Double diastereoselective SuperQuat glycolate aldol reactions: Application to the asymmetric synthesis of polyfunctionalised lactones

Article abstract of DOI:10.1039/b411724g

Polyfunctionalised lactones with up to five contiguous stereocentres may be prepared with high stereocontrol by a double diastereoselective aldol protocol with protected homochiral α,β-dihydroxy- or α,β-γ-trihydroxyaldehydes and a chiral glycolate oxazoli

Full text of DOI:10.1039/b411724g

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A R T I C L E
Double diastereoselective SuperQuat glycolate aldol reactions:
Application to the asymmetric synthesis of polyfunctionalised
lactones
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 30th July 2004, Accepted 13th September 2004
First published as an Advance Article on the web 11th October 2004
Polyfunctionalised lactones with up to five contiguous stereocentres may be prepared with high stereocontrol by a
double diastereoselective aldol protocol with protected homochiral a,b-dihydroxy- or a,b-c-trihydroxyaldehydes and
a chiral glycolate oxazolidinone, followed by subsequent O-desilylation and lactonisation.
dergo base promoted fragmentation (K2CO3/MeOH) to give the
highly functionalised and differentially protected a,b-dihydroxy-
Introduction
The aldol reaction is one of the most powerful transformations
for the stereocontrolled formation of C–C bonds available to the
aldehydes 7 in good yield and without loss of stereochemical
integrity (Fig. 2).19
synthetic chemist today. Stereocontrol in these reactions may be
achieved through the application of chiral catalysts,1 chiral Lewis
acids2 and chiral auxiliaries,3 with the relationship between eno-
late geometry and product configuration generally well defined
and understood.4 Within this context, the glycolate aldol reaction
represents a powerful transformation for the stereocontrolled
formation of 1,2-diol units and has found numerous applica-
tions in total synthesis and the preparation of natural product
fragments.5 Stereocontrol in these reactions has been achieved
through the use of chiral catalysts, reagents or auxiliaries. While
examples of catalytic and chiral reagent controlled asymmetric
glycolate aldol reactions are somewhat limited, the use of tin(II)6
and zinc7 catalysts and, more recently, proline organocatalysis8
have been reported, although the use of chiral reagents has been
largely confined to the use of chiral enol borinates.9 In contrast,
a number of chiral auxiliaries have been used in glycolate aldol
reactions including the boron enolates of norephedrine ester,10
4-oxapyrone11 and selone12 auxilaries. The most widely used aux-
iliary for these reactions is arguably Evans’ oxazolidinone13 and
its thio-oxazolidinethione derivatives, with highly stereoselective
routes to syn- and anti-stereoisomers available by judicious choice
of the Lewis acid used to generate the enolate. For example, syn-
aldol products 2 are observed for the boron14 and titanium15
Fig. 2 Asymmetric synthesis of differentially protected a,b-dihydroxy-
enolate aldol additions of glycolate oxazolidinones 1, while con-
versely, the titanium16 enolates of glycolate oxazolidinethiones
and the tin(II)17 enolates of glycolate oxazolidinones generate the
corresponding anti- aldol products such as 3 (Fig. 1).
aldehydes.
As part of our ongoing research directed toward the asym-
metric synthesis of carbohydrates and highly functionalised
building blocks,20 the iteration of this asymmetric aldol strategy
was investigated. The high and predictable levels of selectivity
observed using oxazolidinone aldol reactions has facilitated
their previous limited use in double diastereoselective aldol
reactions.21 For instance, boron mediated oxazolidinone aldol
reactions with chiral aldehydes that have inherently low levels of
facial control proceed under the stereocontrol of the chiral aux-
iliary and over-ride the low facial control of the aldehyde, giv-
ing the expected syn-aldol products.22 However, if the aldehyde
has a high diastereofacial bias, the oxazolidinone auxiliary may
control the configuration of the newly formed a-stereocentre,
while the aldehyde controls the b-stereocentre, which can result
in the formation of the anti-aldol product.23 We report herein
that marked double asymmetric induction is found in the aldol
reaction of homochiral a,b-dihydroxyaldehydes such as 7 with
chiral glycolate oxazolidinones, give a rationale for the asym-
metric induction observed in these systems, and demonstrate
that highly functionalised and stereodefined lactones may be
readily prepared from the aldol products.
Fig. 1 Asymmetric glycolate aldol reactions using chiral oxazo-
lidinones.
Building on this literature precedent, previous investigations
from this laboratory have shown that the glycolate18 SuperQuat
derivative
(S)-N-a-benzyloxyacetyl-4-benzyl-5,5-dimethyl-
oxazolidin-2-one (S)-4 readily undergoes highly stereoselective
boron mediated syn-aldol reactions with a range of aromatic
and aliphatic aldehydes, generating the corresponding syn-aldol
products 5 in good to excellent yields as single diastereoisomers
after purification. Subsequent O-silyl protection of the aldol
products, and DIBAL reduction gives stereoselectively the cor-
responding N-1-hydroxyalkyloxazolidin-2-ones 6, which un-
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 4
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 3 3 8 5 – 3 4 0 0
3 3 8 5

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Results and discussion
The development of a double diastereoselective iterative
aldol strategy; evaluation of the stereodirecting capability of
oxazolidinone and aldehyde components
Initial studies were directed towards the development of an
iterative aldol strategy, with (2S,3R)-2-benzyloxy-3-(tert-butyl-
dimethylsilanyloxy)-3-phenyl–propionaldehyde 819 used as a
model homochiral aldehyde for this protocol. In an attempt to
understand fully and predict the stereochemical outcome of the
aldol reaction between a chiral aldehyde and a chiral glycolate
oxazolidinone, it was necessary to quantify the diastereofacial
bias of each reaction component. The inherent diastereocontrol
that chiral aldehyde 8 exerts upon the aldol reaction in the
formation of both the a- and b-stereogenic centres was first
assessed through an aldol reaction with an achiral oxazolidi-
none. The desired substrate for this model study, N-a-benzyloxy-
acetyl–oxazolidin-2-one 9, was readily prepared by treatment of
5,5-dimethyl–oxazolidin-2-one with n-BuLi and benzyloxyacetyl
chloride in 86% yield. The diastereocontrol in the boron mediated
aldol reaction with an achiral aldehyde was first assessed, with
treatment of oxazolidinone 9 with Et2BOTf followed by Hünig’s
base and subsequent addition of benzaldehyde giving the aldol
product 10 as single diastereoisomer (>98% de) in 59% isolated
yield. The relative syn-configuration within 10 was assigned by 1H
NMR (JC(2)H–C(3)H4.5 Hz),24 consistent with the reaction proceed-
ing via the (Z)-boron enolate, controlling the relative configura-
tion of the a- and b-stereogenic centres via a Zimmerman–Traxler
transition state. With this information in hand, quantification of
the asymmetric induction offered by homochiral a,b-dihydroxy-
aldehyde 8 in the aldol reaction with achiral oxazolidinone 9 was
investigated. Boron mediated aldol reaction between aldehyde 8
and N-acyl–oxazolidin-2-one 9 initially proved unreliable, with in-
complete conversion being observed. Storage of the hygroscopic
aldehyde as a solution in DCM over 4 Å molecular sieves allowed
the reaction to be driven to completion, furnishing a 66:11:23
mixture of three components 11:12:13, with purification by
chromatography affording the anti-aldol (2S,3S,4R,5R)-13
in 18% yield and in >95% de, and an inseparable 86:14 mixture
of syn-aldols (2R,3S,4R,5R)-11 and (2S,3R,4R,5R)-12 in
55% yield. Analysis of this product distribution indicates that
the (Z)-boron enolate of 9 preferentially adds to the Si face of
aldehyde 8 with high (89:11) selectivity, indicating that the chiral
aldehyde exerts high levels of stereocontrol in the formation of
the b-centre, while the aldehyde exercises only low stereocontrol
(66:34) over the formation of the a-stereocentre, with addition to
the Re face of the enolate being favoured (Scheme 1).25
Scheme 1 Reagents and conditions: (i) Et2BOTf, i-Pr2NEt, CH2Cl2,
then PhCHO, −78 to 0 °C; (ii) Et2BOTf, i-Pr2NEt, CH2Cl2, then 8, −78
to 0 °C.
formation of the b-centre would be opposed, and a mixture of
aldol products 15 and 16 would be expected (Fig. 3).
To investigate this hypothesis, homochiral aldehyde 8 was used
in an aldol reaction with the (Z)-boron enolate of glycolate oxa-
zolidin-2-one (S)-4,27 affording a 57:43 mixture of the separable
diastereoisomeric aldol products (2S,3R,4S,4R,5R)-15 and
(2S,3S,4S,4R,5R)-16, isolated in 35% and 34% yield respec-
tively as single diastereoisomers after chromatographic purifica-
tion. This mismatched addition is consistent with the (Z)-boron
enolate providing the dominant stereochemical control in the aldol
reaction, with addition to aldehyde 8 occurring exclusively on the
Si face of the enolate, giving the aldol products that only differ in
configuration at the b-centre. In contrast, the aldol addition be-
tween (R)-4 and aldehyde 8 furnished (2R,3S,4R,4R,5R)-14 as
the sole aldol product in >98% de, giving 14 in 54% isolated yield
and as a single diastereoisomer after chromatography (Scheme 2).
The generality of this double diastereoselective aldol protocol
was next investigated, with (2S,3S)-2-benzyloxy-3-(tert-butyldi-
methylsilanyloxy)-3-furyl–propionaldehyde 17 (>95% de)19 used
in the boron mediated aldol reaction with (R)- and (S)-glycolate
oxazolidinones 4. Generation of the (Z)-boron enolate of (R)-
glycolate oxazolidinone 4 and treatment with aldehyde 17 gave
aldol product 18 as a single diastereoisomer.28 In contrast, ad-
dition of the (Z)-boron enolate of (S)-glycolate oxazolidinone
4 to aldehyde 17 gave a 58:42 mixture of the separable dia-
stereoisomeric aldol products 19 and 20, which were isolated in
39% and 32% yield respectively as single diastereoisomers after
chromatographic purification (Scheme 3).28
Double diastereoselective aldol reactions for the asymmetric
synthesis of polyfunctionalised lactones
With this information in hand, double asymmetric induction was
anticipated for the aldol reactions between aldehyde 8 and the
chiral glycolate oxazolidin-2-ones (S)-4 and (R)-4.26 As the chiral
aldehyde exerts only a small (66:34) bias over the preferred con-
figuration of the a-centre in the aldol reaction with achiral oxa-
zolidinone 9, it was predicted that the chiral oxazolidinone would
exert dominant control over the preferred absolute configuration
at this centre upon reaction with the chiral aldehyde. However, as
both the aldehyde and the oxazolidinone exert high stereocontrol
in the formation of the b-centre of the aldol products, matched
and mismatched reactions with the products differing in con-
figuration at the b-centre of the aldol products, may be expected.
Furthermore, the sense of the matched and mismatched pairings
could be predicted. In the reaction of the (Z)-boron enolate of
(R)-glycolate oxazolidinone 4 with chiral aldehyde 8 with an in-
herent Si facial bias, the stereochemical elements controlling the
formation of the b-centre are predicted to be mutually reinforcing,
furnishing a single diastereoisomeric product 14. In contrast, the
reaction of the (Z)-boron enolate of (S)-glycolate oxazolidinone
4 with aldehyde 8, the diastereofacial elements controlling the
In order to determine the relative configurations within the
aldol products arising from these double diastereoselective aldol
3 3 8 6
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 3 3 8 5 – 3 4 0 0

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Scheme 3 Reagents and conditions: (i) (R)-4, Et2BOTf, i-Pr2NEt,
CH2Cl2, −78 °C to 0 °C (ii) (S)-4, Et2BOTf, i-Pr2NEt, CH2Cl2, −78 °C
to 0 °C.
that would be amenable to configurational analysis by NMR
spectroscopy. Initial studies concentrated upon deprotection and
lactonisation within the “matched” reaction series, with model
studies conducted on aldol product 14. Treatment of aldol 14 with
TBAF in THF at both 0 °C and rt resulted in a complex mixture
of products, presumably due to decomposition upon attempted
deprotection due to the highly basic nature of the fluoride ion.
Buffering the solution with acetic acid proved successful,29 giving
the desired lactone (2R,3S,4R,5R)-21 as a single diastereoisomer
in 70% yield, and returning the auxiliary (R)-22 in 95% yield,
after chromatography. The relative configuration within lactone
Fig. 3 Proposed matched and mismatched reaction pairings in the
double asymmetric aldol reaction.
1
21 was assigned on the basis of H NMR spectroscopy, which
indicated that lactone 21 adopts a chairlike conformation in solu-
1
tion. Analysis of H–1H coupling constants was used to indicate
the typical axial and equatorial relationships between the C(2)H,
C(3)H, C(4)H and C(5)H ring protons, with NOE difference anal-
ysis confirming the 1,3 diaxial relationship between C(3)H and
C(5)H. The absolute (2R,3S,4R,5R)-configuration within lactone
21 was then assigned upon the known stereodirecting preference
of oxazolidinone auxiliaries in simple glycolate aldol reactions.30
Similarly, treatment of C(5)-furyl aldol 18 with TBAF in AcOH
generated the corresponding lactone 23 in 62% isolated yield as
a single stereoisomer and returned the oxazolidinone auxiliary in
81% yield, with the relative configuration within lactone 23 as-
signed by analogy to that within 21 (Scheme 4).
Having developed a protocol for desilyation and lactonisation
in the matched aldol series, this methodology was extended to
the mismatched aldol products. Treatment of the major diastereo-
isomers 15 and 19 arising from the mismatched reactions with
TBAF in AcOH gave the corresponding lactones 24 and 25 in 85%
and 80% yield respectively, and returned the auxiliary in 83% and
90% yield. The relative configuration within lactone 24 was deter-
mined by a combination of 1H NMR and NOE difference analysis,
with the absolute configuration assigned relative to the known con-
figuration at C(5) and C(6). The relative and absolute configura-
tion within lactone 25 was assigned by analogy (Scheme 5).
In an attempt to prepare a crystalline derivative of lactones 24
and 25 for X-ray crystallographic analysis, derivatisation of the
free hydroxyl functionality within lactones 24 and 25 by treatment
Scheme 2 Reagents and conditions: (i) (R)-4, Et2BOTf, i-Pr2NEt,
CH2Cl2, −78 °C to 0 °C (ii) (S)-4, Et2BOTf, i-Pr2NEt, CH2Cl2, −78 °C
to 0 °C.
reactions, it was envisaged that treatment of the aldol products
with a fluoride source would induce O-desilylation and concomi-
tant lactonisation, giving homochiral poly-substituted lactones
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 3 3 8 5 – 3 4 0 0
3 3 8 7

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ment with benzoyl chloride furnished a partially separable mix-
ture of (S)-3-benzoyl-4-benzyl-5,5-dimethyl–oxazolidin-2-one
and O-benzoylated lactone 33 which proved amenable to NOE
difference studies, allowing determination of the relative configu-
ration within (2S,3S,4R,5S)-33 (Scheme 7).
Scheme 4 Reagents and conditions: (i) TBAF, AcOH, THF, rt.
Scheme 5 Reagents and conditions: (i) TBAF, AcOH, THF, rt.
with benzoyl chloride, as previously described by Clive et al. was
investigated.31 However, treatment of both lactones 24 and 25
with benzoyl chloride resulted in elimination, furnishing the cor-
responding ab-unsaturated lactones 26 and 27 in good yield after
chromatography. In order to ascertain whether elimination under
these conditions was general to all lactones, or a consequence of
the relative configuration within them, treatment of the lactones
21 and 23 under identical conditions gave selectively the corre-
sponding O-benzoyl lactones 28 and 29 in 83% and 60% yield,
with no evidence of elimination, confirming that the relative
configuration within each of the pairs of aldol diastereoisomers
14 and 18 and 15 and 19 is identical, but that the relative configu-
ration between the pairs differs (Scheme 6).
Scheme 7 Reagents and conditions: (i) TBAF, AcOH, THF, rt;
(ii) toluene, D; (iii) PhCOCl, NEt3, DMAP, CH2Cl2.
Having demonstrated that the preparation of lactones 24–33
facilitated their configurational analysis, the relative configu-
ration within the aldol products derived from reaction of the
achiral oxazolidinone 9 with the chiral aldehyde 8 were estab-
lished by chemical correlation. Treatment of the 86:14 mixture
of syn-aldols (2R,3S,4R,5R)-11 and (2S,3R,4R,5R)-12
with TBAF in AcOH gave an inseparable 86:14 mixture of the
lactones (2R,3S,4R,5R)-21 and (2S,3R,4R,5R)-24 in 86% yield.
Treatment of the anti-aldol 13 with TBAF and acetic acid gave
an inseparable 66:34 mixture of the desilylated aldol 34 and the
corresponding lactone 31, consistent with the relative configu-
ration within the anti-aldol 13 disfavouring the intramolecular
cyclisation (Scheme 8).
Scheme 6 Reagents and conditions: (i) PhCOCl, NEt3, DMAP,
CH2Cl2.
Models for double diastereoselective aldol reactions
Treatment of the minor diastereoisomer 16 from the mis-
matched aldol reaction of aldehyde 8 with TBAF in AcOH gave
a mixture of the corresponding lactone (2S,3S,4R,5R)-31 in 34%
isolated yield, the O-deprotected aldol product 30 in 45% yield
and auxiliary (S)-22 in 28% yield after chromatographic purifica-
tion. Further conversion of the desilylated aldol adduct 30 to the
lactone 31 was achieved by refluxing in toluene, giving lactone
31 in 76% yield and returning oxazolidinone (S)-22 in 99% yield.
The relative configuration within lactone 31 was determined by
1H NMR and NOE difference analysis, with the absolute con-
figuration assigned relative to the known configuration at C(5)
and C(6). Treatment of the minor diastereoisomer 20 with TBAF
under identical conditions furnished an inseparable mixture of
the desired lactone 32 and the auxiliary (S)-22, which upon treat-
The prediction of the stereochemical course of nucleophilic addi-
tion to chiral a-substituted carbonyl components has been much
studied, with the seminal contributions of Cram and Elhafez,32
Cornforth et al.,33 Karabatsos,34 Felkin et al.35 and Anh and Eisen-
stein36 having been used extensively to delineate the contributing
factors to stereocontrol in these reactions.37 While these models
are usually used to rationalise the inherent diastereofacial bias of
the aldehyde, a range of groups have investigated the aldol reac-
tions of a-oxygen substituted aldehydes with either boron, lithium
or titanium enolates derived from achiral donors, and have shown
that high levels of syn-C(2)–C(3)- and anti-C(3)–C(4)-selectivity is
usually noted.38 Recent reports by Evans et al.39 have studied ex-
tensively the origin of this asymmetric induction, with the modi-
3 3 8 8
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 3 3 8 5 – 3 4 0 0

