Desymmetrization of prochiral anhydrides with Evans' oxazolidinones: An efficient route to homochiral glutaric and adipic acid derivatives

Article abstract of DOI:10.1039/a808838a

The prochiral recognition between enantiotopic carbonyl groups in the reaction of 3-substituted glutaric and 3,4-disubstituted adipic anhydrides with anions of Evans' oxazolidinones has been investigated. Each of the σ-symmetric anhydrides provided a diastereoisomeric mixture of half-acids which were separated either by fractional crystallization or by column chromatography of their esters. The diastereoselectivity of the desymmetrization reaction is dependent on the substituents present in the anhydrides.

Full text of DOI:10.1039/a808838a

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Desymmetrization of prochiral anhydrides with Evans’
oxazolidinones: an efficient route to homochiral glutaric and
adipic acid derivatives
Rekha Verma, Seturam Mithran and Sunil K. Ghosh*
Bio-Organic Division, Bhabha Atomic Research Centre, Mumbai 400 085, India
Received (in Cambridge) 12th November 1998, Accepted 9th December 1998
The prochiral recognition between enantiotopic carbonyl groups in the reaction of 3-substituted glutaric and
3,4-disubstituted adipic anhydrides with anions of Evans’ oxazolidinones has been investigated. Each of the
σ-symmetric anhydrides provided a diastereoisomeric mixture of half-acids which were separated either by
fractional crystallization or by column chromatography of their esters. The diastereoselectivity of the
desymmetrization reaction is dependent on the substituents present in the anhydrides.
Table 1 Diastereoselectivities during opening up anhydride 1a with
the anions of 2a and 2b
Introduction
Enantio- or diastereo-selective differentiation of prochiral
functional groups in a symmetrical bifunctional molecule1 has
always been a challenge to chemists. An important prochiral
intermediate, viz. a σ-symmetric dicarboxylic anhydride can
provide strategically located chiral centre(s) by such transform-
ations. Most of the known methods using various chiral
reagents2–4 have displayed high diastereoselectivities when bi-
and tri-cyclic 2,3-disubstituted meso-dicarboxylic anhydrides
were used. Among these, only a few reagents3 have been tested
on 3-substituted glutaric anhydrides resulting in varying select-
ivity. The disadvantage of these methods is that the diastereo-
isomeric acids and their derivatives were generally inseparable.
Moreover, in most of the cases, the chiral reagents were pre-
pared in multistep reactions and also were not recoverable due
to destruction by further chemical transformations.
Diastereoisomer
ratiob
(3a or 5:4a or 6)
Oxazolidone
Reaction conditionsa
2a
2a
THF, room temp., 24 h
THF, 5 equiv. DMPU,
room temp., 15 min
67:33
63:37
2a
2b
2b
2b
2b
THF, 5 equiv. DMPU, Ϫ78 ЊC, 1 h 65:35
THF, room temp., 24 h 63:37
THF, 5 equiv. DMPU, 10 ЊC, 0.5 h 65:35
THF, 5 equiv. DMPU, Ϫ78 ЊC, 1 h 62:38
THF, 1 equiv. MgBr2, room temp., 50:50
20 h
a Deprotonation of 2a and 2b was done with BuLi at Ϫ40 ЊC. b The
diastereoisomer ratios were ascertained from the NMR spectra of the
methyl esters of the crude reaction mixtures.
During the course of our synthesis of (ϩ)-preussin5 (see the
following paper), we were in need of a suitable method for
desymmetrization of the prochiral 3-[dimethyl(phenyl)silyl]-
glutaric anhydride (1a). Initially, we attempted the desym-
R
O
R
O
O
O
Nu–
1a–d
+
HO
Nu
Nu
OH
NuH = 2a
NuH = 2b
NuH = 2a
NuH = 2a
NuH = 2a
3a; R = PhMe2Si
5; R = PhMe2Si
3b; R = t-BuMe2SiO
3c; R = Ph
4a; R = PhMe2Si
6; R = PhMe2Si
4b; R = t-BuMe2SiO
4c; R = Ph
R
O
O
HN
R
3d; R = i-Pr
4d; R = i-Pr
O
O
O
Scheme 1
1a; R = PhMe2Si
1b; R = t-BuMe2SiO
1c; R = Ph
2a; R = Bn
2b; R = i-Pr
isomeric acids 3a and 4a in a ratio of ca. 67:33 (ascertained as
their methyl esters by NMR spectroscopy).
1d; R = i-Pr
metrization with several chiral reagents, but none were found
suitable including Heathcock’s 1-(1Ј-naphthyl)ethanol.4b,c The
selectivities were moderate to poor and the diastereoisomeric
half-acids or their esters were also not separable. To overcome
this problem, we introduced a method for desymmetrization of
the prochiral anhydride 1a using the lithium salt of Evans’
oxazolidinone 2a. We wish to report here a general method
for desymmetrisation of 3-substituted glutaric and 3,4-bis-
substituted adipic acid anhydrides using Evans’ oxazolidinones.
Although these have been widely used as a key stereodirecting
group in the introduction of chirality in many organic reac-
tions,6 to the best of our knowledge, the present work forms the
first example of its application for the desymmetrization of
σ-symmetric anhydrides. Thus, the reaction of 1a with the
lithium salt of 2a (Scheme 1) provided a mixture of diastereo-
Results and discussion
To improve the diastereoselectivity, we carried out many
experiments under varying conditions (Table 1) with the anions
of oxazolidinones 2a and 2b, but, with little success. When
lithium ion was replaced with magnesium, the selectivity was
totally lost. Similarly, steric bulk on the oxazolidinone (benzyl
vs. isopropyl) also had little effect. However, the presence of
1,3-dimethyl-3,4,5,6-tetrahydropyrimidin-2(1H)-one (DMPU)
even in small quantities drastically increased the rate of the
reaction without much change in stereoselectivites. Although
the selectivity was not very high, the acids 3a (mp 100–101 ЊC)
and 4a (mp 160–162 ЊC) were separable by fractional crystal-
lization. The Me, Bn and t-Bu esters were also easily separable
by ordinary column chromatography in a preparative scale. The
J. Chem. Soc., Perkin Trans. 1, 1999, 257–264
257

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analogs4,7 and 7 for nonactin.8 It was observed that in all the
cases the stereoselectivities were not very high and the diastereo-
isomer ratios lay in the range of 60–70:40–30. Again, the Me,
Bn and t-Bu esters of the diastereoisomeric acids were easily
separable by ordinary column chromatography. The benzyl
esters of 3c (mp 118–119 ЊC) and 4c (mp 113–114 ЊC) were also
separable by fractional crystallization.
The results from the table clearly indicate that the diastereo-
facial selectivity of the opening of anhydrides 1a–1d and 7 was
dependent on the substituents on the anhydrides. The C–Si
and C–OSi substitutions (1a,b and 7) showed preferences for
same diastereofacial selectivity. On the contrary, the C-aryl and
C-alkyl substituted anhydrides, 1c and 1d displayed diastereo-
facial selectivity opposite to those of 1a and 1b or 7.
Table 2 Diastereoselectivities during opening up anhydride 1b–1d and
7 with the anion of 2a
Diastereoisomer
ratioc
(3b–d) or 8:
(4b–d) or 9
Anhydride Reaction conditions
1b
1c
1c
1c
1c
1d
1d
7
THF, 5 equiv. DMPU, Ϫ78 ЊC, 1 ha
65:35d
36:64
40:60
40:60
THF, 5 equiv. DMPU, Ϫ78 ЊC, 1 ha
THF, 2 equiv. DMPU, Ϫ50 ЊC, 15 hb
THF, 0 ЊC, 3 hb
CH2Cl2, 2 equiv. DMAP, Ϫ40 ЊC, 15 hb 47:53
THF, 5 equiv. DMPU, Ϫ78 ЊC, 1 ha
THF, 2 equiv. DMAP, Ϫ50 ЊC, 15 ha
THF, Ϫ45 ЊC, 3 da
40:60
47:53
65:35e
50:50
65:35
50:50
55:45
7
THF, 5 equiv. DMPU, Ϫ78 ЊC, 1 ha
THF, Ϫ78 ЊC to room temp., 3 ha
THF, DMAP, Ϫ45 ЊC, 45 ha
7
Preparation of anhydrides 1a–1d, 7
7
7
THF, DMAP, room temp., 15 hb
The PhMe2Si substituted anhydride 1a was obtained in a
few steps from β-silyl acrylate 109 as shown in Scheme 3.
a Deprotonation of 2a was done with BuLi at Ϫ40 ЊC. b Deprotonation
of 2a was done with EtMgBr at 0 ЊC. c The crude products were esteri-
fied with diazomethane and the diastereoisomer ratios were ascertained
by NMR. d Diastereoisomer ratio determined from SiBut and SiMe
peaks. e Diastereoisomer ratio determined from TolMe and SiMe peaks.
SiMe2Ph
PhMe2Si
i
CO2Me
85%
CO2Me
MeO2C
CO2Me
chromatographic procedure was found to be much easier and
faster than the fractional crystallization, and hence we adopted
the former for the present purpose.
10
11
We were not convinced at this stage whether the dimethyl-
(phenyl)silyl (PhMe2Si) substitution in 1a is responsible for this
observed stereoselectivity. Theisen and Heathcock4c have
recently studied the effect of the bulkiness of the group in 3-
substituted glutaric anhydrides on opening with 1-(1Ј-
naphthyl)ethanol and concluded that the degree of prochiral
recognition (diastereoselectivity) is inversely related to the
steric bulk of the stereodifferentiating group. The diastereo-
selectivity was very high when the substituent was OTBDMS
but decreased with increasing steric bulk e.g. t-Bu < i-Pr < Ph
< Et < Me. Suda et. al.3g have observed that the chiral alcoholy-
sis of 3-substituted glutaric anhydrides with 1-phenyl-3,3-
bis(trifluoromethyl)propane-1,3-diol proceeded with moderate
to high diastereoselectivity depending on the size of the
3-substituents. They concluded that with a more sterically
bulky substituent, the chiral induction was higher.
