A SuperQuat glycolate aldol approach to the asymmetric synthesis of hexose monosaccharides

Article abstract of DOI:10.1039/b415943h

A stereoselective two-carbon homologation protocol has been developed and applied to the asymmetric synthesis of the hexose monosaccharides D-galactose, D-fucose, D-idose, D-6-deoxyidose, D-talose and D-6-deoxytalose.

Full text of DOI:10.1039/b415943h

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A R T I C L E
A SuperQuat glycolate aldol approach to the asymmetric synthesis
of hexose monosaccharides
Stephen G. Davies,* Rebecca L. Nicholson and Andrew D. Smith
The Department of Organic Chemistry, University of Oxford, Chemistry Research Laboratory,
Mansfield Road, Oxford, UK OX1 3TA. E-mail: steve.davies@chem.ox.ac.uk
Received 15th October 2004, Accepted 16th November 2004
First published as an Advance Article on the web 15th December 2004
A stereoselective two-carbon homologation protocol has been developed and applied to the asymmetric synthesis of
the hexose monosaccharides D-galactose, D-fucose, D-idose, D-6-deoxyidose, D-talose and D-6-deoxytalose.
with base promoted fragmentation (K2CO3/MeOH) giving
the highly functionalised and differentially protected a,b-
Introduction
Monosaccharides play an essential part in biochemical pro-
cesses. The traditional route for the preparation of bespoke
dihydroxyaldehydes 3 in good yield and with high diastereo-
selectivity.19 These aldehydes readily undergo double diastereos-
monosaccharides typically involves chemical manipulation of
elective aldol reactions with glycolate oxazolidinones (S)-1 and
(R)-1, an approach that has previously been used for the syn-
pre-existing functionality in common, readily available sugars.1
Although versatile, this approach is inherently limited to the
thesis of polyfunctionalised lactones with multiple contiguous
elaboration of common chiral pool building blocks and typically
stereocentres.20 The application of this double diastereoselective
involves laborious protecting group manipulation. As a result,
glycolate aldol methodology for the asymmetric synthesis of a
a wide variety of asymmetric approaches to these valuable syn-
range of monosaccharides is described herein, part of which has
thetic targets have been developed, including the use of asymmet-
been communicatedpreviously.21 In this approach, each iteration
ric Diels–Alder reactions,2 alkene dihydroxylation,3 chemoenzy-
of the aldol protocol accomplishes a stereoselective two-carbon
matic approaches,4 diastereoselective additions of nucleophiles
chain extension, furnishing hexose monosaccharides after two
to alkoxyaldehydes5 and chiral Lewis acid catalysis.6 Perhaps the
iterations of the aldol protocol (Fig. 1).
most general and widely recognised asymmetric approach to a
diverse range of monosaccharides is that employed by Sharpless
et al. for the synthesis of the L-hexoses, utilising asymmetric
epoxidation from a four-carbon starting unit.7
An alternative strategy for the synthesis of monosaccharides
and their derivatives is the use of the aldol reaction,8,9 as elegantly
demonstrated by Kobayashi et al. who have combined the cat-
alytic asymmetric aldol reaction with asymmetric dihydroxyla-
tion for the asymmetric synthesis of L-fucose.10 The asymmetric
aldol reaction is arguably the most reliable synthetic protocol
available to organic chemists, capable of the selective formation
of a C–C bond and two stereogenic centres in a predictable
fashion, with the relationship between enolate geometry and
product configuration generally well defined.11 The glycolate
aldol reaction represents an important sub-class of this powerful
transformation that allows the stereocontrolled formation of
1,2-diol units and has found numerous applications in total
synthesis and the preparation of natural product fragments.12
Fig. 1 Proposed iterative aldol protocol for the asymmetric synthesis
of monosaccharides.
Iterative aldol strategies have been used for the synthesis of
molecular fragments containing multiple stereogenic centres,13
notably for the synthesis of polypropionates,14 with only limited
examples of this approach being directed toward the synthesis of
monosaccharides.15 A recent advance within this area has been
reported by MacMillan et al., who have shown that proline
can catalyse the direct aldol reaction of a-hydroxyaldehydes
enantioselectively,16 and that subsequent tandem Mukaiyama
aldol–cyclisation catalysed by a Lewis acid allows the asymmet-
ric synthesis of a variety of monosaccharides.17
Previous investigations from this laboratory have demon-
strated that reduction of N-acyl 5,5-dimethyloxazolidinones
with DIBAL-H allows direct access to highly enantiomerically
enriched aldehydes.18 Our recent studies have also shown
that (S)-N-a-benzyloxyacetyl-4-benzyl-5,5-dimethyloxazolidin-
2-one 1 undergoes highly stereoselective boron-mediated syn-
glycolate aldol reactions, with O-silyl protection giving the
protected aldols 2. Subsequent DIBAL-H reduction fur-
nishes the corresponding N-1ꢀ-hydroxyalkyloxazolidin-2-ones,
Results and discussion
Asymmetric synthesis of protected tetroses
Initial investigations concentrated upon the asymmetric syn-
thesis of homochiral tetroses, following the reported procedure
from the known chiral glycolate oxazolidinone 1,22 with ac-
etaldehyde and benzyloxyacetaldehyde used as the two-carbon
chain extension components in this reaction manifold. Boron-
mediated aldol reactions with the (Z)-enolate of glycolate
oxazolidinone 1 with both benzyloxyacetaldehyde and acetalde-
hyde gave the expected syn-aldol products (4S,2ꢀS,3ꢀR)-5 and
(4S,2ꢀS,3ꢀR)-6 in 94% and >95% d.e. respectively, as shown by
1H NMR spectroscopic analysis of the crude reaction product
mixtures. Chromatographic purification on silica gave syn-
aldol products (4S,2ꢀS,3ꢀR)-5 (J 3.6 Hz) and (4S,2ꢀS,3ꢀR)-6
(J 3.3 Hz) as single diastereoisomers in 77% and 79% yield
3 4 8
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 4 8 – 3 5 9
T h i s j o u r n a l i s
T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 5
©

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respectively.23 To facilitate formation of the corresponding N-
1ꢀ-hydroxyoxazolidinones upon reduction,24 the single hydroxyl
functionalities within aldol produts 5 and 6 were protected as
their silyl ethers by treatment with TBDMSCl and imidazole,
giving O-silyl protected (4S,2ꢀS,3ꢀR)-7 and (4S,2ꢀS,3ꢀR)-8 in
90% and 85% yield respectively. DIBAL-H reduction of 7 and
8 gave the stable N-1ꢀ-hydroxy species25 9 and 10 as single
diastereoisomers in 94% and 96% isolated yield respectively.26
Fragmentation of N-1ꢀ-hydroxy species 9 and 10 to the required
tetrose was efficiently promoted by treatment with K2CO3
(1.4 eq.) in MeOH–H2O (4 : 1) for fifteen minutes, giving the 3-
O-silyloxy-D-threose derivative (2S,3R)-11 and the 3-O-silyloxy-
4-deoxythreose derivative (2S,3R)-12 in good yield and in >95%
d.e. in each case (Scheme 1).
11 and 12 furnished in each case the corresponding syn-aldol
products (4R,2ꢀR,3ꢀS,4ꢀR,5ꢀR)-13 and (4R,2ꢀR,3ꢀS,4ꢀR,5ꢀR)-14
in >95% d.e., with purification furnishing the desired aldol
products 13 and 14 as single diastereoisomers in 63% and 53%
yield respectively. Treatment of both 13 and 14 with TBAF in
AcOH–THF29 promoted desilylation of the C(4ꢀ)-O-TBDMS
protected hydroxyl group and concomitant in situ cyclisation,
giving the lactones (2R,3S,4R,5R)-15 and (2R,3S,4R,5R)-16 in
81% and 73% yield respectively (Scheme 2). Both lactones 15
1
and 16 showed well dispersed H NMR spectra, allowing the
relative configurations within them to be readily determined by
1H NMR NOE difference spectroscopy, with the absolute con-
figurations following from the known stereodirecting preference
of oxazolidinone auxiliaries in simple glycolate aldol reactions.
Scheme 1 Reagents and conditions: (i). Et2BOTf, iPr2NEt, benzyloxy-
acetaldehyde or acetaldehyde, THF, −78 ◦C; (ii). TBDMSCl, imidazole,
DMAP, DMF, rt; (iii). DIBAL-H, DCM, −78 ◦C; (iv). K2CO3 (1.4 eq.),
MeOH–H2O (4 : 1), rt.
Scheme 2 Reagents and conditions: (i). Et2BOTf, iPr2NEt, THF,
−78 ◦C; (ii). TBAF, AcOH, THF, rt.
Conclusive proof of the configurational assignment within
lactones 15 and 16 was achieved by their selective conversion to
the monosaccharides D-galactose and D-fucose respectively via
reduction and hydrogenolytic O-benzyl deprotection. Treatment
of lactone 15 with DIBAL in DCM and quenching of the reac-
tion with a minimal quantity of saturated aqueous ammonium
chloride solution allowed efficient reduction and product isola-
tion, giving 2,4,6-tris(O-benzyl)-D-galactose (2R,3S,4R,5R)-17
in 73% yield as a 67 : 33 mixture of anomers after purification by
chromatography. Further treatment of lactol 17 in an EtOAc–
EtOH mixture with palladium on carbon under a hydrogen
atmosphere furnished D-galactose (2R,3S,4R,5R)-18 in 74%
yield as a 67 : 33 mixture of anomers {[a]2D5 +79.8 (c 0.5,
H2O, 10 min), lit.30 [a]D25 +80.2 (c 0.5, H2O, 10 min)} after
recrystallisation. The 1H (400 MHz) spectroscopic properties of
synthetic 18 were identical to those of a commercially available
sample of D-galactose by mixed 1H (400 MHz) spectroscopy and
mixed melting point. Repetition of this protocol with lactone 16
similarly gave 2,4-bis(O-benzyl)-D-fucose (2R,3S,4R,5R)-19 as
an inseparable 67 : 33 mixture of anomers in 79% yield, with
debenzylation furnishing D-fucose 20 in 67% yield as a 67 : 33
mixture of anomers {[a]2D5 +38.4 (c 0.25, H2O, 10 min), lit.31
[a]2D5 +39.1 (c 0.25, H2O, 10 min)} after recrystallisation, with
Double diastereoselective iterative aldol reactions and
monosaccharide synthesis
(i) Matched aldol series – asymmetric synthesis of D-fucose
and D-galactose. Our previous investigations concerned with
the double diastereoselective27 aldol reaction of aldehydes such
as 11 and 12 with homochiral glycolate oxazolidinones (R)-
1 or (S)-1 have demonstrated that the (Z)-boron enolate of
the oxazolidinone 1 shows high levels of stereocontrol at both
the newly formed a- and b-stereogenic centres of the aldol
product.20 In contrast, aldehydes such as 11 and 12 show high
stereocontrol upon the formation of the b-stereogenic centre, but
only low control in the formation of the a-stereocentre. Upon
their mutual reaction, aldehydes such as 11 and 12 and the
boron enolates of homochiral glycolate oxazolidinones (R)-1 or
(S)-1 result in matched and mismatched combinations, giving a
matched syn-aldol configuration, and mismatched syn- and anti-
combinations with the products differing in configuration at the
b-centre of the aldol products.28 With these results in hand, it
was expected that the matched combination for the iteration of
the aldol protocol with homochiral tetrose derivatives 11 and 12
would be with the (Z)-boron enolate of the oxazolidinone (R)-1.
Thus, reaction of (R)-N-glycolate oxazolidinone 1 and tetroses
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 4 8 – 3 5 9
3 4 9