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the stereocontrol of the enolate (high stereocontrol at both a-
and b-stereocentres) and the aldehyde (high stereocontrol at
b-stereocentre) are therefore additive, with addition of the Re
face of the enolate to the Si face of the aldehyde giving a single
diastereoisomeric product (Fig. 5).42
Fig. 5 Proposed transition state for the matched double diastereo-
selective aldol reactions.
Scheme 8 Reagents and conditions: (i) TBAF, AcOH, THF, rt.
fied Cornforth dipolar model receiving increasing attention over
the previously accepted polar Felkin–Anh model for the reaction
of (Z)-enolates, due to destabilising syn-pentane interactions in
the reactive conformer of the Felkin–Anh model (Fig. 4).40
In the mismatched reaction manifold, the formation of two
diastereoisomeric products is consistent with the reaction pro-
ceeding via two competing transition states, in which the stereo-
chemical elements controlling the stereoselective formation of the
b-centre are opposed. Assuming that the reaction occurs via the
(Z)-boron enolate and a chelated transition state, the formation
of the major diastereoisomer in the mismatched case is consistent
with the reaction proceeding under the predominant control of
the oxazolidinone via the Zimmerman–Traxler chair-type transi-
tion state 35, with addition of the Si face of the enolate to the Re
face of the aldehyde (contrary to that expected under Cornforth
control) giving the syn-C(2)–C(3) and syn-C(3)–C(4) configura-
tion. The formation of the minor anti-C(2)–C(3) and anti-C(3)–
C(4) diastereoisomer is consistent with addition of the Si face of
the oxazolidinone enolate to the Cornforth favoured Si face of the
aldehyde. While aldol reaction via chair transition state 37 is disfa-
voured by 1,3 diaxial interactions between the oxazolidinone and
aldehyde alkyl substituents, addition via the boat transition state
36 is preferred, and competes effectively with the alternative chair
transition state 35, resulting in low diastereoselectivity (Fig. 6).
Double diastereoselective aldol reactions: application to
the asymmetric synthesis of a differentially protected
polyhydroxylated lactone
Fig. 4 Comparison of Cornforth and Felkin–Anh models for the
reaction of a metallated (Z)-enolate and an a-heteroatom substituted
aldehyde.
Having shown that double diastereoselection is observed in the
aldol reaction of aldehydes such as 8 and 17 with chiral glyco-
late oxazolidinones, a demonstration of the versatility of this
protocol was undertaken. It was envisaged that aldol reaction
of glycolate oxazolidinones (S)-4 and (R)-4 with the aldehyde
38 prepared from mannitol43 would exhibit double asymmetric
induction, with subsequent formation of the aldehyde from the
‘matched’ reaction, and iteration of the aldol protocol, giving
rise to a polyhydroxylated lactone after deprotection. Upon
the assumption that addition to aldehyde 38 proceeds under
Cornforth control, it was predicted that the aldehyde would
inherently prefer enolate addition to its Si face, and should
therefore be “matched” upon reaction with the (Z)-boron eno-
late of (S)-4, and mismatched upon reaction with the (Z)-boron
enolate of (R)-4. In practice, boron mediated aldol addition of
(S)-4 to aldehyde 38 afforded the syn-product (1R,2S,3S,4S)-
39 in 93% de, with chromatographic purification giving 39 as a
single diastereoisomer in 73% yield. The absolute configuration
within aldol 39 was established by conversion to the known triol
41. Reduction of 39 with lithium borohydride afforded the cor-
While these models consider the predominant effect of the
a-heteroatom substituted stereogenic centre upon the preferred
facial selectivity upon addition to the aldehyde, a b-stereocentre
may also have an effect upon the preferred aldehyde facial selec-
tivity, and the stereochemical mutually reinforcing potential of
combinations of a- and b-stereocentres has also been explored.41
With these precedents in mind, simple models that account for
the stereochemical outcome of these double diastereoselective
asymmetric aldol reactions may be rationalised. In the matched
case, the formation of a single diastereoisomeric product with
syn-selectivity between the newly formed a- and b-sterogenic
centres is consistent with the reaction proceeding via a chelated
transition state between the (Z)-boron enolate of the glycolate
oxazolidinone and the aldehyde. Upon the assumption that ad-
dition to the aldehyde proceeds under the predominant influence
of the a-stereocentre via the preferred Cornforth conformation,
a distinct preference for nucleophilic addition to its Si face can
be predicted, consistent with the results of the aldol reaction of
aldehyde 8 and achiral oxazolidinone 9. In this transition state,
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 3 3 8 5 – 3 4 0 0
3 3 8 9

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of the aldehyde, giving a 67:33 mixture of two diastereoisomers
in 40% conversion.45 Chromatographic purification furnished
an inseparable 67:33 mixture of 42 and 43 in 34% combined yield.
Reduction of the 67:33 mixture of 42 and 43 with lithium boro-
hydride gave a 67:33 mixture of diols 44 and 45, with subsequent
purification furnishing the diol 44 as a single diastereoisomer in
43% yield, and a mixture of 44 and 45 in 44% yield. Hydrogeno-
lysis of the homogenous diol 44 afforded the known triol 46
in 93% yield with comparable spectroscopic properties to the
literature {[a]D25 +8.2 (c = 0.9, EtOH), lit.44 [a]D25 +8.31 (c = 3.05,
EtOH)}, allowing unambiguous assignment of the configuration
within the major diastereoisomeric aldol adduct. Repeated chro-
matography of the mixture of the diols 44 and 45 failed to isolate
a homogenous sample of the minor diastereoisomeric diol 45.
The anti-relative configuration within 45 was therefore assigned
by analogy to the minor diastereoisomer formed in the previously
observed mismatched aldol reactions, upon the assumption that
the oxazolidinone controls the configuration at the a-centre and
the aldehyde in the b-centre in the aldol reaction (Scheme 10).
Fig. 6 Proposed transition states for the mismatched double
diastereoselective aldol reactions.
responding diol 40 in 87% yield, with subsequent hydrogenolysis
giving the known triol 41 in 93% yield with comparable spectro-
scopic properties to the literature {[a]2D5 −0.69 (c = 1.2, EtOH),
lit.44 [a]2D5 −0.63 (c = 2.35, EtOH)} (Scheme 9).
In contrast, the mismatched aldol reaction of (R)-4 and 38
proved to be highly capricious, and did not proceed to completion
(with respect to the enolate) even in the presence of a large excess
Scheme 10 Reagents and conditions: (i) Et2BOTf, i-Pr2NEt, RCHO,
CH2Cl2: (ii) LiBH4, H2O, Et2O; (iii) Pd/C, AcOH, MeOH, H2 (1 atm).
Given the unreliable nature, and low stereoselectivity, of the
mismatched aldol reaction of (R)-4 and 38, no further studies
were carried out on this system. However, iteration of the aldol re-
action with the aldehyde derived from the matched aldol reaction
was investigated. Attempted silylation of 39 with TBDMSOTf led
to decomposition, while treatment with TBDMSCl at rt returned
only starting material. However, treatment of 39 with TDBMSCl
in the presence of 4 Å molecular sieves followed by warming to
60 °C resulted in the formation of the desired TBDMS ether 47 in
84% yield. Treatment of 47 with DIBAL furnished a 88:12 mix-
ture of the stable 1-hydroxyalkyloxazolidin-2-one 4846,47 and the
formate ester 49 (the product of endocyclic cleavage), which after
chromatographic purification gave an inseparable 88:12 mixture
Scheme 9 Reagents and conditions: (i) Et2BOTf, i-Pr2NEt, 38,
CH2Cl2, −78–0 °C; (ii) LiBH4, H2O, Et2O; (iii) Pd/C, AcOH, MeOH,
H2 (1 atm).
3 3 9 0
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 3 3 8 5 – 3 4 0 0

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of 48 (>98% de) and 49 in 68% combined yield. Treatment of
the inseparable mixture of 48–49 with K2CO3 in MeOH–H2O
resulted in fragmentation of 48 to the desired aldehyde 50 and
hydrolysis of the formate ester 49 to the corresponding alcohol
51, with purification affording the aldehyde 50 in 52% yield and
87% de, and the alcohol 51 in 8% yield (Scheme 11).
Scheme 12 Reagents and conditions: (i) Et2BOTf, i-Pr2NEt, 50,
CH2Cl2: (ii) TBAF, AcOH, THF, rt.
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 PARA-
GON 1000 FT-IR spectrometer. Selected peaks are reported
Scheme 11 Reagents and conditions: (i) TBDMSCl, imidazole,
DMAP, DMF, 60 °C; (ii) DIBAL, CH2Cl2, −78 °C; (iii) K2CO3, MeOH,
H2O, rt.
1
in cm−1. H 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 sol-
vent peak. Coupling constants (J) are measured in hertz. Two
dimensional COSY spectra were recorded on the Bruker DPX-
200 (200 MHz), the Bruker AVANCE AV-400 (400 MHz) or the
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-400ortheBrukerDPX-400spectrometersandat125.77 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 the 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 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. Spe-
cific rotations were recorded on a Perkin-Elmer 241 polarimeter,
using a path length of 10 cm, in spectroscopic grade solvents
With aldehyde 50 (87% de) in hand, its iterative aldol reaction
in the predicted matched series was investigated, with addition
of the (Z)-boron enolate of (R)-glycolate oxazolidinone 4 to al-
dehyde 50 evaluated, giving 52 as a single diastereoisomer in 42%
yield after purification.48 Treatment of 52 with TBAF in AcOH
gave, after O-desilylation and concomitant lactonisation, the
polyfunctionalised lactone 53 that contains five contiguous ste-
reocentres as a single diastereoisomer in 58% yield (Scheme 12).
In conclusion, we have shown that polyfunctionalised lactones
with up to five contiguous stereocentres may be prepared with
high stereocontrol by a double diastereoselective aldol protocol
with protected homochiral a,b-dihydroxy- or a,b,c-trihydroxy-
aldehydes and a homochiral glycolate oxazolidinone, followed
by subsequent O-desilylation and lactonisation. The further ap-
plication of this methodology for the asymmetric total synthesis
of carbohydrates and derivatives thereof is currently underway
within our laboratory.
Experimental
General experimental
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
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 3 3 8 5 – 3 4 0 0
3 3 9 1

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(Aldrich), with concentrations (c) given in g 100 cm−3, solvent
and temperature as recorded. Elemental analyses were obtained
by Mrs A. Douglas of the Inorganic Chemistry Analytical De-
partment using an Elementar Vario EL combustion elemental
analyser. Melting points were recorded on a Gallenkamp Hot
Stage apparatus and are uncorrected.
1.43 [3H, s, C(CH3)A(CH3)B], 3.49–3.59 [2H, ABq, J 11.0, NCH2],
4.49–4.60 [2H, ABq, J 11.6, CHOCH2Ph], 5.03 [1H, d, J 4.5,
CH(OH)], 5.51 [1H, d, J 4.5, CHOCH2Ph], 7.16–7.47 [10H, m,
PhH]; dC (100 MHz, CDCl3) 27.0, 27.1 [C(CH3)2], 54.1 [NCH2],
73.3 [CHOCH2Ph], 75.0 [CH(OH)], 79.3 [C(CH3)2], 80.9
[CHOCH2Ph], 128.0, 128.1 [p-Ph], 126.6, 128.2, 128.3, 128.4 [m/
o-Ph], 139.0, 136.74 [i-Ph], 152.2 [CO endocyclic], 171.1 [CO
exocyclic]; mmax(KBr disc, cm−1) 1764 [CO endocyclic], 1709
[CO exocyclic]; HRMS C21H24NO5 [MH+] requires 370.1654,
found 370.1654; m/z ES+ 352 [100%, MH+–H2O], 370 [25%,
MH+], 387 [75%, MNH4+], 392 [97%, MNa+].
Representative procedure 1 for the aldol addition of a N-acyl-
oxazolidin-2-one to an aldehyde. 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 solu-
tion was cooled to 0 °C and added to a solution of N-acyl–oxa-
zolidin-2-one (1.0 eq) in CH2Cl2 via cannula. After stirring for
10 min, i-Pr2NEt (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 ei-
ther 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 (v:v 1:1), extracted with CH2Cl2, washed with
brine, dried and concentrated in vacuo. The crude product was
purified by column chromatography.
Preparation of (2S,3S,4R,5R)-3-[2,4-bis-benzyloxy-5-
(tert-butyl-dimethyl-silanyloxy)-3-hydroxy-5-phenyl-
pentanoyl]-5,5-dimethyl-oxazolidin-2-one (2S,3S,4R,5R)-13,
(2R,3S,4R,5R)-3-[2,4-bis-benzyloxy-5-(tert-butyl-di-
methyl-silanyloxy)-3-hydroxy-5-phenyl-pentanoyl]-5,5-di-
methyl-oxazolidin-2-one (2R,3S,4R,5R)-11 and (2S,3R,
4R,5R)-3-[2,4-bis-benzyloxy-5-(tert-butyl-dimethyl-silanyl-
oxy)-3-hydroxy-5-phenyl-pentanoyl]-5,5-dimethyl-oxazolidin-
2-one (2S,3R, 4R,5R)-12. Following representative procedure
1, CF3SO3H (0.15 mL, 1.70 mmol), Et3B (1.70 mL, 1.70 mmol),
9 (370 mg, 1.42 mmol), i-Pr2NEt (0.35 mL, 1.99 mmol) and 8
(537 mg, 1.45 mmol) in CH2Cl2 (30 mL) furnished a 23:66:11
mixture of 13:11:12 which after purification by column chro-
matography gave 13 (165 mg, 0.26 mmol, 18%) as a pale yellow
oil and a 86:14 mixture of 11:12 (495 mg, 0.78 mmol, 55%) as
a clear colourless oil.
13: Rf 0.33 [3:1 40–60 °C petrol–Et2O]; dH (400 MHz,
CDCl3) −0.17 [3H, s, Si(CH3)A(CH3)B], 0.07 [3H, s, Si(CH3)A-
(CH3)B], 0.92 [9H, s, SiC(CH3)3], 1.06 [3H, s, C(CH3)A(CH3)B],
1.32 [3H, s, C(CH3)A(CH3)B], 2.78 [1H, d, J 10.7, NCHAHB],
3.30 [1H, d, J 10.7, NCHAHB], 3.31 [1H, d, J 7.8, CH(OH)],
3.77 [1H, dd, J 7.0, 4.5, CHOCH2Ph.CH(OTBDMS)], 4.02–4.07
[1H, m, CH(OH)], 4.20 [1H, d, J 10.5, CHOCHAHBPh], 4.39
[1H, d, J 10.5, CHOCHAHBPh], 4.51 [1H, d, J 11.5, CHO-
CHCHDPh], 4.73 [1H, d, J 11.5, CHOCHCHDPh], 5.05 [1H, d,
J 4.5, CH(OTBDMS)], 5.34 [1H, d, J 3.4, CO.CHOCH2Ph],
7.20–7.43 [15H, m, PhH]; dC (100 MHz, CDCl3) −5.2, −4.6
[Si(CH3)2], 18.1 [SiC(CH3)3], 25.8 [SiC(CH3)3], 26.7 [C(CH3)2],
53.7 [NCH2], 72.6 [CH(OH)], 73.2, 73.9 [2 × CHOCH2Ph],
74.2 [CH(OTBDMS)], 77.9 [CO.CHOCH2Ph], 79.2 [C(CH3)2],
82.8 [CHOCH2Ph.CH(OTBDMS)], 126.9, 127.7, 128.0, 128.2,
128.3, 128.4 [m/o-Ph], 127.3, 127.4 [p-Ph], 137.6, 138.5, 141.4
[i-Ph], 152.5 [CO endocyclic], 170.5 [CO exocyclic]; mmax(thin
film, cm−1) 3450 [O–H], 1774 [CO endocyclic], 1711 [CO
exocyclic]; C36H47NO7Si requires C 68.2, H 7.5, N 2.2%, found
C 68.3, H 7.5, N 2.2%; [a]2D5 −51.0 (c = 1.25, CHCl3); m/z
LD+ (MALDI) 656, 657 [100%, 40%, MNa+].
11–12: Rf 0.22 [3:1 30–40 °C petrol–Et2O]; dH (400 MHz,
CDCl3) −0.23 [3H, s, Si(CH3)A(CH3)B (12)], −0.136 [3H, s,
Si(CH3)A(CH3)B (11)], −0.01 [3H, s, Si(CH3)A(CH3)B (12)], 0.02
[3H, s, Si(CH3)A(CH3)B (11)], 0.82 [9H, s, SiC(CH3)3 (12)], 0.89
[9H, s, SiC(CH3)3 (11)], 1.26 [3H, s, C(CH3)A(CH3)B (12)], 1.36
[3H, s, C(CH3)A(CH3)B (11)], 1.40 [3H, s, C(CH3)A(CH3)B (12)],
1.45 [3H, s, C(CH3)A(CH3)B (11)], 3.34 [1H, d, J 10.9, NCHAHB
(12)], 3.55 [1H, d, J 10.9, NCHAHB (12)], 3.59–3.66 [2H, ABq, J
10.9, NCH2 (11)], 3.72 [1H, dd, J 8.9, 2.9, CHOCH2Ph.CHPh
(11)], 3.84–3.86 [1H, m, CHOCH2Ph.CHPh (12)], 4.11 [1H, dd, J
2.4, 8.9, CH(OH) (11)], 4.17 [1H, d, J 11.8, CHOCHAHBPh (11)],
4.27 [2H, d, J 11.3, CHOCHAHBPh and CHOCHCHDPh (11)],
4.29 [1H, d, J 11.0, CHOCHAHBPh (12)], 4.57 [1H, d, J 11.0,
CHOCHCHDPh (11)], 4.59–4.62 [1H, m, CH(OH) (12)], 4.70 [2H,
d, J 11.0, CHOCH2Ph (12)], 4.89 [1H, d, J 7.1, COCHOCH2Ph
(12)], 4.96 [1H, d, J 11.0, CHOCHAHBPh (12)], 5.06 [1H, d, J
2.8, CH(OTBDMS) (11)], 5.18 [1H, d, J 3.7, CH(OTBDMS)
(12)], 5.54 [1H, d, J 2.7, CO.CHOCH2Ph (11)], 7.21–7.48
[30H, m, PhH (11 and 12)]; dC (100 MHz, CDCl3) −5.2, −4.7
[Si(CH3)2 (11 and 12)], 18.1 [SiC(CH3)3 (12)], 18.3 [SiC(CH3)3
(11)], 25.9 [SiC(CH3)3 (12)], 25.9 [SiC(CH3)3 (11)], 26.9 and 27.4
Representative procedure 2 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-acyl–oxazolidin-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 chromatography.
Representative procedure 3 for the acylation of lactones with
PhCOCl. Et3N (2.5 eq), PhCOCl (1.3 eq) and DMAP (0.1 eq) were
added sequentially to a solution of lactone (1 eq) in CH2Cl2 at am-
bient temperature. After stirring for 18 h, the reaction mixture was
quenched with saturated, aqueous NH4Cl solution, extracted with
CH2Cl2, washedwithdiluteaqueousNaHCO3 andbrineanddried.
The crude product was purified by column chromatography.
Preparationof 3-(2-benzyloxyacetyl)-5,5-dimethyl-oxazolidin-
2-one 9. n-BuLi (5.74 mL, 14.35 mmol) was added to a stirred
solution of 5,5-dimethyl–oxazolidin-2-one (1.50 g, 13.04 mmol)
in THF at −78 °C. After 15 min, PhCH2OCH2COCl (2.70 mL,
16.95 mmol) was added dropwise via syringe and stirred
at −78 °C for 15 min before being warmed to ambient tempera-
ture. After 2 h, the reaction mixture was quenched with satu-
rated aqueous NH4Cl solution and acetic acid, extracted with
EtOAc, washed sequentially with saturated aqueous NaHCO3
and brine, dried over MgSO4 and concentrated in vacuo. Purifi-
cation by column chromatography furnished 9 as a white solid
(2.95 g, 11.22 mmol, 86%).
9: Rf 0.2 [2:1 pentane–Et2O]; mp 63–64 °C [pentane–Et2O];
dH (200 MHz, CDCl3) 1.50 [6H, s, C(CH3)2], 3.75 [2H, s, NCH2],
4.67 [2H, s, CH2OCH2Ph], 4.70 [2H, s, CH2OCH2Ph], 7.27–7.40
[5H, m, PhH]; dC (50 MHz, CDCl3) 27.3 [C(CH3)2], 53.8 [NCH2],
69.5 [CH2OCH2Ph], 73.4 [CH2OCH2Ph], 80.1 [C(CH3)2], 127.9
[p-Ph], 128.0, 128.5 [m/o-Ph], 137.2 [i-Ph], 152.6 [CO endo-
cyclic], 170.5 [CO exocyclic]; mmax(KBr disc, cm−1) 1773 [CO
endocyclic], 1717 [CO exocyclic]; C14H17NO4 requires C 63.9,
H 6.5, N 5.3%; found C 63.9, H 6.5, N 5.3%; m/z APCI+ 116
[100%, SQH+], 264 [2%, MH+].
Preparation of 3-(2-benzyloxy-3-hydroxy-3-phenyl)-pro-
pionyl)-5,5-dimethyl-oxazolidin-2one 10. Following represen-
tative procedure 1, CF3SO3H (0.15 mL, 1.71 mmol), Et3B
(1.71 mL, 1.71 mmol),
9 (300 mg, 1.14 mmol), i-Pr2NEt
(0.28 mL, 1.80 mmol) and PhCHO (0.14 mL, 1.37 mmol) in
CH2Cl2 (20 mL) furnished 10 (248 mg, 0.67 mmol, 59%) as a
white solid after column chromatography.
10: Rf 0.23 [1:2 30–40 °C petrol–Et2O]; mp 59–60 °C [30–40 °C
petrol–Et2O]; dH (400 MHz, CDCl3) 1.25 [3H, s, C(CH3)A(CH3)B],
3 3 9 2
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 3 3 8 5 – 3 4 0 0