SiMe2Ph
SiMe2Ph
ii
v
97%
100%
CO2R
CO2R
O
O
O
1a
R = Me; 12
R = H; 14
iii,iv
92%
vi
85%
12
MeO2C
CO2Me
13
Scheme 3 Reagents: i, NaCH(CO2Me)2, MeOH; ii, NaCl, H2O,
DMSO; iii, NaOH; iv, H3Oϩ; v, Ac2O; vi, (PhMe2Si)2CuLi.
Dimethyl malonate addition on this gave the triester 11 which
on Krapcho decarboxylation10 provided the diester 12.11 The
latter was also obtained in one step from the known unsatur-
ated diester 1312 by a silylcupration reaction.13 The anhydride
1a was subsequently obtained from 12 by a simple hydrolysis to
diacid 14 and subsequent treatment with acetic anhydride in
quantitative yield. The anhydrides 1b–d4b and 78 were prepared
following the literature procedures.
We were obviously interested to know which of the above
mentioned propositions is operative and also the effect of
anhydride ring size on the desymmetrization selectivity. For
this, the various σ-symmetric 3-substituted glutaric anhydrides
1b–1d and meso 3,4-bis-silyl-substituted adipic anhydride 7
were treated with 2a under the conditions (Schemes 1,2)
O
TolMe2Si
Determination of absolute stereochemistry of 3a–d and 8
O
TolMe2Si
O
To ascertain the sense of chiral induction in the anhydride
opening reactions, it was essential to establish the absolute
stereochemistry of the products. The configuration of the
major acid 3a was established by converting it to a known
derivative 153f as depicted in Scheme 4. Thus, the mixture of
acids 3a and 4a were converted to their respective benzyl esters
and separated by column chromatography. The major benzyl
ester was hydrogenolysed and the resulting acid 3a was sub-
jected to the conditions for silicon to hydroxy conversion.14 The
hydroxy acid obtained was coupled to (S)-phenylethylamine to
give the amide 16 from which the oxazolidinone was removed
under standard conditions.15 The resulting acid was esterified
and the hydroxy group was protected as the TBDMS ether to
give 15. Although, the absolute configurations of half-acids 5
and 6 (obtained from the reaction of the anion of 2b with 1a)
were not ascertained, it could be safely assumed that the
anhydride opening was following the same course as observed
7
anion of 2a
TolMe2Si
TolMe2Si
O
O
O
O
HO
HO
+
N
N
O
O
O
SiMe2Tol
O
SiMe2Tol
Bn
Bn
8
9
Scheme 2
described in Table 2. The anhydrides were selected so that their
products could be useful as key intermediates in the synthesis
of various natural products, e.g. 1b for compactin and its
258
J. Chem. Soc., Perkin Trans. 1, 1999, 257–264

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OH
O
TolMe2Si
O
O
O
O
t-BuO
i,ii
i-iii
iv
3a
Ph
N
H
N
N
O
8 + 9
50%
O
O
SiMe2Tol
Bn
Bn
16
iii,iv
69%
TolMe2Si
O
O
TolMe2Si
O
v-vii
t-BuO
t-BuO
OTBDMS
O
OBn
O
O
SiMe2Tol
O
SiMe2Tol
Np
Ph
N
H
OMe
22
23
Scheme 6 Reagents: i, (COCl)2, DMF; ii, t-BuOH, DMAP; iii, chro-
matography; iv, (TiOBn)4, BnOH; v, H2, Pd/C; vi, 2,4,6-trichloro-
benzoyl chloride; vii, (1R)-1-(1Ј-naphthyl)ethanol, DMAP.
15
Scheme 4 Reagents: i, KBr, AcOOH, NaOAc; ii, (S)-phenylethyl-
amine, DCCI, DMAP; iii, LiOH, H2O2, then CH2N2; iv, TBDMS-Cl,
imidazole.
and esterified with (R)-1-(1Ј-naphthyl)ethanol to give the
diester 23. An authentic rac-23 was made from anhydride 7
by ring opening with ( )-1-(1Ј-naphthyl)ethanol followed by
esterification.8b
with oxazolidinone 2a. The TLC behaviour (major diastereo-
isomer moves faster) and the NMR characteristics of the
methyl esters of 5 (major) and 6 (minor) (OMe resonance of
major diastereoisomer appears downfield) had similarities with
those of 3a and 4a, respectively. The configuration of the major
product from the opening of anhydride 1b was assigned by con-
verting it to 15 (Scheme 5). For this, the diastereoisomeric acid
In conclusion, the results of this investigation show that
Evans’ oxazolidinones in stoichiometric amounts could be effi-
ciently employed for the desymmetrization of σ-symmetric
anhydrides on a preparative scale. Although the diastereo-
selectivity is not very high, the diastereoisomeric acids and
their methyl, benzyl or tert-butyl esters are practically separ-
able by fractional crystallization, and/or normal chrom-
atography. Therefore, this could form a convenient method for
both enantioconvergent and enantiodivergent syntheses of dif-
ferentially substituted glutaric and adipic acid derivatives. The
diastereoselectivity does not seem to depend much on the reac-
tion conditions and the substituents on either the anhydride or
the oxazolidinone. But the selectivity drops when the counter
ion changed from lithium to magnesium. The facial selectivity
was dependent on the substituents. The reaction period and the
temperature could be drastically reduced when additives like
DMPU were used. Moreover, the oxazolidinones could easily
be prepared and be recovered without any loss of quantity and
purity.
O
R
O
O
i
N
H
N
Ph
O
3b + 4b
Bn
17; α R = t-BuMe2SiO
18; β R = t-BuMe2SiO
Scheme 5 Reagent: i, (S)-phenylethylamine, DCCI, DMAP.
mixture (3b and 4b) was coupled to (S)-phenylethylamine to
give the mixture of amides 17 and 18 which were easily separ-
ated. Removal of the oxazolidinone from major amide 17 under
standard conditions followed by esterification gave 15. The
stereochemistry of the major product from the opening up of
the anhydride 1c was assigned by converting the diastereo-
isomeric mixture of acids 3c and 4c to a mixture of diesters 19
and 20. For this, the diastereoisomeric mixture of acids 3c and
Experimental
General methods
1
All mps are recorded with a Fisher-Johns apparatus. The H
NMR and 13C NMR spectra are recorded on a Bruker (model
AC200) 200 MHz or Varian (model VXR300) 300 MHz instru-
ment. 1H NMR chemical shifts (δ) are given in ppm downfield
from internal tetramethylsilane (δ = 0.00) or from residual
chloroform (δ = 7.26) and J (coupling constant) values in Hz.
The IR spectra are recorded on a Perkin-Elmer 783 spectro-
photometer or Nicolet Impact 410 FT IR spectrometer. Optical
rotations are measured in a JASCO DIP polarimeter. Air sensi-
tive reactions were carried out under Ar or N2 atmosphere.
Solvents were freshly dried and distilled prior to use. The
unsaturated esters 10,9 13;12 oxazolidinones 2a,b;19 (R)-1-
(1Ј-naphthyl)ethanol16 and anhydrides 1b–d,4b and 78 were pre-
pared following the literature procedures and are not included
in the Experimental section.
Ph
O
O
OMe
O
O
O
Np
19; 3α
20; 3β
21
4c was converted to their benzyl esters which on fractional crys-
tallization provided a new mixture of benzyl esters (major:
minor = 8:2). The mixture was hydrogenolysed and coupled
with (R)-1-(1Ј-naphthyl)ethanol.16 Subsequent removal of the
oxazolidinone followed by esterification with diazomethane
provided a mixture of known4c diesters 19 and 20 in a ratio of
8:2. The configuration of the major product from the opening
up of the anhydride 1d was assigned by converting it to the
known lactone 21.17 The diastereoisomeric mixture of acids 3d
and 4d was converted to the corresponding benzyl esters and
separated as usual. The oxazolidinone was removed from the
major benzyl ester and the resulting acid was reduced with
borane in THF.18 Upon acidification it provided the lactone 21.
The configuration of the major product from the opening up of
7 was assigned as shown in Scheme 6. The mixture of acids
(8 and 9) was separated after converting into their t-Bu esters.
The major ester was then subjected to oxazolidinone removal
conditions to give the benzyl ester 22 which was hydrogenolysed
Dimethyl 3-[dimethyl(phenyl)silyl]glutarate 12
Dimethyl malonate (9.2 cm3, 80 mmol) was added to a stirred
solution of sodium methoxide [prepared using sodium (1.85 g,
80 mmol) in methanol] in methanol (15 cm3) at room temp. and
stirred for 0.5 h. A solution of the acrylate 10a (8.8 g, 40 mmol)
in methanol (10 cm3) was added to the above reaction mixture
at 0 ЊC and left for 2 days at room temp. The reaction mixture
was neutralized with dil. HCl, methanol was removed and
extracted with ether. The organic extract was washed with water
and with brine, dried (Na2SO4) and evaporated under reduced
J. Chem. Soc., Perkin Trans. 1, 1999, 257–264
259

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pressure. The residue was subjected under Kugelrohr distil-
lation to remove the excess dimethyl malonate and the residue
was purified by chromatography to give 11 (12 g, 85%); Rf(ben-
zene) 0.3; νmax(film)/cmϪ1 1735, 1250, 1110. A stirred solution
of this triester 11 (12 g, 34 mmol), sodium chloride (2 g) and
water (1.5 cm3) in DMSO (150 cm3) was heated at 160 ЊC under
nitrogen for 2.5 h. The reaction mixture was diluted with water
(500 cm3) and extracted with ether. The organic extract was
washed with water and with brine, dried (Na2SO4) and evapor-
ated under reduced pressure. The residue was purified by chro-
matography to give 1210 (9.67 g, 97%); Rf(benzene) 0.4;
νmax(film)/cmϪ1 1745, 1260, 1120; δH(200 MHz, CDCl3) 0.32 (6
H, s), 1.80–2.00 (1 H, m), 2.26 (2 H, dd, J 8.6, 16), 2.43 (2 H, dd,
J 5.4, 16), 3.58 (6 H, s), 7.35–7.52 (5 H, m).