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1H (400 MHz) spectroscopic properties identical to those of a
commercial sample (Scheme 3).
76% yield, with subsequent DIBAL reduction affording an
inseparable 80 : 20 anomeric mixture of 2,4-bis(O-benzyl)-D-
6-deoxyidose 26 in 97% yield. Hydrogenation furnished D-6-
deoxyidose 27 as a mixture of pyranose and furanose species in
88% yield {[a]2D5 +12.0 (c 1.5, H2O, 24 h), lit.32 [a]2D5 +12.0 (c 2.67,
H2O)} after trituration with Et2O (Scheme 5).
Scheme 3 Reagents and conditions: (i). DIBAL, CH2Cl2, −78 ◦C; (ii).
Pd/C, EtOH–EtOAc (1 : 5), H2 (1 atm).
(ii) Mismatched double diastereoselective aldol series – asym-
metric synthesis of D-idose, D-6-deoxyidose, D-6-deoxytalose and
D-talose. Having demonstrated the utility of the matched
iterative aldol approach for the synthesis of D-galactose and D-
fucose, it was predicted that the stereochemically mismatched
aldol reaction of tetroses (2S,3R)-11 and (2S,3R)-12 with
the (Z)-boron enolate of (S)-glycolate 1 would result in
a diastereoisomeric mixture of syn-(2ꢀS,3ꢀR,4S,4ꢀR,5ꢀR)- and
anti-(2ꢀS,3ꢀS,4S,4ꢀR,5ꢀR)-aldol products. In practice, boron-
mediated aldol reaction of (S)-1 with the 3-O-silyloxy-D-
threose derivative (2S,3R)-11 proceeded to completion to give
a 77 : 23 mixture of syn-(2ꢀS,3ꢀR,4S,4ꢀR,5ꢀR)-21 and anti-
(2ꢀS,3ꢀS,4S,4ꢀR,5ꢀR)-22. Chromatographic purification gave 21
and 22 in 46% and 9% yield respectively, and in >95%
d.e. in each case. The 3-O-silyloxy-4-deoxythreose derivative
(2S,3R)-12 similarly gave a separable 69 : 31 mixture of syn-
(2ꢀS,3ꢀR,4S,4ꢀR,5ꢀR)-23 and anti-(2ꢀS,3ꢀS,4S,4ꢀR,5ꢀR)-24 upon
reaction with (S)-1, giving 23 and 24 in 58% and 19% yield
respectively, and in >95% d.e. in each case after purification
(Scheme 4).
Scheme 5 Reagents and conditions: (i). TBAF, AcOH, THF, rt; (ii).
DIBAL, CH2Cl2, −78 ◦C; (iii). Pd/C, EtOH–EtOAc (1 : 5), H2 (1 atm).
Attempted deprotection of syn-aldol product 21 with AcOH–
THF proved unsuccessful, necessitating the development of an
alternative desilylation protocol in this series. Treatment of
21 with 1.5 equivalents of HF–pyridine in THF resulted in
partial desilylation, although the reaction could not be forced to
completion even after addition of 5 equivalents of HF–pyridine.
A range of alternative methods for O-silyl deprotection were also
investigated, with CAN in MeOH,33 a mixture of formic acid,
THF and water,34 trimethylsilyl triflate and neutral alumina35
and (PhCN)2PdCl2 in acetone and water36 all resulting in less
than 10% desilylation. However, treatment of aldol 21 with a
1% solution of iodine in MeOH at 70 ◦C promoted smooth
desilylation,37 giving the desilylated aldol adduct 28 in 68%
yield, which after refluxing in toluene for 16 hours furnished the
desired lactone (2S,3R,4R,5R)-29 as a single diastereoisomer
in 88% yield. Subsequent reduction of lactone 29 gave 2,4,6-
tris(O-benzyl)-D-idose (2S,3R,4R,5R)-30 as an inseparable 67 :
33 mixture of anomers in 89% yield, with hydrogenation giving
D-idose as a mixture of pyranose and furanose species in 89%
yield {[a]2D5 +7.7 (c 0.3, H2O, 10 min), lit.38 ent-[a]2D5 −9.8 (c 0.45,
1
H2O, 10 min)} after trituration with Et2O. The H (400 MHz)
spectroscopic properties of synthetic 31 were identical with those
of a commercially available sample of L-idose (Scheme 6).
Scheme 4 Reagents and conditions: (i). Et2BOTf, iPr2NEt, THF,
−78 ◦C.
With homogenous samples of the each aldol product aris-
ing from the mismatched aldol protocol in hand, the syn-
diastereoisomers 21 and 23 were deprotected to their corre-
sponding monosaccharides. Following the standard protocol,
AcOH–THF promoted desilylation of aldol product 23 proved
efficient, furnishing the desired lactone (2S,3R,4R,5R)-25 in
Scheme 6 Reagents and conditions: (i). 1% solution of I2 in MeOH,
70 ◦C; (ii). toluene, D; (iii). DIBAL, CH2Cl2, −78 ◦C; (iv). Pd/C,
EtOH–EtOAc (1 : 5), H2 (1 atm).
3 5 0
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 4 8 – 3 5 9

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The minor anti-diastereoisomers from the mismatched aldol
protocol 22 and 24 were next submitted to a similar protocol
for the synthesis of D-talose and D-6-deoxytalose respectively.
Treatment of aldol 22 with TBAF/AcOH furnished an insepa-
rable 67 : 33 mixture of the desired lactone (2S,3S,4R,5S)-32 and
the SuperQuat auxiliary in 50% yield, with DIBAL-H reduction
of the mixture giving the desired lactol (2S,3S,4R,5R)-33 as
a single diastereoisomer of unknown anomeric configuration,
as an inseparable mixture with the SuperQuat auxiliary. Hy-
drogenolysis of the mixture of the lactol 33 and oxazolidin-2-
one, and subsequent trituration of the crude reaction mixture
with Et2O, afforded D-talose 34 as a mixture of pyranose and
furanose species and facilitated separation from the auxiliary.
oxazolidinone auxiliary are used in this strategy, this protocol
is equally applicable to the synthesis of the enantiomeric L-
series of monosaccharides. Further work is currently being
directed toward the extension of this strategy to allow the
incorporation of both syn- and anti-aldol combinations and the
use of amino aldehydes in this iterative, three-stage, two-carbon
homologation protocol for the asymmetric synthesis of natural
product fragments.
Experimental
General
All reactions were carried out under nitrogen or argon using
standard vacuum line techniques, using glassware that was flame
dried and cooled under nitrogen. Reactions described as being
performed at −78 ◦C were◦cooled by means of an acetone–
dry ice bath and those at 0 C by an ice bath. THF and Et2O
were distilled from sodium–benzophenone ketyl under nitrogen
prior to use. CH2Cl2 was distilled from calcium hydride under
nitrogen prior to use. Toluene was distilled from sodium under
nitrogen prior to use. n-Butyllithium was used as a solution in
hexanes and was titrated against diphenylacetic acid prior to
use. DIBAL was used as supplied (Aldrich) as a 1 M solution in
hexanes. All other reagents were used as supplied without further
purification. Column chromatography was performed on silica
gel (Kieselgel 60). TLC was performed on Merck aluminium
sheets coated with 0.2 mm silica gel 60 F254. Plates were visualised
either by UV light (254 nm), iodine, ammonium molybdate
(7% solution in ethanol) or potassium permanganate (1% in
2% aqueous acetic acid, containing 7% potassium carbonate).
Infra-red spectra were recorded as thin films or KBr discs using
a Perkin–Elmer PARAGON 1000 FT-IR spectrometer. Selected
peaks are reported in cm−1. 1H NMR spectra were recorded on
Bruker DPX-400 (400 MHz), Bruker DQX-400 (400 MHz) or
Bruker AM-500 (500 MHz) spectrometers. Chemical shifts (dH)
are reported in parts per million (ppm) and are referenced to the
residual solvent peak. Coupling constants (J) are measured in
hertz. Two-dimensional COSY spectra were recorded on Bruker
DPX-200 (200 MHz), Bruker AVANCE AV-400 (400 MHz) or
Bruker DPX-400 (400 MHz) spectrometers. 13C spectra were
recorded at 50.31 MHz on the Varian Gemini 200 or the
Bruker DPX-200 spectrometers, at 100.62 MHz on the Bruker
AVANCE AV-400 or the Bruker DPX-400 spectrometers and at
125.77 MHz on the Bruker AM-500 spectrometer. Chemical
shifts (dC) are quoted in ppm and referenced using residual
solvent peaks. Two-dimensional HMQC and HMBC spectra
were recorded on the Bruker DQX-400 (400 MHz) or the
Bruker DPX-400 (400 MHz) spectrometers. NOE difference
and NOESY spectra were recorded on a Bruker AM-500
spectrometer. 19F spectra were recorded on a Bruker DPX-250
(235 MHz). Low resolution mass spectra (m/z) were recorded
on either a VG Masslab 20–250 instrument (CI, NH3) or a
Platform instrument (APCI). MALDI spectra were recorded
on a Micromass MALDI TOF SPEC 2E spectrometer. Major
peaks are listed with intensities quoted as percentages of the
base peak. Accurate mass measurements were recorded on a
VG Autospec and a Waters 2790-Micromass LCT electrospray
ionisation mass spectrometer operating at a resolution of 5000
full width half height. Positive ion spectra were calibrated
relative to PEG with tetraoctylammonium bromide as the
internal lock mass. Negative ion spectra were calibrated relative
to poly-DL-alanine with leucine enkephalin as the internal lock
mass. Optical rotations were recorded on a Perkin–Elmer 241
polarimeter, using a path length of 10 cm, in spectroscopic
grade solvents (Aldrich), with concentrations (c) given in g
per 100 cm3, solvent and temperature as recorded. Elemental
analyses were obtained by Mrs A. Douglas of the Inorganic
Chemistry Analytical Department using an Elementar Vario EL
combustion elemental analyser. Melting points were recorded on
a Gallenkamp hot stage apparatus and are uncorrected.
1
The H (400 MHz) spectrum and specific rotation of synthetic
D-talose 34 were consistent with those of commercially available
a-D-talose {[a]D25 +19.4 (c 0.25, H2O, 24 h), lit.39 [a]2D5 +19.8
(c 0.35, H2O, 24 h)} (Scheme 7).
Scheme 7 Reagents and conditions: (i). TBAF, AcOH, THF, rt; (ii).
DIBAL, CH2Cl2, −78 ◦C; (iii). Pd/C, EtOH–EtOAc (1 : 5), H2 (1 atm).
In a similar fashion, treatment of aldol-24 with TBAF/AcOH
gave an inseparable 58 : 42 mixture of the desired lactone
(2S,3S,4R,5S)-35 and the SuperQuat auxiliary in 89% yield,
with reduction to the lactol 36 and hydrogenation affording
a mixture of D-6-deoxytalose 37 and the oxazolidin-2-one.
Trituration of the crude reaction product with Et2O enabled
the isolation of D-6-deoxytalose 37 as a mixture of pyranose
and furanose species {[a]2D5 +17.7 (c 0.35, H2O, 24 h), lit.40 ent-
[a]2D5 −17.3 (c 0.35, H2O, 24 h)} with spectroscopic properties
consistent with that of the literature (Scheme 8).
Scheme 8 Reagents and conditions: (i). TBAF, AcOH, THF, rt; (ii).
DIBAL, CH2Cl2, −78 ◦C; (iii). Pd/C, EtOH–EtOAc (1 : 5), H2 (1 atm).
In conclusion, we have demonstrated that iterative glycolate
aldol reactions may be used to prepare a range of monosac-
charides. As both (R)- and (S)-enantiomers of the SuperQuat
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 4 8 – 3 5 9
3 5 1