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mmax(thin film, cm−1) 1776 [CO endocyclic], 1710 [CO exo-
[C(CH3)2 (12)], 27.0, 27.1 [C(CH3)2 (11)], 54.1 [NCH2 (12)], 54.2
[NCH2 (11)], 70.7 [CH(OH) (12)], 71.7 [CH(OH) (11)], 72.6 and
73.1 [2 × CHOCH2Ph (11)], 72.8 and 74.3 [2 × CHOCH2Ph
(12)], 74.1 [CH(OTBDMS) (11)], 77.0 [CH(OTBDMS) (12)],
77.7 [CO.CHOCH2Ph (11)], 78.5 [CO.CHOCH2Ph (12)], 79.2
[C(CH3)2 (11)], 79.3 [C(CH3)2 (12)], 82.0 [CHOCH2Ph.CHPh
(11)], 82.4 [CHOCH2Ph.CHPh (12)], 127.3, 128.0 [p-Ph (11)],
127.1, 127.9, 128.2, 128.3 [m/o-Ph (11)], 127.6, 127.7, 128.1,
128.2 [p- and m/o-Ph (12)], 137.3, 138.5, 141.2 [i-Ph (11)],
137.2, 138.7, 141.6 [i-Ph (12)], 152.1 [CO endocyclic (11)],
152.6 [CO endocyclic (12)], 171.0 [CO exocyclic (12)], 171.7
[CO exocyclic (11)]; mmax(thin film, cm−1) 3471 [O–H], 1780
[CO endocyclic], 1711 [CO exocyclic]; HRMS C36H51N2O7Si
[MNH4+]requires651.3466, found651.3471; m/zLD+ (MALDI)
656, 657, 658 [100%, 40%, 15%, MNa+].
+
cyclic]; HRMS C43H57N2O7Si [MNH4 ] requires 741.3935, found
741.3934; [a]2D5 +130.4 (c = 1.05, CHCl3); m/z LD+ (MALDI)
746.29, 747.25, 748.21 [100%, 50%, 15%, MNa+].
Preparation of (2R,3S,4R,4R,5R)-4-benzyl-3-[2,4-bis-
benzyloxy-5-(tert-butyl-dimethyl-silanyloxy)-3-hydroxy-
5-phenyl–pentanoyl]-5,5-dimethyl–oxazolidin-2-one
(2R,3S,4R,4R,5R)-14. Following representative procedure
1, CF3SO3H (0.12 mL, 1.36 mmol), Et3B (1.36 mL, 1.36 mmol),
(R)-4 (400 mg, 1.13 mmol), i-Pr2NEt (0.28 mL, 1.58 mmol) and
8 (400 mg, 1.14 mmol) in CH2Cl2 (15 mL) furnished 14 (442 mg,
0.61 mmol, 54%) as a white solid after column chromatography.
14: Rf 0.25 [1:1 pentane–Et2O]; mp 142–144 °C [pentane–
Et2O]; dH (400 MHz, CDCl3) −0.15 [3H, s, Si(CH3)A(CH3)B],
0.01 [3H, s, Si(CH3)A(CH3)B], 0.890 [9H, s, SiC(CH3)3], 1.31
[3H, s, C(CH3)A(CH3)B], 1.343 [3H, s, C(CH3)A(CH3)B],
2.86 [1H, dd, J 14.4, 9.6, CHCHAHBPh], 2.89 [1H, d, J 7.3,
CH(OH)], 3.14 [1H, dd, J 14.4, 3.8, CHCHAHBPh], 3.69 [1H,
dd, J 8.9, 2.6, CH(OCH2Ph).CH(OTBDMS)], 4.00–4.05 [1H,
m, CH(OH)], 4.09 [1H, d, J 11.7, CHOCHAHBPh], 4.16 [1H, d,
J 11.0, CHOCHCHDPh], 4.25 [1H, d, J 11.7, CHOCHAHBPh],
4.44 [1H, d, J 11.0, CHOCHCHDPh], 4.47 [1H, dd, J 9.6,
3.8, CHCH2Ph], 5.05 [1H, d, J 2.6, CH(OTBDMS)], 5.55
[1H, d, J 2.0, CO.CHOCH2Ph], 7.19–7.42 [20H, m, PhH];
dC (100 MHz, CDCl3) −4.9, −4.7 [Si(CH3)2], 18.2 [C(CH3)3],
22.1, 28.1 [C(CH3)2], 25.9 [C(CH3)3], 35.3 [CHCH2Ph], 64.0
[CHCH2Ph], 71.5 [CH(OH)], 72.3, 73.3 [2 × CHOCH2Ph],
74.1 [CH(OTBDMS)], 77.6 [CO.CHOCH2Ph], 81.9
[CHOCH2Ph.CH(OTBDMS)], 83.1 [C(CH3)2], 126.7, 127.0,
127.2, 127.4, 127.6, 127.8, 128.1, 128.3, 128.4, 128.5, 128.6,
129.1 [p- and m/o-Ph], 137.0, 137.3, 138.5, 141.3 [i-Ph], 152.1
[CO endocyclic], 171.2 [CO exocyclic]; mmax(KBr disc, cm−1)
1782 [CO endocyclic], 1702 [CO exocyclic]; C43H53NO7Si
requires C 71.3, H 7.4, N 1.9%, found C 71.3, H 7.4, N 2.0%;
[a]2D0 +14.6 (c = 1.0, CHCl3); m/z LD+ (MALDI) 746, 747, 748
[100%, 45%, 15%, MNa+].
Preparation of (2S,3R,4S,4R,5R)-4-benzyl-3-[2,4-bis-
benzyloxy-5-(tert-butyl-dimethyl-silanyloxy)-3-hydroxy-5-phenyl-
pentanoyl]-5,5-dimethyl-oxazolidin-2-one (2S,3R, 4S,4R,5R)-
15 and (2S,3S,4S,4R, 5R)-4-benzyl-3-[2, 4-bis-benzyloxy-
5-(tert-butyl-dimethyl-silanyloxy)-3-hydroxy-5-phenyl-penta-
noyl]-5,5-dimethyl-oxazolidin-2-one (2S,3S,4S,4R,5R)-16.
Following representative procedure 1, CF3SO3H (0.29 mL,
3.24 mmol), Et3B (3.24 mL, 3.24 mmol), (S)-4 (950 mg,
2.70 mmol), i-Pr2NEt (0.61 mL, 3.51 mmol) and 8 (1.00 g,
2.70 mmol) in CH2Cl2 (20 mL) furnished a 57:43 ratio of 15:16
which after purification by column chromatography gave 15
(690 mg, 0.95 mmol, 35%) and 16 (667 mg, 0.92 mmol, 34%)
as white solids.
15: Rf 0.14 [5:1 pentane–Et2O]; mp 124–125 °C [pentane–
Et2O]; dH (400 MHz, CDCl3) −0.16 [3H, s, Si(CH3)A(CH3)B],
0.077 [3H, s, Si(CH3)A(CH3)B], 0.92 [9H, s, SiC(CH3)3], 0.94
[3H, s, C(CH3)A(CH3)B], 1.12 [3H, s, C(CH3)A(CH3)B], 2.70
[1H, dd, J 14.4, 9.6, CHCHAHBPh], 3.09 [1H, dd, J 14.4, 2.5,
CHCHAHBPh], 3.23 [1H, d, J 7.4, CH(OH)], 3.74–3.78 [2H,
m, CHOCH2Ph.CH(OTBDMS) and CHCH2Ph], 4.04–4.10
[2H, m, CH(OH) and CHOCHAHBPh], 4.47 [2H, app. t, J 11.9,
CHOCH2Ph], 4.76 [1H, d, J 11.4, CHOCHAHBPh], 5.07 [1H,
d, J 3.7, CH(OTBDMS)], 5.31 [1H, d, J 1.7, CO.CHOCH2Ph],
7.01–7.45 [20H, m, PhH]; dC (100 MHz, CDCl3) −5.2 and −4.7
[Si(CH3)2], 18.1 [SiC(CH3)3], 22.0 and 27.8 [C(CH3)2], 25.8
[SiC(CH3)3], 34.8 [CHCH2Ph], 63.4 [CHCH2Ph], 72.2 [CH(OH)],
73.1 and 73.7 [2 × CHOCH2Ph], 74.1 [CH(OTBDMS)], 79.1
[CO.CHOCH2Ph], 81.9 [CH(OCH2Ph).CH(OTBDMS)], 83.3
[C(CH3)2], 126.5, 127.0, 127.1, 127.4 [p-Ph], 127.4, 127.8, 128.1
128.4, 128.5, 128.6, 128.7, 128.9 [m/o-Ph], 137.1, 137.8, 138.5,
141.2 [i-Ph], 152.7 [CO endocyclic], 169.7 [CO exocyclic];
mmax(KBr disc, cm−1) 1768 [CO endocyclic], 1712 [CO exo-
Preparation of (2R,3S,4R,4R,5S)-4-benzyl-3-[2,4-bis-
benzyloxy-5-(tert-butyl-dimethyl-silanyloxy)-5-furan-2-
yl-3-hydroxy-pentanoyl]-5,5-dimethyl–oxazolidin-2-one
(2R,3S,4R,4R,5S)-18. Following representative procedure
1, CF3SO3H (0.24 mL, 2.72 mmol), Et3B (2.72 mL, 2.72 mmol),
(R)-4 (800 mg, 2.27 mmol), i-Pr2NEt (0.55 mL, 3.18 mmol)
and 17 (817 mg, 2.27 mmol) in CH2Cl2 (20 mL) furnished 18
(565 mg, 0.91 mmol, 40%) as a white solid contaminated
with <10% of (R)-4 after column chromatography.
18:Rf 0.1[1:1pentane–Et2O];dH(400 MHz,CDCl3) −0.08 [3H,
s, Si(CH3)A(CH3)B], 0.01 [3H, s, SiC(CH3)A(CH3)B], 0.87
[9H, s, SiC(CH3)3], 1.34 [3H, s, C(CH3)A(CH3)B], 1.35 [3H,
s, C(CH3)A(CH3)B], 2.83–2.94 [2H, m, CHCHAHBPh and
CH(OH)], 3.14 [1H, dd, J 14.4, 3.7, CHCHAHBPh], 3.86 [1H,
dd, J 8.8, 3.3, CHOCH2Ph.CH(OTBDMS)], 4.20 [2H, app. d, J
11.0, CH(OH) and CHOCHAHBPh], 4.39 [2H, s, CHOCH2Ph],
4.45 [1H, d, J 11.0, CHOCHAHBPh], 4.48 [1H, dd, J 11.6, 3.8,
CHCH2Ph], 5.06 [1H, d, J 3.3, CH(OTBDMS)], 5.56 [1H, d, J
2.2, CO.CHOCH2Ph], 6.30–6.34 [2H, m, CH(furan)], 7.20–7.42
[16H, m, ArH]; dC (100 MHz, CDCl3) −5.4, −5.1 [SiC(CH3)2],
18.2 [SiC(CH3)3], 22.1, 28.2 [C(CH3)2], 25.8 [SiC(CH3)3], 35.2
[CHCH2Ph], 64.0 [CHCH2Ph], 69.1 [CH(OTBDMS)], 71.3
[CH(OH)], 72.4, 72.7 [2 × CHOCH2Ph], 77.7 [CO.CHOCH2Ph],
80.1 [CHOCH2Ph.CH(OTBDMS)], 83.7 [C(CH3)2], 107.8,
110.4, 141.3 [CH(furan)], 126.7, 126.9, 127.2 [p-Ph], 127.5,
127.9, 128.0, 128.3, 128.6, 129.1 [m/o-Ph], 137.0, 137.3, 138.7
[i-Ph], 152.5 [i-Ar furan], 154.4 [CO endocyclic], 171.1 [CO
exocyclic]; mmax(KBr disc, cm−1) 3531 [O–H], 1779 [CO endo-
cyclic], 1708 [CO endocyclic]; HRMS C41H55N2O8Si [MNH4+]
requires 731.3728, found 731.3727; m/z LD+ (MALDI) 736,
737, 738, 739 [100%, 60%, 20%, 5%, MNa+], 752, 753, 754, 755
[80%, 30%, 20%, 5%, MK+].
+
cyclic]; HRMS C43H57N2O7Si [MNH4 ] requires 741.3935, found
741.3937; [a]2D5 −12.0 (c = 1, CHCl3); m/z LD+ (MALDI) 746
[100%, MNa+], 762 [50%, MK+].
16: Rf 0.11 [5:1 pentane–Et2O]; mp 116–117 °C [pentane–
Et2O]; dH (400 MHz, CDCl3) −0.21 [3H, s, Si(CH3)A(CH3)B],
0.01 [3H, s, Si(CH3)A(CH3)B], 0.84 [9H, s, SiC(CH3)3], 1.04 [3H,
s, C(CH3)A(CH3)B], 1.23 [3H, s, C(CH3)A(CH3)B], 2.73 [1H, d, J
7.6, CH(OH)], 2.79 [1H, dd, J 14.5, 9.8, CHCHAHBPh], 3.08
[1H, dd, J 14.5, 3.5, CHCHAHBPh], 3.79–3.83 [1H, m, CH(OH)],
3.92 [1H, dd, J 6.9, 1.7, CHOCH2Ph.CH(OTBDMS)], 4.16 [1H,
dd, J 9.8, 3.5, CHCH2Ph], 4.26 [1H, d, J 11.2, CHOCHAHBPh],
4.49 [1H, d, J 11.2, CHOCHAHBPh], 4.63 [1H, d, J 10.8, CHO-
CHCHDPh], 4.91 [1H, d, J 6.9, CH(OTBDMS)], 4.94 [1H, d,
J 10.8, CHOCHCHDPh], 5.25 [1H, d, J 4.0, CO.CHOCH2Ph],
7.18–7.42 [20H, m, PhH]; dC (100 MHz, CDCl3) −4.9, −4.7
[Si(CH3)2], 18.0 [SiC(CH3)3], 22.0, 27.8 [C(CH3)2], 25.8
[SiC(CH3)3], 35.1 [CHCH2Ph], 63.8 [CHCH2Ph], 70.5 [CH(OH)],
72.6, 74.3 [2 × CHOCH2Ph], 76.7 [CH(OTBDMS)], 77.8
[CO.CHOCH2Ph], 82.2 [CHOCH2Ph.CH(OTBDMS)], 83.1
[C(CH3)2], 126.7, 127.3, 127.3, 127.4 [p-Ph], 127.7, 127.8, 128.0,
128.1, 128.3, 128.5, 128.8, 129.1 [m/o-Ph], 137.0, 137.2, 138.7,
141.6 [i-Ph], 152.7 [CO endocyclic], 170.6 [CO exocyclic];
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 3 3 8 5 – 3 4 0 0
3 3 9 3