This compound was also prepared from 13. Dimethyl-
(phenyl)silyllithium (94 cm3 of a 0.9 M solution in THF; 84.5
mmol) was added to a stirred suspension of copper() cyanide
(3.8 g, 42 mmol) in THF (70 cm3) under argon at 0 ЊC. After 0.5
h, the solution was cooled to Ϫ78 ЊC and the diester 13 (6.32 g,
40 mmol) was added. The mixture was stirred under that condi-
tion for 3 h, quenched with a saturated solution of ammonium
chloride and extracted with hexane. The extract was washed
with water and brine, dried over Na2SO4 and evaporated under
reduced pressure. The residue was chromatographed to give the
diester 12 (10 g, 85%).
J 4.8, 16), 2.63–2.76 (2 H, m), 3.20–3.31 (2 H, m), 3.59 (3 H, s),
4.05–4.20 (2 H, m), 4.40–4.52 (1 H, m), 7.16–7.56 (10 H, m);
δC(50 MHz, CDCl3) 173.8, 173.0, 153.5, 137.0, 135.7, 134.2,
129.4, 128.9, 127.9, 127.2, 66.2, 55.4, 51.3, 38.1, 36.1, 34.4, 18.3,
Ϫ4.5 (Found: C, 65.3; H, 6.8; N, 3.0. C24H29NO5Si requires C,
65.6; H, 6.6; N, 3.2%). Minor ester (from 4a): Rf(hexane–
EtOAc; 90:10) 0.28; mp 90 ЊC; [α]D25 ϩ27.9 (c 0.4, CHCl3);
νmax(KBr)/cmϪ1 1789, 1734, 1683, 1245, 1113; δH(200 MHz,
CDCl3) 0.37 (6 H, s), 2.02–2.17 (1 H, m), 2.31 (1 H, dd,
J 8.5, 15.5), 2.46 (1 H, dd, J 5.4, 15.5), 2.64 (1 H, dd, J 10,
13.4), 2.88 (1 H, dd, J 8.8, 17), 3.09 (1 H, dd, J 4.8, 17), 3.23
(1 H, dd, J 3.2, 13.4), 3.57 (3 H, s), 4.08–4.18 (2 H, m), 4.49–
4.62 (1 H, m), 7.15–7.78 (10 H, m); δC(50 MHz, CDCl3)
173.8, 173.0, 153.5, 137.1, 135.8, 134.2, 129.4, 129.0, 127.9,
127.3, 66.3, 55.4, 51.3, 38.2, 36.0, 34.7, 29.7, 18.3, Ϫ4.3
(Found: C, 65.2; H, 6.8; N, 2.9. C24H29NO5Si requires C,
65.6; H, 6.6; N, 3.2%).
The mixture of acids was converted to benzyl esters. For this,
a solution of pivaloyl chloride (4 cm3, 33 mmol) in THF (3 cm3)
was added to a stirred solution of crude acid mixture (3a and
4a) (11.73 g, 27.6 mmol) and triethylamine (4.6 cm3, 33 mmol)
at Ϫ78 ЊC. The reaction mixture was stirred at 0 ЊC for 1 h and
cooled to Ϫ78 ЊC followed by addition of benzyl alcohol (7.14
cm3, 69 mmol) and DMAP (90 mg, 0.72 mmol). The reaction
mixture was stirred at room temp. overnight and the solvent
was removed. The residue was diluted with water and extracted
with EtOAc. The organic extract was washed with water and
with brine, dried and evaporated under reduced pressure. The
residue was purified by chromatography to give (3ЈR,4S)-3-{4-
(benzyloxycarbonyl)-3-[dimethyl(phenyl)silyl]-1-oxobutyl}-4-
benzyloxazolidin-2-one (benzyl ester of major acid 3a) (8 g,
56%) and its 3ЈS diastereoisomer (benzyl ester of minor acid
4a) (3.84 g, 27%). For benzyl ester of major acid 3a: Rf(hexane–
EtOAc; 90:10) 0.37; [α]D24 ϩ24.3 (c 1.02, CHCl3); νmax(film)/cmϪ1
1780, 1732, 1696, 1249, 1111; δH(200 MHz, CDCl3) 0.36 (6 H,
s), 2.02–2.14 (1 H, m), 2.31–2.56 (2 H, m), 2.56–2.75 (2 H, m),
3.16–3.35 (2 H, m), 4.03–4.14 (2 H, m), 4.34–4.44 (1 H, m),
4.95–5.10 (2 H, m), 7.13–7.53 (15 H, m); δC(50 MHz, CDCl3)
173.2, 172.7, 153.3, 136.5, 135.5, 134.0, 129.2, 128.7, 128.4,
128.0, 127.7, 127.0, 66.1, 66.0, 55.1, 37.8, 35.9, 34.3, 17.8, Ϫ4.7
(Found: C, 69.6; H, 6.3; N, 3.0. C30H33NO5Si requires C, 69.9;
H, 6.4; N, 2.7%). For benzyl ester of minor acid 4a: Rf(hexane–
EtOAc; 90:10) 0.31; mp 90–91 ЊC; [α]D23 ϩ43.3 (c 0.98, CHCl3);
νmax(KBr)/cmϪ1 1794, 1736, 1682, 1251, 1110; δH(200 MHz,
CDCl3) 0.37 (6 H, s), 2.09–2.21 (1 H, m), 2.30–2.66 (3 H, m),
2.85–3.24 (3 H, m), 3.97–4.10 (2 H, m), 4.44–4.54 (1 H, m), 5.01
(2 H, s), 7.13–7.55 (15 H, m); δC(50 MHz, CDCl3) 173.1, 172.6,
153.2, 136.6, 135.8, 135.4, 133.9, 129.1, 128.7, 128.3, 127.9,
127.7, 127.0, 66.0, 55.0, 37.6, 35.7, 34.5, 17.6, Ϫ4.6 (Found: C,
69.9; H, 6.7; N, 2.5. C30H33NO5Si requires C, 69.9; H, 6.4; N,
2.7%).
3-[Dimethyl(phenyl)silyl]glutaric acid 14
Sodium hydroxide (5 M in water) (50 cm3, 250 mmol) was
added to a stirred solution of the diester 12 (9.67 g, 32.7 mmol)
in methanol (300 cm3). After 24 h, the solvent was removed
under reduced pressure and the residue was acidified with dil.
HCl and extracted with EtOAc. The organic extract was
washed with water and with brine, dried (Na2SO4) and evapor-
ated under reduced pressure to give 14 (8 g, 92%); mp 104–
105 ЊC; νmax(KBr)/cmϪ1 3400–2400 (br), 1720, 1250, 1110;
δH(200 MHz, CDCl3) 0.34 (6 H, s), 1.91–2.21 (3 H, m), 2.44
(2 H, dd, J 1.9, 15.6), 7.32–7.51 (5 H, m) (Found: C, 58.4; H,
6.9; C13H18O4Si requires C, 58.7; H, 6.8%).
3-[Dimethyl(phenyl)silyl]glutaric anhydride 1a
A solution of the diacid 14 (8 g, 30 mmol) in acetic anhydride
(15 cm3) was heated at 100 ЊC under nitrogen for 2.5 h. After
cooling to room temp., excess acetic anhydride and acetic acid
were removed under high vacuum. The residue was crystallized
from EtOAc to give 1a (7.44 g, 100%); mp 142 ЊC; νmax(KBr)/
cmϪ1 1805, 1760, 1250, 1110; δH(200 MHz, CDCl3) 0.40 (6 H, s),
1.45–1.70 (1 H, m), 2.31 (2 H, dd, J 14, 17), 2.80 (2 H, dd, J 4,
17), 7.32–7.48 (5 H, m).
The mixture of acids was also converted to tert-butyl esters.
For this, oxalyl chloride (0.7 cm3, 8 mmol) was added to a
stirred solution of crude acid mixture (3a and 4a) (850 mg, 2
mmol) and DMF (0.01 cm3) at 0 ЊC. After 2 h at room temp.,
the solvent and excess oxalyl chloride was removed under
vacuum. The residue was dissolved in dry tert-butyl alcohol (5
cm3) and DMAP (370 mg, 3 mmol) was added. The reaction
mixture was stirred at room temp. overnight and the solvent was
removed. The residue was purified by chromatography to give
(3ЈR,4S)-3-{4-(tert-butyloxycarbonyl)-3-[dimethyl(phenyl)-
silyl]-1-oxobutyl}-4-benzyloxazolidin-2-one (tert-butyl ester of
major acid 3a) (530 mg, 55%) and its 3ЈS diastereoisomer (tert-
butyl ester of minor acid 4a) (285 mg, 30%). For tert-butyl ester
of major acid 3a: Rf(hexane–EtOAc; 95:5) 0.76; [α]D24 ϩ12.3
(c 1.56, CHCl3); νmax(film)/cmϪ1 1783, 1724, 1697, 1251, 1111;
δH(200 MHz, CDCl3) 0.35 (3 H, s), 0.36 (3 H, s), 1.41 (9 H, s),
1.94–2.10 (1 H, m), 2.24 (1 H, dd, J 9.3, 16.5), 2.39 (1 H, dd,
J 4.4, 16.5), 2.56 (1 H, dd, J 9.1, 15.7), 2.66 (1 H, dd, J 9.8,
13.3), 3.25 (1 H, dd, J 3.2, 13.3), 3.32 (1 H, dd, J 5, 15.8), 4.04–
(3ЈR,4S)-3-{3-[Dimethyl(phenyl)silyl]-4-carboxy-1-oxobutyl}-4-
benzyloxazolidin-2-one 3a and its 3ЈS diastereoisomer 4a
Butyllithium (1.5 M in hexane ) (0.4 cm3, 0.6 mmol) was added
to a stirred solution of the oxazolidinone 2a (90 mg, 0.5 mmol)
in THF (3 cm3) at Ϫ35 ЊC under argon atmosphere. The mix-
ture was stirred for 10 min, cooled to Ϫ78 ЊC and the required
amount of additive (DMPU or DMAP) was added. A solution
of the anhydride 1a (125 mg, 0.5 mmol) in THF (3 cm3) was
added to this stirred mixture at Ϫ78 ЊC and then brought to the
required temperature and stirred. The reaction mixture was
acidified with citric acid solution and extracted with EtOAc.