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Representative procedure 1 for the aldol addition of
N-acyloxazolidin-2-one to aldehydes
acetaldehyde (625 mg, 4.15 mmol) in CH2Cl2 (50 mL) fur-
nished 5 (1.46 g, 2.90 mmol, 77%) as a white solid after
column chromatography. Rf 0.09 [1 : 1 pentane–Et2O]; mp 83–
84 ◦C [30–40 ◦C petrol–Et2O]; dH (400 MHz, CDCl3) 1.29
[3H, s, C(CH3)A(CH3)B], 1.35 [3H, s, C(CH3)A(CH3)B], 2.84
[1H, dd, J 14.4, 9.5, CHCHAHBPh], 3.09 [1H, dd, J 14.4, 4.0,
CHCHAHBPh], 3.63 [1H, dd, J 10.0, 6.7, CHAHBOCH2Ph],
3.69 [1H, dd, J 10.0, 5.6, CHAHBOCH2Ph], 4.20–4.22 [1H, m,
CH(OH)], 4.41 [1H, d, J 11.4, CHOCHAHBPh], 4.45 [1H, dd,
J 9.5, 4.0, CHCH2Ph], 4.50 [1H, d, J 11.8, CH2OCHAHBPh],
4.55 [1H, d, J 11.4, CHOCHAHBPh], 4.59 [1H, d, J 11.8,
CH2OCHAHBPh], 5.41 [1H, d, J 3.6, CHOCH2Ph], 7.21–7.38
[15H, m, PhH]; dC (100 MHz, CDCl3) 22.1, 28.2 [C(CH3)2],
35.2 [CHCH2Ph], 63.8 [CHCH2Ph], 70.8 [CH(OH)], 70.9
[CH2OCH2Ph], 72.9 [CHOCH2Ph], 73.4 [CH2OCH2Ph], 77.5
[CHOCH2Ph], 83.4 [C(CH3)2], 126.8, 127.7, 128.1 [p-Ph], 127.9,
128.3, 128.4, 128.7, 128.8, 129.1 [m/o-Ph], 136.8, 137.1, 138.0 [i-
CF3SO3H (1.2 eq.) was added to Et3B (1 M in hexanes; 1.2 eq.)
at ambient temperature then warmed to 40 ◦C. After stirring
for 10 min, the resultant solution was cooled to 0 ◦C and added
to a solution of N-acyloxazolidin-2-one (1.0 eq.) in CH2Cl2 via
cannula. After stirring for 10 min, iPr2NEt (1.4 eq.) was added
and the reaction mixture was stirred for a further 20 min. The
reaction was then cooled to −78 ◦C and freshly distilled aldehyde
(1.1 eq.) was added either via syringe or via cannula as a solution
in CH2Cl2. After stirring for 30 min, the resultant mixture was
warmed to 0 ◦C and stirred for a further hour. The reaction was
quenched with MeOH–H2O2 (1 : 1 v/v), extracted with CH2Cl2,
washed with brine, dried and concentrated in vacuo. The crude
product was purified by column chromatography.
Representative procedure 2 for the protection of aldol adducts
with TBDMSCl
=
=
Ph], 152.7 [C O endocyclic], 170.6 [C O exocyclic]; mmax (thin
−1
=
=
film, cm ) 3745 [O–H], 1775 [C O endocyclic], 1707 [C O
exocyclic]; C30H47NO6Si requires C 71.55, H 6.61, N 2.78%,
found C 71.23, H 6.54, N 2.81%; [a]2D5 −37.1 (c 1.0, CHCl3);
m/z ES+ 504 [10%, MH+], 525 [100%, MNa+].
Imidazole (5.0 eq.), TBDMSCl (2.5 eq.) and DMAP (0.1 eq.)
were added sequentially to a solution of N-acyloxazolidin-2-
one (1.0 eq.) in DMF at ambient temperature. After stirring for
18 h, the reaction was quenched with MeOH, diluted with Et2O,
washed with water, dried and concentrated in vacuo. The crude
product was purified by column chromatography.
Preparation of (2ꢀS,3R,4S)-4-benzyl-3-(2ꢀ-benzyloxy-3-
hydroxybutyryl)-5,5-dimethyloxazolidin-2-one 6
Following Representative procedure 1, CF3SO3H (0.75 mL,
8.5 mmol), Et3B (8.50 mL, 8.50 mmol), (S)-1 (2.50 g,
7.08 mmol), iPr2NEt (1.73 mL, 9.91 mmol) and MeCHO
(0.43 mL, 7.79 mmol) in CH2Cl2 (40 mL) furnished 6 (2.23 g,
5.62 mmol, 79%) as a white solid after column chromatography.
Rf 0.11 [1 : 1 pentane–Et2O]; mp 92–94 ◦C [pentane–Et2O];
dH (400 MHz, CDCl3) 1.30 [3H, d, J 6.4, CH(OH)CH3], 1.38
[3H, s, C(CH3)A(CH3)B], 1.39 [3H, s, C(CH3)A(CH3)B], 2.37 [1H,
d, J 8.3, CH(OH)], 2.86 [1H, dd, J 14.4, 4.0, CHCHAHBPh],
3.06 [1H, dd, J 14.4, 9.4, CHCHAHBPh], 4.05–4.01 [1H, m,
CH(OH)], 4.43 [1H, d, J 11.4, CHOCHAHBPh], 4.52 [1H, dd,
J 9.4, 4.0, CHCH2Ph], 4.57 [1H, d, J 11.4, CHOCHAHBPh],
5.16 [1H, d, J 3.3, CHOCH2Ph], 7.21–7.37 [10H, m, PhH]; dC
(100 MHz, CDCl3) 19.5 [CH(OH)CH3], 22.1, 28.4 [C(CH3)2],
35.3 [CHCH2Ph], 63.8 [CH(OH)], 68.8 [CHCH2Ph], 72.9
[CHOCH2Ph], 80.2 [CHOCH2Ph], 83.4 [C(CH3)2], 126.9, 128.1
[p-Ph], 128.3, 128.4, 128.7, 129.1 [m/o-Ph], 136.7, 137.1 [i-
Representative procedure 3 for the DIBAL reduction of aldol
adducts and lactones
DIBAL (2.0 eq.) was added dropwise to a stirred solution of
N-acyloxazolidin-2-one (1.0 eq.) in CH2Cl2 at −78 ◦C. The
◦
reaction was quenched at −78 C after 20 min with saturated
aqueous NH4Cl solution, warmed to room temperature and
stirred for a further 20 min. The resultant mixture was filtered
R
through Celiteꢀ (eluent: CH2Cl2), dried over MgSO4. The
organic extracts were concentrated in vacuo and purified by
column chromatography on silica gel to give the desired product.
Representative procedure 4 for the fragmentation of aminols with
K2CO3
K2CO3 (1.4 eq.) was added to a suspension of aminol (1.0 eq.) in
MeOH–H2O (4 : 1 v/v) at ambient temperature. After stirring for
15 min, the reaction mixture was diluted with CH2Cl2, washed
with water and brine and dried. The crude product was purified
by column chromatography.
=
=
Ph], 152.8 [C O endocyclic], 170.8 [C O exocyclic]; mmax (KBr
−1
=
=
disc, cm ) 1761 [C O endocyclic], 1715 [C O exocyclic];
C23H27NO5 requires C 69.50, H 6.85, N 3.52%, found C 69.54,
H 6.81, N 3.50%; [a]2D4 −89.9 (c 1.0, CHCl3); m/z APCI+ 206
[75%, SQH+], 398 [100%, MH+].
Representative procedure 5 for the formation of lactones
A mixture of TBAF (1 M in THF; 1.5 eq.) and AcOH (1.0 eq.)
was added to a stirred solution of N-acyloxazolidin-2-one
(1.0 eq.) in THF at ambient temperature. After stirring for
16 h, the reaction mixture was diluted with CH2Cl2, washed
with dilute aqueous NaHCO3 and brine, dried and concentrated
in vacuo. The crude product was purified by column chromatog-
raphy.
Preparation of (2ꢀS,3ꢀR,4S)-4-benzyl-3-(2ꢀ,4ꢀ-bis(benzyloxy)-3ꢀ-
(tert-butyldimethylsilanyloxy)butyryl)-5,5-dimethyloxazolidin-
2-one 7
Following Representative procedure 2, 5 (1.57 g, 3.12 mmol),
TBDMSCl (1.18 g, 7.80 mmol), imidazole (1.06 g, 15.6 mmol)
and DMAP (40 mg, 0.3 mmol) in DMF (10 mL) furnished 7
(1.73 g, 2.80 mmol, 90%) as a pale yellow oil after column chro-
matography. Rf 0.22 [10 : 1 pentane–Et2O]; dH (400 MHz, CDCl3)
0.08 [3H, s, Si(CH3)A(CH3)B], 0.09 [3H, s, Si(CH3)A(CH3)B], 0.89
[9H, s, SiC(CH3)3], 1.02 [3H, s, C(CH3)A(CH3)B], 1.22 [3H, s,
C(CH3)A(CH3)B], 2.59 [1H, dd, J 14.5, 10.3, CHCHAHBPh], 3.00
[1H, dd, J 14.5, 2.8, CHCHAHBPh], 3.52 [1H, dd, J 10.7, 5.2,
CHAHBOCH2Ph], 3.76 [1H, dd, J 10.7, 6.2, CHAHBOCH2Ph],
4.19 [1H, dd, J 10.3, 2.8, CHCH2Ph], 4.27–4.31 [1H, m,
CH(OTBDMS)], 4.41–4.53 [2H, ABq, J 11.4, CH2OCH2Ph],
4.55–4.66 [2H, ABq, J 11.8, CHOCH2Ph], 5.47 [1H, d, J 6.0,
CHOCH2Ph], 7.20–7.38 [15H, m, PhH]; dC (100 MHz, CDCl3)
−4.9, −4.6 [Si(CH3)2], 18.2 [SiC(CH3)3], 22.4, 28.0 [C(CH3)2],
25.8 [SiC(CH3)3], 34.7 [CHCH2Ph], 63.9 [CHCH2Ph], 71.7
[CH2OCH2Ph], 72.4 [CH(OTBDMS)], 73.2, 73.3 [CHOCH2Ph
and CH2OCH2Ph], 78.6 [CHOCH2Ph], 82.4 [C(CH3)2], 126.6,
Representative procedure 6 for the hydrogenolysis of lactols
10% Pd/C was added to a solution of lactol in EtOAc–EtOH
(5 : 1 v/v) at ambient temperature. After stirring under a
hydrogen atmosphere for 54 h, the reaction mixture was filtered
R
through Celiteꢀ (eluent: MeOH) and concentrated in vacuo.
The crude product was purified by recrystallisation or column
chromatography.
Preparation of (2ꢀS,3ꢀR,4S)-4-benzyl-3-(2ꢀ,4ꢀ-bis(benzyloxy)-3-
hydroxybutyryl)-5,5-dimethyloxazolidin-2-one 5
Following Representative procedure 1, CF3SO3H (0.40 mL,
4.52 mmol), Et3B (4.52 mL, 4.52 mmol), (S)-1 (1.33 g,
i
3.77 mmol), Pr2NEt (0.92 mL, 5.28 mmol) and benzyloxy-
3 5 2
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 4 8 – 3 5 9

View Article Online
127.5, 127.8 [p-Ph], 128.0, 128.2, 128.3, 128.4, 128.6, 129.0 [m/o-
[3H, s, Si(CH3)A(CH3)B], 0.88 [9H, s, SiC(CH3)3], 1.09 [3H, s,
C(CH3)A(CH3)B], 1.23 [3H, d, J 6.3, CHCH3], 1.27 [3H, s,
C(CH3)A(CH3)B], 2.72 [1H, dd, J 14.8, 9.9, CHCHAHBPh], 3.24
[1H, dd, J 14.8, 4.6, CHCHAHBPh], 4.00 [1H, dd, J 9.9, 4.6,
CHCH2Ph], 4.08–4.15 [2H, m, CH(OTBDMS) and CH(OH)],
4.48 [1H, d, J 4.9, CH(OH)], 4.69 [2H, s, CHOCH2Ph], 5.05
[1H, dd, J 8.3, 4.9, CHOCH2Ph], 7.09–7.37 [10H, m, PhH];
dC (100 MHz, CDCl3) −4.8, −5.3 [Si(CH3)2], 17.4 [CHCH3],
17.9 [SiC(CH3)3], 22.1, 27.6 [C(CH3)2], 25.7 [SiC(CH3)3],
35.5 [CHCH2Ph], 65.2 [CHCH2Ph], 68.6 [CH(OTBDMS)],
73.1 [CHOCH2Ph], 77.8 [CHOCH2Ph], 79.2 [CH(OH)], 81.2
[C(CH3)2], 126.6, 127.9 [p-Ph], 127.9, 128.5, 128.6, 128.8 [m/o-
=
Ph], 137.2, 137.8, 138.0 [i-Ph], 152.4 [C O endocyclic], 171.4
−1
=
=
[C O exocyclic]; mmax (thin film, cm ) 1776 [C O endocyclic],
+
=
1704 [C O exocyclic]; HRMS C36H47NO6NaSi [MNa ] requires
640.3070, found 640.3055; [a]2D4 +2.0 (c 0.65, CHCl3); m/z ES+
618 [30%, MH+], 634 [100%, MNH4+], 663 [100%, MNa2+].
Preparation of (2ꢀS,3ꢀR,4S)-4-benzyl-3-[2ꢀ-benzyloxy-3ꢀ-(tert-
butyldimethylsilanyloxy)butyryl]-5,5-dimethyloxazolidin-2-
one 8
Following Representative procedure 7, 6 (2.00 g, 3.91 mmol),
TBDMSCl (1.48 g, 9.78 mmol), imidazole (1.33 g,19.55 mmol)
and DMAP (47 mg, 0.39 mmol) in DMF (10 mL) fur-
nished 8 (1.70 g, 3.33 mmol, 85%) as a white solid af-
ter flash column chromatography. Rf 0.15 [10 : 1 pentane–
Et2O]; mp 62–63 ◦C [pentane–Et2O]; dH (400 MHz, CDCl3)
0.05 [3H, s, Si(CH3)A(CH3)B], 0.07 [3H, s, Si(CH3)A(CH3)B],
0.88 [9H, s, SiC(CH3)3], 1.20 [3H, d, J 10.2, CHCH3], 1.34
[3H, s, C(CH3)A(CH3)B], 1.36 [3H, s, C(CH3)A(CH3)B], 2.77
[1H, dd, J 14.5, 9.7, CHCHAHBPh], 2.97 [1H, dd, J 14.5,
3.4, CHCHAHBPh], 4.13–4.16 [1H, m, CH(OTBDMS)], 4.43
[1H, dd, J 9.7, 3.4, CHCH2Ph], 4.54 [2H, s, CHOCH2Ph],
5.42 [1H, d, J 5.4, CHOCH2Ph], 7.20–7.38 [10H, m, PhH]; dC
(100 MHz, CDCl3) −4.7 [Si(CH3)2], 18.3 [SiC(CH3)3], 19.0, 22.2
[C(CH3)2], 25.9 [SiC(CH3)3], 28.4 [CHCH3], 35.1 [CHCH2Ph],
64.1 [CHCH2Ph], 70.0 [CHOCH2Ph], 73.1 [CHOCH2Ph], 79.5
[CH(OTBDMS)], 82.6 [C(CH3)2], 126.7, 127.8 [p-Ph], 128.3,
=
=
Ph], 137.0, 138.0 [i-Ph], 157.0 [C O endocyclic]; mmax (KBr
−1
=
disc, cm ) 3328 [O–H broad], 1725 [C O]; C29H43NO5Si
requires C 67.80, H 8.44, N 2.73%, found C 67.84, H 8.49,
N 2.91%; [a]2D0 +9.1 (c 1.0, CHCl3); m/z ES+ 496 [35%, MH+ −
H2O], 536 [100%, MNa+].
Preparation of (2S,3R)-2,4-bis(benzyloxy)-3-(tert-
butyldimethylsilanyloxy)butrylaldehyde 11
Following Representative procedure 4, 9 (1.60 g, 2.58 mmol) and
K2CO3 (500 mg, 3.62 mmol) in MeOH–H2O (4 : 1 v/v; 50 mL)
furnished 11 (764 mg, 1.84 mmol, 72%) as a clear colourless
oil. dH (400 MHz, CDCl3) 0.01 [3H, s, Si(CH3)A(CH3)B], 0.03
[3H, s, Si(CH3)A(CH3)B], 0.86 [9H, s, SiC(CH3)3], 3.53 [1H,
dd, J 9.8, 4.9, CHAHBOCH2Ph], 3.61 [1H, dd, J 9.8, 5.6,
CHAHBOCH2Ph], 3.87 [1H, dd, J 4.5, 1.3, CHOCH2Ph],
4.15–4.19 [1H, m, CH(OTBDMS)], 4.48 [2H, q, J 12.2,
CH2OCH2Ph], 4.56 [1H, d, J 12.0, CHOCHAHBPh], 4.76 [1H,
d, J 12.0, CHOCHAHBPh], 7.27–7.37 [10H, m, PhH], 9.75 [1H,
d, J 1.3, CHO]; dC (100 MHz, CDCl3) −4.8, −4.6 [Si(CH3)2],
18.0 [SiC(CH3)3], 25.7 [SiC(CH3)3], 70.4 [CH2OCH2Ph], 72.5
[CH(OTBDMS)], 73.1, 73.3 [2 × OCH2Ph], 84.1 [CHOCH2Ph],
128.4, 128.6, 129.1 [m/o-Ph], 137.0, 137.7 [i-Ph], 152.3 [C
O
endocyclic], 171.4 [C O exocyclic]; mmax (KBr disc, cm−1) 1778
=
=
=
[C O endocyclic], 1702 [C O exocyclic]; C29H41NO5Si requires
C 68.07, H 8.08, N 2.74%, found C 68.28, H 8.08, N 2.69%; [a]D23
−10.1 (c 1.1, CHCl3); m/z APCI+ 206 [70%, SQH+], 380 [100%,
MH+ − OTBDMS], 512 [35%, MH+].
127.6, 128.0, 128.1, 128.3, 128.5 [p- and m/o-Ph], 137.4, 137.9
−1
Preparation of (2ꢀS,3ꢀR,4S)-benzyl-3-[2ꢀ,4ꢀ-bis(benzyloxy)-3ꢀ-
(tert-butyldimethylsilanyloxy)-1ꢀ-hydroxybutyl]-5,5-
dimethyloxazolidin-2-one 9
=
[i-Ph], 202.7 [CHO]; mmax (thin film, cm ) 1733 [C O]; HRMS
C24H35O4Si requires 415.2305, found 415.2311; [a]2D4 −18.5 (c
1.05, CHCl3); m/z ES+ 415 [100%, MH+].
Following Representative procedure 3, DIBAL (5.5 mL,
5.51 mmol) and 7 (1.70 g, 2.75 mmol) in CH2Cl2 (50 mL)
furnished 9 (1.59 g, 2.58 mmol, 94%) as a very viscous
oil. dH (400 MHz, CDCl3) 0.08 [3H, s, Si(CH3)A(CH3)B],
0.09 [3H, s, Si(CH3)A(CH3)B], 0.89 [9H, s, SiC(CH3)3], 1.07
[3H, s, C(CH3)A(CH3)B], 1.26 [3H, s, C(CH3)A(CH3)B], 2.67
[1H, dd, J 14.8, 10.1, CHCHAHBPh], 3.19 [1H, dd, J 14.8, 4.5,
CHCHAHBPh], 3.54 [1H, dd, J 9.6, 6.6, CHAHBOCH2Ph], 3.66
[1H, dd, J 9.6, 4.5, CHAHBOCH2Ph], 4.01 [1H, dd, J 10.1, 4.5,
CHCH2Ph], 4.18–4.21 [1H, m, CH(OTBDMS)], 4.24 [1H, dd,
J 8.8, 3.4, CHOCH2Ph], 4.31 [1H, br s, OH], 4.49 [2H, ABq,
J 12.0, CH2OCH2Ph], 4.70 [2H, ABq, J 11.8, CHOCH2Ph],
4.97 [1H, d, J 8.7, CH(OH)], 7.06–7.36 [15H, m, PhH]; dC
(100 MHz, CDCl3) −4.8, −4.6 [Si(CH3)2], 18.0 [SiC(CH3)3],
22.1, 27.6 [C(CH3)2], 25.8 [SiC(CH3)3], 35.4 [CHCH2Ph], 65.4
[CHCH2Ph], 70.9 [CH2OCH2Ph], 71.4 [CH(OTBDMS)], 73.2,
73.3 [2 × OCH2Ph], 76.8 [CHOCH2Ph], 79.2 [CH(OH)], 81.6
[C(CH3)2], 126. 7, 127.6, 127.7 [p-Ph], 127.8, 128.3, 128.4, 128.6,
Preparation of (2S,3R)-2-benzyloxy-3-(tert-
butyldimethylsilanyloxy)butyraldehyde 12
Following Representative procedure 4, 10 (1.60 g, 3.12 mmol)
and K2CO3 (603 mg, 4.37 mmol) in MeOH–H2O (4 : 1 v/v;
50 mL) furnished 12 (672 mg, 2.18 mmol, 70%) as a clear
colourless oil and the auxiliary (556 mg, 2.71 mmol, 87%) as a
white solid after column chromatography. dH (400 MHz, CDCl3)
0.04 [3H, s, Si(CH3)A(CH3)B], 0.06 [3H, s, Si(CH3)A(CH3)B], 0.87
[9H, s, SiC(CH3)3], 1.21 [3H, d, J 6.3, CHCH3], 3.73 [1H, dd,
J 5.0, 1.4, CHOCH2Ph], 4.12–4.18 [1H, m, CH(OTBDMS)],
4.54 [1H, d, J 12.0, CHOCHAHBPh], 4.77 [1H, d, J 12.0,
CHOCHAHBPh], 7.27–7.36 [5H, m, PhH], 9.77 [1H, d, J 1.4,
CHO]; dC (100 MHz, CDCl3) −4.6 [Si(CH3)2], 18.0 [SiC(CH3)3],
19.5 [CHCH3], 25.7 [SiC(CH3)3], 69.1 [CHOCH2Ph], 72.8
[CHOCH2Ph], 86.4 [CH(OTBDMS)], 128.0 [p-Ph], 128.0, 128.4
[m/o-Ph], 137.4 [i-Ph], 203.6 [CHO]; mmax (thin film, cm−1) 1735
+
=
[C O]; HRMS C17H29O3Si [MH ] requires 309.1886, found
309.1899; [a]2D5 −48.4 (c 0.5, CHCl3); m/z ES+ 279 [40%, MH+ −
CHO], 291 [35%, MH+ − H2O], 309 [100%, MH+], 331 [15%,
MNa+].
=
128.8 [m/o-Ph], 136.8, 138.1, 138.1 [i-Ph], 157.1 [C O endo-
−1
=
cyclic]; mmax (thin film, cm ) 3401 [O–H], 1728 [C O]; HRMS
C37H46N2O6Si [MNH4+] requires 642.3125, found 642.3136; [a]2D4
+1.25 (c 1.6, CHCl3); m/z ES+ 607 [100%, MH+ − H2O], 642
[100%, MNH4+].
Preparation of (2ꢀR,3ꢀS,4R,4ꢀR,5ꢀR)-4-benzyl-3-[2ꢀ,4ꢀ,6-
tris(benzyloxy)-5ꢀ-(tert-butyldimethylsilanyloxy)-3ꢀ-
hydroxyhexanoyl]-5,5-dimethyloxazolidin-2-one 13
Preparation of (2ꢀS,3ꢀR,4S)-4-benzyl-3-[2ꢀ-benzyloxy-3ꢀ-(tert-
butyldimethylsilanyloxy)-1ꢀ-hydroxypropyl]-5,5-
dimethyloxazolidin-2-one 10
Following Representative procedure 1, CF3SO3H (0.16 mL,
1.87 mmol), Et3B (1.90 mL, 1.87 mmol), (R)-1 (550 mg,
i
Following Representative procedure 3, DIBAL (6.7 mL,
6.66 mmol) and 8 (1.70 g, 3.33 mmol) in CH2Cl2 (40 mL)
furnished 10 (1.65 g, 3.21 mmol, 96%) as a very viscous
oil. dH (400 MHz, CDCl3) 0.07 [3H, s, Si(CH3)A(CH3)B], 0.08
1.56 mmol), Pr2NEt (0.38 mL, 2.18 mmol) and 11 (700 mg,
1.69 mmol) in CH2Cl2 (30 mL) furnished 13 (751 mg,
0.98 mmol, 63%) as a clear colourless oil after column
chromatography. Rf 0.09 [5 : 1 pentane–Et2O; double eluted];
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 4 8 – 3 5 9
3 5 3