View Article Online
21: Rf 0.19 [1:1 pentane–Et2O]; mp 142–144 °C
[pentane–Et2O]; dH (400 MHz, CDCl3) 4.05 [1H, d,
Preparation of (2S,3R,4S,4R,5S)-4-benzyl-3-[2,4-bis-
benzyloxy-5-(tert-butyl-dimethyl-silanyloxy)-5-furan-2-
yl-3-hydroxy-pentanoyl]-5,5-dimethyl-oxazolidin-2-one
(2S,3R,4S,4R,5S)-19 and (2S,3S,4S,4R,5S)-4-benzyl-
3-[2,4-bis-benzyloxy-5-(tert-butyl-dimethyl-silanyloxy)-5-
furan-2-yl-3-hydroxy-pentanoyl]-5,5-dimethyl-oxazolidin-2-one
(2S,3S,4S,4R,5S)-20. Following representative procedure 1,
CF3SO3H (0.28 mL, 3.23 mmol), Et3B (3.23 mL, 3.23 mmol),
(S)-4 (950 mg, 2.69 mmol), i-Pr2NEt (0.66 mL, 3.77 mmol)
and 17 (1 g, 2.78 mmol) in CH2Cl2 (30 mL) furnished a 58:42
mixture of 19:20 which after purification by column chroma-
tography gave 19 (651 mg, 1.05 mmol, 39%) as a yellow oil
contaminated with <10% of (S)-4 and 20 (531 mg, 0.85 mmol,
32%) as a pale yellow oil after column chromatography.
J
11.1, CH(OCHAHBPh).CHPh], 4.08 [1H, t, J 2.3,
CH(OCH2Ph).CHPh], 4.25 [1H, dd, J 9.7, 2.7, CH(OH)],
4.32 [1H, d, J 11.1, CH(OCHAHBPh).CHPh], 4.41 [1H, J 9.7,
CO.CHOCH2Ph], 4.76 [1H, d, J 11.1, CO.CHOCHCHDPh],
5.24 [1H, d, J 11.1, CO.CHOCHCHDPh], 5.39 [1H, d, J 1.7,
CHPh], 6.89–6.91 [2H, m, PhH], 7.20–7.26 [4H, m, PhH],
7.33–7.47 [9H, m, PhH]; dC (100 MHz, CDCl3) 72.2 [CH(OH)],
74.8 [CO.CHOCH2Ph], 75.2 [CHOCH2Ph.CHPh], 77.0
[CO.CHOCH2Ph], 78.4 [CHOCH2Ph.CHPh], 80.4 [CHPh],
126.3, 127.9, 128.0, 128.3, 128.4, 128.6 [p- and m/o-Ph], 135.7,
137.1, 137.2 [i-Ph], 170.3 [CO]; mmax(KBr disc, cm−1) 3528
+
[O–H], 1727 [CO]; HRMS C25H28NO5 [MNH4 ] requires
422.1967, found 422.1973; [a]2D6 +80.4 (c = 0.55, CHCl3); m/z
19: Rf 0.12 [3:1 pentane–Et2O]; dH (400 MHz, CDCl3) −0.14
[3H, s, Si(CH3)A(CH3)B], 0.01 [3H, s, Si(CH3)A(CH3)B], 0.83
[9H, s, SiC(CH3)3], 1.11 [3H, s, C(CH3)A(CH3)B], 1.27 [3H, s,
C(CH3)A(CH3)B], 2.77–2.86 [2H, m, CHCHAHBPh and CH(OH)],
3.09 [1H, dd, J 14.4, 3.4, CHCHAHBPh], 3.80–3.83 [1H, m,
CH(OH)], 4.08 [1H, dd, J 7.8, 1.7, CHOCH2Ph.CH(OTBDMS)],
4.22 [1H, dd, J 3.5, 9.8, CHCH2Ph], 4.34 [1H, d, J 11.1, CHO-
CHAHBPh], 4.53 [1H, d, J 11.4, CHOCHCHDPh], 4.53 [1H, d,
J 11.1, CHOCHAHBPh], 4.94–4.97 [2H, m, CHOCHCHDPh
and CH(OTBDMS)], 5.31 [1H, d, J 3.9, CO.CHOCH2Ph],
6.27–6.33 [2H, m, CH furan], 7.20–7.41 [16H, m, ArH]; dC
(100 MHz, CDCl3) −5.2, −5.0 [Si(CH3)2], 18.1 [SiC(CH3)3],
22.0, 27.8 [C(CH3)2], 25.7 [SiC(CH3)3], 35.2 [CHCH2Ph],
63.9 [CHCH2Ph], 70.4 [CH(OTBDMS)], 70.7 [CH(OH)],
72.7, 74.3 [2 × CHOCH2Ph], 78.1 [CO.CHOCH2Ph], 80.4
[CHOCH2Ph.CH(OTBDMS)], 83.7 [C(CH3)2], 108.3, 110.2,
142.0 [CH furan], 126.7, 126.9, 127.3 [p-Ph], 127.9, 128.1, 128.2,
128.5, 128.6, 129.1 [m/o-Ph], 136.6, 137.0, 137.2 [i-Ph], 152.5 [i-Ar
furan], 152.7 [CO endocyclic], 170.3 [CO exocyclic]; mmax(thin
film, cm−1) 3535 [O–H], 1777 [CO endocyclic], 1713 [CO
endocyclic]; HRMS C41H55N2O8Si [MNH4+] requires 731.3728,
found 731.3722; m/z LD+ (MALDI) 736, 737, 738 [35%, 20%,
3%, MNa+], 752, 753, 754, 755 [100%, 45%, 15%, 3%, MK+].
20: Rf 0.23 [3:1 pentane–Et2O]; dH (400 MHz, CDCl3) −0.62
[3H, s, Si(CH3)A(CH3)B], 0.08 [3H, s, Si(CH3)A(CH3)B], 0.86
[9H, s, SiC(CH3)3], 0.91 [9H, s, C(CH3)A(CH3)B], 1.11 [3H, s,
C(CH3)A(CH3)B], 2.72 [1H, dd, J 14.6, 10.4, CHCHAHBPh], 3.11
[1H, dd, J 14.6, 2.7, CHCHAHBPh], 3.16 [1H, d, J 8.0, CH(OH)],
3.80 [1H, dd, J 10.4, 3.0, CHCH2Ph], 3.92 [1H, dd, J 7.7, 3.9,
CHOCH2Ph.CH(OTBDMS)], 4.09–4.14 [1H, m, CH(OH)],
4.17 [1H, d, J 10.2, CHOCHAHBPh], 4.47–4.50 [2H, m, CHO-
CHAHBPh and CHOCHCHDPh], 4.75 [1H, d, J 11.4, CHO-
CHCHDPh], 5.12 [1H, d, J 3.9, CH(OTBDMS)], 5.33 [1H, d, J
3.6, CO.CHOCH2Ph], 6.30–6.32 [2H, m, CH(furan)], 7.07–7.45
[16H, m, ArH]; dC (100 MHz, CDCl3) −5.2, −5.0 [Si(CH3)2],
18.1 [SiC(CH3)3], 22.0, 27.7 [C(CH3)2], 25.7 [SiC(CH3)3], 34.8
[CHCH2Ph], 63.4 [CHCH2Ph], 68.5 [CH(OTBDMS)], 72.1
[CH(OH)], 73.1, 73.3 [2 × CHOCH2Ph], 79.3 [CO.CHOCH2Ph],
80.1 [CHOCH2Ph.CH(OTBDMS)], 83.3 [C(CH3)2], 107.8,
110.4, 141.4 [CH furan], 126.5, 127.5, 127.9 [p-Ph], 128.0,
128.2, 128.3, 128.4, 128.6, 128.9 [m/o-Ph], 137.1, 137.7, 138.5
[i-Ph], 152.8 [CO endocyclic], 154.2 [i-Ar furan], 169.8 [CO
exocyclic]; mmax(thin film, cm−1) 3527 [O–H], 1774 [CO endo-
cyclic], 1707 [CO endocyclic]; HRMS C41H55N2O8Si [MNH4+]
requires 731.3728, found 731.3721; [a]2D6 −12.4 (c = 1.0, CHCl3);
m/z LD+ (MALDI) 736, 737, 738, 739 [100%, 60%, 25%, 3%,
MNa+], 752, 753, 754 [50%, 30%, 10%, MK+].
+
ES+ 422 [100%, MNH4 ].
Preparation of (2R,3S,4R,5S)-2,4-bis-benzyloxy-3-hydroxy-
5-furan-2-yl-tetrahydro-pyran-2-one (2R,3S,4R,5S)-23 and (R)-
4-benzyl-5,5-dimethyl-oxazolidin-2-one
(R)-22.
Following
representative procedure 2, 18 (200 mg, 0.28 mmol), TBAF
(0.42 mL, 0.42 mmol) and AcOH (0.02 mL, 0.28 mmol) in THF
(10 mL) furnished 23 (66 mg, 0.17 mmol) as a clear colourless
oil and (R)-22 (47 mg, 0.22 mmol) as a white solid and returned
(R)-4 (18 mg, 0.05 mmol) as a pale yellow oil after column chro-
matography.
23: Rf 0.08 [2:1 pentane–Et2O]; dH (400 MHz, CDCl3)
4.18 [1H, dd, J 9.5, 2.8, CH(OH)], 4.25 [1H, d, J 2.6,
CH(OCH2Ph).CH(C4H3O)], 4.35 [1H, d, J 11.2, CHOCHAHBPh],
4.39 [1H, d, J 9.5, CO.CHOCH2Ph], 4.52 [1H, d, J 11.2, CHO-
CHAHBPh],4.74[1H,d,J11.1,CHOCHCHDPh],5.20[1H,d,J11.1,
CHOCHCHDPh], 5.40 [1H, d, J 0.9, CH(OCH2Ph).CH(C4H3O)],
6.42–6.44 [1H, m, CH furan], 6.51–6.99 [1H, m, CH furan], 7.09–
7.45 [11H, m, ArH]; dC (100 MHz, CDCl3) 71.8 [CH(OH)], 74.7,
74.8 [2 × CHOCH2Ph], 75.1 [CHOCH2Ph.CH(C4H3O)], 76.2
[CHOCH2Ph.CH(C4H3O)], 77.0 [CO.CHOCH2Ph], 109.0, 110.9,
142.3 [CH furan], 127.9, 128.0, 128.3, 128.4, 128.5, 128.6 [p- and
m/o-Ph], 137.1, 137.2 [i-Ph], 148.4 [i-Ar furan], 169.5 [CO];
mmax(thin film, cm−1) 3436 [O–H], 1743 [CO]; HRMS C23H23O6
requires 395.1495, found 395.1489; [a]D25 +61.0 (c = 1.35, CHCl3);
m/z APCI+ 395 [25%, MH+].
Preparation of (2S,3R,4S,5R)-2,4-bis-benzyloxy-3-hydroxy-
5-phenyl-tetrahydro-pyran-2-one (2S,3R,4S,5R)-24 and (S)-
4-benzyl-5,5-dimethyl-oxazolidin-2-one
(S)-22.
Following
representative procedure 2, 15 (500 mg, 0.70 mmol), TBAF
(1.05 mL, 1.05 mmol) and AcOH (0.04 mL, 0.70 mmol) in THF
(10 mL) furnished 24 (184 mg, 0.46 mmol) as a white solid,
(S)-22 (93 mg, 0.45 mmol) as a white solid and (S)-4 (27 mg,
0.08 mmol) as a pale yellow oil after column chromatography.
24: Rf 0.18 [1:1 pentane–Et2O]; mp 132–134 °C [pen-
tane–Et2O]; dH (500 MHz, CDCl3) 2.81 [1H, br s, OH],
3.76 [1H, t, J 1.6, CH(OCH2Ph).CHPh], 4.15 [1H, dd,
J 7.7, 1.2, CH(OH)], 4.20 [1H, J 7.7, CO.CHOCH2Ph],
4.22 [1H, d, J 12.2, CH(OCHAHBPh).CHPh], 4.44 [1H,
d, J 12.2, CH(OCHAHBPh).CHPh], 4.66 [1H, d, J 11.5,
CO.CHOCHCHDPh], 5.15 [1H, d, J 11.5, CO.CHOCHCHDPh],
5.47 [1H, d, J 1.8, CHPh], 6.89–6.90 [2H, m, PhH], 7.15–7.22
[3H, m, PhH], 7.34–7.47 [10H, m, PhH]; dC (125 MHz,
CDCl3) 71.6 [CH(OCH2Ph).CHPh], 73.3 [CO.CHOCH2Ph],
74.3 [CO.CHOCH2Ph], 78.12 [CHPh], 78.8 [CH(OH)], 80.4
[CH(OCH2Ph).CHPh], 126.7, 127.7, 127.8, 128.1, 128.2, 128.3,
128.4, 128.5, 128.7 [p- and m/o-Ph], 134.9, 136.7, 136.9 [i-Ph],
169.4 [CO]; mmax(KBr disc, cm−1) 3436 [O–H], 1756 [CO];
C25H24O5 requires C 74.2, H 6.0%, found C 74.1, H 5.7%;
Preparation of (2R,3S,4S,5R)-2,4-bis-benzyloxy-3-hydroxy-
5-phenyl-tetrahydro-pyran-2-one (2R,3S,4S,5R)-21 and (R)-4-
benzyl-5,5-dimethyl-oxazolidin-2-one (R)-22. Following repre-
sentative procedure 2, 14 (230 mg, 0.32 mmol), TBAF (0.48 mL,
0.48 mmol) and AcOH (0.02 mL, 0.32 mmol) in THF (30 mL)
furnished 21 (90 mg, 0.22 mmol, 70%) as a white solid and
(R)-22 (62 mg, 0.301 mmol, 95%) as a white solid after column
chromatography.
[a]2D0 −109.6 (c = 0.25, CHCl3); m/z ES+ 422 [100%, MNH4 ].
+
Preparation of (2S,3R,4R,5S)-2,4-bis-benzyloxy-3-hydroxy-
5-furan-2-yl-tetrahydro–pyran-2-one (2S,3R,4R,5S)-25 and
(S)-4-benzyl-5,5-dimethyl-oxazolidin-2-one (S)-22. Following
representative procedure 2, 19 (120 mg, 0.168 mmol), TBAF
3 3 9 4
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 3 3 8 5 – 3 4 0 0