The crude acid mixture of 3a and 4a (215 mg, 100%) was esteri-
fied with ethereal diazomethane to give a mixture of esters (220
mg, 96%). The major and minor esters were separated by
column chromatography. Major ester (from 3a); Rf(hexane–
EtOAc; 90:10) 0.35; [α]D25 ϩ43.1 (c 2.2, CHCl3); νmax(film)/cmϪ1
1780, 1732, 1694, 1251, 1110; δH(200 MHz, CDCl3) 0.36 (6 H,
s), 1.97–2.11 (1 H, m), 2.31 (1 H, dd, J 9.1, 16), 2.47 (1 H, dd,
260
J. Chem. Soc., Perkin Trans. 1, 1999, 257–264

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4.25 (2 H, m), 4.37–4.50 (1 H, m), 7.15–7.60 (10 H, m); δC(50
MHz, CDCl3) 173.1, 172.8, 153.4, 137.2, 135.8, 134.2, 129.3,
129.1, 128.9, 127.8, 127.2, 80.2, 66.1, 55.4, 38.1, 36.2, 35.6, 28.2,
18.0, Ϫ4.3, Ϫ4.5 (Found: C, 67.1; H, 7.6; N, 3.0. C27H35NO5Si
requires C, 67.3; H, 7.3; N, 2.9%). For tert-butyl ester of minor
acid 4a: Rf(hexane–EtOAc; 95:5) 0.55; [α]D24 ϩ35.6 (c 0.5,
CHCl3); νmax(film)/cmϪ1 1788, 1730, 1697, 1252, 1111; δH(200
MHz, CDCl3) 0.36 (6 H, s), 1.40 (9 H, s), 2.00–2.15 (1 H, m),
2.22 (1 H, dd, J 8.8, 15.8), 2.40 (1 H, dd, J 5, 15.8), 2.61 (1 H,
dd, J 10, 13.4), 2.88 (1 H, dd, J 7.8, 17.1), 3.08 (1 H, dd, J 5.2,
17.1), 3.22 (1 H, dd, J 3.2, 13.4), 4.08–4.16 (2 H, m), 4.45–4.61
(1 H, m), 7.14–7.60 (10 H, m); δC(50 MHz, CDCl3) 173.0, 172.7,
153.4, 137.4, 135.8, 134.2, 129.4, 129.2, 128.9, 127.9, 127.2,
80.3, 66.2, 55.3, 38.1, 36.0, 28.2, 17.9, Ϫ4.1, Ϫ4.3 (Found: C,
67.0; H, 7.4; N, 2.8. C27H35NO5Si requires C, 67.3; H, 7.3; N,
2.9%).
[3ЈR,4S]-3-(4-Carboxy-1-oxo-3-phenylbutyl)-4-benzyloxazolidin-
2-one 3c and its 3ЈS diastereoisomer 4c
This reaction was performed following the general procedure
for the preparation of 3a and 4a from anhydride 1a using
DMPU (5 equiv.) as an additive. The crude acid (mixture of 3c
and 5c) was esterified with diazomethane to give esters (98%)
which were separated by chromatography. Major ester (from
3c): Rf(hexane–EtOAc; 80:20) 0.5; mp 92–93 ЊC; [α]D25 ϩ43.0 (c
0.7, CHCl3); νmax(KBr)/cmϪ1 1786, 1730, 1691; δH(200 MHz,
CDCl3) 2.62–2.85 (3 H, m), 3.16–3.28 (2 H, m), 3.49 (1 H, dd,
J 8.3, 16.8), 3.61 (3 H, s), 3.73–3.88 (1 H, m), 4.00–4.14 (2 H,
m), 4.46–4.58 (1 H, m), 7.14–7.37 (10 H, m) (Found: C, 69.4; H,
6.3; N, 3.5. C22H23NO5 requires C, 69.3; H, 6.1; N, 3.7%). Minor
ester (from 4c): Rf(hexane–EtOAc; 80:20) 0.34; mp 99–100 ЊC;
[α]D25 ϩ54.8 (c 0.29, CHCl3); νmax(KBr)/cmϪ1 1767, 1736, 1693;
δH(200 MHz, CDCl3) 2.58 (1 H, dd, J 9.2, 13.5), 2.68 (1 H, dd,
J 6.3, 15.6), 2.79 (1 H, dd, J 7.2, 15.6), 3.02 (1 H, dd, J 3.3,
13.5), 3.18 (1 H, dd, J 6.5, 16.8), 3.56 (1 H, dd, J 8, 16.8), 3.60
(3 H, s), 3.75–3.90 (1 H, m), 4.06–4.20 (2 H, m), 4.55–4.67 (1 H,
m), 6.99–7.07 (2 H, m), 7.15–7.37 (8 H, m) (Found: C, 69.4; H,
6.3; N, 3.5. C22H23NO5 requires C, 69.0; H, 6.4; N, 3.7%).
The crude acid mixture was also converted to the benzyl
esters following the procedure described for acids 3a and 4a.
The overall yield after esterification is 82% and the isolated
yields of (3ЈR,4S)-3-{1-oxo-3-phenyl-4-benzyloxycarbonyl)-
butyl}-4-benzyloxazolidin-2-one (benzyl ester of major acid 3c)
is 55% and its 3ЈS diastereoisomer (benzyl ester of minor acid
4c) is 27%. For benzyl ester of major acid 3c: Rf(EtOAc–
hexane; 15:85) 0.41; mp 118–119 ЊC, [α]D22 ϩ41.6 (c 0.62,
CHCl3); νmax(KBr)/cmϪ1 1786, 1727, 1689; δH(300 MHz,
CDCl3) 2.67 (1 H, dd, J 9.7, 13.4), 2.75 (1 H, dd, J 7.9, 15.6),
2.84 (1 H, dd, J 7.3, 15.6), 3.21 (1 H, dd, J 6.2, 16.7), 3.22 (1 H,
dd, J 2.9, 13.4), 3.49 (1 H, dd, J 8.4, 16.7), 3.76–3.88 (1 H, m),
4.01–4.12 (2 H, m), 4.46–4.53 (1 H, m), 5.04 (2 H, s), 7.15–7.36
(15 H, m) (Found: C, 73.2; H, 6.1; N, 2.9. C28H27NO5 requires
C, 73.5; H, 5.9; N, 3.1%). For benzyl ester of minor acid 4c:
Rf(EtOAc–hexane; 15:85) 0.34; mp 113–114 ЊC, [α]D22 ϩ59 (c
0.88, CHCl3); νmax(KBr)/cmϪ1 1766, 1727, 1708; δH(300 MHz,
CDCl3) 2.56 (1 H, dd, J 9.3, 13.6), 2.75 (1 H, dd, J 7.9, 15.4),
2.83 (1 H, dd, J 7, 15.4), 3.02 (1 H, dd, J 2.9, 13.6), 3.18 (1 H,
dd, J 6.6, 16.7), 3.55 (1 H, dd, J 8, 16.7), 3.79–3.90 (1 H, m),
4.06–4.16 (2 H, m), 4.54–4.64 (1 H, m), 5.03 (2 H, s), 7.00–7.03
(2 H, m), 7.17–7.36 (13 H, m) (Found: C, 73.6; H, 6.0; N, 3.0.
C28H27NO5 requires, C, 73.5; H, 5.9; N, 3.1%).
(3ЈR,4S)-3-{3-[Dimethyl(phenyl)silyl]-4-carboxyl-1-oxobutyl}-4-
isopropyloxazolidin-2-one 5 and its 3ЈS diastereoisomer 6
This reaction was performed following the general procedure as
described for the preparation of 3a and 4a except the oxazolidi-
none 2b was used instead of 2a. The crude acid mixture (5 and
6) was esterified with ethereal diazomethane to give a mixture
of esters (95%). The major and minor esters were separated by
column chromatography. Major ester (from 5); Rf(hexane–
EtOAc; 85:15) 0.45; [α]D25 ϩ54.6 (c 0.9, CHCl3); νmax(film)/cmϪ1
1780, 1733, 1698, 1251, 1112; δH(200 MHz, CDCl3) 0.34 (3 H,
s), 0.35 (3 H, s), 0.84 (3 H, d, J 7), 0.88 (3 H, d, J 7), 1.93–2.07
(1 H, m), 2.22–2.35 (2 H, m), 2.44 (1 H, dd, J 5, 16), 2.63 (1 H,
dd, J 9.5, 16), 3.27 (1 H, dd, J 4.7, 16), 3.57 (3 H, s), 4.09–4.31
(3 H, m), 7.31–7.55 (5 H, m); δC(50 MHz, CDCl3) 173.8, 173.0,
154.1, 137.1, 134.2, 129.3, 127.9, 63.6, 58.9, 51.3, 36.2, 34.4,
28.8, 18.2, 18.0, 15, Ϫ4.4 (Found: C, 61.2; H, 7.6; N, 3.3.
C20H29NO5Si requires C, 61.4; H, 7.5; N, 3.6%). Minor ester
(from 6): Rf(hexane–EtOAc; 85:15) 0.33; [α]D25 ϩ70.0 (c 0.2,
CHCl3); νmax(film)/cmϪ1 1780, 1732, 1694, 1250, 1111; δH(200
MHz, CDCl3) 0.34 (6 H, s), 0.84 (3 H, d, J 7), 0.87 (3 H, d, J 7),
1.99–2.10 (1 H, m), 2.20–2.32 (2 H, m), 2.40 (1 H, dd, J 5.8,
15.5), 2.89 (1 H, dd, J 8.5, 17), 3.06 (1 H, dd, J 5, 17), 3.56 (3 H,
s), 4.14–4.22 (2 H, m), 4.25–4.36 (1 H, m), 7.33–7.54 (5 H, m)
(Found: C, 61.1; H, 7.7; N, 3.4. C20H29NO5Si requires C, 61.4;
H, 7.5; N, 3.6%).