View Article Online
dH (400 MHz, CDCl3) 0.04 [3H, s, Si(CH3)A(CH3)B], 0.05
[3H, s, Si(CH3)A(CH3)B], 0.88 [9H, s, SiC(CH3)3], 1.34 [3H, s,
C(CH3)A(CH3)B], 1.37 [3H, s, C(CH3)A(CH3)B], 2.89 [1H, dd,
J 14.4, 9.6, CHCHAHBPh], 1.37 [1H, d, J 7.1, CH(OH)], 3.17
[1H, dd, J 14.4, 3.7, CHCHAHBPh], 3.62 [1H, dd, J 9.6, 6.5,
CHAHBOCH2Ph], 3.73 [1H, dd, J 9.6, 4.9, CHAHBOCH2Ph],
3.83 [1H, dd, J 9.2, 3.0, CHOCH2Ph.CH(OTBDMS)], 4.18–
4.22 [3H, m, CH(OH), CH(OTBDMS) and 1 × CHOCH2Ph],
CHCHDPh], 7.21–7.43 [15H, m, PhH]; dC (100 MHz, CDCl3)
67.5 [CH2OCH2Ph], 72.0 [CH(OH)], 73.6 [CH2OCH2-
Ph], 74.0 [CH(OCH2Ph).CHCH2OCH2Ph], 74.7 [CH(OCH2-
Ph).CHCH2OCH2Ph], 75.1 [CO.CHOCH2Ph], 76.7 [CO.CHO-
CH2Ph], 77.8 [CH(OCH2Ph).CHCH2OCH2Ph], 127.8, 127.9,
128.0, 128.3, 128.4, 128.5, 128.6, 128.7 [p- and m/o-Ph], 137.1,
137.3, 137.7 [i-Ph], 169.7 [C O]; mmax (thin film, cm−1) 3457 [O–
=
=
H], 1743 [C O]; C27H28O6 requires C 72.30, H 6.29%, found C
4.49–4.59 [6H, m, CHCH2Ph and
5
×
CHOCH2Ph],
72.33, H 6.30%; [a]2D6 +41.5 (c 0.55, CHCl3); m/z ES+ 467 [60%,
5.51 [1H, d, J 2.0, CO.CHOCH2Ph], 7.21–7.40 [20H, m,
PhH]; dC (100 MHz, CDCl3) −4.8, −4.6 [Si(CH3)2], 18.1
[SiC(CH3)3], 22.1, 28.2 [C(CH3)2], 25.9 [SiC(CH3)3], 35.3
[CHCH2Ph], 64.1 [CHCH2Ph], 71.2 [CH2OCH2Ph], 71.4, 71.5
[CH(OTBDMS) and CH(OH)], 72.3, 72.5, 73.2 [CH2OCH2Ph
and 2 × CHOCH2Ph], 77.4 [CHOCH2Ph.CH(OTBDMS)], 78.0
[CO.CHOCH2Ph], 83.3 [C(CH3)2], 126.8, 127.4, 127.5, 127.8 [p-
Ph], 127.3, 127.6, 128.3, 128.5, 128.6, 128.7, 128.0, 129.1 [m/o-
MNH4+], 471 [100%, MNa+].
Preparation of (2R,3S,4R,5R)-2,4-bis(benzyloxy)-3-hydroxy-5-
methyltetrahydropyran-2-one 16
Following Representative procedure 5, 14 (200 mg, 0.30 mmol),
TBAF (0.45 mL, 0.45 mmol) and AcOH (0.02 mL, 0.30 mmol)
in THF (10 mL) furnished 16 (75 mg, 0.22 mmol, 73%)
as a white solid after column chromatography. Rf 0.25
[2 : 1 pentane–Et2O]; dH (400 MHz, CDCl3) 1.37 [3H, d,
J 6.5, CHCH3], 2.51 [1H, br s, OH], 3.83 [1H, t, J 2.2,
CHOCH2Ph.CHCH3], 4.09 [1H, dd, J 10.0, 2.5, CH(OH)],
4.31 [1H, d, J 10.0, CO.CHOCH2Ph], 4.42 [1H, qd, J 6.5, 1.9,
CHCH3], 4.68 [1H, d, J 11.4, CHOCHAHBPh], 4.71 [1H, d,
J 11.2, CHOCHCHDPh], 4.89 [1H, d, J 11.4, CHOCHAHBPh],
5.22 [1H, d, J 11.2, CHOCHCHDPh], 7.16–7.44 [10H, m, PhH];
dC (100 MHz, CDCl3) 17.0 [CHCH3], 72.4 [CH(OH)], 74.7,
75.2 [2 × CHOCH2Ph], 76.2 [CHCH3], 76.3 [CO.CHCH2Ph],
76.7 [CHOCH2Ph.CHCH3], 128.0, 128.1, 128.3, 128.6, 128.8,
=
Ph], 137.0, 137.4, 138.2, 138.7 [i-Ph], 152.4 [C O endocyclic],
170.9 [C O exocyclic]; mmax (thin film, cm−1) 3455 [O–H],
=
=
=
1778 [C O endocyclic], 1708 [C O endocyclic]; C45H57NO8Si
requires C 70.37, H 7.48, N 1.82%, found C 70.26, H 7.53, N
1.81%; [a]2D6 +32.9 (c 0.65, CHCl3); m/z LD+ (MALDI) 790,
791, 792 [100%, 50%, 20%, MNa+].
Preparation of (2ꢀR,3ꢀS,4R,4ꢀR,5ꢀR)-4-benzyl-3-[2ꢀ,4ꢀ-
bis(benzyloxy)-5ꢀ-(tert-butyldimethylsilanyloxy)-3ꢀ-
hydroxypentanoyl]-5,5-dimethyloxazolidin-2-one 14
Following Representative procedure 1, CF3SO3H (0.12 mL,
1.36 mmol), Et3B (1.36 mL, 1.36 mmol), (R)-1 (400 mg,
=
129.1 [p- and m/o-Ph], 137.2, 137.6 [i-Ph], 170.4 [C O]; mmax
(thin film, cm ) 3443 [O–H], 1732 [C O]; HRMS C20H23O5Na
−1
=
i
1.13 mmol), Pr2NEt (0.28 mL, 1.58 mmol) and 12 (375 mg,
[MNa+] requires 343.1544, found 343.1545; [a]2D5 +130.2 (c 2.5,
CHCl3); m/z ES+ 365 [90%, MNa+].
1.22 mmol) in CH2Cl2 (15 mL) furnished 14 (395 mg,
0.60 mmol, 53%) as a pale yellow oil after column chromato-
graphy. Rf 0.08 [1 : 1 pentane–Et2O]; dH (400 MHz, CDCl3)
0.02 [3H, s, Si(CH3)A(CH3)B], 0.03 [3H, s, Si(CH3)A(CH3)B],
0.86 [9H, s, SiC(CH3)3], 1.35 [3H, d, J 5.1, CHCH3], 1.37
[3H, s, C(CH3)A(CH3)B], 1.40 [3H, s, C(CH3)A(CH3)B], 2.86
[1H, dd, J 14.4, 9.8, CHCHAHBPh], 3.18 [1H, dd, J 14.4, 3.4,
CHCHAHBPh], 3.68 [1H, dd, J 9.0, 3.6, CHOCH2Ph.CH-
(OTBDMS)], 4.09–4.12 [1H, m, CH(OTBDMS)], 4.25–4.29
[1H, m, CHCH2Ph], 4.28 [1H, d, J 11.2, CHOCHAHBPh], 4.49–
4.55 [3H, m, CH(OH) and CHOCH2Ph], 4.57 [1H, d, J 11.3,
CHOCHAHBPh], 5.50 [1H, d, J 2.2, CO.CHOCH2Ph], 7.20–
7.39 [15H, m, PhH]; dC (100 MHz, CDCl3) −4.7, −4.6
[Si(CH3)2], 17.6 [CHCH3], 18.0 [SiC(CH3)3], 22.1, 28.2
[C(CH3)2], 25.8 [SiC(CH3)3], 35.2 [CHCH2Ph], 64.2 [CH(OH)],
69.0 [CH(OTBDMS)], 71.3 [CHCH2Ph], 72.4, 72.5 [2 ×
CHOCH2Ph], 78.2, 78.3 [2 × CHOCH2Ph], 83.3 [C(CH3)2],
126.7, 127.7, 127.4 [p-Ph], 128.3, 128.5, 128.6, 128.7, 129.0, 129.1
Preparation of 2,4,6-tris(O-benzyl)-D-galactose 17
Following Representative procedure 3, DIBAL (0.50 mL,
0.50 mmol), 15 (114 mg, 0.25 mmol) in CH2Cl2 (5 mL) furnished
1741 (89 mg, 83%, 2 : 1 mixture of anomers) as a white solid
after column chromatography. Rf 0.12 and 0.05 [1 : 1 30–40 ◦C
◦
petrol–Et2O]; mp 104–106 C [MeOH–Et2O] {lit.41b mp 126–
128 ◦C [MeOH]}; dH (400 MHz, CDCl3) 2.30 [1H, d, J 5.2,
C3HOH (major)], 2.33 [1H, d, J 5.0, C3HOH (minor)], 3.24
[1H, s, C1HOH (major)], 3.48–3.67 [6H, m, CHCH2OCH2Ph
(major and minor), C3HOH (minor) and C4HOCH2Ph (major)],
3.79 [1H, dd, J 3.5, 9.9, C2HOCH2Ph (major)], 3.83 [1H,
d, J 3.2, C2HOCH2Ph (minor)], 3.89 [1H, dd, J 0.9, 3.1,
C4HOCH2Ph (minor)], 4.03–4.07 [1H, m, C3HOH], 4.21 [1H,
dt, J 0.7, 6.3, C5HCH2OCH2Ph (major)], 4.43 [1H, d, J 11.9,
CHOCHAHBPh (minor)], 4.44 [1H, d, J 12.0, CHOCHAHBPh
(major)], 4.52 [1H, d, J 12.0, CHOCHAHBPh (major)],
4.61–4.73 [7H, m, C5HCH2OCH2Ph (minor), CH2OCH2Ph
(major), CHOCHCHDPh (major) CH2OCH2Ph (minor) and
CHOCHAHBPh (minor)], 4.98 [1H, d, J 11.5, CHOCHC HDPh
(minor)], 4.79 [1H, d, J 11.6, CHOCHCHDPh (major)], 4.80
[1H, d, J 11.5, CHOCHCHDPh (minor)], 5.30 [2H, br s, C1HOH
(major and minor)], 7.27–7.41 [30H, m, PhH (major and
minor)]; dC (100 MHz, CDCl3) 68.9 [CH2OCH2Ph (minor)],
69.0 [CH2OCH2Ph (major)], 69.2 [C5HCH2OCH2Ph (major)],
69.9 [C3H(OH) (major)], 72.8 [CH2OCH2Ph (major and mi-
nor)], 73.5, 75.0 [CHOCH2Ph (major)], 73.5, 74.6 [CHOCH2Ph
(minor)], 73.7, 73.9 [C5HCH2OCH2Ph (minor) and C3H(OH)
(minor)], 75.60 [C2HOCH2Ph (minor)], 76.6 [C4HOCH2Ph (ma-
jor)], 77.4 [C2HOCH2Ph (major)], 80.8 [C4HOCH2Ph (minor)],
91.1 [C1H(OH) (major)], 97.6 [C1H(OH) (minor)], 127.9, 128.1,
128.2, 128.4, 128.6 [p- and m/o-Ph (major)], 127.7, 127.8, 128.2,
128.4, 128.5 [p- and m/o-Ph (minor)], 137.6, 137.7, 137.8, 138.3,
138.3 [i-Ph (major and minor)]; mmax (KBr disc, cm−1) 3435 [O–H],
1105, 1027, 1167 [C–O]; HRMS C28H31O8 [MCO2H−] requires
495.2019, found 495.2032; [a]2D5 +21.7 (c 0.3, CHCl3, 15 min),
[a]D25 +21.0 (c 0.3, CHCl3, 22 h) {lit.41 [a]D25 +40.4 (c 1.0, CHCl3,
=
[m/o-Ph], 137.1, 137.6, 1386, [i-Ph], 152.5 [C O endocyclic],
171.0 [C O exocyclic]; mmax (thin film, cm−1) 3460 [O–H], 1778
=
=
=
[C O endocyclic], 1712 [C O exocyclic]; C38H51NO7Si requires
C 68.95, H 7.77, N 2.12%, found C 68.67, H 7.70, N 2.27%;
[a]2D6 +27.6 (c 1.15, CHCl3); m/z LD+ (MALDI) 684, 685, 686
[100%, 40%, 15%, MNa+], 700, 701, 702 [60%, 25%, 10%, MK+].
Preparation of (2R,3S,4R,5R)-2,4-bis(benzyloxy)-5-
benzyloxymethyl-3-hydroxytetrahydropyran-2-one 15
Following Representative procedure 5, 13 (130 mg, 0.17 mmol),
TBAF (0.26 mL, 0.26 mmol) and AcOH (0.01 mL, 0.17 mmol)
in THF (7 mL) furnished 15 (62 mg, 0.14 mmol, 81%) as
a pale yellow oil after column chromatography. Rf 0.14 [1 :
1 pentane–Et2O]; dH (400 MHz, CDCl3) 2.55 [1H, d, J 2.3,
CH(OH)], 3.67–3.75 [2H, m, CH2OCH2Ph], 4.08 [1H, d, J 9.8,
CH(OH)], 4.16 [1H, t, J 2.3, CH(OCH2Ph).CHCH2OCH2Ph],
4.31 [1H, d, J 9.8, CO.CHOCH2Ph], 4.43–4.46 [1H, m,
CHCH2OCH2Ph], 4.47–4.56 [2H, ABq, J 11.7, CH2OCH2Ph],
4.61 [1H, d, J 11.2, CH(OCHAHBPh).CH2OCH2Ph], 4.71
[1H, d, J 11.2, CO.CHOCHC HDPh], 4.85 [1H, d, J 11.2,
CHOCHAHBPh.CH2OCH2Ph], 5.19 [1H, d, J 11.2, CO.CHO-
3 5 4
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 4 8 – 3 5 9