View Article Online
(0.25 mL, 0.25 mmol) and AcOH (0.01 mL, 0.17 mmol) in THF
(10 mL) furnished 25 (50 mg, 0.14 mmol, 80%) as a pale yellow
oil and (S)-22 (31 mg, 0.15 mmol, 90%) after column chroma-
tography.
5.56 [1H, d, J 0.61, CHPh], 5.61 [1H, dd, J 10.2, 2.4, CH(OBz)],
6.78–8.19 [20H, m, PhH]; dC (100 MHz, CDCl3) 73.3
[CO.CHOCH2Ph], 74.0 [CH(OBz)], 74.5 [CO.CHOCH2Ph], 75.0
[CHOCH2Ph.CHPh], 77.0 [CHOCH2Ph.CHPh], 79.9 [CHPh],
126.3, 127.5, 127.8, 127.9, 128.1, 128.3, 128.3, 128.4, 128.5,
128.6, 128.8, 129.0, 129.2, 129.8, 130.0, 130.5 [p- and m/o-Ph],
135.4, 136.4, 137.0 [i-Ph], 165.6 [CH(COBz)], 169.8 [CO lac-
tone]; mmax(thin film, cm−1) 1753, 1722 [CO]; HRMS C32H30O6
[MH+] requires 509.1886, found 509.1887; [a]2D5 −17.7 (c = 1.0,
CHCl3); m/z CI+ 491 [40%, MH+–H2O], 509 [30%, MH+].
25: Rf 0.24 [1:1 pentane–Et2O]; dH (400 MHz, CDCl3) 3.93
[1H, t, J 3.0, CH(OCH2Ph).CH(C4H3O)], 4.10 [1H, d, J 7.9,
CO.CHOCH2Ph], 4.20–4.25 [1H, m, CH(OH)], 4.48 [1H, d,
J 11.9, CHOCHAHBPh], 4.62 [1H, d, J 11.9, CHOCHAHBPh],
4.67 [1H, d, J 11.4, CHOCHCHDPh], 5.13 [1H, d, J 11.4,
CHOCHCHDPh], 5.47 [1H, d, J 2.7, CH(OCH2Ph).CH(C4H3O)],
6.33–6.40 [1H, m, CH furan], 6.50 [1H, m, CH furan],
7.17–7.46 [11H, m, ArH]; dC (100 MHz, CDCl3) 72.4,
74.0 [2 × CHOCH2Ph], 73.2 [CHOCH2Ph.CH(C4H3O)],
73.9 [CH(OH)], 78.7 [CHOCH2Ph.CH(C4H3O)], 79.0
[CO.CHOCH2Ph], 110.6, 111.2, 143.1 [CH(furan)], 128.4, 128.8,
128.9, 129.0, 129.1, 129.2 [p- and m/o-Ph], 137.2, 137.3 [i-Ph],
148.4 [C4(furan)], 169.3 [CO]; mmax(thin film, cm−1) 3431 [O–H],
1761 [CO]; HRMS C23H22O6Na [MNa+] requires 417.1314,
found 417.1306; [a]2D5 −33.7 (c = 0.3, CHCl3); m/z ES+ 395
Preparation of (2R,3S,4R,5S)-2,4-bis-benzyloxy-3-benzoyl-
5-furan-2-yl-tetrahydro-pyran-2-one (2R,3S,4R,5S)-29. Follow-
ing representative procedure 3, Et3N (0.02 mL, 0.16 mmol),
PhCOCl (0.02 mL, 0.12 mmol), DMAP (2 mg, 0.01 mmol) and
23 (25 mg, 0.06 mmol) in CH2Cl2 (10 mL) furnished 29 (18 mg,
0.036 mmol, 60%) as a pale yellow oil after column chromatog-
raphy.
29:Rf 0.23[3:1pentane–Et2O];dH (400 MHz,CDCl3)4.18[1H,
d, J 11.4, CHOCHAHBPh], 4.30 [1H, d, J 11.4, CHOCHAHBPh],
4.49 [1H, t, J 2.0, CH(OBz)], 4.71 [1H, d, J 10.2, CHC4H4O], 4.91
[1H, d, J 11.8, OCHCHDPh], 5.13 [1H, d, J 11.7, OCHCHDPh],
5.55 [1H, dd, J 10.2, 2.5, CHOCH2Ph.CHC4H4O], 5.58 [1H,
s, CO.CHOCH2Ph], 6.44–6.45 [1H, m, CH(furan)], 6.54–6.55
[1H, m, CH(furan)], 6.97–7.34 [6H, m, ArH], 7.44–7.65 [9H,
m, ArH], 7.89–7.91 [1H, m, ArH]; dC (100 MHz, CDCl3) 73.4,
73.5 [CO.CHOCH2Ph and CHC4H4O], 74.5, 74.6 [CHOCH2Ph],
74.8, 74.9 [CH(OBz) and CHOCH2Ph.CHC4H4O], 109.1, 111.0,
142.3 [CH(furan)], 127.9, 128.0, 128.2, 128.4, 128.5, 128.8, 128.9,
129.3, 129.9 [p- and m/o-Ph], 133.6, 136.6, 136.8 [i-Ph], 148.0
[CH(COBz)], 165.5 [C4 furan], 169.2 [CO lactone]; mmax(thin
film, cm−1) 1726 [CO]; HRMS C30H27O7 [MH+] requires
499.1757, found 499.1759; [a]2D6 +26.7 (c = 0.3, CHCl3); m/z
CI+ 377 [MH+–PhCO2H and H2O, 20%], 394 [MH+–PhCO2H,
100%], 499 [MH+, 5%].
+
[35%, MH+], 412 [45%, MNH4 ], 417 [85%, MNa+].
Preparation of (4R,5R)-2,4-bis-benzyloxy-5-phenyl-3,4-
dihydro-pyran-2-one 26. Following representative procedure 3,
Et3N (0.02 mL, 0.12 mmol), PhCOCl (0.01 mL, 0.10 mmol),
DMAP (1 mg, 0.001 mmol) and 24 (20 mg, 0.05 mmol) in
CH2Cl2 (5 mL) furnished 26 (18 mg, 0.05 mmol, 93%) after
column chromatography.
26: Rf 0.25 [1:1 pentane–Et2O]; mp 105–106 °C [pentane–
Et2O]; dH (400 MHz, CDCl3) 4.08 [2H, s, OCH2Ph], 4.16 [1H,
dd, J 6.5, 2.6, CHOCH2Ph], 4.97 [2H, ABq, J 12.7, OCH2Ph],
5.50 [1H, d, J 2.5, CHPh], 5.80 [1H, d, J 6.5, CHCOCH2Ph],
6.91–6.93 [2H, m, PhH], 7.22–7.69 [13H, m, PhH]; dC (100 MHz,
CDCl3) 70.4, 71.2 [OCH2Ph], 70.8 [CHOCH2Ph], 81.5 [CHPh],
109.2 [CHCOCH2Ph], 126.6, 127.3, 127.5, 128.3, 128.4, 128.8,
130.5, 134.5 [m/o-Ph], 127.7, 128.7, 128.8 [p-Ph], 135.1, 135.1,
137.4 [i-Ph], 146.0 [CHCOCH2Ph], 160.3 [CO]; mmax(KBr
disc, cm−1) 1723 [CO], 1641 [CC]; HRMS C25H26NO4
[MH+] requires 404.1861, found 404.1857; [a]2D5 −106.3 (c = 1.5,
Preparation of (2S,3S,4S,4S,5R)-4-benzyl-3-(2,4-bis-
benzyloxy-3,5-dihydroxy-5-phenyl–pentanoyl)-5,5-dimethyl–
oxazolidin-2-one30,(2S,3S,4R,5R)-2,4-bis-benzyloxy-3-hydroxy-
5-phenyl-tetrahydro-pyran-2-one (2S,3S,4R,5R)-31 and (S)-4-
benzyl-5,5-dimethyl-oxazolidin-2-one (S)-22. Following repre-
sentative procedure 2, 16 (220 mg, 0.3 mmol), TBAF (0.46 mL,
0.46 mmol) and AcOH (0.02 mL, 0.30 mmol) in THF (20 mL)
furnished a 66:34 mixture of 30:31 which after purification by
column chromatography gave 30 (82 mg, 0.13 mmol, 45%) as a
pale yellow oil, 31 (41 mg, 0.10 mmol, 34%) as a white solid and
(S)-22 (17 mg, 0.08 mmol, 28%) as a white solid.
+
CHCl3); m/z APCI+ (NH3) 108.9 [PhCH2OH2 , 38%], 387.1
+
[MH+, 13%], 404.1 [MNH4 , 11%].
Preparation of (4R,5S)-2,4-bis-benzyloxy-5-furan-2-yl-3, 4-
dihydro-pyran-2-one 27. Following representative procedure 3,
Et3N (0.014 mL, 0.10 mmol), PhCOCl (0.006 mL, 0.05 mmol),
DMAP (1 mg, 0.001 mmol) and 25 (16 mg, 0.04 mmol) in
CH2Cl2 (5 mL) furnished 27 (12 mg, 0.03 mmol, 79%) as a pale
yellow oil after column chromatography.
30: Rf 0.09 [1:1 30–40 °C petrol–Et2O]; dH (400 MHz, CDCl3)
1.10 [3H, s, C(CH3)A(CH3)B], 1.27 [3H, s, C(CH3)A(CH3)B],
2.84 [1H, dd, J 14.4, 9.5, CHCHAHBPh], 3.052[1H, dd,
J 14.4, 4.2, CHCHAHBPh], 3.1 [1H, br s, CH(OH)Ph],
3.43 [1H, d, J 7.1, CO.CH(OCH2Ph).CH(OH)], 3.86 [1H,
dd, J 5.4, 2.5, CH(OCH2Ph).CH(OH)Ph], 4.13 [1H, d, J
10.7, CH(OCHAHBPh).CH(OH)Ph], 4.17 [1H, d, J 5.6,
27: Rf 0.24 [1:1 pentane–Et2O]; dH (400 MHz, CDCl3)
4.31 [2H, ABq, J 11.9, CHOCH2Ph], 4.39 [1H, dd, J 6.2, 3.0,
CHOCH2Ph], 4.94 [2H, ABq, J 12.2, CHCOCH2Ph], 5.53 [1H,
d, J 2.8, CHC4H4O], 5.77 [1H, d, J 6.2, CHCOCH2Ph], 6.43–6.44
[1H, m, CH(furan)], 6.62–6.63 [1H, m, CH(furan)], 7.12–7.45
[11H, m, ArH]; dC (100 MHz, CDCl3) 69.2 [CHOCH2Ph], 70.4
[CHCOCH2Ph], 70.9 [CHOCH2Ph], 76.0 [CHC4H4O], 109.2
[CHCOCH2Ph], 109.6, 110.8, 142.4 [CH(furan)], 127.8, 128.0
[p-Ph],127.4,128.3,128.4,128.7,128.8[m/o-Ph],135.0,137.1[i-Ph],
145.8 [C4 furan], 148.1 [CO]; mmax(thin film, cm−1) 1725 [CO];
HRMS C23H21O3 [MH+] requires 377.1389, found 377.1388;
[a]D25 −101.2 (c = 1.1, CHCl3); m/z ES+ 398 [70%, MNa+].
CO.CH(OCH2Ph).CH(OH)], 4.23 [1H, dd,
J 9.5, 4.2,
CHCH2Ph], 4.32 [1H, d, J 11.5, CO.CH(OCHCHDPh).CH(OH)],
4.46 [1H, d, J 10.7, CH(OCHAHBPh).CH(OH)Ph], 4.59 [1H, d, J
11.5, CO.CH(OCHCHDPh).CH(OH)], 5.10 [1H, s, CH(OH)Ph],
5.47 [1H, d, J 6.2, CO.CHOCH2Ph], 7.15–7.40 [20H, m, PhH];
dC (100 MHz, CDCl3) 21.9, 27.7 [C(CH3)2], 35.4 [CHCH2Ph],
63.5 [CHCH2Ph], 72.3 [CO.CH(OCH2Ph).CH(OH)], 72.6, 72.8
[2 × CHOCH2Ph], 72.9 [CO.CHOCH2Ph], 77.3 [CH(OH)Ph],
80.4 [CH(OCH2Ph).CH(OH)Ph], 83.4 [C(CH3)2], 126.8, 127.4,
127.7, 128.2 [p-Ph], 126.1, 128.2, 128.5, 128.6, 128.7, 129.1 [m/o-
Ph], 136.8, 137.1, 137.5, 141.3 [i-Ph], 153.1 [CO endocyclic],
170.6 [CO exocyclic]; mmax(thin film, cm−1) 1771 [CO endo-
cyclic], 1709 [CO exocyclic]; HRMS C37H39NO7Na [MNa+]
requires 632.2624, found 632.2626; [a]2D3 −24.5 (c = 1.0, CHCl3);
m/z ES+ 632 [100%, MNa+].
Preparation of (2R,3S,4R,5R)-2,4-bis-benzyloxy-3-benzoyl-
5-phenyl-tetrahydro-pyran-2-one (2R,3S,4R,5R)-28. Follow-
ing representative procedure 3, Et3N (0.02 mL, 0.12 mmol),
PhCOCl (0.01 mL, 0.10 mmol), DMAP (1 mg, 0.005 mmol) and
21 (20 mg, 0.05 mmol) in CH2Cl2 (5 mL) furnished 28 (21 mg,
0.041 mmol, 83%) as a pale yellow oil after column chromatog-
raphy [3:1 pentane–Et2O].
28: dH (400 MHz, CDCl3) 4.00 [2H, ABq,
J 11.2,
CHOCH2Ph.CHPh], 4.30 [1H, d, J 2.0, CHOCH2Ph.CHPh],
4.73 [1H, J 10.2, CO.CHOCH2Ph], 4.94 [1H, d, J 11.8,
CO.CHOCHAHBPh], 5.15 [1H, d, J 11.8, CO.CHOCHAHBPh],
31: Rf 0.07 [1:1 30–40 °C petrol–Et2O]; mp 164–
165 °C [pentane–Et2O]; dH (400 MHz, CDCl3) 3.98
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 3 3 8 5 – 3 4 0 0
3 3 9 5

View Article Online
[1H, dd, J 3.1, 5.9, CH(OCH2Ph).CHPh], 4.09 [1H, d,
11.5, CH(OCHAHBPh).CHPh], 4.18 [1H, d, 11.5,
found 499.1748; m/z CI+ 377.24 [MH+–PhCO2H and H2O,
J
J
40%], 394.45 [MH+–PhCO2H, 70%], 499.27 [MH+, 7%].
CH(OCHAHBPh).CHPh], 4.21 [1H, J 4.8, CO.CHOCH2Ph],
4.41 [1H, dd, J 4.9, 5.8, CH(OH)], 4.76 [1H, d, J 12.2,
CO.CHOCHCHDPh], 5.13 [1H, d, J 12.2, CO.CHOCHCHDPh],
5.28 [1H, d, J 3.1, CHPh], 6.89–6.92 [2H, m, PhH], 7.17–7.42
[13H, m, PhH]; dC (125 MHz, CDCl3) 67.4 [CH(OH)],
73.1 [CO.CHOCH2Ph], 73.8 [CO.CHOCH2Ph], 74.2
[CHOCH2Ph.CHPh], 75.2 [CHOCH2Ph.CHPh], 79.1 [CHPh],
127.9, 128.0, 128.2 [p-Ph], 126.7, 127.7, 128.1, 128.2, 128.4,
128.5 [m/o-Ph], 134.6, 136.3, 136.8 [i-Ph], 169.1 [CO]; mmax(KBr
disc, cm−1) 3444 [O–H], 1764 [CO]; HRMS C25H24O5Na
[MNa+] requires 427.1521, found 427.1535; [a]D25 +64.0 (c = 0.28,
CHCl3); m/z ES+ 427 [100%, MNa+].
(S)-3-benzoyl-4-benzyl-5,5-dimethyl–oxazolidin-2-one:
Rf
0.2 [3:1 pentane–Et2O]; dH (400 MHz, CDCl3) 1.30 [3H, s,
C(CH3)A(CH3)B], 1.52 [3H, s, C(CH3)A(CH3)B], 2.87 [1H, dd, J
14.0, 9.8, CHCHAHBPh], 3.50[1H, dd, J14.0, 4.3, CHCHAHBPh],
4.68 [1H, dd, CHCH2Ph], 7.22–7.42 [5H, m, PhH], 7.43–7.50
[2H, m, PhH], 7.52–7.58 [1H, m, PhH], 7.63–7.71 [5H, m, PhH];
dC (100 MHz, CDCl3) 22.6, 28.1 [C(CH3)2], 34.5 [CHCH2Ph],
64.6 [CHCH2Ph], 82.3 [C(CH3)2], 127.0, 130.6 [p-Ph], 127.9,
128.8, 129.2, 129.3 [m/o-Ph], 133.4, 136.5 [i-Ph], 152.6 [CO
endocyclic], 170.4 [CO exocyclic]; mmax(KBr disc, cm−1) 1776
[CO endocyclic], 1687 [C–O exocyclic]; HRMS C19H20NO3
[MH+] requires 310.1443, found 310.1456; [a]D25 +36.4 (c = 1.25,
CHCl3); m/z CI+ (NH3) 105 [100%, MH+-SQ], 310 [60%, MH+].
Preparation of (2S,3S,4R,5R)-2,4-bis-benzyloxy-3-hydroxy-
5-phenyl-tetrahydro-pyran-2-one (2S,3S,4R,5R)-31 and (S)-4-
benzyl-5,5-dimethyl-oxazolidin-2-one (S)-22. A solution of 30
(75 mg, 0.12 mmol) in PhMe (5 mL) was refluxed for 16 h, then
cooled to ambient temperature and concentrated in vacuo. Pu-
rification by column column chromatography gave 31 (37 mg,
0.09 mmol, 76%) as a white solid and (S)-22 (24 mg, 0.12 mmol,
99%) as a white solid.
Preparation of (2R,3S,4R,5R)-2,4-bis-benzyloxy-3-hydroxy-5-
phenyl-tetrahydro-pyran-2-one (2R,3S,4R,5R)-21, (2S,3R,4R,5R)-
2,4-bis-benzyloxy-3-hydroxy-5-phenyl-tetrahydro–pyran-2-one
(2S,3R,4R,5R)-24 and 5,5-dimethyl-oxazolidin-2-one. Follow-
ing representative procedure 2, a mixture of 11–12 (190 mg,
0.30 mmol), TBAF (0.45 mL, 0.45 mmol) and AcOH (0.02 mL,
0.30 mmol) in THF (10 mL) furnished an inseparable mixture
of 21–24 (81 mg, 0.26 mmol, 86%) as a white solid and 5,5-di-
methyl–oxazolidin-2-one (30 mg, 0.19 mmol, 64%) as a white
solid after column chromatography.
Preparation of (2S,3S,4R,5S)-2,4-bis-benzyloxy-3-hydroxy-
5-furan-2-yl-tetrahydro-pyran-2-one (2S,3S,4R,5S)-32 and
(S)-4-benzyl-5,5-dimethyl-oxazolidin-2-one (S)-22. Following
representative procedure 2, 20 (300 mg, 0.42 mmol), TBAF
(0.63 mL, 0.63 mmol) and AcOH (0.02 mL, 0.42 mmol) in THF
(10 mL) furnished a 50:50 inseparable mixture of 32 and (S)-22
(131 mg) as a pale yellow oil after column chromatography.
32: Rf 0.14 [2:1 Et2O–pentane]; dH (400 MHz, CDCl3) 4.05–
4.09 [2H, m, CH(OH) and CO.CHOCH2Ph], 4.14 [1H, d, J 10.3,
CHOCHAHBPh], 4.21–4.26 [1H, m, CH(OCH2Ph).CH(C4H3O)],
4.41 [1H, d, J 11.4, CHOCHCHDPh], 4.49 [1H, d, J 10.3, CHO-
CHAHBPh], 4.67 [1H, d, J 11.4, CHOCHCHDPh], 5.36 [1H, d, J
5.0, CH(OCH2Ph).CH(C4H3O)], 6.34–6.36 [2H, m, CH furan],
7.18–7.42 [11H, m, ArH]; dC (100 MHz, CDCl3) 63.5 [CH(OH)],
72.2 [CHOCH2Ph.CH(C4H3O)], 72.6, 72.9 [2 × CHOCH2Ph],
78.2 [CO.CHOCH2Ph and CH(OCH2Ph).CH(C4H3O)], 107.0,
110.5, 141.6 [CH furan], 127.8, 127.9 [p-Ph], 128.1, 128.3,
128.5, 128.9 [m/o-Ph], 136.9, 137.7 [i-Ph], 152.9 [i-Ar furan],
169.9 [CO]; mmax(thin film, cm−1) 3400 [O–H], 1770 [CO];
HRMS C23H23O6 [MH+] requires 395.1495, found 395.1491; m/z
CI+ 377 [25%, MH+–H2O], 395 [15%, MH+].
Preparation
of
(2S,3S,4S,5R)-4-benzyl-3-(2,4-bis-
benzyloxy-3,5-dihydroxy-5-phenyl-pentanoyl)-5,5-dimethyl-
oxazolidin-2-one 34, (2S,3S,4R,5R)-2,4-bis-benzyloxy-3-
hydroxy-5-phenyl-tetrahydro-pyran-2-one (2S,3S,4R,5R)-31
and 5,5-dimethyl-oxazolidin-2-one. Following representative pro-
cedure 2, 13 (70 mg, 0.11 mmol), TBAF (0.16 mL, 0.16 mmol)
and AcOH (0.006 mL, 0.11 mmol) in THF (10 mL) furnished
a 66:34 mixture of 34:31 which after purification by column
chromatography furnished an inseparable 66:34 mixture of
34:31 (48 mg) as a pale yellow oil and 5,5-dimethyl-oxazolidin-
2-one (9 mg, 0.08 mmol, 71%) as a pale peach solid.
34: Rf 0.12 [1:1 pentane–Et2O; double eluted]; dH
(400 MHz, CDCl3) 1.20 [3H, s, C(CH3)A(CH3)B], 1.40 [3H, s,
C(CH3)A(CH3)B], 3.19 [1H, d, J 10.8, NCHAHB], 3.49 [1H, d, J
10.8, NCHAHB], 3.89 [1H, dd, J 5.6, 3.0, CH(OCH2Ph).CHPh],
4.13 [1H, d, J 10.8, CHOCHAHBPh], 4.21–4.23 [2H, m,
2 × CH(OH)], 4.40 [1H, d, J 10.8, CHOCHAHBPh], 4.47 [1H,
d, J 11.5, CHOCHCHDPh], 4.70 [1H, d, J 11.5, CHOCHC-
HDPh], 5.46 [1H, d, J 5.6, CO.CHOCH2Ph], 7.14–7.43 [15H, m,
PhH]; dC (100 MHz, CDCl3) 26.7, 26.8 [C(CH3)2], 53.9 [NCH2],
72.4, 72.8 [2 × CH(OH)], 73.0, 73.1 [2 × CHOCH2Ph], 76.7
[CO.CHOCH2Ph], 79.4 [C(CH3)2], 81.3 [CH(OCH2Ph).CHPh],
127.4, 127.7, 127.8 [p-Ph], 128.1, 128.2, 128.3, 128.4, 128.5,
128.6 [m/o-Ph], 137.0, 137.6, 141.4 [i-Ph], 152.7 [CO endo-
cyclic], 170.9 [CO exocyclic]; mmax(thin film, cm−1) 3438 [O–H],
1769 [CO endocyclic], 1708 [CO exocylic]; C30H33NO7Na
[MNa+] requires 542.2155, found 542.2167; m/z ES+ 542 [100%,
MNa+].
Preparation of (2S,3S,4R,5S)-2,4-bis-benzyloxy-3-benzoyl-
5-furan-2-yl-tetrahydro-pyran-2-one (2S,3S,4R,5S)-33 and
(S)-3-benzoyl-4-benzyl-5,5-dimethyl-oxazolidin-2-one. Follow-
ing representative procedure 3, Et3N (0.04 mL, 0.32 mmol),
PhCOCl (0.03 mL, 0.25 mmol), DMAP (2 mg, 0.01 mmol) and
a 50:50 mixture of 32 and (S)-22 (50 mg, 0.127 mmol) in CH2Cl2
(10 mL) furnished 33 (63 mg) as a pale yellow oil contaminated
with (S)-3-benzoyl-4-benzyl-5,5-dimethyl–oxazolidin-2-one and
(S)-3-benzoyl-4-benzyl-5,5-dimethyl–oxazolidin-2-one (12 mg,
0.04 mmol) as a white foam after column chromatography.
33: Rf 0.26 [1:1 pentane–Et2O]; dH (400 MHz, CDCl3) 4.52
[1H, d, J 10.4, CHOCHAHBPh.CHC4H4O], 4.65 [1H, dd, J
7.4, 4.5, CH(OBz)], 4.70 [2H, s, CO.CHOCH2Ph], 4.87 [1H,
d, J 10.4, CHOCHAHBPh.CHC4H4O], 5.58 [1H, dd, J 6.5,
4.5, CHOCH2Ph.CHC4H4O], 5.88 [1H, d, J 6.6, CHC4H4O],
6.33–6.34 [1H, m, CH(furan)], 6.48–6.49 [1H, m, CH(furan)],
6.56 [1H, d, J 6.6, CO.CHOCH2Ph], 7.12–7.63 [16H, m, ArH];
dC (100 MHz, CDCl3) 69.1 [CHC4H4O], 73.1 [CH(OBz)],
73.5 [CO.CHOCH2Ph], 74.4 [CHOCH2Ph.CHC4H4O], 75.2
[CO.CHOCH2Ph], 78.8 [CHOCH2Ph.CHC4H4O], 110.2, 110.6,
142.8 [CH (furan)], 126.6, 127.5, 128.0 [p-Ph], 128.0, 128.2,
128.3, 128.4, 128.4, 128.5, 128.5, 128.7, 128.8, 129.8, 129.9,
130.0, 130.1 [m/o-Ph], 136.9, 137.2, 137.7 [i-Ph], 152.1 [C4 furan],
164.2 [CH(COBz)], 170.2 [CO lactone]; mmax(thin film, cm−1)
1777, 1728 [CO]; HRMS C30H27O7 [MH+] requires 499.1757,
Preparation of (1R,2S,3S,4S)-4-benzyl-3-(2-benzyloxy-
3-(2,2-dimethyl-[1,3]dioxolan-4-yl)-3-hydroxy-propionyl)-
5,5-dimethyl-oxazolidin-2-one (1R,2S,3S,4S)-39. Following
representative procedure 1, CF3SO3H (0.90 mL, 10.19 mmol),
Et3B (10.20 mL, 10.20 mmol), (S)-4 (3.00 g, 8.50 mmol),
i-Pr2NEt (2.07 mL, 11.90 mmol) and 38 (1.43 g, 11.01 mmol)
in CH2Cl2 (70 mL) furnished 39 (3.00 g, 6.20 mmol, 73%) as a
white solid after column chromatography.
39: Rf 0.15 [2:1 pentane–Et2O]; m.p 100–101 °C [pen-
tane–Et2O]; dH (400 MHz, CDCl3) 1.33 [3H, s, C(CH3)A(CH3)B
(acetonide)], 1.37 [3H, s, C(CH3)A(CH3)B (auxiliary)], 1.39 [3H,
s, C(CH3)A(CH3)B (auxiliary)], 1.44 [3H, s, C(CH3)A(CH3)B
(acetonide)], 2.50 [1H, d, J 7.4, CH(OH)], 2.84 [1H, dd, J 14.4,
9.4, CHCHAHBPh], 3.06 [1H, dd, J 14.4, 4.0, CHCHAHBPh],
3.82–3.87 [1H, m, CH(OH)], 4.06 [2H, d, J 5.4, OCHCH2O],
3 3 9 6
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 3 3 8 5 – 3 4 0 0