(3ЈR,4S)-3-(3-tert-Butyldimethylsilyloxy-4-carboxy-1-oxobutyl)-
4-benzyloxazolidin-2-one 3b and its 3ЈS diastereoisomer 4b
The mixture of these compounds 3c and 4c was also prepared
using the magnesium salt of 2a. For this, ethylmagnesium
bromide (2.5 M in hexane ) (0.4 cm3, 1 mmol) was added to a
stirred solution of the oxazolidinone 2a (180 mg, 1 mmol) in
THF (5 cm3) at 0 ЊC under argon atmosphere. The mixture was
stirred for 10 min, cooled to Ϫ78 ЊC and the required amount
of additive (DMPU or DMAP) was added. A solution of the
anhydride 1c (250 mg, 1 mmol) in THF (5 cm3) was added to
this stirred mixture at Ϫ78 ЊC and then brought to the required
temperature and stirred. The reaction mixture was acidified
with citric acid solution and extracted with EtOAc. The crude
acid (mixture of 3c and 4c) was esterified with ethereal diazo-
methane to give methyl esters (335 mg, 87%).
This reaction was performed following the general procedure
for the preparation of 3a and 4a from anhydride 1a using
DMPU (5 equiv.) as an additive. The crude acid (mixture of 3b
and 4b) was esterified with diazomethane to give esters (94%)
which were separated by chromatography. Major ester (from
3b): Rf(hexane–EtOAc; 90:10) 0.35; [α]D25 ϩ41.6 (c 0.64, CHCl3);
νmax(film)/cmϪ1 1784, 1738, 1703; δH(200 MHz, CDCl3) 0.09
(6 H, s), 0.84 (9 H, s), 2.50–2.65 (2 H, m), 2.74 (1 H, dd, J
9.7, 13.3 ), 3.07 (1 H, dd, J 6, 16.4 ), 3.30 (1 H, dd, J 3.2,
13.3), 3.38 (1 H, dd, J 6.3, 16.4 ), 3.68 (3 H, s), 4.13–4.24 (2
H, m), 4.58–4.75 (2 H, m), 7.20–7.40 (5 H, m); δC(50 MHz,
CDCl3) 171.3, 170.7, 153.3, 135.5, 129.4, 129.0, 127.4, 66.2,
55.3, 51.3, 43.0, 42.6, 38.1, 25.8, 17.9, Ϫ4.7, Ϫ4.9 (Found: C,
60.4; H, 7.8; N, 3.3. C22H33NO6Si requires C, 60.7; H, 7.6; N,
3.2%). Minor ester (from 4b): Rf(hexane–EtOAc; 90:10) 0.15;
[α]D25 ϩ37.8 (c 0.56, CHCl3); νmax(film)/cmϪ1 1787, 1738, 1693;
δH(200 MHz, CDCl3) 0.11 (6 H, s), 0.85 (9 H, s), 2.56 (1 H,
dd, J 6.5, 15.1 ), 2.65 (1 H, dd, J 6, 15.1 ), 2.76 (1 H, dd, J
9.7, 13.3 ), 3.13 (dd, 1 H, J 6, 16.7 ), 3.29 (1 H, dd, J 6, 16.7),
3.30 (1 H, dd, J 3, 13.3), 3.68 (3 H, s), 4.13–4.24 (2 H, m), 4.60–
4.76 (2 H, m), 7.19–7.39 (5 H, m); δC(50 MHz, CDCl3) 171.2,
170.5, 153.3, 135.5, 129.4, 129.0, 127.4, 66.2, 65.9, 55.2, 51.3,
43.3, 42.6, 38.1, 25.8, 17.9, Ϫ4.7, Ϫ4.9 (Found: C, 60.8; H,
7.8; N, 3.1. C22H33NO6Si requires C, 60.7; H, 7.6; N, 3.2%).
(3ЈR,4S)-3-(4-Carboxy-3-isopropyl-1-oxobutyl)-4-benzyloxazol-
idin-2-one 3d and its 3ЈS diastereoisomer 4d
This reaction was performed following the general procedure
for the preparation of 3a and 4a from anhydride 1a using
DMPU (5 equiv.) as an additive. The crude acid (mixture of 3d
and 4d) was esterified with diazomethane to give esters (92%)
which were separated by chromatography. Major ester (from
3d): Rf(hexane–EtOAc; 80:20) 0.48; [α]D25 ϩ42.8 (c 4.3, CHCl3);
νmax(film)/cmϪ1 1780, 1732, 1695; δH(200 MHz, CDCl3) 0.91
(3 H, d, J 6.8), 0.92 (3 H, d, J 6.8 ), 1.72–1.88 (1 H, m), 2.25–
2.54 (3 H, m), 2.75 (1 H, dd, J 9.9, 13.6), 2.80 (1 H, dd, J 7.7,
J. Chem. Soc., Perkin Trans. 1, 1999, 257–264
261

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16.3), 3.07 (1 H, dd, J 4.5, 16.3), 3.31 (1 H, dd, J 3.3, 13.3), 3.67
(3 H, s), 4.12–4.26 (2 H, m), 4.57–4.69 (1 H, m), 7.19–7.38 (5 H,
m); δC(50 MHz, CDCl3) 173.4, 172.7, 153.4, 135.7, 129.4, 128.9,
127.3, 66.2, 55.4, 51.3, 38.1, 37.4, 37.2, 35.9, 31.1, 29.7, 19.0
(Found: C, 65.5; H, 7.6; N, 4.1. C19H25NO5 requires C, 65.7; H,
7.3; N, 4.0%). Minor ester (from 4d): Rf(hexane–EtOAc; 80:20)
0.32; [α]D25 ϩ39.6 (c 0.7, CHCl3); νmax(film)/cmϪ1 1783, 1732,
1698; δH(200 MHz, CDCl3) 0.93 (6 H, d, J 7), 1.75–1.90 (1 H,
m), 2.23–2.44 (2 H, m), 2.45–2.56 (1 H, m), 2.75 (1 H, dd, J 10,
13.4), 2.84 (1 H, dd, J 7.8, 14.4), 3.07 (1 H, dd, J 4.9, 17), 3.30
(1 H, dd, J 3.3, 13.2), 3.66 (3 H, s), 4.11–4.25 (2 H, m), 4.60–
4.72 (1 H, m), 7.19–7.38 (5 H, m); δC(50 MHz, CDCl3) 173.5,
172.8, 153.5, 135.7, 129.5, 129.0, 127.4, 66.3, 55.4, 51.4, 38.3,
37.4, 37.2, 36.1, 31.2, 29.7, 19.1 (Found: C, 65.5; H, 7.6; N, 4.1.
C19H25NO5 requires C, 65.7; H, 7.3; N, 4.0%).
The crude acid mixture was also converted to the benzyl
esters following the procedure described for acids 3a and 4a.
The overall yield after esterification is 85% and the isolated
yields of (3ЈR,4S)-3-[3-isopropyl-1-oxo-4-(benzyloxycarbonyl)-
butyl]-4-benzyloxazolidin-2-one (benzyl ester of major acid 3d)
is 57% and its 3ЈS diastereoisomer (benzyl ester of minor acid
4d) is 28%. For benzyl ester of major acid 3d: Rf(hexane–
EtOAc; 90:10) 0.31; [α]D27 ϩ55 (c 1.2, CHCl3); νmax(film)/cmϪ1
1781, 1731, 1697; δH(200 MHz, CDCl3) 0.91 (3 H, d, J 6.8), 0.92
(3 H, d, J 6.8), 1.74–1.88 (1 H, m), 2.31–2.55 (3 H, m), 2.68
(1 H, dd, J 9.7, 13.4), 2.80 (1 H, dd, J 7.7, 16.3), 3.13 (1 H, dd,
J 4.3, 16.3), 3.28 (1 H, dd, J 3.3, 13.4), 4.08–4.22 (2 H, m), 4.52–
4.64 (1 H, m), 5.04–5.17 (2 H, m), 7.14–7.37 (10 H, m) (Found:
C, 70.8; H, 7.1; N, 3.0. C25H29NO5 requires C, 71.0; H, 6.9; N,
3.3%). For benzyl ester of minor acid 4d: Rf(hexane–EtOAc;
90:10) 0.28; [α]D27 ϩ40.4 (c 2.6, CHCl3); νmax(film)/cmϪ1 1783,
1731, 1698; δH(200 MHz, CDCl3) 0.93 (6 H, d, J 6.8), 1.74–1.90
(1 H, m), 2.29–2.62 (3 H, m), 2.72 (1 H, dd, J 9.8, 13.2), 2.87
(1 H, dd, J 7.8, 17), 3.07 (1 H, dd, J 4.7, 17), 3.29 (1 H, dd, J 3.2,
13.2), 4.05–4.15 (2 H, m), 4.54–4.66 (1 H, m), 5.10 (2 H, s),
7.17–7.38 (10 H, m) (Found: C, 71.1; H, 7.0; N, 3.1. C25H29NO5
requires C, 71.0; H, 6.9; N, 3.3%).
filtered, the filtrate was washed with dil. HCl and with brine,
dried (Na2SO4) and evaporated under reduced pressure. The
residue was chromatographed to give 16 (600 mg, 50%);
Rf(CHCl3–MeOH; 95:5) 0.36; [α]D24 Ϫ11.3 (c 1.42, CHCl3);
νmax(film)/cmϪ1 3306, 1780, 1697, 1648, 1540; δH(300 MHz,
CDCl3) 1.50 (3 H, d, J 6.8), 2.40–2.48 (2 H, m), 2.79 (1 H, dd,
J 9.5, 13.5), 3.04–3.20 (2 H, m), 3.29 (1 H, dd, J 3.5, 13.5), 4.00
(1 H, d, J 2.4), 4.17–4.25 (2 H, m), 4.50–4.62 (1 H, m), 4.64–
4.72 (1 H, m), 5.14 (1 H, quintet, J 7.3), 6.37 (1 H, d, J 7.6),
7.19–7.38 (10 H, m) (Found: C, 67.0; H, 6.7; N, 6.7. C23H26N2O5
requires C, 67.3; H, 6.4; N, 6.8%).