View Article Online
2 min), [a]2D5 +36.3 (c 1, CHCl3, 20 h)}; m/z ES− 449 [20%, M −
1.69 mmol) in CH2Cl2 (30 mL) furnished a 3.3 : 1 mixture of
21 and 22 which after purification by column chromatography
gave 21 (553 mg, 0.72 mmol, 46%) as a pale yellow oil and 22
(107 mg, 0.14 mmol, 9%) as a pale yellow oil. 21: Rf 0.17 [3 :
1 pentane–Et2O, double eluted]; dH (400 MHz, CDCl3) 0.03
[3H, s, Si(CH3)A(CH3)B], 0.04 [3H, s, Si(CH3)A(CH3)B], 0.87
[9H, s, SiC(CH3)3], 1.07 [3H, s, C(CH3)A(CH3)B], 1.26 [3H, s,
C(CH3)A(CH3)B], 2.83 [1H, dd, J 14.5, 9.8, CHCHAHBPh],
3.11 [1H, dd, J 14.5, 3.4, CHCHAHBPh], 3.21 [1H, d, J
6.9, CH(OH)], 3.61 [1H, dd, J 10.3, 6.1, CHAHBOCH2Ph],
H+], 495 [100%, MCO2H−].
Preparation of D-galactose 18
Following Representative procedure 6, Pd/C (30 mg) and 17
(83 mg, 0.18 mmol) in EtOAc–EtOH (6 mL) furnished 18
(24 mg, 0.13 mmol, 78%) after recrystallisation. Mp 158–
◦
159 C [MeOH–Et2O] {lit.30 mp 159–162 ◦C [MeOH–Et2O]};
dH (400 MHz, D2O) 3.35 [1H, dd, J 7.9, 9.9, C2HOH (major)],
3.51 [1H, dd, J 3.4, 9.9, C3HOH (major)], 3.56–3.67 [6H, m,
C5HCH2OH (major and minor), C3HOH (minor) and C5HOH
(major)], 3.69 [1H, dd, J 3.4, 11.4, C2HOH (minor)], 3.79 [1H,
d, J 3.2, C4HOH (major)], 3.84 [1H, d, J 7.4, C4HOH (minor)],
3.95 [1H, t, J 6.2, C5HCH2OH (minor)], 4.44 [1H, d, J 7.8,
C1HOH (major)], 5.13 [1H, d, J 3.6, C1HOH (minor)]; [a]2D5
+79.8 (c 0.25, H2O, 15 min), [a]2D5 +76.8 (c 0.25, H2O, 24 h),
{lit.30 [a]2D5 +80.2 (c 0.25, H2O, 15 min), [a]D25 +75.6 (c 0.25, H2O,
24 h)}.
3.73 [1H, dd,
J 9.6, 4.9, CHAHBOCH2Ph], 3.80 [1H,
d, J 5.1, CHOCH2Ph.CH(OTBDMS)], 4.08–4.12 [1H, m,
CH(OTBDMS)], 4.19 [1H, dd, J 9.7, 3.5, CHCH2Ph], 4.33–
4.36 [1H, m, CH(OH)], 4.41 [1H, d, J 11.3, CHOCHAHBPh],
4.52 [2H, s, CH2OCH2Ph], 4.53–4.56 [1H, m, CHOCHC HDPh],
4.60 [1H, d,
J 11.3, CHOCHAHBPh], 4.61 [1H, d, J
10.8, CHOCHCHDPh], 5.46 [1H, d, J 4.3, CO.CHOCH2Ph],
7.21–7.37 [20H, m, PhH]; dC (100 MHz, CDCl3) −4.9,
−4.6 [Si(CH3)2], 18.1 [SiC(CH3)3], 22.0, 27.7 [C(CH3)2],
25.8 [SiC(CH3)3], 35.2 [CHCH2Ph], 64.0 [CHCH2Ph], 69.6
[CH(OH)], 70.7 [CH(OTBDMS)], 71.8 [CH2OCH2Ph], 72.7,
Preparation of 2,4-bis(O-benzyl)-D-fucose 19
Following Representative procedure 3, DIBAL (0.53 mL,
0.26 mmol), (2R,3S,4R,5R)-16 (90 mg, 0.26 mmol) in CH2Cl2
(5 mL) furnished (2R,3S,4R,5R)-1942 (71 mg, 0.21 mmol, 79%,
2 : 1 mixture of anomers) as a white solid after column
chromatography. Rf 0.11 and 0.04 [1 : 1 30–40 ◦C petrol–Et2O];
mp 126–127 ◦C [petrol/Et2O]; dH (400 MHz, CDCl3) 1.20 [3H, d,
J 6.6, CHCH3 (major)], 1.25 [3H, d, J 6.4, CHCH3 (minor)], 2.30
[1H, br s, C3H(OH) (major)], 2.41 [1H, br s, C3H(OH) (minor)],
3.00 [1H, br s, C1H(OH)], 3.49–3.53 [2H, m, C1H(OH) (minor)
and C2HOCH2Ph (minor)], 3.58 [1H, app. d, J 3.2, C4HOCH2Ph
(minor)], 3.60–3.69 [2H, m, C5HCH3 (minor) and C3H(OH)
(minor)], 3.65 [1H, app. d, J 2.6, C4HOCH2Ph (major)], 3.78
[1H, dd, J 3.5, 9.9, C2HOCH2Ph (major)], 4.05 [1H, dd, J
2.6, 9.9, C3H(OH) (major)], 4.16 [1H, q, J 6.6, C5HCH3
(major)], 4.61 [1H, t, J 6.8, C1H(OH) (minor)], 4.64–4.83 [5H,
m, CHOCHAHBPh, CHOCH2Ph (major) and CHOCHAHBPh,
CHOCHCHDPh (minor)], 4.85 [1H, d, J 11.7, CHOCHAHBPh
(major)], 4.90 [1H, d, J 11.4, CHOCHAHBPh (minor)], 4.99
[1H, d, J 11.3, CHOCHCHDPh (minor)], 5.30 [1H, d, J 3.2,
C1HOH (major)], 7.26–7.44 [20H, m, PhH (major and minor)];
[a]D25 +64.0 (c 0.35, CHCl3,10 min), [a]D25 +62.6 (c 0.2, CHCl3,
24 h) {lit.42 ent-[a]D25 −75.5 (c 1.16, CHCl3}.
72.7, 73.3 [CH2OCH2Ph and
2
×
CHOCH2Ph], 77.7
[CHOCH2Ph.CH(OTBDMS)], 77.9 [CO.CHOCH2Ph], 83.1
[C(CH3)2], 126.6, 127.4, 127.5, 127.9 [p-Ph], 127.6, 128.1, 128.2,
128.3, 128.5, 129.1 [m/o-Ph], 137.1, 137.3, 138.2 [i-Ph], 153.0
[C O endocyclic], 171.0 [C O exocyclic]; mmax (thin film, cm−1)
=
=
=
=
3419 [O–H], 1775 [C O endocyclic], 1707.9 [C O endocyclic];
C45H57NO8 requires C 70.37, H 7.48, N 1.82%, found C 70.83, H
7.48, N 2.04%; [a]2D6 +9.3 (c 0.30, CHCl3); m/z LD+ (MALDI)
790, 791, 792 [100%, 60%, 20%, MNa+]. 22: Rf 0.26 [3 :
1 pentane–Et2O; double eluted]; dH (400 MHz, CDCl3) 0.09
[3H, s, Si(CH3)A(CH3)B], 0.11 [3H, s, Si(CH3)A(CH3)B], 0.85
[3H, s, C(CH3)A(CH3)B], 0.89 [9H, s, SiC(CH3)3], 1.14 [3H, s,
C(CH3)A(CH3)B], 2.76 [1H, dd, J 14.5, 10.1, CHCHAHBPh],
3.11 [1H, dd, J 14.5, 3.0, CHCHAHBPh], 3.63–3.67 [1H,
m, CHAHBOCH2Ph], 3.67 [1H, d, J 6.4, CH(OH)], 3.74
[1H, dd, J 9.7, 4.4, CHAHBOCH2Ph], 3.86–3.90 [2H, m,
CHOCH2Ph.CH(OTBDMS) and CHCH2Ph], 4.10–4.14 [1H,
m, CH(OH)], 4.25–4.28 [1H, m, CH(OTBDMS)], 4.45–4.57
[5H, m, CO.CHOCHAHBPh, CHOCH2Ph.CH(OTBDMS) and
CH2OCH2Ph], 4.72 [1H, d, J 11.5, CO.CHOCHAHBPh], 5.27
[1H, d, J 3.4, CO.CHOCH2Ph], 7.11–7.42 [20H, m, PhH];
dC (100 MHz, CDCl3) −4.6 [Si(CH3)2], 18.0 [SiC(CH3)3],
22.0, 27.6 [C(CH3)2], 25.8 [SiC(CH3)3], 35.0 [CHCH2Ph], 63.5
[CHCH2Ph], 70.9 [CH2OCH2Ph], 71.6 [CH(OTBDMS)], 72.3
[CH2OCH2Ph], 72.9 [CH(OH)], 73.2, 73.2 [2 × CHOCH2Ph],
76.2 [CHOCH2Ph.CH(OTBDMS)], 79.9 [CO.CHOCH2Ph],
83.3 [C(CH3)2], 126.5, 127.5, 127.6, 127.6, 127.7, 128.0, 128.1,
128.2, 128.3, 128.4, 128.5, 129.0 [p-Ph and m/o-Ph], 137.2,
Preparation of D-fucose 20
Following Representative procedure 6, Pd/C (15 mg) and 19
(65 mg, 0.19 mmol) in EtOAc–EtOH (6 mL) furnished 20 (21 mg,
0.13 mmol, 67%, 2 : 1 mixture of anomers) after recrystallisation.
Mp 144–146 ◦C [MeOH–Et2O], {lit.31 mp 145–146 ◦C [MeOH–
Et2O]}; dH (400 MHz, D2O) 1.07 [3H, d, J 6.6, C5HCH3 (major)],
1.11 [3H, d, J 6.4, C5HCH3 (minor)], 3.31 [1H, dd, J 7.9,
10.0, C2HOH (major)], 3.50 [1H, dd, J 3.4, 10.0, C3HOH
(major)], 3.60 [1H, app. d, J 2.8, C4HOH (major)], 3.63–3.73
[4H, m, C2HOH (minor), C3HOH (minor), C4HOH (minor)
and C5HCH3 (major)], 4.06 [1H, q, J 6.6, C5HCH3 (minor)],
4.41 [1H, d, J 7.8, C1HOH (major)], 5.06 [1H, d, J 3.7, C1HOH
(minor)]; [a]2D5 +38.4 (c 0.25, H2O, 15 min), [a]2D5 +74.8 (c 0.25,
H2O, 24 h), {lit.31 [a]D25 +39.1 (c 0.25, H2O, 15 min), [a]2D5 +76.0
(c 0.25, H2O, 24 h)}.
Preparation of (2ꢀS,3ꢀR,4S,4ꢀR,5ꢀR)-4-benzyl-3-[2ꢀ,4ꢀ,6-
tris(benzyloxy)-5ꢀ-(tert-butyldimethylsilanyloxy)-3ꢀ-
hydroxyhexanoyl]-5,5-dimethyloxazolidin-2-one 21 and
(2ꢀS,3ꢀS,4S,4ꢀR,5ꢀR)-4-benzyl-3-[2ꢀ,4ꢀ,6-tris(benzyloxy)-5ꢀ-(tert-
butyldimethylsilanyloxy)-3ꢀ-hydroxyhexanoyl]-5,5-
dimethyloxazolidin-2-one 22
=
=
137.9, 138.1, 138.3 [i-Ph], 152.7 [C O endocyclic], 169.7 [C
O
−1
=
exocyclic]; mmax (thin film, cm ) 3458 [O–H], 1774 [C O
=
endocyclic], 1707 [C O endocyclic]; HRMS C45H57NO8NaSi
[MNa+] requires 790.3751, found 790.3773; [a]2D6 +18.3 (c 0.80,
CHCl3); m/z LD+ (MALDI) 790, 791, 792, 793 [100%, 65%,
30%, 10%, MNa+].
Preparation of (2ꢀS,3ꢀR,4S,4ꢀR,5ꢀR)-4-benzyl-3-[2ꢀ,4ꢀ-
bis(benzyloxy)-5ꢀ-(tert-butyldimethylsilanyloxy)-3ꢀ-
hydroxypentanoyl]-5,5-dimethyloxazolidin-2-one 23 and
(2ꢀS,3ꢀS,4S,4ꢀR,5ꢀR)-4-benzyl-3-[2ꢀ,4ꢀ-bis(benzyloxy)-5ꢀ-(tert-
butyldimethylsilanyloxy)-3ꢀ-hydroxypentanoyl]-5,5-
dimethyloxazolidin-2-one 24
Following Representative procedure 1, CF3SO3H (0.19 mL,
2.20 mmol), Et3B (2.20 mL, 2.20 mmol), (S)-1 (650 mg,
i
1.84 mmol), Pr2NEt (0.45 mL, 2.58 mmol) and 12 (600 mg,
1.95 mmol) in CH2Cl2 (20 mL) furnished a 2.2 : 1 ratio of
23 and 24 which after purification by column chromatography
gave 23 (226 mg, 0.34 mmol, 19%) as a pale yellow oil and 24
(677 mg, ∼1.02 mmol, ∼56%) as a white solid contaminated
Following Representative procedure 1, CF3SO3H (0.16 mL,
1.87 mmol), Et3B (1.90 mL, 1.87 mmol), (S)-1 (550 mg,
i
1.56 mmol), Pr2NEt (0.38 mL, 2.18 mmol) and 11 (700 mg,
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 4 8 – 3 5 9
3 5 5