View Article Online
4.16–4.21 [1H, m, OCHCH2O], 4.46–4.52 [3H, m, CHCH2Ph
and CHOCH2Ph], 5.49 [1H, d, J 3.8, CHOCH2Ph], 7.20–7.38
[15H, m, PhH]; dC (100 MHz, CDCl3) 22.2, 28.5 [C(CH3)2
(auxiliary)], 25.3, 26.6 [C(CH3)2 (acetonide)], 35.3 [CHCH2Ph],
63.8 [CHCH2Ph], 66.7 [OCHCH2O], 73.0 [CHOCH2Ph],
73.2 [CH(OH)], 75.6 [OCHCH2O], 77.9 [CHOCH2Ph], 83.2
[C(CH3)2 (auxiliary)], 109.5 [C(CH3)2 (acetonide)], 126.8, 128.1
[p-Ph], 128.4, 128.7, 129.1 [m/o-Ph], 136.8, 137.1 [i-Ph], 152.4
[CO endocyclic], 170.7 [CO exocyclic]; mmax(KBr disc, cm−1)
3456 [O–H], 1775 [CO endocyclic], 1707 [CO exocyclic];
C27H33NO7 requires C 67.1, H 6.9, N 2.9%, found C 66.8, H
6.9, N 3.0%; [a] −43.1 (c = 1.4, CHCl3); m/z ES+ 426 [20%,
MH+–Me2CO], 506 [100%, MNa+].
CHCHAHBPh (42)], 3.03 [1H, dd, J 14.4, 3.9, CHCHAHBPh
(43)], 3.10 [1H, dd, J 14.4, 4.4, CHCHAHBPh (42)], 3.64–3.70
[1H, m, OCHCHAHBO (43)], 3.74–3.79 [1H, m, OCHCHAHBO
(43)], 3.77 [1H, dd, J 5.0, 3.9, OCHCHAHBO (42)], 3.82–3.89 [1H,
m, CH(OH) (42)], 3.84 [1H, dd, J 5.0, 6.4, OCHCHAHBO (42)],
4.21–4.24 [2H, m, OCHCH2O (42) and CH(OH) (43)], 4.27 [1H,
d, J 11.5, CHOCHAHBPh (42)], 4.31–4.35 [1H, m, OCHCH2O
(43)], 4.41 [1H, d, J 11.5, CHOCHAHBPh (43)], 4.49–4.58 [6H,
m, CHOCHAHBPh (42 and 43) and CHCH2Ph (42 and 43)], 5.22
[1H, d, J 3.1, CHOCH2Ph (42)], 5.50 [1H, d, J 4.2, CHOCH2Ph
(43)], 7.17–7.38 [20H, m, PhH]; dC (100 MHz, CDCl3) 22.0,
22.1, 25.6, 26.6, 26.8, 27.1, 28.3, 28.4 [C(CH3)2(acetonide and
auxiliary; 42 and 43)], 35.3 [CHCH2Ph (43)], 35.4 [CHCH2Ph
(42)], 62.3 [OCHCH2O (43)], 63.9 [CHCH2Ph (42 and 43)], 65.9
[OCHCH2O (42)], 72.7 [CHOCH2Ph (43)], 72.8 [CHOCH2Ph
(42)], 73.1 [CH(OH) (42)], 75.2 [CHOCH2Ph (43)], 76.5
[CHOCH2Ph (42)], 76.8, 77.1, 77.2 [OCHCH2O (42 and 43)
and CH(OH) (43)], 83.3 [C(CH3)2 (auxiliary; 43)], 83.7 [C(CH3)2
(auxiliary; 42)], 109.4 [C(CH3)2 (acetonide; 42)], 109.9 [C(CH3)2
(acetonide; 43)], 126.9, 127.2, 128.1 [p-Ph (42 and 43)], 128.2,
128.3, 128.4, 128.5, 128.7, 129.1, 129.2 [m/o-Ph (42 and 43)],
136.6, 136.7, 126.8, 136.9 [i-Ph (42 and 43)], 152.7 [CO endo-
cyclic (43)], 152.8 [CO endocyclic (42)], 169.8 [CO exocyclic
(42)], 170.1 [CO exocyclic (43)]; mmax(KBr disc, cm−1) 1772
[CO endocyclic], 1713 [CO exocyclic]; HRMS C27H33NO7Na
[MNa+] requires 506.2155, found 506.2152; m/z ES+ 501 [50%,
MNH4+], 506 [100%, MNa+].
Preparation of (1R,2R,3S)-2-benzyloxy-1-(2,2-dimethyl-
[1,3]dioxolan-4-yl)-propane-1,3-diol (1R,2R,3S)-40 and (S)-
4-benzyl-5,5-dimethyl-oxazolidin-2-one (S)-22. LiBH4 (0.52 mL,
1.04 mmol) was added to a solution of 39 (500 mg, 1.04 mmol)
in THF (20 mL) and H2O (0.19 mL, 1.04 mmol) at 0 °C. After
stirring for 20 min, the reaction mixture was quenched with 0.5
M NaOH solution, warmed to ambient temperature and stirred
for a further 45 min. The layers were separated and the aqueous
layer extracted with Et2O, washed with brine, dried and concen-
trated in vacuo. The crude product was purified by column chro-
matography to afford 40 (256 mg, 0.91 mmol, 87%) as a white
gum and (S)-22 (209 mg, 1.02 mmol, 98%).
40: Rf 0.05 [35:1 CHCl3–MeOH]; dH (400 MHz, CDCl3)
1.35 [3H, s, C(CH3)A(CH3)B], 1.40 [3H, s, C(CH3)A(CH3)B],
3.61–3.66 [1H, m, CH(OH)], 3.67–3.69 [1H, m, OCHCH2O],
3.76 [1H, dd, J 11.8, 4.3, OCHCHAHBO], 3.82 [1H, dd, J 11.8,
5.4, OCHCHAHBO], 3.96–4.02 [1H, m, CHAHBOH], 4.03–4.12
[2H, m, CHAHBOH and CHOCH2Ph], 4.63 [1H, d, J 11.4,
CHOCHAHBPh], 4.73 [1H, d, J 11.4, CHOCHAHBPh], 7.29–
7.40 [5H, m, PhH]; dC (100 MHz, CDCl3) 25.3, 26.7 [C(CH3)2],
62.3 [OCHCH2O], 67.4 [CH2OH], 73.0 [CHOCH2Ph], 73.7
[CH(OH)], 75.5 [CHOCH2Ph], 78.6 [OCHCH2O], 109.3
[C(CH3)2], 128.0 [p-Ph], 128.0, 128.5 [m/o-Ph], 137.9 [i-Ph]; mmax
(thin film, cm−1) 3391 [O–H]; HRMS C15H22O5Na [MNa+] re-
quires 305.1389, found 305.1392; [a] −19.3 (c = 1.5, CHCl3); m/z
ES+ 305 [100%, MNa+].
Preparation of (1R,2S,3R)-2-benzyloxy-1-(2,2-dimethyl-
[1,3]dioxolan-4-yl)-propane-1,3-diol(1R,2S,3R)-44,(1R,2S,3S)-
2-benzyloxy-1-(2,2-dimethyl-[1,3]dioxolan-4-yl)-propane-
1,3-diol(1R,2S,3S)-45and(R)-4-benzyl-5,5-dimethyl-oxazolidin-
2-one (R)-22. LiBH4 (0.16 mL, 0.31 mmol) was added to a so-
lution of 42 and 43 (150 mg, 0.31 mmol) in THF (20 mL) and
H2O (0.02 mL, 0.31 mmol) at 0 °C. After stirring for 20 min,
the reaction mixture was quenched with 0.5 M NaOH solution,
warmed to ambient temperature and stirred for a further 45 min.
The layers were separated and the aqueous layer extracted with
Et2O, washed with brine, dried and concentrated in vacuo. The
crude product was purified by column chromatography to af-
ford 44 (38 mg, 0.13 mmol, 43%) as a clear colourless oil, an
84:16 mixture of 44:45 (17 mg, 0.06 mmol, 19%) and a 28:72
mixture of 44:45 (22 mg, 0.08 mmol, 25%) and (R)-22 (53 mg,
0.26 mmol, 83%).
44: Rf 0.14 [80:1 CH2Cl2–MeOH]; dH (400 MHz, CDCl3)
1.37 [3H, s, C(CH3)A(CH3)B], 1.43 [3H, s, C(CH3)A(CH3)B], 2.42
[1H, br s, CH2OH], 2.66 [1H, d, J 6.0, CH(OH)], 3.52–3.56
[1H, m, CH(OH)], 3.65–3.74 [1H, m, OCHCH2O], 3.74–3.80
[1H, m, CHAHBOH], 3.78 [1H, dd, J 8.2, 7.0, OCHCHAHBO],
3.86–3.91 [1H, m, CHAHBOH], 3.91 [1H, dd, J 8.2, 6.5,
OCHCHAHBO], 4.26–4.30 [1H, m, CHOCH2Ph], 4.61 [1H, d,
J 11.7, CHOCHAHBPh], 4.70 [1H, d, J 11.7, CHOCHAHBPh],
7.29–7.40 [5H, m, PhH]; dC (100 MHz, CDCl3) 25.4, 26.5
[C(CH3)2], 61.3 [CH2OH], 66.1 [OCHCH2O], 71.6 [OCHCH2O],
72.4 [CHOCH2Ph], 75.7 [CHOCH2Ph], 78.9 [CH(OH)], 109.5
[C(CH3)2], 128.6 [p-Ph], 128.1, 128.6 [m/o-Ph], 137.8 [i-Ph]; mmax
(thin film, cm−1) 3414.5 [O–H]; HRMS C15H21O5 [M–H+] re-
quires 281.1389, found 281.1390; [a]2D2 +13.2 (c = 0.85, CHCl3);
m/z ES− 223 [100%, M–Me2CO+], 281 [95%, M–H+].
Preparation of (1R,2R,3S)-1-(2,2-dimethyl-[1,3]dioxolan-
4-yl)-propane-1,2,3-triol (1R,2R,3S)-41. Pd/C (25 mg) was
added to a solution of 40 (50 mg, 0.18 mmol) in MeOH (4 mL)
and AcOH (0.32 mL) at ambient temperature. After stirring
under a hydrogen atmosphere for 16 h, the reaction was filtered
through Celite® (eluent: MeOH) and concentrated in vacuo. The
crude product was purified by trituration with Et2O to afford 41
(32 mg, 0.17 mmol, 93%) as a white oil.
41: dH (200 MHz, MeOD) 1.38 [3H, s, C(CH3)A(CH3)B], 1.41
[3H, s, C(CH3)A(CH3)B], 3.55–3.72 [2H, m], 3.77–3.82 [2H,
m], 3.86–4.02 [2H,m], 4.08–4.25 [1H, m]; [a]2D5 −0.69 (c = 1.2,
EtOH), {lit.44 [a]2D5 −0.63 (c = 2.35, EtOH).
Preparation of (1R,2R,3R,4R)-4-benzyl-3-(2-benzyloxy-
3-(2,2-dimethyl-[1,3]dioxolan-4-yl)-3-hydroxy-propionyl)-
5,5-dimethyl–oxazolidin-2-one (1R,2R,3R,4R)-42 and
(1R,2R,3S,4R)-4-benzyl-3-(2-benzyloxy-3-(2,2-dimethyl-
[1,3]dioxolan-4-yl)-3-hydroxy–propionyl)-5,5-dimethyl-oxa-
zolidin-2-one (1R,2R,3S,4R)-43. Following representative
procedure 1, CF3SO3H (0.15 mL, 1.70 mmol), Et3B (1.70 mL,
1.70 mmol), (R)-4 (500 mg, 1.42 mmol), i-Pr2NEt (0.35 mL,
1.99 mmol) and 35 (203 mg, 1.56 mmol) in CH2Cl2 (40 mL)
furnished an inseparable 66:34 mixture of 42:43 (230 mg,
0.48 mmol, 34%) as a clear colourless oil and returned (R)-4
(222 mg, 0.63 mmol, 44%) as a pale yellow solid after column
chromatography.
45: Rf 0.09 [80:1 CH2Cl2–MeOH]; dH (400 MHz, CDCl3)
1.42 [3H, s, C(CH3)A(CH3)B], 1.43 [3H, s, C(CH3)A(CH3)B],
3.60–3.69 [2H, m, OCHCHAHBO and CHAHBOH], 3.72–3.87
[2H, m, OCHCHAHBO and CHAHBOH], 3.89–3.94 [1H, m,
CHOCH2Ph], 4.09–4.14 [2H, m, CH(OH) and OCHCH2O],
4.67–4.76 [2H, ABq, J 11.7, CHOCH2Ph], 7.26–7.41 [5H, m,
PhH]; dC (100 MHz, CDCl3) 26.8, 27.0 [C(CH3)2], 61.6 [CH2OH],
62.4 [OCHCH2O], 72.4 [CHOCH2Ph], 77.0 [OCHCH2O], 77.1
[CH(OH)], 78.3 [CHOCH2Ph], 109.2 [C(CH3)2], 128.0 [p-Ph],
128.0, 128.6 [m/o-Ph], 137.5 [i-Ph]; mmax (thin film, cm−1) 3387
[O–H]; HRMS C15H21O5 [M–H+] requires 281.1389, found
281.1392; m/z ES− 223 [100%, M–Me2CO], 281 [85%, M–H+].
42:43: Rf 0.09 [1:1 30–40 °C petrol–Et2O]; dH (400 MHz,
CDCl3) 1.38–1.43 [24H, m, C(CH3)2(auxiliary and acetonide;
42 and 43)], 2.69 [2H, d, J 8.4, CH(OH) (42 and 43)], 2.85 [1H,
dd, J 14.4, 9.5, CHCHAHBPh (43)], 2.93 [1H, dd, J 14.4, 9.1,
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 3 3 8 5 – 3 4 0 0
3 3 9 7