(1ЈS,3S)-N-(1-Phenylethyl)-3-tert-butyldimethylsilyloxy-4-
(methoxycarbonyl)butanamide 15
A solution of amide 16 (108 mg, 0.27 mmol) in THF (4 cm3)
was added to a stirred solution of LiOHؒH2O (23 mg, 0.54
mmol) and H2O2 (30%) (0.11 cm3) in water (1.3 cm3) at 0 ЊC.21c
After 45 min, a solution of Na2SO3 (151 mg, 1.06 mmol) in
water (0.8 cm3) was added followed by addition of a solution of
NaHSO4 till the mixture became acidic, and the reaction mix-
ture was extracted with EtOAc. The organic extract was washed
with water and with brine, dried and evaporated under reduced
pressure. The residue was esterified with ethereal diazomethane
and column chromatography provided (1ЈS,3S)-N-(1-phenyl-
ethyl)-3-hydroxy-4-(methoxycarbonyl)butanamide (100 mg,
76%); Rf(CHCl3–MeOH; 98:2) 0.23; [α]D29 Ϫ57 (c 1, CHCl3);
νmax(film)/cmϪ1 3298, 1730, 1648, 1540; δH(300 MHz, CDCl3)
1.49 (3 H, d, J 7), 2.34–2.46 (2 H, m), 2.47–2.60 (2 H, m), 3.71
(3 H, s), 4.11 (1 H, d, J 7), 4.37–4.42 (1 H, m), 5.12 (1 H,
quintet, J 7), 6.35 (1 H, d, J 7), 7.26–7.75 (5 H, m).
A solution of this amide (83 mg, 0.31 mmol), TBDMS-Cl
(110 mg, 0.73 mmol) and imidazole (55 mg, 0.8 mmol) in DMF
(2 cm3) was stirred at room temp. overnight. The reaction mix-
ture was diluted with water and extracted with ether. The
organic extract was washed with water and with brine, dried
and evaporated under reduced pressure. The residue was chrom-
atographed to give 15 (108 mg, 91%); Rf(EtOAc–hexane; 2:8)
0.51; [α]D24 Ϫ24.6 (c 1, CHCl3); lit.3f [α]D24 Ϫ22.6 (c 0.9, CHCl3);
νmax(film)/cmϪ1 3298, 1740, 1640, 1540; δH(300 MHz, CDCl3)
0.08 (3 H, s), 0.10 (3 H, s), 0.85 (9 H, s), 1.47 (3 H, d, J 7), 2.38–
2.60 (4 H, m), 3.65 (3 H, s), 4.49 (1 H, quintet, J 5.8), 5.12 (1 H,
quintet, J 7), 6.59 (1 H, d, J 7.8), 7.24–7.36 (5 H, m).
(3ЈR,4S)-3-{3-[Dimethyl(phenyl)silyl]-4-carboxy-1-oxobutyl}-4-
benzyloxazolidin-2-one 3a
A mixture of (3ЈR,4S)-3-{4-(benzyloxycarbonyl)-3-[dimethyl-
(phenyl)silyl]-1-oxobutyl}-4-benzyloxazolidin-2-one
(benzyl
ester of major acid 3a) (2.62 g, 5.09 mmol) and Pd/C (10% in
Pd) (100 mg) in EtOAc (10 cm3) was stirred under hydrogen
atmosphere for 48 h. The mixture was passed through a Celite
pad and the residue was washed thoroughly with EtOAc. The
combined organic mixture was evaporated under reduced pres-
sure to give the acid 3a (2.16 g, 93%); mp 100–101 ЊC; [α]D23 ϩ48.6
(c 1.28, CHCl3); νmax(KBr)/cmϪ1 3400–2500, 1780, 1710, 1700,
1250, 1110; δH(200 MHz, CDCl3) 0.37 (6 H, s), 1.96–2.08 (1 H,
m), 2.26–2.77 (4 H, m), 3.21 (1 H, dd, J 3.4, 13.4), 3.31 (1 H,
dd, J 4.6, 16), 4.08–4.17 (2 H, m), 4.44–4.56 (1 H, m), 7.16–7.55
(10 H, m).
This compound was also prepared from 17. A solution of
amide 17 (160 mg, 0.3 mmol) in THF (4.5 cm3) was added to a
stirred solution of lithium hydroxide (26 mg, 1 mmol) and
hydrogen peroxide (30%) (0.125 cm3) in water (1.4 cm3) at 0 ЊC.
After 45 min, a solution of sodium sulfite (170 mg, 1.35 mmol)
in water (1 cm3) was added followed by addition of a solution
of sodium bisulfate till the mixture became acidic, and the reac-
tion mixture was extracted with EtOAc. The organic extract
was washed with water and with brine, dried (Na2SO4) and
evaporated under reduced pressure. The residue was esterified
with ethereal diazomethane and column chromatography
provided the ester 15 (107 mg, 93%).
(3ЈS,1ЉS,4S)-3-{3-Hydroxy-1-oxo-4-[(1-phenylethyl)amino-
carbonyl]butyl}-4-benzyloxazolidin-2-one 16
(3ЈS,1ЉS,4S)-3-[3-tert-Butyldimethylsilyloxy-1-oxo-4-(1-phenyl-
ethyl)aminocarbonylbutyl]-4-benzyloxazolidin-2-one 17 and its
3ЈR isomer 18
Peracetic acid (about 30% solution in acetic acid) (7.5 cm3) was
added to a stirred mixture of acid 3a (1.2 g, 2.92 mmol), potas-
sium bromide (417 mg, 3.5 mmol) and sodium acetate (500 mg,
6 mmol) at 0 ЊC. The reaction mixture was stirred for 1 day at
room temp. and evaporated under vacuum. The residue was
diluted with water and extracted with EtOAc. The organic
extract was washed with water and with brine, dried and evap-
orated under reduced pressure. The residue was dissolved in dry
CH2Cl2 (10 cm3), and (S)-phenylethylamine (0.52 cm3, 4 mmol)
and DMAP (65 mg, 0.5 mmol) was added into this solution. A
solution of DCCI (740 mg, 3.6 mmol) in CH2Cl2 (5 cm3) was
added to the above solution at 0 ЊC and the reaction mixture
was stirred at room temp. overnight. The reaction mixture was
A solution of DCCI (115 mg, 0.55 mmol) in CH2Cl2 (2 cm3)
was added to a stirred solution of crude acid mixture (5b and
6b) (210 mg, 0.5 mmol), (S)-phenylethylamine (0.135 cm3, 1
mmol), 1-hydroxybenzotriazole (135 mg, 1 mmol) and DMAP
(60 mg, 0.5 mmol) in CH2Cl2 (3 cm3) at 0 ЊC. The reaction
mixture was stirred at room temp. overnight and was filtered.
The filtrate was washed with water and with brine, dried
(Na2SO4) and evaporated under reduced pressure. The residue
was chromatographed to give major amide 17 (145 mg, 55%)
and minor amide 18 (74 mg, 28%). For 17; Rf(hexane–EtOAc;
80:20) 0.5; [α]D24 ϩ4.9 (c 0.8, CHCl3); νmax(film)/cmϪ1 3370, 1783,
262
J. Chem. Soc., Perkin Trans. 1, 1999, 257–264

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1695, 1661, 1515; δH(200 MHz, CDCl3) 0.09 (3 H, s), 0.13 (3 H,
s), 0.85 (9 H, s), 1.48 (3 H, d, J 7), 2.48 (1 H, dd, J 5, 15), 2.60
(1 H, dd, J 4.8, 15), 2.71 (1 H, dd, J 9.7, 13.3), 3.13 (1 H, dd,
J 6.6, 16.2), 3.28 (1 H, dd, J 2.8, 13.3), 3.29 (1 H, dd, J 6, 16.2),
4.10–4.21 (2 H, m), 4.53–4.70 (2 H, m), 5.12 (1 H, quintet, J 7),
6.57 (1 H, d, J 7.7), 7.16–7.35 (10 H, m); δC(50 MHz, CDCl3)
170.6, 169.1, 153.2, 143.6, 135.5, 129.4, 129.0, 128.7, 127.2,
126.3, 66.6, 66.2, 55.2, 48.9, 44.3, 42.2, 38.1, 25.8, 21.9, 17.9,
Ϫ4.8 (Found: C, 66.3; H, 8.0; N, 5.0. C29H40N2O5Si requires C,
66.4; H, 7.7; N, 5.3). For 18; Rf(hexane–EtOAc; 80:20) 0.32;
[α]D23 Ϫ9.62 (c 0.52, CHCl3); νmax(film)/cmϪ1 3360, 1781, 1699,
1659, 1529; δH(200 MHz, CDCl3) 0.08 (3 H, s), 0.11 (3 H, s),
0.81 (9 H, s), 1.52 (3 H, d, J 6.9), 2.47 (1 H, dd, J 4.3, 15), 2.58
(1 H, dd, J 4.9, 15), 2.76 (1 H, dd, J 9.7, 13.5), 3.18–3.41 (3 H,
m), 4.08–4.26 (2 H, m), 4.59–4.71 (2 H, m), 5.12 (1 H, quintet,
J 7.2), 6.72 (1 H, d, J 7.7), 7.15–7.39 (10 H, m); δC(50 MHz,
CDCl3) 170.5, 169.1, 153.3, 143.5, 135.5, 129.4, 129.0, 128.6,
127.4, 127.3, 126.4, 125.9, 66.4, 55.3, 48.9, 44.0, 41.8, 38.1, 25.8,
21.8, 17.9, Ϫ4.9 (Found: C, 66.2; H, 7.9; N, 5.2. C29H40N2O5Si
requires C, 66.4; H, 7.7; N, 5.3%).
(0.43 cm3, 0.6 mmol) was added18 slowly into the above mixture
and allowed to warm to 0 ЊC (2 h) and then to room temp. (1 h).