View Article Online
with <5% of (S)-1 after column chromatography. 23: Rf 0.12
[5 : 1 pentane–Et2O]; dH (400 MHz, CDCl3) 0.01 [3H, s,
Si(CH3)A(CH3)B], 0.04 [3H, s, Si(CH3)A(CH3)B], 0.88 [9H, s,
SiC(CH3)3], 1.19 [3H, s, C(CH3)A(CH3)B], 1.21 [3H, d, J
6.3, CHCH3], 1.30 [3H, s, C(CH3)A(CH3)B], 2.86 [1H, dd,
J 14.5, 9.7, CHCHAHBPh], 3.00 [1H, d, J 8.1, CH(OH)],
3.13 [1H, dd, J 14.4, 3.6, CHCHAHBPh], 3.62 [1H, dd,
J 5.4, 1.7, CHOCH2Ph.CH(OTBDMS)], 3.97–4.00 [1H, m,
CH(OTBDMS)], 4.24–4.27 [1H, m, CH(OH)], 4.33 [1H, dd, J
9.7, 3.6, CHCH2Ph], 4.41 [1H, d, J 11.2, CHOCHAHBPh], 4.56–
4.67 [3H, m, CHOCHAHBPh and CHOCH2Ph], 5.39 [1H, d, J
3.9, CO.CHOCH2Ph], 7.21–7.40 [15H, m, PhH]; dC (100 MHz,
CDCl3) −4.8, −4.7 [Si(CH3)2], 18.1 [SiC(CH3)3], 19.0 [CHCH3],
22.1, 27.9 [C(CH3)2], 25.9 [SiC(CH3)3], 35.2 [CHCH2Ph],
64.0 [CHCH2Ph], 68.2 [CH(OTBDMS)], 69.5 [CH(OH)],
72.8, 73.3 [2 × CHOCH2Ph], 78.9 [CO.CHOCH2Ph], 79.9
[CHOCH2Ph.CH(OTBDMS)], 83.1 [C(CH3)2], 126.7, 127.1,
127.5, [p-Ph], 127.9, 128.0, 128.2, 128.3, 128.7, 129.1 [m/o-Ph],
26 (127 mg, 0.37 mmol, 97%, 4 : 1 mixture of anomers) as a
white solid after column chromatography. Rf 0.12 and 0.04 [1 :
1 30–40 ◦C petrol–Et2O]; mp 108–109 ◦C [MeOH–Et2O]; dH
(400 MHz, CDCl3)43 1.27 [3H, d, J 6.9, C5HCH3 (a-p)], 1.39
[3H, d, J 6.5, C5HCH3 (b-p)], 2.10 [1H, d, J 3.2, C3H(OH)
(b-p)], 2.75 [1H, d, J 3.7, C3H(OH) (a-p)], 3.22–3.23 [1H, m,
C4HOCH2Ph (b-p)], 3.31 [1H, dd, J 7.9, 5.7, C2HOCH2Ph (a-
p)], 3.38 [1H, dd, J 4.5, 2.6, C2HOCH2Ph (b-p)], 3.48 [1H, dd,
J 7.0, 4.5, C4HOCH2Ph (a-p)], 3.74 [1H, d. J 9.6, C1H(OH)
(b-p)], 3.94 [1H, app. td, C3H(OH) (a-p)], 4.05 [1H, qd, J
6.8, 3.2, C5HCH3 (b-p)], 4.15–4.18 [1H, m, C3H(OH) (b-p)],
4.29 [1H, qd, J 6.9, 4.6, C5HCH3 (a-p)], 4.57 [1H, d, J 12.0,
CHOCHAHBPh (b-p)], 4.61 [1H, d, J 11.8, CHOCHAHBPh (a-
p)], 4.64 [1H, d, J 2.6, CHOCHC HDPh (b-p)], 4.67 [1H, d, J 2.6,
CHOCHCHDPh (b-p)], 4.68–4.73 [2H, ABq, J 5.4, CHOCH2Ph
(a-p)], 4.74 [1H, d, J 12.0, CHOCHAHBPh (b-p)], 4.84 [1H, d,
J 11.8, CHOCHAHBPh (a-p)], 5.02 [1H, dd, J 9.4, 2.6, C1HOH
(b-p)], 5.04–5.06 [1H, m, C1H(OH) (a-p)], 7.27–7.42 [20H, m,
PhH (a-p and b-p)]; dC (100 MHz, CDCl3) 14.3 [C5HCH3 (a-
p)], 16.9 [C5HCH3 (b-p)], 66.5 [C3HOH (b-p)], 66.9 [C5HCH3
(a-p)], 69.8 [C5HCH3(b-p)], 70.6 [C3H(OH) (a-p)], 72.7, 73.6
[2 × CHOCH2Ph (a-p)], 72.8, 73.1 [2 × CHOCH2Ph (b-p)],
77.5 [C2HOCH2Ph and C4HOCH2Ph (b-p)], 78.8 [C4HOCH2Ph
(a-p)], 80.3 [C2HOCH2Ph (a-p)], 92.0 [C1H(OH) (b-p)], 93.6
[C1H(OH) (a-p)], 127.8, 127.9 [p-Ph (a-p)], 127.9, 128.1, 128.4,
128.5 [m/o-Ph (a-p)], 128.0, 128.2, 128.4, 128.6 [p- and m/o-Ph
(b-p)], 138.1 [i-Ph (a-p and b-p)]; mmax (KBr disc, cm−1) 3427
[O–H], 1095 [C–O]; C28H31O8 [MNa+] requires 367.1521, found
367.1525; [a]2D5 +2.0 (c 0.2, CHCl3, 15 min), [a]2D5 +2.1 (c 0.2,
CHCl3, 24 h); m/z ES+ 367 [100%, MNa+].
=
=
137.0, 137.2, 138.3 [i-Ph], 152.7 [C O endocyclic], 170.8 [C
exocyclic]; mmax (KBr disc, cm ) 3435 [O–H], 1765 [C O endo-
O
−1
=
+
=
cyclic], 1705 [C O exocyclic]; HRMS C38H55N2O7Si [MNH4
]
requires 679.3779, found 679.3769; m/z LD+ (MALDI) 684,
685, 686, 687 [100%, 50%, 20%, 5%, MNa+], 700, 701, 702
[40%, 30%, 10%, MK+]. 24: Rf 0.19 [5 : 1 pentane: Et2O];
dH (400 MHz, CDCl3) 0.09 [3H, s, Si(CH3)A(CH3)B], 0.10
[3H, s, Si(CH3)A(CH3)B], 0.89 [9H, s, C(CH3)3], 0.92 [3H, s,
C(CH3)A(CH3)B], 1.17 [3H, s, C(CH3)A(CH3)B], 1.30 [3H, d,
J 6.4, CHCH3], 2.79 [1H, dd, J 14.5, 10.0, CHCHAHBPh],
3.11 [1H, dd, J 14.5, 3.3, CHCHAHBPh], 3.75 [1H, dd, J 7.8,
3.6, CHOCH2Ph.CH(OTBDMS)], 3.97 [1H, dd, J 10.0, 3.3,
CHCH2Ph], 4.14–4.20 [2H, m, CH(OTBDMS) and CH(OH)],
4.47–4.56 [3H, m, CHOCHAHBPh and CHOCH2Ph], 4.72 [1H,
d, J 11.6, CHOCHAHBPh], 5.31 [1H, d, J 3.3, CO.CHOCH2Ph],
7.15–7.44 [15H, m, PhH]; dC (100 MHz, CDCl3) −4.9, −4.7
[Si(CH3)2], 17.7 [CHCH3], 17.9 [C(CH3)3], 22.0, 27.5 [C(CH3)2],
25.7 [C(CH3)3], 35.1 [CHCH2Ph], 63.6 [CHCH2Ph], 68.6
[CH(OTBDMS)], 72.3, 73.3 [2 × CHOCH2Ph], 73.2 [CH(OH)],
77.5 [CHOCH2Ph.CH(OTBDMS)], 79.9 [CO.CHOCH2Ph],
83.2 [C(CH3)2], 126.6, 127.5, 127.7 [p-Ph], 127.9, 128.1,
128.3, 128.5, 129.0, 129.1 [m/o-Ph], 137.2, 138.1, 138.2 [i-
Preparation of D-6-deoxyidose 27
Following Representative procedure 6, Pd/C (25 mg) and 26
(150 mg, 0.43 mmol) in EtOAc–EtOH (12 mL) furnished 2744
(62 mg, 0.38 mmol, 89%) as a viscous oil after titration with Et2O.
dH (400 MHz, D2O, selected peaks) 1.14–1.22 [12H, m, a-p, a-
f, b-p, b-p C5HCH3], 3.22–3.26 [3H, m, a-p, b-p, a-f C3HOH],
3.39 [1H, s, b-f C3HOH], 3.57–3.67 [4H, m, a-p, b-p, a-f, b-f
C4HOH], 3.85–3.89 [1H, m, f, C5HCH3], 3.91–3.99 [1H, m, f,
C5HCH3], 4.01–4.09 [1H, m, p, C5HCH3], 4.12–4.18 [1H, m, p,
C5HCH3], 4.44 [1H, s, a-p, C1HOH], 4.79 [1H, d, J 6.9, b-p,
C1HOH], 5.00 [1H, s, a-f, C1HOH], 5.13 [1H, s, b-f, C1HOH];
dC (100 MHz, D2O) 12.9, 16.0 [a-p, b-p C5HCH3], 18.2, 18.6
[a-f, b-f C5HCH3], 64.4, 66.6, 67.5, 75.2, 75.8, 76.6, 82.6, 86.2
[a-f, b-f], 69.9, 70.0, 70.5, 70.7 [b-p], 70.2, 71.9, 72.1, 74.2 [a-p],
92.5 [a-p C1HOH], 92.7 [b-p C1HOH], 96.3 [b-f C1HOH], 102.4
[a-f C1HOH]; mmax (thin film, cm−1) 3423 [O–H], 1495, 1457 [C–
O]; HRMS C6H11O5 [M–H+] requires 163.0606, found 163.0607;
[a]D25 +9.0 (c 1.5, H2O; 15 min), [a]D25 +12.0 (c 1.5, H2O; 24 h)
{lit.44 [a]2D5 +12.0 (c 2.67, H2O), lit.32 [a]D25 +14.7 (c 0.7, H2O);
m/z ES− 163.0 [100%, M − H+].
=
=
Ph], 152.8 [C O endocyclic], 170.2 [C O exocyclic]; mmax (thin
−1
=
=
film, cm ) 3459 [O–H], 1777 [C O endocyclic], 1706 [C O
exocyclic]; HRMS C38H55N2O7Si [MNH4+] requires 679.3779,
found 679.3774; [a]2D6 +9.6 (c 1.5, CHCl3); m/z LD+ (MALDI)
684, 685, 686, 687 [100%, 40%, 15%, 5%, MNa+], 700, 701, 702
[50%, 20%, 10%, MK+].
Preparation of (2S,3R,4R,5R)-2,4-bis(benzyloxy)-3-hydroxy-5-
methyltetrahydropyran-2-one 25
Following Representative procedure 5, 23 (200 mg, 0.30 mmol),
TBAF (0.45 mL, 0.45 mmol) and AcOH (0.02 mL, 0.30 mmol) in
THF (10 mL) furnished 25 (78 mg, 0.228 mmol, 76%) as a white
solid after column chromatography. Rf 0.12 [1 : 1 pentane–Et2O];
mp 84–85 ◦C [pentane–Et2O]; dH (400 MHz, CDCl3) 1.39 [3H,
d, J 6.5, CHCH3], 3.56 [1H, t, J 2.1, CH(OCH2Ph).CHCH3],
4.03–4.08 [2H, m, CH(OH) and CO.CHOCH2Ph], 4.51 [1H,
d, J 12.0, CHOCHAHBPh], 4.53–4.57 [1H, m, CHCH3],
4.60 [1H, d, J 11.4, CHOCHCHDPh], 4.76 [1H, d, J 12.0,
CHOCHAHBPh], 5.12 [1H, d, J 11.4, CHOCHCHDPh], 7.27–
7.43 [10H, m, PhH]; dC (100 MHz, CDCl3) 15.7 [CHCH3], 71.1,
73.2 [2 × CHOCH2Ph], 73.7 [CHCH3], 74.1 [CO.CHCH2Ph],
77.9 [CH(OH)], 79.3 [CHOCH2Ph.CHCH3], 127.9, 127.9 [p-Ph],
Preparation of (2ꢀS,3ꢀR,4S,4ꢀS,5ꢀR)-4-benzyl-3-(2ꢀ,4ꢀ,5ꢀ-
tris(benzyloxy)-3ꢀ,5ꢀ-dihydroxyhexanoyl)-5,5-
dimethyloxazolidin-2-one 28
A solution of iodine in methanol (1% m/v; 30 mL) was added
to 21 (280 mg, 0.36 mmol) at ambient temperature and the
resultant mixture refluxed at 85 ◦C for 6 h. After cooling
to ambient temperature, the reaction mixture was quenched
with a saturated aqueous sodium thiosulfate solution, diluted
with CH2Cl2, washed with brine, dried and concentrated in
vacuo. Purification by column chromatography furnished 28
(159 mg, 0.24 mmol, 68%) as a clear colourless oil. Rf 0.07
[1 : 1 30–40 ◦C petrol–Et2O]; dH (400 MHz, CDCl3) 1.26
[3H, s, C(CH3)A(CH3)B], 1.32 [3H, s, C(CH3)A(CH3)B], 2.87
[1H, dd, J 14.4, 9.5, CHCHAHBPh], 3.13 [1H, dd, J 14.4, 3.8,
CHCHAHBPh], 3.54 [1H, dd, J 9.5, 6.0, CHAHBOCH2Ph], 3.59
[1H, dd, J 9.5, 3.8, CHAHBOCH2Ph], 3.87 [1H, dd, J 5.9,
2.9, CH(OCH2Ph).CH(OH)CH2OCH2Ph], 3.97–4.01 [1H, m,
128.2, 128.3, 128.4, 128.6 [m/o-Ph], 136.8, 137.0 [i-Ph], 169.6
−1
=
=
[C O]; mmax (thin film, cm ) 3447 [O–H], 1717 [C O]; HRMS
C20H22O5Na [MNa+] requires 365.1365, found 365.1352; [a]2D6
−95.8 (c 1.5, CHCl3); m/z ES+ 365 [MNa+, 100%].
Preparation of 2,4-di-O-benzyl-D-6-deoxyidose 26
Following Representative procedure 3, DIBAL (0.76 mL,
0.76 mmol), 25 (130 mg, 0.38 mmol) in CH2Cl2 (5 mL) furnished
3 5 6
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 4 8 – 3 5 9

