C, 73.9; H, 6.1. C20H20O4 requires C, 74.06; H, 6.21%).
For further elucidation of the configuration at C-3 in product
43, the hydroxy group in compound 30a (0.55 mmol) was
benzoylated under standard conditions40 to give, after column
chromatography (petroleum spirit–ethyl acetate 8:1), 1,5-
anhydro-3-O-benzoyl-4-O-benzyl-2,6-dideoxy--lyxo-hex-1-
enitol 42 (53 mg, 30%) as an oil; [α]D20 ϩ109 (c 1.22, CHCl3);
δH(400 MHz; CDCl3) 7.6–7.2 (10H, m, Ph), 6.47 (1H, dd, J 6.2
and 1.2, 1-H), 5.78 (1H, dddd, J 4.6, 3.2, 1.6 and 1.0, 3-H), 4.85
(1H, ddd, J 6.2, 3.2, 0.8, 2-H), 4.81 and 4.58 (2H, 2 d, J 12.4,
CH2Ph), 4.25 (1H, ddq, J 6.6, 2.8 and 1.0, 5-H), 3.96 (1H, ddd,
J 4.6, 2.8 and 0.8, 4-H) and 1.37 (3H, d, J 6.6, 6-H); δC(100
MHz; CDCl3) 166.5 (s, OBz), 146.0 (d, 1-C), 137.9 (Ph), 133.4–
128.0 (d, Ph), 98.0 (d, 2-C), 73.5 (t, CH2Ph), 72.8 and 72.3 (d,
3- and 4-C), 66.4 (d, 5-C) and 15.6 (q, 6-C) (Found: C, 73.8; H,
6.3. C20H20O4 requires C, 74.06; H, 6.21%).
5 A. Kirschning, A. Bechthold and J. Rohr, Top. Curr. Chem., 1997,
188, 1; K. Toshima and K. Tatsuta, Chem. Rev., 1993, 93, 1503.
6 S. Bouhroum and P. J. A. Vottero, Tetrahedron Lett., 1990, 31, 7441;
H. B. Mereyala and V. R. Kulkarni, Carbohydr. Res., 1989, 187, 154.
7 W. Klaffke, D. Springer and J. Thiem, Carbohydr. Res., 1991, 216,
475; J. Thiem and W. Klaffke, J. Org. Chem., 1989, 54, 2006.
8 S. Köpper, I. Lundt, C. Pedersen and J. Thiem, Liebigs Ann. Chem.,
1987, 531.
9 D. Horton, W. Priebe and O. Varela, Carbohydr. Res., 1985, 144, 325.
10 T. Henkel, J. Rohr, J. Beale and L. Schwenen, J. Antibiot. (Tokyo),
1990, 43, 492; J. S. Weber, C. Zolke, J. Rohr and J. Beale, J. Org.
Chem., 1994, 59, 401.
11 Recently, the synthesis of the hexasaccharide fragment has been
accomplished by: Y. Guo and G. A. Sulikowski, J. Am. Chem. Soc.,
1998, 120, 1392.
12 A. Kirschning, J. Org. Chem., 1995, 60, 1228.
13 A. Kirschning, Eur. J. Org. Chem., 1998, 2276.
14 J. Harders, A. Garming, A. Jung, V. Kaiser, H. Monenschein,
M. Ries, L. Rose, K.-U. Schöning, T. Weber and A. Kirschning,
Liebigs Ann./Recueil., 1997, 2125; A. Kirschning, Liebigs Ann.,
1995, 2053.
15 A. Kirschning and J. Harders, Tetrahedron, 1997, 53, 7867; Synlett,
1996, 772; R. Benhaddou, S. Czernecki and G. Ville, J. Org. Chem.,
1992, 57, 4612; T. E. Goodwin, N. M. Rothman, K. L. Salazar and
L. S. Shannon, J. Org. Chem., 1992, 57, 2469; M. Takiya, M. Ishii,
K. Shibata, Y. Mikami and O. Mitsunobu, Chem. Lett., 1992, 1917;
T. Kaufmann, W. Klaffke, C. Philip and J. Thiem, Carbohydr. Res.,
1990, 207, 33; V. Bellosta and S. Czernecki, Carbohydr. Res., 1987,
171, 279.
1,5-Anhydro-3-azido-4-O-benzyl-2,3,6-trideoxy-L-xylo-hex-1-
enitol 44
To a solution of alcohol 30a (100 mg, 0.45 mmol) and LiN3
(151 mg, 2.97 mmol) in dry DMF (3 ml) at 45 ЊC was added
CBr4 (280 mg, 0.86 mmol) in one portion. After a while, a yellow
solution resulted and PPh3 (225 mg, 0.86 mmol) was added in
small portions with external cooling. After the addition was
complete, the orange solution was stirred for 12 h at rt, and
hydrolysed in an ice-cold mixture of NH4Claq–CH2Cl2. Extrac-
tion of the aqueous phase with CH2Cl2 (3 ×) followed by wash-
ing of the combined organic extracts with brine, drying
(MgSO4), and concentration in vacuo gave a brown oil (930 mg).