View Article Online
Preparation of (1R,2S,3R)-1-(2,2-dimethyl-[1,3]dioxolan-
4-yl)-propane-1,2,3-triol (1R,2S,3R)-46. Pd/C (10 mg) was
added to a solution of 44 (35 mg, 0.12 mmol) in MeOH (4 mL)
and AcOH (0.32 mL) at ambient temperature. After stirring
under a hydrogen atmosphere for 16 h, the reaction was filtered
through Celite® (eluent: MeOH) and concentrated in vacuo. The
crude product was purified by trituration with Et2O to afford 46
(21 mg, 0.11 mmol, 93%) as a clear colourless oil.
1.78 [3H, s, C(CH3)A(CH3)B (auxiliary, 49)], 2.60–2.66 [1H, m,
CHCHAHBPh (49)], 2.63 [1H, dd, J 14.7, 9.4, CHCHAHBPh (48)],
3.08 [1H, dd, J 14.7, 5.1, CHCHAHBPh (48)], 3.14 [1H, dd, J 14.4,
4.8, CHCHAHBPh (49)], 3.54–3.58 [2H, m, OCHCHAHBO and
CH(OTBDMS) (49)], 3.66 [1H, dd, J 6.8, 3.2, OCHCHAHBO
(49)], 3.77–3.81 [1H, m, OCHCHAHBO (48)], 3.84–3.87 [2H, m,
OCHCHAHBO (48) and OCHCH2O (49)], 4.05 [1H, dd, J 9.4,
5.1, CHCH2Ph (48)], 4.09 [1H, d, J 9.1, CH(OH) (48)], 4.15–4.20
[2H, m, OCHCH2O (48) and CHOCH2Ph (49)], 4.30 [1H, dd,
J 9.2, 2.1, CH(OTBDMS) (48)], 4.32–4.39 [1H, m, CHCH2Ph
(49)], 4.44 [1H, d, J 11.6, CHOCHAHBPh (49)], 4.54 [1H, d, J
11.6, CHOCHAHBPh (49)], 4.68 [1H, app. t, J 9.1, CHOCH2Ph
(48)], 4.72–4.80 [2H, ABq, J 11.8, CHOCH2Ph (48)], 7.08–7.41
[20H, m, PhH (48 and 49)], 7.88 [1H, s, CHO (49)]; dC (100 MHz,
CDCl3) −4.6, −4.5 [Si(CH3)2 (48)], −4.2, −4.1 [Si(CH3)2 (49)],
18.1 [SiC(CH3)3 (49)], 18.2 [SiC(CH3)3 (48)], 22.1, 27.5 [C(CH3)2
(auxiliary, 48)], 23.8, 24.6 [C(CH3)2 (auxiliary, 49)], 25.2, 26.5
[C(CH3)2 (acetonide, 48)], 25.2, 26.4 [C(CH3)2 (acetonide, 49)],
25.9 [SiC(CH3)3 (48)], 26.0 [SiC(CH3)3 (49)], 35.3 [CHCH2Ph
(48)], 35.8 [CHCH2Ph (49)], 57.0 [CHCH2Ph (49)], 64.4
[OCHCH2O (49)], 65.9 [CHCH2Ph (48)], 65.9 [OCHCH2O (48)],
72.2 [OCHCH2O (49)], 72.8 [CH(OH) (48)], 73.4 [CHOCH2Ph
(48)], 73.8 [CHOCH2Ph (49)], 75.2 [CH(OTBDMS) (49)], 75.6
[CH(OTBDMS) (48)], 77.3 [OCHCH2O (48)], 79.3 [CHOCH2Ph
(48)], 81.9 [C(CH3)2 (auxiliary, 48)], 82.4 [C(CH3)2 (auxiliary,
49)], 84.8 [CHOCH2Ph (49)], 108.1 [C(CH3)2 (acetonide, 48)],
108.2 C(CH3)2 (acetonide, 49)], 126.8, 127.6 [p-Ph (48)], 127.0,
128.1 [p-Ph (49)], 127.4, 128.5, 128.7, 128.9 [m/o-Ph (48)], 127.8,
128.4, 128.6, 129.1 [m/o-Ph (49)], 136.6, 138.3 [i-Ph (48)], 137.0,
137.6 [i-Ph (49)], 157.4 [CO (48)], 160.0 [CO ester (49)], 169.9
[CO amide (49)]; mmax(thin film, cm−1) 3406 [O–H (48)], 1730
[CO (48)]; HRMS C33H50NO7Si [MH+] requires 600.3357,
found 600.3359; m/z APCI+ 206 [70%, SQH+], 600 [5%, MH+].
46: dH (200 MHz, MeOD) 1.37 [3H, s, C(CH3)A(CH3)B], 1.43
[3H, s, C(CH3)A(CH3)B], 3.51–3.73 [5H, m], 3.72–3.82 [2H, m];
[a]D22 +8.2 (c = 0.9, EtOH), {lit.44 [a]2D5 +8.31 (c = 3.05, EtOH).
Preparation of (1R,2S,3S,4S)-benzyl-3-[2-benzyloxy-3-
(2,2-dimethyl-[1,3]dioxolan-4-yl)-3-(tert-butyl-dimethyl-
silanyloxy)-propionyl]-5,5-dimethyl-oxazolidin-2-one 47. Imida-
zole (1.47 g, 21.55 mmol), TBDMSCl (1.63 g, 10.78 mmol)
and DMAP (56 mg, 0.43 mmol) were added sequentially to a
solution of 39 (2.08 g, 4.31 mmol) in DMF (15 mL) at ambient
temperature. The reaction mixture was then warmed to 60 °C.
After stirring for 18 h, the reaction mixture was quenched with
MeOH, diluted with Et2O, washed with water, dried and con-
centrated in vacuo. Purification by column chromatography
furnished 47 (2.16 g, 3.62 mmol, 84%) as a white solid.
47: Rf 0.2 [5:1 30–40 °C petrol–Et2O]; mp 70–71 °C [30–40 °C
petrol–Et2O];dH (400 MHz, CDCl3)0.73[3H, s, Si(CH3)A(CH3)B],
0.88 [9H, s, SiC(CH3)3], 0.12 [3H, s, Si(CH3)A(CH3)B], 1.26 [3H,
s, C(CH3)A(CH3)B (acetonide)], 1.31 [3H, s, C(CH3)A(CH3)B
(auxiliary)], 1.33 [3H, s, C(CH3)A(CH3)B (auxiliary)], 1.38 [3H,
s, C(CH3)A(CH3)B (acetonide)], 2.58 [1H, dd, J 14.5, 10.4,
CHCHAHBPh], 2.96 [1H, dd, J 14.5, 4.0, CHCHAHBPh], 3.93–
4.01 [2H, m, OCHCH2O], 4.07 [1H, t, J 6.8, CH(OTBDMS)],
4.20–4.23 [1H, m, OCHCH2O], 4.35 [1H, dd, J 10.4, 4.0,
CHCH2Ph], 4.47 [1H, d, J 11.6, CHOCHAHBPh], 4.61 [1H,
d, J 11.6, CHOCHAHBPh], 5.42 [1H, d, J 6.7, CHOCH2Ph],
7.21–7.38 [10H, m, PhH]; dC (100 MHz, CDCl3) −4.7, −3.7
[Si(CH3)2], 18.3 [SiC(CH3)3], 22.6, 28.8 [C(CH3)2(auxiliary)],
25.2, 26.5 [C(CH3)2(acetonide)], 26.0 [SiC(CH3)3], 34.7
[CHCH2Ph], 64.2 [CHCH2Ph], 66.5 [OCHCH2O], 73.2
[CHOCH2Ph], 74.8 [CH(OTBDMS)], 76.3 [OCHCH2O], 79.1
[CHOCH2Ph], 82.2 [C(CH3)2 (auxiliary)], 109.2 [C(CH3)2 (aceto-
nide)], 126.7, 127.9 [p-Ph], 128.3, 128.6, 128.7, 128.9 [m/o-Ph],
137.1, 127.5 [i-Ph], 152.5 [CO endocyclic], 171.6 [CO exo-
cyclic]; mmax(KBr disc, cm−1) 1776 [CO endocyclic], 1706 [CO
exocyclic]; C33H47NO7Si requires C 66.3, H 7.9, N 2.3%, found C
66.4, H 7.7, 2.3%; [a] +3.4 (c = 0.5, CHCl3); m/z ES+ 540 [100%,
MH+–Me2CO], 620 [75%, MNa+].
Preparation of (1R,2S,3S)-2-benzyloxy-3-(tert-butyl-
dimethyl-silanyloxy)-3-(2,2-dimethyl-[1,3]dioxolan-4-yl)-
propionaldehyde 50, (1R,2S,2S,3S)-N-(1-benzyl-2-hydroxy-
2-methyl-propyl)-2-benzyloxy-3-(tert-butyl-dimethyl-silany-
loxy)-3-(2,2-dimethyl-[1,3]dioxolan-4-yl)-propionamide 51
and (S)-4-benzyl-5,5-dimethyl-oxazolidn-2-one (S)-22. K2CO3
(81 mg, 0.58 mmol) was added to a suspension of 48 and 49
(250 mg, 0.42 mmol) in MeOH–H2O (v:v 4:1; 10 mL) at ambi-
ent temperature. After stirring for 15 min, the reaction mixture
was diluted with CH2Cl2, washed with water and brine and
dried. Purification by column chromatography furnished 50
(86 mg, 0.22 mmol, 52%, 87% de) as a clear colourless oil, 51
(20 mg, 0.03 mmol, 8%) as a pale yellow oil and (S)-22 (50 mg,
0.24 mmol, 58%) as a white solid.
50: dH (400 MHz, CDCl3) 0.000 [3H, s, Si(CH3)A(CH3)B], 0.07
[3H, s, Si(CH3)A(CH3)B], 0.87 [9H, s, SiC(CH3)3], 1.32 [3H, s,
C(CH3)A(CH3)B], 1.36 [3H, s, C(CH3)A(CH3)B], 3.87 [1H, dd, J
8.1, 6.6, OCHCHAHBO], 3.90 [1H, dd, J 3.8, 1.5, CHOCH2Ph],
3.98 [1H, dd, J 8.1, 6.3, OCHCHAHBO], 4.12–4.14 [1H, m,
OCHCH2O], 4.18–4.22 [1H, m, CH(OTBDMS)], 4.60 [1H, d,
J 11.8, CHOCHAHBPh], 4.74 [1H, d, J 11.8, CHOCHAHBPh],
7.27–7.38 [5H, m, PhH], 9.71 [1H, d, J 1.5, CHO]; dC
(100 MHz, CDCl3) −4.8, −4.4 [Si(CH3)2], 18.2 [SiC(CH3)3],
25.2, 26.5 [C(CH3)2], 25.8 [SiC(CH3)3], 66.2 [OCHCH2O],
73.2 [CHOCH2Ph], 73.6 [OCHCH2O], 75.6 [CHOCH2Ph],
84.8 [CH(OTBDMS)], 108.9 [C(CH3)2], 128.1, 128.5 [p- and
m/o-Ph], 137.2 [i-Ph], 203.2 [CHO]; mmax(thin film, cm−1) 1734
[CO]; HRMS C21H34O5NaSi [MNa+] requires 417.2073, found
417.2083; [a]2D5 −15.3 (c = 0.75, CHCl3); m/z ES+ 337 [35%,
MH+–Me2CO], 417 [100%, MNa+].
Preparation of (1R,2S,3S,4S)-4-benzyl-3-[2-benzyloxy-3-
(tert-butyl-dimethyl-silanyloxy)-3-{2,2-dimethyl-[1,3]dioxolan-
4-yl}-1-hydroxy–propyl]-5,5-dimethyl-oxazolidin-2-one 48 and
(1R,2S,2S,3S)-2-[2-benzyloxy-3-(tert-butyl-dimethyl-silany-
loxy)-3-{2,2-dimethyl-[1,3]dioxolan-4-yl}-propionylamino]-
1,1-dimethyl-3-phenyl-propyl formate 49. DIBAL (1.68 mL,
1.68 mmol) was added dropwise to a stirred solution of 47
(500 mg, 0.84 mmol) in CH2Cl2 (10 mL) at −78 °C. The reac-
tion was quenched at −78 °C after 30 min with saturated,
aqueous NH4Cl solution, warmed to ambient temperature and
stirred for a further 30 min. The reaction mixture was filtered
through Celite® (eluent: CH2Cl2), the layers separated, dried and
concentrated in vacuo. Purification by column chromatography
furnished an inseparable 88:12 mixture of 48 and 49 (342 mg,
0.57 mmol, 68%) as a pale yellow oil.
48:49: Rf 0.28 [1:1 30–40 °C petrol–Et2O]; dH (400 MHz,
CDCl3) −0.02 [3H, s, Si(CH3)A(CH3)B (49)], 0.079 [3H, s,
Si(CH3)A(CH3)B (49)], 0.11 [6H, s, Si(CH3)2(48)], 0.87 [9H,
s, SiC(CH3)3 (49)], 0.90 [9H, s, SiC(CH3)3 (48)], 1.11 [3H, s,
C(CH3)A(CH3)B (auxiliary, 48)], 1.25 [3H, s, C(CH3)A(CH3)B
(acetonide, 48)], 1.26 [3H, s, C(CH3)A(CH3)B (auxiliary, 49)],
1.31 [3H, s, C(CH3)A(CH3)B (acetonide, 48)], 1.39 [3H, s,
C(CH3)A(CH3)B (acetonide, 49)], 1.42 [3H, s, C(CH3)A(CH3)B
(auxiliary, 48)], 1.45 [3H, s, C(CH3)A(CH3)B (acetonide, 49)],
51: dH (400 MHz, CDCl3) −0.12 [3H, s, Si(CH3)A(CH3)B], 0.03
[3H, s, Si(CH3)A(CH3)B], 0.83 [9H, s, SiC(CH3)3], 1.19 [6H, s,
C(CH3)2 (auxiliary)], 1.28 [3H, s, C(CH3)A(CH3)B (acetonide)],
1.39 [3H, s, C(CH3)A(CH3)B (acetonide)], 2.60 [1H, dd, J 14.1,
10.5, CHCHAHBPh], 2.81 [1H, s, OH], 3.08 [1H, dd, J 14.1, 4.3,
CHCHAHBPh], 3.72–3.81 [4H, m, OCHCHAHBO, OCHCH2O,
CHOCH2Ph and CH(OTBDMS)], 3.92 [1H, dd, J 7.3, 6.2,
3 3 9 8
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 3 3 8 5 – 3 4 0 0