View Article Online
CH(OH)CH2OCH2Ph], 4.27 [1H, dd, J 5.9, 3.4, CO.CH-
(OCH2Ph).CH(OH)], 4.38–4.43 [2H, m, CHCH2Ph and 1 ×
OCH2Ph], 4.72–4.47 [4H, m, 4 × OCH2Ph], 4.82 [1H, d, J 11.2,
1 × OCH2Ph], 5.39 [1H, d, J 3.4, CO.CHOCH2Ph], 7.18–7.45
[20H, m, PhH]; dC (100 MHz, CDCl3) 22.0, 28.1 [C(CH3)2], 35.2
[CHCH2Ph], 63.9 [CHCH2Ph], 69.6 [CH(OH)CH2OCH2Ph],
71.0 [CH2OCH2Ph], 71.5 [CO.CHOCH2Ph.CH(OH)], 72.8,
138.0, 138.1 [i-Ph (major and minor)]; mmax (thin film, cm−1) 3419
[O–H], 1496, 1454 [C–O]; HRMS C27H34O6N [MNH4+] requires
468.2386, found 468.2386; [a]2D5 −3.5 (c 0.2, CHCl3, 15 min), [a]2D5
−3.7 (c 0.2, CHCl3, 24 h); m/z ES+ 473 [100%, MNa+].
Preparation of D-idose 31
73.3, 74.7 [CH2OCH2Ph and
2
×
CHOCH2Ph], 77.5
Following Representative procedure 6, Pd/C (25 mg) and 30
(70 mg, 0.15 mmol) in EtOAc–EtOH (6 mL) furnished 3138
(24 mg, 0.13 mmol, 89%) as an oil after trituration with Et2O. dH
(400 MHz) 3.30 [1H, dd, J 8.1, 6.1, a-p C6HAHBOH], 3.37 [1H,
dd, J 9.3, 4.7, a-f C6HAHBOH], 3.46–3.51 [1H, m], 3.55–3.61
[5H, m], 3.62–3.80 [6H, m], 3.87–3.91 [3H, m], 3.96 [1H, t, J
3.7], 3.99–4.06 [3H, m], 4.09 [1H, t, J 4.8], 4.87 [1H, d, J 6.1, b-p
C1HOH], 4.96 [1H, d, J 1.5, a-p C1HOH], 5.10 [1H, d, J 1.2,
b-f C1HOH], 5.31 [1H, d, J 4.3, a-f C1HOH]; [a]2D5 +7.7 (c 0.3,
H2O; 15 min), [a]D25 +6.3 (c 0.3, H2O; 24 h) {lit.38 ent-[a]2D5 −9.8
(c 0.45, H2O; 15 min), [a]2D5 −8.0 (c 0.45, H2O; 24 h)}.
[CO.CHOCH2Ph], 78.8 [CH(OCH2Ph).CH(OH)CH2OCH2Ph],
83.7 [C(CH3)2], 126.8, 127.7, 128.1, 128.9 [p-Ph], 127.8, 128.3,
128.4, 128.4, 128.6, 128.7, 129.1 [m/o-Ph], 136.8, 137.0, 137.9 [i-
=
=
Ph], 152.5 [C O endocyclic], 170.1 [C O exocyclic]; mmax (thin
−1
=
=
film, cm ) 3482 [O–H], 1773 [C O endocyclic], 1706 [C O
exocyclic]; HRMS C39H43NO8Na [MNa+] requires 676.2886,
found 676.2877; [a]2D6 +18.2 (c 0.3, CHCl3); m/z ES+ 676 [100%,
MNa+].
Preparation of (2S,3R,4R,5R)-2,4-bis(benzyloxy)-3-hydroxy-5-
(benzyloxymethyl)tetrahydropyran-2-one 29
A solution of 28 (263 mg, 0.40 mmol) in PhMe (20 mL) was
refluxed for 16 h, then cooled to ambient temperature and con-
centrated in vacuo. Purification by column column chromato-
graphy gave (2S,3R,4R,5R)-29 (158 mg, 0.35 mmol, 88%) as
a clear colourless oil. Rf 0.17 [1 : 1 30–40 ◦C petrol–Et2O];
dH (400 MHz, C6D6) 2.37 [1H, d, J 2.8, OH], 3.60 [1H, dd,
J 10.0, 5.2, CHAHBOCH2Ph], 3.66 [1H, t, J 2.9, CH(OCH2-
Ph).CHCH2OCH2Ph], 3.79 [1H, dd, J 10.0, 6.0, CHAHB-
OCH2Ph], 3.81 [1H, d, J 8.7, CO.CHOCH2Ph], 4.08 [1H, dt,
J 8.7, 2.8, CH(OH)], 4.25–4.33 [3H, m, CHCH2OCHAHBPh
and CHOCHAHBPh], 4.36 [1H, d, J 13.9, CHCH2OCHAHBPh],
4.55 [1H, d, J 11.3, CHOCHC HDPh], 4.62 [1H, d, J 11.8,
CHOCHAHBPh], 5.19 [1H, d, J 11.3, CHOCHCHDPh], 7.04–
7.31 [13H, m, PhH], 7.42–7.48 [2H, m, PhH]; dC (100 MHz,
C6D6) 68.5 [CH2OCH2Ph], 71.6 [CH2OCH2Ph], 73.6, 73.7
[2 × CHOCH2Ph], 74.4 [CH(OH)], 76.2 [CHCH2OCH2Ph],
78.1 [CH(OCH2Ph).CHCH2OCH2Ph], 78.9 [CO.CHOCH2Ph],
128.0, 128.2, 128.5, 128.1 [m/o-Ph], 128.1, 128.4, 128.6 [p-Ph],
Preparation of (2S,3S,4R,5R)-2,4-bis(benzyloxy)-3-hydroxy-5-
(benzyloxymethyl)tetrahydropyran-2-one 32
Following Representative procedure 5, 22 (100 mg, 0.13 mmol),
TBAF (0.2 mL, 0.20 mmol) and AcOH (0.007 mL, 0.13 mmol)
in THF (5 mL) furnished a 1 : 2 mixture of 32 and
(S)-4-benzyl-5,5-dimethyloxazolidin-2-one (55 mg) as a pale
yellow oil after column chromatography. 32: Rf 0.09 [1 :
1 pentane–Et2O]; dH (400 MHz, CDCl3) 3.45 [1H, d, J
4.8, OH], 3.75–3.77 [2H, m, CH2OCH2Ph], 3.97–4.00 [2H,
m, CH(OCH2Ph).CH2OCH2Ph and CO.CHOCH2Ph], 4.33–
4.37 [1H, m, CH(OH)], 4.43–4.48 [1H, m, CHCH2OCH2Ph],
4.51–4.57 [3H, m, CHOCHAHBPh, CHOCHC HDPh and
CH2OCHAHBPh], 4.69–4.96 [2H, m, CHOCHAHBPh and
CHOCHCHDPh], 5.07 [1H, d, J 12.1, CH2OCHAHBPh], 7.17–
7.39 [15H, m, PhH]; dC (100 MHz, CDCl3) 67.2 [CH(OH)],
67.9 [CH2OCH2Ph], 72.1 [CH(OCH2Ph).CHCH2OCH2Ph],
73.1, 73.5, 73.7 [CH2OCH2Ph and 2 × CHOCH2Ph], 74.1
[CO.CHOCH2Ph], 77.3 [CHCH2OCH2Ph], 127.8, 127.9, 128.0,
128.2, 128.3, 128.4, 128.5, 128.6, 129.1 [p- and m/o-Ph], 136.6,
138.1, 138.3, 138.5 [i-Ph], 169.2 [C O]; mmax (thin film, cm−1)
=
3445 [O–H], 1749 [C O]; HRMS C27H32NO6 [MNH4+] requires
=
136.8, 137.2 [i-Ph], 168.9 [C O]; mmax (thin film, cm−1) 3328 [O–
H], 1751 [C O]; HRMS C27H28O6Na [MNa ] requires 471.1784,
=
466.2230, found 466.2226; [a]2D5 −73.0 (c 0.5, CHCl3); m/z ES+
+
=
466 [100%, MNH4+], 471 [40%, MNa+].
found 471.1778; m/z ES+ 466 [60%, MNH4+], 471 [100%,
MNa+].
Preparation of 2,4,6-tri-O-benzyl-D-idose 30
Following Representative procedure 3, DIBAL (0.36 mL,
0.36 mmol), 29 (80 mg, 0.17 mmol) in CH2Cl2 (10 mL) furnished
30 (72 mg, 0.16 mmol, 89%, 2 : 1 mixture of anomers) as a
clear colourless oil after column chromatography. Rf 0.1 [1 : 1
30–40 ◦C petrol–Et2O]; dH (400 MHz, CDCl3) 1.71 [1H, br s,
C1H(OH) (major)], 2.20 [1H, br s, C1H(OH) (minor)], 2.86 [1H,
d, J 5.2, C3H(OH) (major)], 3.35–3.39 [2H, m, C2HOCH2Ph
(major and minor)], 3.51–3.54 [2H, m, C4HOCH2Ph (major
and minor)], 3.59 [1H, dd, J 10.6, 3.7, CHAHBOCH2Ph (major)],
3.70 [1H, dd, J 10.5, 5.2, CHAHBOCH2Ph (minor)], 3.78–3.82
[2H, m, C6HAHBOCH2Ph (major and minor)], 3.99 [1H, q,
J 5.8, C3H(OH) (major)], 3.99 [1H, br s, C3H(OH) (minor)],
4.12 [1H, q, J 4.8, C5HCH2OCH2Ph (minor)], 4.16–4.21 [1H,
m, C3H(OH) (minor)], 4.32–4.36 [1H, m, C5HCH2OCH2Ph
(major)], 4.48–4.79 [12H, m, 6 × OCH2Ph (major and minor)],
5.07 [1H, dd, J 10.2, 3.1, C1H(OH) (minor)], 5.22 [1H, t, J 4.1,
C1H(OH) (major)], 7.19–7.42 [30H, m, PhH (major and minor)];
dC (100 MHz, CDCl3) 69.2 [C5HCH2OCH2Ph (minor)], 68.4
[C5HCH2OCH2Ph (major)], 69.0, 69.1 [CH2OCH2Ph (major
and minor)], 72.5, 73.3, 73.5 [CH2OCH2Ph and 2 × CHOCH2Ph
(major)], 72.6, 72.8 [C3H(OH) (major and minor)], 73.0, 73.4,
73.6 [CH2OCH2Ph and 2 × CHOCH2Ph (minor)], 76.6, 76.7
[C4HOCH2Ph (major and minor)], 78.0, 78.2 [C2HOCH2Ph
(major and minor)], 94.3 [C1H(OH) (major)], 95.7 [C1H(OH)
(minor)], 127.7, 127.8, 127.9, 128.0, 128.1, 128.2, 128.3, 128.4,
128.5, 128.6 [p- and m/o-Ph (major and minor)], 137.8, 137.9,
Preparation of 2,4,6-tri-O-benzyl-D-talose 33
Following Representative procedure 3, DIBAL (0.58 mL,
0.58 mmol), 32 (130 mg, 1 : 2 mixture of 32 and (S)-4-benzyl-
5,5-dimethyloxazolidin-2-one) in CH2Cl2 (5 mL) furnished a
mixture of 33 and (S)-4-benzyl-5,5-dimethyloxazolidin-2-one
(120 mg, one anomer, 1 : 2 mixture of 33 and (S)-4-benzyl-
5,5-dimethyloxazolidin-2-one) as a clear colourless oil after
column chromatography. 33: Rf 0.22 [1 : 2 30–40 ◦C petrol–
Et2O]; dH (400 MHz, C6D6) 3.17 [1H, d, J 11.2, C3HOH],
3.58–3.62 [2H, m, CHAHBOCH2Ph and C4HOCH2Ph], 3.72
[1H, dd, J 1.6, 4.1, C2HOCH2Ph], 3.76 [1H, dd, J 7.3, 9.6,
CHAHBOCH2Ph], 4.10 [1H, br s, C1HOH], 4.18–4.22 [1H, m,
C3HOH], 4.23 [1H, d, J 11.8, CHOCHAHBPh], 4.29 [1H, d, J
11.8, CHOCHAHBPh], 4.31 [1H, d, J 11.8, CHOCHC HDPh],
4.39–4.43 [1H, m, C5HCH2OCH2Ph], 4.52 [1H, d, J 11.8,
CHOCHCHDPh], 4.56 [1H, d, J 11.8, CH2CHOCHAHBPh],
4.72 [1H, d, J 11.8, CH2CHOCHAHBPh], 5.46 [1H, app. s,
C1HOH], 7.11–7.43 [15H, m, PhH]; dC (100 MHz, C6D6)
66.8 [C3H(OH)], 69.4 [C5HCH2OCH2Ph], 70.5 [CH2OCH2Ph],
73.1 [CH2OCH2Ph and CHOCH2Ph], 75.5 [CHOCH2Ph], 77.4
[C4HOCH2Ph], 78.5 [C2HOCH2Ph], 92.4 [C1H(OH)], 127.6,
127.9 [p-Ph], 127.6, 127.7, 128.8, 129.2 [m/o-Ph], 139.0, 139.3,
139.7 [i-Ph]; mmax (thin film, cm−1) 3411 [O–H], 1644, 1604 [C–O];
HRMS C27H30O6Na [MNa+] requires 473.1940, found 473.1944;
m/z ES+ 473 [100%, MNa+].
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 4 8 – 3 5 9
3 5 7