The reaction was quenched with methanol and the solvent was
removed by downward distillation. The process was repeated
three times with addition of methanol and the residue was dis-
solved in EtOAc. The mixture was stirred under hydrogen after
adding catalytic amount of Pd/C (10% Pd) for 4 h, filtered
through a pad of Celite and the filtrate was evaporated under
reduced pressure. The residue was dissolved in benzene (5 cm3)
and toluene-4-sulfonic acid (5 mg) was added to it and the
solution was refluxed. After 4 h, the mixture was washed
with sodium bicarbonate solution and with brine, dried
(Na2SO4) and evaporated under reduced pressure to give the
lactone 21 (50 mg, 68%); Rf(hexane–EtOAc; 80:20) 0.34; [α]D25
ϩ22.4 (c 0.54, EtOH); lit.,4c for (S)-isomer [α]D25 Ϫ22.6 (c 1,
EtOH); νmax(film)/cmϪ1 1735; δH(300 MHz, CDCl3) 0.92 (d, 3 H,
J 6.7), 0.93 (d, 3 H, J 6.7), 1.48–1.62 (m, 2 H), 1.67–1.80 (m,
1 H), 1.87–1.96 (m, 1 H), 2.21 (dd, 1 H, J 10.7, 17.3), 2.65 (ddd,
1 H, J 1.5, 6, 17.3), 4.22 (dt, 1 H, J 3.6, 11.3), 4.40 (ddd, 1 H,
J 4, 4.8, 11.3).
Methyl (1R)-1-(1Ј-naphthyl)ethyl (3S)-3-phenylpentane-1,5-
dioate 19 and its 3R diastereoisomer 20
(3ЈR,4ЈS,4S)-3-{3,4-Bis[dimethyl(p-tolyl)silyl]-5-carboxy-1-
oxopentyl}-4-benzyloxazolidin-2-one 8 and its (3ЈS,4ЈR)
diastereoisomer 9
A mixture of benzyl esters of acids 3c and 4c (67:33) were
crystallized from hexane–EtOAc to give another crop of mixture
of benzyl esters (80:20). A mixture of benzyl esters with this
new proportion (100 mg, 0.22 mmol) was dissolved in ethyl
acetate (2 cm3) and stirred under hydrogen in the presence of
Pd/C (10% Pd; 10 mg). After 24 h, the resulting acid was dis-
solved in dry CH2Cl2 and treated with 2,4,6-trichlorobenzoyl
chloride (0.033 cm3, 0.22 mmol) and DMAP (34 mg, 0.25
mmol). After 2 h at room temp., (1R)-1-(1Ј-naphthyl)ethanol
(60 mg, 0.3 mmol), and DMAP (36 mg, 0.3 mmol) were added.
After 18 h, the mixture was diluted with EtOAc, washed with
dil. HCl, NaHCO3 solution and brine, dried and concentrated
to give the ester [νmax(film)/cmϪ1 1780, 1731, 1702]. This ester
was dissolved in THF (3 cm3) and a mixture of water (0.8 cm3),
H2O2 (0.077 cm3 of a 30% solution, 1 mmol) and LiOHؒH2O
(15 mg, 0.35 mmol) was added to it at 0 ЊC under argon. After
1 h, the reaction mixture was treated with Na2SO3 (91 mg, 0.72
mmol) and water (1 cm3) was added followed by NaHCO3 solu-
tion (0.5 M, 1 cm3). The reaction mixture was acidified with
NaHSO4 and extracted with EtOAc. The organic extract was
washed with water and with brine, dried (Na2SO2) and evapor-
ated under reduced pressure. The residue was esterified with
ethereal diazomethane and after chromatography gave a mix-
ture of diesters 19 and 20 (35 mg, 55%); Rf(hexane–EtOAc;
95:5) 0.4; νmax(film)/cmϪ1 1735; δH(300 MHz, CDCl3) 1.53 (3 H,
d, J 6.5 from 20), 1.58 (3 H, d, J 6.5 from 19), 2.59–2.89 (4 H,
m), 3.56 (3 H, s, from 20), 3.59 (3 H, s, from 19), 3.62–3.74 (1 H,
m), 6.55 (1 H, q, J 6.5), 7.18–8.10 (12 H, m).
A solution of DCCI (75 mg, 0.36 mmol) in CH2Cl2 (35 cm3)
was added dropwise over 1.5 h to a stirred solution of the diacid
(3ЈSR,4ЈRS)-3,4-bis[dimethyl(p-tolyl)silyl]hexane-1,6-dioic
acid8 (150 mg, 0.36 mmol) in CH2Cl2 (35 cm3) at 0 ЊC. After 12
h at room temp., the solvent was evaporated, the residue was
triturated with hexane and filtered. The filtrate was evaporated
to give the anhydride 7 (142 mg, 100%) [νmax(CH2Cl2)/cmϪ1
1816, 1750, 1260, 1104]. A solution of this anhydride in THF (2
cm3) was added to a stirred solution of the anion of 2a at Ϫ78 ЊC
[prepared using butyllithium (1.25 M in hexane) (0.35 cm3, 0.43
mmol) and oxazolidinone 2a (77 mg, 0.43 mmol)]. The mixture
was then brought to the required temperature and stirred. The
reaction mixture was acidified with citric acid solution and
extracted with EtOAc. The crude mixture of acids (8 and 9) was
esterified with diazomethane and chromatographed to yield
major methyl ester (from 8) (122 mg, 55%) and minor methyl
ester (from 9) (62 mg, 28%). Data for methyl ester from 8:
Rf(hexane–EtOAc; 9:1) 0.6; [α]D29 ϩ51.3 (c 0.6, CHCl3);
νmax(film)/cmϪ1 1782, 1732, 1698, 1602, 1258, 1103; δH(200
MHz, CDCl3) 0.23 (3 H, s), 0.31 (3 H, s), 0.37 (6 H, s), 1.85–
2.05 (2 H, m), 2.29 (6 H, s), 2.38–2.62 (3 H, m), 2.94 (1 H, dd,
J 5.9, 18.6), 3.06–3.22 (2 H, m), 3.56 (3 H, s), 3.81–4.01 (2 H,
m), 4.10–4.42 (1 H, m), 7.09–7.47 (13 H, m); δC(50 MHz,
CDCl3) 174.0, 173.1, 153.2, 138.6, 135.8, 135.6, 134.4, 129.4,
129.0, 128.6, 127.3, 66.0, 55.2, 51.3, 38.1, 37.5, 36.3, 29.7, 23.8,
23.2, 21.3, Ϫ1.6, Ϫ2.3, Ϫ2.5, Ϫ2.6 (Found: C, 68.0; H, 7.6; N,
2.0. C35H45NO5Si2 requires C, 68.3; H, 7.4; N, 2.3%). Data for
methyl ester from 9: Rf(hexane–EtOAc; 9:1) 0.45; [α]D29 Ϫ4.0 (c
0.5, CHCl3); νmax(film)/cmϪ1 1783, 1731, 1698, 1602, 1251, 1103;
δH(200 MHz, CDCl3) 0.28 (3 H, s), 0.30 (3 H, s), 0.32 (3 H, s),
0.33 (3 H, s), 1.86–2.01 (2 H, m), 2.29 (3 H, s), 2.32 (3 H, s),
2.35–2.60 (3 H, m), 2.90–3.21 (3 H, m), 3.56 (3 H, s), 3.90–4.04
(2 H, m), 4.20–4.36 (1 H, m), 7.09–7.40 (13 H, m); δC(50 MHz,
CDCl3) 174.2, 173.1, 153.3, 138.7, 135.8, 135.6, 135.3, 134.5,
129.4, 129.0, 128.6, 127.3, 66.2, 55.3, 51.3, 38.1, 37.5, 36.2, 29.7,
24.3, 23.0, 21.3, Ϫ1.7, Ϫ2.1, Ϫ2.4, Ϫ2.7 (Found: C, 68.1; H,
7.5; N, 2.1. C35H45NO5Si2 requires C, 68.3; H, 7.4; N, 2.3%).
The crude acid mixture was also converted to the tert-butyl
esters following the procedure described for acids 3a and
4a. Yield of (3ЈR,4ЈS,4S)-3-{5-tert-butyloxycarbonyl-3,4-bis-
[dimethyl(p-tolyl)silyl]-1-oxopentyl}-4-benzyloxazolidin-2-one
(ester of major acid 8) is (425 mg, 45%) and that of its (3ЈS,4ЈR)
diastereoisomer is (212 g, 23%). For the ester of major acid 8:
Rf(hexane–EtOAc; 90:10) 0.47; [α]D23 ϩ31.3 (c 1.42, CHCl3);
νmax(film)/cmϪ1 1782, 1726, 1699, 1250, 1103; δH(300 MHz,
(3R)-3-Isopropylpentanolactone 21
A solution of (3ЈR,4S)-3-[3-isopropyl-1-oxo-4-(benzyloxycarb-
onyl)butyl]-4-benzyloxazolidin-2-one (benzyl ester of major
acid 3d) (217 mg, 0.5 mmol) in THF (5 cm3) was added to a
stirred solution of lithium hydroxide (40 mg, 1.03 mmol) and
hydrogen peroxide (30%) (0.23 cm3) in water (2.45 cm3) at 0 ЊC.
After 45 min, a solution of sodium sulfite (280 mg, 2.2 mmol) in
water (1.5 cm3) was added followed by addition of a solution of
sodium bisulfate till the mixture became acidic, and the reac-
tion mixture was extracted with EtOAc. The organic extract
was washed with water and with brine, dried (Na2SO4) and
evaporated under reduced pressure to give (3R)-3-isopropyl-
pentane-1,5-dioic acid 1-benzyl ester (130 mg, 98%); νmax(film)/
cmϪ1 3600–2500, 1735, 1712; δH(200 MHz, CDCl3) 0.88 (6 H, d,
J 6.8), 1.70–1.93 (1 H, m), 2.24–2.51 (5 H, m), 5.11 (2 H, s),
7.24–7.52 (5 H, m). This acid was dissolved in dry THF (2 cm3)
and cooled to Ϫ15 ЊC. A solution of diborane in THF (1.4 M)
J. Chem. Soc., Perkin Trans. 1, 1999, 257–264
263

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CDCl3) 0.24 (3 H, s), 0.33 (3 H, s), 0.36 (3 H, s), 0.37 (3 H, s),
1.43 (9 H, s), 1.89 (1 H, q, J 6.2), 2.03 (1 H, q, J 6.4), 2.27 (3 H,
s), 2.29 (3 H, s), 2.42 (2 H, dd, J 1.5, 6.4), 2.52 (1 H, dd, J 9.5,
13.4), 2.88 (1 H, dd, J 5.7, 18.8), 3.08 (1 H, dd, J 3.4, 14.8), 3.13
(1 H, dd, J 6.6, 18.8), 3.82 (1 H, t, J 8.4), 3.95 (1 H, dd, J 2.7,
8.8), 4.15–4.25 (1 H, m), 7.07–7.43 (13 H, m) (Found: C, 69.2;
H, 8.0; N, 2.0. C38H51NO5Si2 requires C, 69.4; H, 7.8; N, 2.1%).