View Article Online
OCHCHAHBO], 4.01–4.07 [1H, m, CHCH2Ph], 4.44 [1H, d,
J 11.5, CHOCHAHBPh], 4.56 [1H, d, J 11.5, CHOCHAHBPh],
6.70 [1H, d, J 8.7, NH], 7.14–7.39 [10H, m, PhH]; dC (100 MHz,
CDCl3) −4.4, −4.1 [Si(CH3)2], 18.1 [SiC(CH3)3], 25.3, 26.5
[C(CH3)2 (acetonide)], 25.8, 28.2 [C(CH3)2 (auxiliary)],
25.9 [SiC(CH3)3], 36.1 [CHCH2Ph], 59.4 [CHCH2Ph], 65.3
[OCHCH2O], 72.6 [OCHCH2O], 73.2 [C(CH3)2 (auxiliary)],
74.0 [CHOCH2Ph], 75.3 [CH(OTBDMS)], 82.0 [CHOCH2Ph],
108.5 [C(CH3)2 (acetonide)], 126.9, 128.2 [p-Ph], 128.1, 128.6,
128.7, 129.0 [m/o-Ph], 137.1, 138.1 [i-Ph], 171.2 [CO]; mmax(thin
film, cm−1) 3408 [O–H], 1660 [CO]; C32H49NO6Si requires C
67.2, H 8.6, N 2.45%, found C 67.0, H 8.7, N 2.4%; [a]2D4 −33.2
(c = 1.3, CHCl3); m/z APCI+ 513 [50%, MH+–Me2CO], 571
[20%, MH+].
72.0 [CH(OCH2Ph).CHOCHCH2O], 72.6 [CHOCHCH2O], 74.4
[CH(OH)], 74.7, 75.4 [2 × CHOCH2Ph], 76.6 [CO.CHOCH2Ph],
79.8 [CHOCHCH2O], 109.7 [C(CH3)2], 128.0, 128.3 [p-Ph], 128.0,
128.4, 128.6, 128.7 [m/o-Ph], 137.1, 137.8 [i-Ph], 169.6 [CO];
mmax(thin film, cm−1) 3446 [O–H], 1751 [CO]; C24H28O7 requires
C 67.3, H 6.6%, found C 67.4, H 6.6%; [a]D24 +72.0 (c = 0.25,
CHCl3); m/z ES+ 429 [40%, MH+], 446 [100%, MNH4+].
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.).
References and Notes
Preparation of (1R,2R,3S,4R,4R,5S)-4-benzyl-3-[2,4-
bis-benzyloxy-5-(2, 2-dimethyl-[1, 3]dioxolan-4-yl)-5-(tert-
butyl–dimethyl-silanyloxy)-3-hydroxy-pentanoyl]-5,5-dimethyl-
oxazolidin-2-one (1R,2R,3S,4R,4R,5S)-52. Following
representative procedure 1, CF3SO3H (0.11 mL, 1.27 mmol),
Et3B (1.27 mL, 1.27 mmol), (R)-4 (375 mg, 1.06 mmol),
i-Pr2NEt (0.26 mL, 1.48 mmol) and 50 (424 mg, 1.07 mmol)
in CH2Cl2 (20 mL) furnished 52 (333 mg, 0.45 mmol, 42%)
as a clear colourless oil contaminated with <8% of (R)-4 after
column chromatography.
1 For selected examples of the recent use of proline as an asymmetric
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L. Hoang, N. Vignola and B. List, Angew. Chem., Int. Ed. Engl.,
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J.-L. Reymond, Bioorg. Med. Chem. Lett., 2003, 13, 2445; K. Oisaki,
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F. Kunisch and P. Heitmann, Tetrahedron Lett., 1986, 27, 4721.
3 For selected recent examples see S. Saito, K. Hatanaka, T. Kano
and H. Yamamoto, Angew. Chem., Int. Ed. Engl., 1998, 37, 2278;
C. Palomo, A. Gonzalez, J. M. Garcia, C. Landa and M. Oiarbide,
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Hung, C.-S. Chang and T.-H. Yan, J. Org. Chem., 1996, 61, 2038;
S. R. Hitchcock, D. M. Casper, J. F. Vaughn, J. M. Finefield, G. M.
Ferrence and J. M. Esken, J. Org. Chem., 2004, 69, 714; J. E. Hein
and P. G. Hultin, Synlett, 2003, 635; S.-M. Kim and J.-G. Jun, Synth.
Commun., 2002, 3851; S. G. Davies, D. J. Dixon, G. Doisneau,
J. C. Prodger and H. J. Sanganee, Tetrahedron: Asymmetry,
2002, 13, 647; R. K. Boeckman, M. A. Laci and A. T. Johnson,
Tetrahedron: Asymmetry, 2001, 12, 205; M. Stover, A. Lutzen
and P. Koll, Tetrahedron: Asymmetry, 2000, 11, 371; T. H. Kim
and G.-J. Lee, Tetrahedron Lett., 2000, 41, 1505; M. T. Crimmins
and K. Chaudhary, Org. Lett., 2000, 2, 775.
4 For an excellent review on asymmetric aldol reactions with
boron enolates see C. J. Cowden and I. Paterson, Org. React.,
1997, 51, 1; for a review of the rational design of enol borinates
see A. Bernardi, C. Gennari, J. M. Goodman and I. Paterson,
Tetrahedron:Asymmetry, 1995, 6, 2613; for the preparation of all
possible diastereoisomeric combinations from a single aldol reagent
see N. A. Van Draanen, S. Arseniyadis, M. T. Crimmins and
C. H. Heathcock, J. Org. Chem., 1991, 56, 2499.
5 For limited examples see S. R. Martin, J. A. Dodge, L. E. Burgess,
C. Limberakis and M. Hartmann, Tetrahedron, 1996, 52, 3229;
J. D. White and J. Deerberg, Chem. Commun., 1997, 1919;
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Andrus, E. L. Meredith and B. B. V. Soma Sekhar, Org. Lett., 2001,
3, 259; C. J. Forsyth, J. Hao and J. Aiguade, Angew. Chem., Int. Ed.
Engl., 2001, 40, 3663.
6 T. Mukaiyama, I. Shiina, H. Uchiro and S. Kobayashi, Bull. Chem.
Soc. Jpn, 1994, 67, 1708.
7 B. M. Trost, H. Ito and E. R. Silcoff, J. Am. Chem. Soc., 2001, 123,
3367.
8 B. List, R. Lerner and C. F. Barbas, J. Am. Chem. Soc., 2000, 122,
2395; W. Notz and B. List, J. Am. Chem. Soc., 2000, 122, 7386;
A. B. Northrup,I. K. Mangion,F. HettcheandD. W. C. MacMillan,
Angew. Chem., Int. Ed. Engl., 2004, 43, 2152.
9 C. Gennari, A. Vulpetti and D. Moresca, Tetrahedron Lett., 1994, 35,
4857; C. Gennari, M. Carcano, M. Donghi, N. Mongelli, E. Vanotti
and A. Vulpetti, J. Org. Chem., 1997, 62, 4746.
10 M. B. Andrus, B. B. V. S. Sekhar, T. M. Turner and E. L. Meredith,
Tetrahedron Lett., 2001, 42, 7197.
11 M. B. Andrus, B. B. V. Soma Sekhar, E. L. Meredith and N. Kent
Dalley, Org. Lett., 2000, 2, 3035.
12 Z. Li, R. Wu, R. Michalczyk, R. B. Dunlap, J. D. Odom and L. A.
Silks III, J. Am. Chem. Soc., 2000, 122, 386.
13 For a review of the diversity of asymmetric synthesis that can be
achieved using oxazolidinone auxiliaries see D. J. Ager, I. Prakash
and D. R. Schaad, Aldrichimica Acta, 1997, 30, 3.
52: Rf 0.16 [1:1 pentane–Et2O]; dH (400 MHz, CDCl3) 0.06
[3H, s, Si(CH3)A(CH3)B], 0.08 [3H, s, Si(CH3)A(CH3)B], 0.87 [9H,
s, SiC(CH3)3], 1.35 [3H, s, C(CH3)A(CH3)B (acetonide)], 1.37 [3H,
s, C(CH3)A(CH3)B (auxiliary)], 1.38 [3H, s, C(CH3)A(CH3)B (auxil-
iary)], 1.41[3H, s, C(CH3)A(CH3)B (acetonide)], 2.84–2.92[2H, m,
CH(OH) and CHCHAHBPh], 3.14 [1H, dd, J 14.4, 3.7, CHCHA-
HBPh], 3.836 [1H, dd, J 9.4, 2.2, CHOCH2Ph.CH(OTBDMS)],
3.91 [1H, t, J 7.6, OCHCHAHBO], 3.96–4.03 [2H, m, CH(OH)
and OCHCHAHBO], 4.17–4.21 [1H, m, CH(OTBDMS)],
4.19 [1H, d, J 11.1, CHOCHAHBPh], 4.29–4.33 [1H, m,
OCHCH2O], 4.46 [1H, d, J 11.1, CHOCHAHBPh], 4.50–4.54
[2H, m, CHOCHCHDPh and CHCH2Ph], 4.66 [1H, d, J 12.0,
CHOCHCHDPh], 5.50 [1H, app. s, CO.CHOCH2Ph], 7.20–7.38
[15H, m, PhH]; dC (100 MHz, CDCl3) −4.5, −4.3 [Si(CH3)2],
18.2 [SiC(CH3)3], 22.1, 28.3 [C(CH3)2 (auxiliary)], 25.2, 26.5
[C(CH3)2 (acetonide)], 26.0 [SiC(CH3)3], 35.3 [CHCH2Ph], 64.0
[CHCH2Ph], 66.0 [OCHCH2O], 71.6 [CH(OH)], 72.2, 72.7
[2 × CHOCH2Ph], 72.7 [CH(OTBDMS)], 75.6 [OCHCH2O],
77.4 [CHOCH2Ph.CH(OTBDMS)], 77.8 [CO.CHOCH2Ph],
83.7 [C(CH3)2 (auxiliary)], 108.0 [C(CH3)2 (acetonide)], 126.8,
127.3, 127.8 [p-Ph], 127.3, 128.2, 128.3, 128.4, 128.6, 129.1 [m/o-
Ph], 136.9, 137.2, 138.5 [i-Ph], 152.3 [CO endocyclic], 170.8
[CO exocyclic]; mmax(thin film, cm−1) 3462 [O–H], 1779 [CO
endocyclic], 1708 [CO endocyclic]; HRMS C42H57NO9NaSi
[MNa+] requires 770.3700, found 770.3689; [a]D26 +43.4 (c = 0.55,
CHCl3); m/z ES+ 748 [50%, MH+], 770 [100%, MNa+].
Preparation of (1R,2R,3S,4R,5S)-2,4-bis-benzyloxy-5-(2,2-
dimethyl-[1,3]dioxolan-4-yl)-4-hydroxy-tetrahydro-pyran-2-one
(1R,2R,3S,4R,5S)-53 and (R)-4-benzyl-5,5-dimethyl-oxazoli-
din-2-one (R)-22. Following representative procedure 2, 52
(330 mg, 0.44 mmol), TBAF (0.66 mL, 0.66 mmol) and AcOH
(0.03 mL, 0.44 mmol) in THF (20 mL) furnished (R)-4 (81 mg,
0.23 mmol) as a pale yellow oil, 53 (82 mg, 0.19 mmol) as a
clear colourless oil and (R)-22 (50 mg, 0.24 mmol) after column
chromatography.
53: Rf 0.17 [1:1 30–40 °C petrol–Et2O]; dH (400 MHz, CDCl3)
1.37 [3H, s, C(CH3)A(CH3)B], 1.43 [3H, s, C(CH3)A(CH3)B],
4.04–4.09 [3H, m, OCHCHAHBO, CHOCHCH2O and
CH(OCH2Ph).CHOCHCH2O], 4.15 [1H, dd, J 9.1, 6.0,
OCHCHAHBO], 4.23 [1H, t, J 2.2, CH(OH)], 4.31–4.38 [1H,
m, CHOCHCH2O], 4.32 [1H, d, J 10.0, CO.CHOCH2Ph],
4.72 [1H, d, J 11.2, CHOCHAHBPh], 4.76 [1H, d, J 11.0,
CHOCHCHDPh], 4.87 [1H, d, J 11.0, CHOCHCHDPh], 5.19
[1H, d, J 11.2, CHOCHAHBPh], 7.25–7.44 [10H, m, PhH]; dC
(100 MHz, CDCl3) 25.1, 27.0 [C(CH3)2], 67.1 [CHOCHCH2O],
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 3 3 8 5 – 3 4 0 0
3 3 9 9

View Article Online
14 D. A. Evans, J. Bartroli and T. L. Shih, J. Am. Chem. Soc., 1981,
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15 M. T. Crimmins, B. W. King, W. J. Zuercher and A. L. Choy, J. Org.
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16 M. T. Crimmins and A. L. Choy, J. Org. Chem., 1997, 62, 7548;
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17 D. A. Evans, J. R. Gage, J. L. Leighton and A. S. Kim, J. Org.
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29 A. B. Smith III and G. R. Ott, J. Am. Chem. Soc., 1996, 118, 13095;
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30 For instance see D. A. Evans, S. L. Bender and J. Morris, J. Am.
Chem. Soc., 1988, 110, 2506; D. Hunziker, N. Wu, K. Kenoshita,
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31 D. L. J. Clive, Y. Tao, Y. Bo, Y.-Z. Hu, N. Selvakumar, S. Sun,
S. Daigneault and Y.-J. Wu, Chem. Commun., 2000, 1341.
32 D. J. Cram and F. A. B. Elhafez, J. Am. Chem. Soc., 1952, 74, 5828;
D. J. Cram and D. R. Wilson, J. Am. Chem. Soc., 1963, 85, 1245.
33 J. W. Cornforth, R. H. Cornforth and K. K. Mathew, J. Chem. Soc.,
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34 G. J. Karasbastos, J. Am. Chem. Soc., 1967, 89, 1367.
35 M. Cherest, H. Felkin and N. Prudent, Tetrahedron Lett., 1968, 9,
2199.
36 N. T. Anh and O. Eisenstein, Nouv. J. Chim., 1977, 1, 61; N. T. Anh,
Top. Curr. Chem., 1980, 88, 145.
18 For selected asymmetric glycolate enolate reactions see; (i) glycolate
enolate alkylations see M. T. Crimmins, K. A. Emmitte and J. D.
Katz, Org. Lett., 2000, 2, 2165; M. T. Crimmins and M. T. Powell,
J. Am. Chem. Soc, 2003, 125, 7592; S. D. Burke, K. J. Quinn and
V. J. Chen, J. Org. Chem., 1998, 63, 8626; D. Enders and U. Reinhold,
Synlett, 1994, 792; D. Enders and U. Reinhold, Angew. Chem., Int.
Edn. Engl., 1995, 34, 1219; D. Enders and U. Reinhold, Liebigs Ann.
Chem., 1996, 11; (ii) for glycolate enolate additions to acyclic ketimines
see P. Bravo, S. Fustero, M. Guidetti, A. Volonterio and M. Zanda, J.
Org. Chem., 1999, 64, 8731; (iii) for representative examples of other
glycolate aldol reactions see K. S. Kim and S. D. Hong, Tetrahedron
Lett., 2000, 41, 5909; S. Sasaki, Y. Hamada and T. Shioiri, Tetrahedron
Lett., 1999, 40, 3187.
19 (a) S. G. Davies, I. A. Hunter, R. L. Nicholson, P. M. Roberts,
E. D. Savory and A. D. Smith, Tetrahedron, 2004, 60, 7553;
(b) for our previous related work in this area with achiral
oxazolidinones see J. Bach, S. D. Bull, S. G. Davies, R. L. Nicholson,
H. J. Sanganee and A. D. Smith, Tetrahedron Lett., 1999, 40, 6677;
(c) J. Bach, C. Blachere, S. D. Bull, S. G. Davies, R. L. Nicholson,
P. D. Price, H. J. Sanganee and A. D. Smith, Org. Biomol. Chem.,
2003, 1(11), 2001. For our studies with chiral oxazolidinones see;
(d) S. D. Bull, S. G. Davies, R. L. Nicholson and A. D. Smith,
Tetrahedron: Asymmetry, 2000, 13, 3475; (e) S. D. Bull, S. G. Davies,
R. L. Nicholson, H. J. Sanganee and A. D. Smith, Org. Biomol.
Chem., 2003, 1(16), 2886.
37 For a study concerned with the diastereofacial selectivity of aldol
reactions of chiral aldehydes with lithium and boron enolates see
W. R. Roush, J. Org. Chem., 1991, 56, 4151.
38 C. H. Heathcock, S. D. Young, J. P. Hagen, M. C. Pirrung, C. T.
White and D. van Derveer, J. Org. Chem., 1980, 45, 3846; C. Gennari,
A. Bernardi, S. Cardani and C. Scolastico, Tetrahedron, 1984, 40,
4059; C. Esteve, M. Ferreró, P. Romea, F. Urpí and J. Vilarrasa,
Tetrahedron Lett., 1999, 40, 5083.
39 D. A. Evans, S. J. Siska and V. J. Cee, Angew. Chem., Int. Ed. Engl.,
2003, 42, 1761.
40 J. A. Marco, M. Carda, S. Díaz-Oltra, J. Murga, E. Falomir and
H. Roeper, J. Org. Chem., 2003, 68, 8577.
41 D. A. Evans,M. J. Dart,J. L. Duffy,M. G. YangandA. B. Kingston,
J. Am. Chem. Soc., 1995, 117, 6619.
42 The same stereochemical result can be rationalised by the reaction
proceeding through the favoured polar Felkin–Anh conformer of
the aldehyde although this transition state would be expected to be
destabilised by syn-pentane interactions.
20 S. G. Davies, R. L. Nicholson and A. D. Smith, Synlett, 2002,
1637; S. G. Davies, R. L. Nicholson, P. D. Price, P. M. Roberts and
A. D. Smith, Synlett, 2004, 901.
21 For selected examples of double diastereoselective aldol reactions
see; (a) D. J. Gustin, M. S. van Nieuwenhze and W. R. Roush,
Tetrahedron Lett., 1995, 36, 3443; (b) S. Sano, X.-K. Liu,
M. Takebayashi, Y. Kobayashi, K. Tabata, M. Shiro and Y. Nagao,
Tetrahedron Lett., 1995, 36, 4104; (c) E. J. Corey, W. Li and
G. A. Reichard, J. Am. Chem. Soc., 1998, 120, 2330; (d) D. A.
Evans, M. J. Dart, J. L. Duffy and D. L. Rieger, J. Am. Chem.
Soc., 1995, 117, 9073; (e) D. A. Evans, P. J. Coleman and B. Cote,
J. Org. Chem., 1997, 62, 788; (f) G. J. Bodwell, S. G. Davies and
A. M. Mortlock, Tetrahedron, 1991, 48, 10077; (g) P. R. Beckett,
S. G. Davies and A. M. Mortlock, Tetrahedron: Asymmetry, 1992,
3, 123; (h) A. N. Hulme and C. H. Montgomery, Tetrahedron Lett.,
2003, 44, 7649.
22 D. A. Evans and J. Bartroli, Tetrahedron Lett., 1982, 23, 807.
23 I. Paterson and M. A. Lister, Tetrahedron Lett., 1988, 29, 585.
24 On the well precedented assumption that the C(3)-hydroxycarbonyl
aldol exists in solution predominantly in an intramolecularly
hydrogen bonded form Ja,b is usually in the range of 2–6 Hz for
syn-aldol products, and 7–10 Hz for anti-aldol products. For leading
references see M. Stiles, R. W. Winkler, Y.-L. Chang and L. Traynor,
J. Am. Chem. Soc., 1964, 86, 3337; H. O. House, D. S. Crumrine,
A. Y. Teranishi and H. D. Olmstead, J. Am. Chem. Soc., 1973, 95,
3310; C. H. Heathcock, M. C. Pirrung and J. E. Sohn, J. Org. Chem.,
1980, 45, 1066; C. H. Heathcock, C. T. Buse, W. A. Kleschick, M. C.
Pirrung, J. E. Sohn and J. Lampe, J. Org. Chem., 1979, 44, 4294.
25 For previous stereoselective reactions of the (Z)-boron enolates of
oxazolidinones with chiral aldehydes see ref. 12 and W. R. Roush and
A. D. Palkowitz, J. Org. Chem., 1989, 54, 3009.
43 M. Daumas, Y. Vo-Quang and F. le Goffic, Synthesis, 1989, 64.
44 T. Katsuki, A. W. M. Lee, P. Ma, V. S. Martin, S. Masamune, K. B.
Sharpless, D. Tuddenham and F. J. Walker, J. Org. Chem., 1982, 47,
1378.
45 A similar phenomenon has been observed by Marco et al.; see ref. 40.
46 The absolute configuration at C(1) within oxazolidinone 48 was
assigned by analogy to that proven unambiguously by X-ray
crystallographic analysis for DIBAL reduction of a related substrate.
See ref. 19a.
47 For a study concerned with the stability of related N-acyl hemi-
aminals see M. P. DeNinno and C. Eller, Tetrahedron Lett., 1997,
38, 6545; M. P. DeNinno, C. Eller and J. B. Etienne, J. Org. Chem.,
2001, 66, 6988; Y.-G. Suh, D.-Y. Shin, J.-K. Jung and S.-H. Kim,
Chem. Commun., 2002, 1064; Y.-G. Suh, S.-H. Kim, J.-K. Jung and
D.-Y. Shin, Tetrahedron Lett., 2002, 43, 3165. Similar 1-hydroxy-oxa-
zolidinones (tetrahedral carbinols) have been reported by Evans et
al. upon reduction of N-acyl pyrroles; see D. A. Evans, G. Borg and
K. A. Scheidt, Angew. Chem., Int. Ed. Engl, 2002, 41, 3188; this ob-
servation led to the use of pyrrole as a protecting group for aldehydes;
D. J. Dixon, M. S. Scott and C. A. Luckhurst, Synlett, 2003, 2317.
48 The possibility of kinetic resolution occuring in this reaction cannot
be discounted as reaction of aldehyde 50 (87% de) gave, after
oxidative work-up, a single diastereoisomer of 52, with no trace of
starting material found in the crude reaction product.
26 S. Masamune, W. Choy, J. S. Petersen and L. R. Sita, Angew. Chem.,
Int. Edn. Engl., 1985, 24, 1.
27 For another example of a glycolate aldol reaction see W. R. Roush,
L. A. Pfeifer and T. G. Marron, J. Org. Chem., 1998, 63, 2064.
28 Aldol products 18 and 19 were isolated contaminated with <10% of
(R)-4 and (S)-4 respectively.
3 4 0 0
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 3 3 8 5 – 3 4 0 0