View Article Online
Preparation of D-talose 34
5.11 [1H, d, J 1.4, a-f C1HOH], 5.23 [1H, s, b-f C1HOH]; dC
(125 MHz, D2O) 15.9 [b-p C5HCH3], 16.1 [a-p C5HCH3], 18.3
[a-f C5HCH3], 18.7 [b-f C5HCH3], 61.6 [a-f C5HCH3], 65.6 [a-
p C3H(OH)], 67.3 [a-p C5HCH3], 67.5 [b-f C5HCH3],69.0 [b-
p C3H(OH)], 69.3 [a-f C3H(OH)], 70.7 [a-p C2H(OH)], 70.8
[b-f C2H(OH)], 71.4 [b-f C3H(OH)], 71.5 [b-p C5HCH3], 71.6
[b-p C4H(OH) and C2H(OH)], 72.5 [a-p C4H(OH)], 75.7 [a-f
C2H(OH)], 86.1 [a-f C4H(OH)], 86.8 [b-f C4H(OH)], 94.2 [a-p
C1H(OH)], 94.9 [b-p C1H(OH)], 96.3 [b-f C1H(OH)], 100.9 [a-f
C1H(OH)]; [a]D25 +19.1 (c 0.35, H2O; 15 min), [a]2D5 +17.7 (c 0.35,
H2O; 24 h), {lit.40ent-[a]D25 −17.3 (c 0.35, H2O; 24 h)}.
Following Representative procedure 6, Pd/C (20 mg) and
an inseparable 1 : 2 mixture of 33 and (S)-4-benzyl-5,5-
dimethyloxazolidin-2-one (130 mg) in EtOAc–EtOH (6 mL)
furnished 3439 (11 mg, 0.06 mmol) after titration with Et2O. Mp
131–134 ◦C [Et2O]; dH (400 MHz, D2O) 3.51–3.55 [2H, m], 3.61
[1H, d, J 4.2], 3.65–3.70 [6H, m], 3.71–3.76 [6H, m], 3.80–3.82
[4H, m], 3.86–3.90 [1H, m], 3.97–4.01 [2H, m], 4.09 [1H, t, J 3.5],
4.22–4.23 [1H, m], 4.72 [1H, d, J 1.1, b-p C1HOH], 5.15 [1H, s,
a-f C1HOH], 5.18 [1H, d, J 1.8, a-p C1HOH], 5.27 [1H, d, J
3.5, b-f C1HOH]; [a]D25 +18.6 (c 0.35, H2O; 15 min), [a]2D5 +19.4
(c 0.35, H2O; 24 h) {lit.39 [a]D25 +22.0 (c 0.5, H2O; 15 min), [a]2D5
+19.8 (c 0.5, H2O; 24 h)}.
Acknowledgements
The authors wish to thank Astra-Zeneca for a studentship
(R. L. N.) and New College, Oxford for a Junior Research
Fellowship (A. D. S.).
Preparation of (2S,3S,4R,5R)-2,4-bis(benzyloxy)-3-hydroxy-5-
methyltetrahydropyran-2-one 35
Following Representative procedure 5, 24 (140 mg, 0.21 mmol),
TBAF (0.32 mL, 0.32 mmol) and AcOH (0.012 mL, 0.21 mmol)
in THF (10 mL) furnished an inseparable 1.4 : 1 mixture
of 35 and (S)-4-benzyl-5,5-dimethyloxazolidin-2-one (128 mg)
as a pale yellow oil after column chromatography. 35: Rf
0.15 [1 : 2 40–60 ◦C petrol–Et2O]; dH (400 MHz, CDCl3)
1.41 [3H, d, J 6.6, CHCH3], 3.21 [1H, d, J 3.5, CH(OH)],
3.76 [1H, dd, J 5.8, 4.2, CH(OCH2Ph).CHCH3], 4.04 [1H,
d, J 3.7, CO.CHOCH2Ph], 4.36–4.43 [2H, m, CHCH3 and
CH(OH)], 4.59 [1H, d, J 11.8, CHOCHAHBPh], 4.71 [1H, d,
J 12.1, CHOCHC HDPh], 4.75 [1H, d, J 11.8, CHOCHAHBPh],
5.09 [1H, d, J 12.1, CHOCHCHDPh], 7.17–7.40 [10H, m,
PhH]; dC (100 MHz, CDCl3) 16.1 [CHCH3], 67.6 [CH(OH)],
72.9, 73.7 [2 × CHOCH2Ph], 73.8 [CHOCH2Ph.CHCH3], 74.2
[CO.CHCH2Ph], 74.8 [CHCH3], 127.2, 128.0, 128.1, 128.4,
References
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=
128.7, 129.1 [p- and m/o-Ph], 136.8, 136.9 [i-Ph], 157.9 [C O];
−1
+
=
mmax (thin film, cm ) 1748 [C O]; HRMS C20H22O5Na [MNa ]
requires 365.1365, found 365.1372; m/z ES+ 343 [12%, MH+],
360 [100%, MNH4+], 365 [35%, MNa+].
Preparation of 2,4-bis(O-benzyl)-D-talose 36
Following Representative procedure 3, DIBAL (0.32 mL,
0.32 mmol), 35 (55 mg, 1 : 1 mixture of 35 and (S)-4-benzyl-
5,5-dimethyloxazolidin-2-one) in CH2Cl2 (5 mL) furnished 36
(46 mg, single anomer, 1 : 2 mixture of 36 and (S)-4-benzyl-
5,5-dimethyloxazolidin-2-one) as a pale yellow oil after column
chromatography. 36: Rf 0.12 [1 : 1 30–40 ◦C petrol–Et2O]; dH
(400 MHz, CDCl3) 1.27 [3H, d, J 6.7, C5HCH3], 3.39 [1H, d,
J 3.0, C1H(OH)], 3.49 [1H, dd, J 3.8, 1.8, C4HOCH2Ph], 3.52–
3.55 [1H, m, C2HOCH2Ph], 3.90–3.95 [1H, m, C3H(OH)], 4.12–
4.17 [1H, m, C5HCH3], 4.49 [1H, d, J 12.0, CHOCHAHBPh],
4.63 [1H, d, J 11.8, CHOCHCHDPh], 4.77 [1H, d, J 11.8,
CHOCHCHDPh], 4.81 [1H, d, J 12.0, CHOCHAHBPh], 5.37 [1H,
app. s, C1H(OH)]; dC (100 MHz, CDCl3) 16.8 [C5HCH3], 66.2,
66.3 [C3H(OH) and C5HCH3], 73.5, 75.8 [2 × CHOCH2Ph],
79.1, 78.4 [2 × CHOCH2Ph], 92.3 [C1H(OH)], 127.6, 127.7 [p-
Ph], 127.8, 127.9, 128.3, 128.4 [m/o-Ph], 138.0, 138.5 [i-Ph];
mmax (thin film, cm−1) 2929 [O–H], 1496, 1455 [C–O]; HRMS
C20H24O5Na [MNa+] requires 367.1521, found 367.1522; m/z
ES+ 367 [100%, MNa+].
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O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 4 8 – 3 5 9

View Article Online
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30 D-Galactose 97%, Aldrich Chemical Company, £11.60 (100 g).
31 D-Fucose 96%, Aldrich Chemical Company, £34.50 (1 g).
32 M. B. Perry and V. Daoust, Can. J. Chem., 1973, 51, 3039.
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19 S. G. Davies, I. A. Hunter, R. L. Nicholson, P. M. Roberts, E. D.
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21 S. G. Davies, R. L. Nicholson and A. D. Smith, Synlett, 2002, 1637.
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23 (a) The syn-configuration within 5 and 6 was assigned upon the
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43 a-p and b-p refer to a-pyranose and b-pyranose species; a-f and b-f
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44 Y. Tsuda, T. Nunozawa and K. Yoshimoto, Chem. Pharm. Bull.,
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O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 3 4 8 – 3 5 9
3 5 9