Purification by flash chromatography on silica gel (petroleum
spirit–ethyl acetate 20:1) afforded the title compound 44 (17 mg,
15%) as an oil, νmax/cmϪ1 2080; δH(400 MHz; C6D6) 7.20–7.0
(5H, m, Ph), 6.36 (1H, d, J 6.4, 1-H), 4.44 (1H, ddd, J 6.4, 5.2
and 1.4, 2-H), 4.23 and 4.04 (2H, 2 d, J 12.0, CH2Ph), 3.78 (1H,
dq, J 6.4 and 2.0, 5-H), 3.54 (1H, dd, J 5.2 and 2.0, 3-H), 3.09
(1H, ddd, J 2.0, 2.0 and 1.4, 4-H), 1.11 (3H, d, J 6.4, 6-H3);
δC(100 MHz; CDCl3) 148.2 (d, 1-C), 133.2 (s, Ph), 128.0–127.8
(d, Ph), 94.3 (d, 2-C), 76.5 and 70.2 (d, 4- and 5-C), 72.3 (t,
CH2Ph), 53.4 (d, 3-C) and 15.9 (q, 6-C) (Found: C, 63.8; H, 6.0.
C13H15N3O2 requires C, 63.66; H, 6.16; N, 17.13%).
16 A. Kirschning, J. Prakt. Chem., 1998, 340, 184.
17 G. F. Koser and R. H. Wettach, J. Org. Chem., 1980, 45, 4988.
18 V. V. Zhdankin, R. Tykwinski, B. L. Williamson, P. J. Stang and
N. S. Zefirov, Tetrahedron Lett., 1991, 32, 733.
19 H. Saltzman and J. G. Sharefkin, Org. Synth., 1963, 43, 60.
20 Due to the two-phase character of the reaction, severe explosions
may occur when PhI(N3)2 is generated from iodosobenzene (PhIO)n.
In our experience, this problem can be avoided when (diacetoxy-
iodo)benzene is employed instead.
21 M. Perez and J.-M. Beau, Tetrahedron Lett., 1989, 30, 75.
22 A. Kirschning, S. Domann, G. Dräger and L. Rose, Synlett, 1995,
767; P. Magnus and M. B. Roe, Tetrahedron Lett., 1996, 37, 303.
23 J. Ehrenfreund and E. Zbiral, Liebigs Ann. Chem., 1973, 290;
Tetrahedron, 1972, 28, 1697.
24 P. Magnus, J. Lacour, P. A. Evans, M. B. Roe and C. Hulme, J. Am.
Chem. Soc., 1996, 118, 3406; P. Magnus and J. Lacour, J. Am. Chem.
Soc., 1992, 114, 3993; 767.
25 J.-L. Luche, J. Am. Chem. Soc., 1978, 100, 2226.
26 For other examples of the selective reduction of 2,3-dihydro-4H-
pyran-4-ones see: K. J. Hale and S. Manaviazar, Tetrahedron
Lett., 1994, 35, 8873; T. Nakata, H. Matsukura, D. Jian and
H. Nagashima, Tetrahedron Lett., 1994, 35, 8229; A. Golebiowski
and J. Jurczak, Tetrahedron, 1991, 47, 1045; S. Danishefsky, S.
Kobayashi and J. F. Kerwin, Jr., J. Org. Chem., 1982, 47, 1883.
27 The Luche reduction did also not work with other 4-O-silylated
glycals such as compounds 11 or 14. Herscovici et al. applied the
Luche reduction to similar enones, quoting much higher selectivities
for threo-configured pyranones. However, we were unable to repeat
their results: J. Herscovici, R. Montserret and K. Astonakis,
Carbohydr. Res., 1988, 176, 219. When the substituent at C-4
(carbohydrate numbering) is missing, the Luche reduction is
governed by the substituent at C-5, exclusively, leading to the
corresponding threo-products: D. Meng, P. Bertinato, A. Balog,
D.-S. Su, T. Kamenecka, E. J. Sorensen and S. J. Danishefsky, J. Am.
Chem. Soc., 1997, 119, 10073 and ref. 26.
Acknowledgements
The authors are grateful to the Deutsche Forschungsgemein-
schaft (grant Ki 379/4-1) and the Fonds der Chemischen
Industrie for financial support. We also thank S. Domann,
A. Eigenbrot, J. Harders and J. Namyslo, Clausthal, for provid-
ing various starting materials.
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