For the ester of major acid 9: Rf(hexane–EtOAc; 90:10) 0.45;
[α]D23 ϩ26.6 (c 0.82, CHCl3); νmax(film)/cmϪ1 1783, 1725, 1698,
1250, 1103; δH(300 MHz, CDCl3) 0.28 (3 H, s), 0.29 (3 H, s),
0.32 (3 H, s), 0.33 (3 H, s), 1.42 (9 H, s), 1.90–1.98 (2 H, m),
2.26–2.38 (1 H, m), 2.27 (3 H, s), 2.33 (3 H, s), 2.39 (1 H, dd, J 6,
8.8), 2.43 (1 H, dd, J 9.9, 13.4), 2.92 (1 H, dd, J 7.3, 18), 3.06
(1 H, dd, J 3.1, 13.4), 3.14 (1 H, dd, J 5.4, 18), 3.91 (1 H, t,
J 8.8), 3.97 (1 H, dd, J 2.8, 8.8), 4.19–4.31 (1 H, m), 7.08–7.43
(13 H, m) (Found: C, 69.4; H, 7.9; N, 2.0. C38H51NO5Si2
requires C, 69.4; H, 7.8; N, 2.1%).
ation of 8 and 9, which was opened up with (1RS)-1-(1Ј-
naphthyl)ethanol (9 mg, 0.05 mmol), and DMAP (12 mg, 0.1
mmol) in dry CH2Cl2 (2 cm3) following the literature proce-
dure.8b The crude mono acid therefore obtained was converted
to the required diester rac-23 following the procedure used for
the preparation of 23 using 2,4,6-trichlorobenzoyl chloride and
DMAP.
References
1 For a review: R. S. Ward, Chem. Soc. Rev., 1990, 19, 1.
2 (a) H. Imado, T. Ishizuka and T. Kunieda, Tetrahedron Lett., 1995,
36, 931 and references cited therein; (b) M. North and G. Zagotto,
Synlett, 1995, 639; (c) I. G. Jones, W. Jones, M. North, M. Teijeira
and E. Uriate, Tetrahedron Lett., 1997, 38, 889; (d) G. Jaeschke and
D. Seebach, J. Org. Chem., 1998, 63, 1190.
3 (a) K. Osakada, M. Obana, T. Ikariya, M. Saburi and S. Yoshikawa,
Tetrahedron Lett., 1981, 22, 4297; (b) Y. Kawakami, J. Hiratake,
Y. Yamamoto and J. Oda, J. Chem. Soc., Chem. Commun., 1984,
779; (c) J. Hiratake, Y. Yamamoto and J. Oda, J. Chem. Soc., Chem.
Commun., 1985, 1717; (d) J. Hiratake, M. Inagaki, Y. Yamamoto
and J. Oda, J. Chem. Soc., Perkin Trans. 1, 1987, 1053; (e) Y. Nagao,
Y. Hagiwara, Y. Hasegawa, M. Ochiai, T. Inoue, M. Shiro and
E. Fujita, Chem. Lett., 1988, 381; ( f ) D. S. Karanewsky, M. F.
Malley and J. Z. Gougoutas, J. Org. Chem., 1991, 56, 3744; (g)
Y. Suda, S. Yago, M. Shiro and T. Taguchi, Chem. Lett., 1992, 389;
(h) K. Matsuki, H. Inoue and M. Takeda, Tetrahedron Lett., 1993,
34, 1167.
4 (a) T. Rosen and C. H. Heathcock, J. Am. Chem. Soc., 1985, 107,
3731; (b) P. D. Theisen and C. H. Heathcock, J. Org. Chem., 1988,
53, 2374; (c) P. D. Theisen and C. H. Heathcock, J. Org. Chem.,
1993, 58, 142.
5 R. Verma and S. K. Ghosh, Chem. Commun., 1997, 1601.
6 (a) D. A. Evans and A. S. Kim, in Encyclopedia of reagents for
organic synthesis, ed. L. A. Paquette, Wiley, NY, 1995, vol. 11,
p. 345; (b) D. Ager, I. Prakash and D. R. Schaad, Chem. Rev., 1996,
96, 835.
(3R,4S) 3,4-Bis[dimethyl(p-tolyl)silyl]hexane-1,6-dioic acid
6-tert-butyl ester 1-benzyl ester 22
Titanium tetrakis(benzyl oxide) (0.38 M in benzyl alcohol) (2.25
cm3, 0.85 mmol) was added to (3ЈR,4ЈS,4S)-3-{5-tert-butyl-
oxycarbonyl-3,4-bis[dimethyl(p-tolyl)silyl]-1-oxopentyl}-4-
benzyloxazolidin-2-one (ester of major acid 8) (272 mg, 0.414
mmol) and the mixture was heated at 75 ЊC for 24 h under
argon. The reaction mixture cooled to room temp. and
water (5 cm3) was added with stirring. The reaction mixture was
filtered through a pad of Celite and the residue was thoroughly
washed with EtOAc. The filtrate was evaporated under reduced
pressure and the benzyl alcohol was removed under high
vacuum. The residue was chromatographed to give ester 22 (208
mg, 87%); Rf(hexane–EtOAc; 95:5) 0.67; [α]D23 Ϫ17.9 (c 1.4,
CHCl3); νmax(film)/cmϪ1 1728, 1601, 1259, 1104; δH(300 MHz,
CDCl3) 0.21 (3 H, s), 0.22 (3 H, s), 0.26 (6 H, s), 1.38 (9 H, s),
1.79–1.92 (2 H, m), 2.32 (s, 3 H), 2.33 (3 H, s), 2.31–2.52 (4 H,
m), 4.87 (2 H, s), 7.09–7.36 (13 H, m) (Found: C, 71.3; H, 8.3.
C35H48O4Si2 requires C, 71.4; H, 8.2%).
7 (a) E. Badder, W. Bartmann, G. Beck, A. Bergmann, H. W.
Fehlhaber, H. Jendralla, K. Kesseler, R. Saric, H. Schussler,
V. Teetz, M. Weber and G. Wess, Tetrahedron Lett., 1988, 29, 2563;
(b) L. Novak, J. Rohaly, L. Poppe, G. Hornsyanszky, P. Kolonits,
I. Zelei, I. Feher, J. Fekete, E. Szabo, U. Zaharszky, A. Javor and
C. Szantay, Liebigs Ann. Chem., 1992, 145.
8 (a) I. Fleming and S. K. Ghosh, J. Chem. Soc., Chem. Commun.,
1992, 1775 and 1777; I. Fleming and S. K. Ghosh, J. Chem. Soc.,
Perkin Trans. 1, 1998, 2711; (b) I. Fleming and S. K. Ghosh,
J. Chem. Soc., Chem. Commun., 1994, 2285 and 2287; I. Fleming
and S. K. Ghosh, J. Chem. Soc., Perkin Trans. 1, 1998, 2733.
9 K. Takeshita, Y. Seki, K. Kawamoto, S. Murai and N. Sonoda,
J. Org. Chem., 1987, 52, 4864.
(3S,4R)-3,4-Bis[dimethyl(p-tolyl)silyl]hexane-1,6-dioic acid
1-tert-butyl (1R)-1-(1Ј-naphthyl)ethyl ester 23
The diester 22 (44 mg, 0.076 mmol) in EtOAc (3 cm3) was
stirred under hydrogen atmosphere for 15 h in the presence of
10% Pd/C (5 mg). The mixture was filtered through a Celite pad
and the filtrate was concentrated to give the acid. A solution of
2,4,6-trichlorobenzoyl chloride (0.017 cm3, 0.1 mmol) in dry
CH2Cl2 (0.5 cm3) was added to a stirred solution of this acid,
(1R)-1-(1Ј-naphthyl)ethanol (15 mg, 0.087 mmol), and DMAP
(12 mg, 0.1 mmol) in dry CH2Cl2 (0.5 cm3) at room temp.
After 15 h, the mixture was diluted with EtOAc, washed with
dil. HCl, NaHCO3 solution and brine, dried and concentrated.
The residue was chromatographed to give 23 (23 mg, 71%);
Rf(hexane–EtOAc; 98:2) 0.4; νmax(film)/cmϪ1 1728, 1603, 1261,
1108; δH(300 MHz, CDCl3) 0.18 (3 H, s), 0.22 (3 H, s), 0.24
(3 H, s), 0.26 (3 H, s), 1.36 (9 H, s), 1.58 (3 H, d, J 6.6), 1.82–
1.92 (2 H, m), 2.29 (3 H, s), 2.31 (3 H, s), 2.31–2.65 (4 H, m),
6.48 (1 H, quintet, J 6.6), 7.06–7.10 (4 H, m), 7.26–7.34 (4 H,
m), 7.40–7.54 (4 H, m), 7.74–7.90 (2 H, m), 8.00–8.04 (1 H, m)
(Found: C, 73.2; H, 8.3. C40H52O4Si2 requires C, 73.6; H, 8.0%).
A racemic sample (rac-23) was made by the following pro-
cedure. The (3SR,4RS)-3,4-bis[dimethyl(p-tolyl)silyl]hexane-
1,6-dioic acid8b (18 mg, 0.046 mmol) was converted into its
anhydride, following the procedure described for the prepar-
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Paper 8/08838A
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