(1S,2S)-1-Amino-2-hydroxy-1,2,3,4-tetrahydronaphthalene: A new chiral auxiliary for asymmetric Reformatsky reactions

Article abstract of DOI:10.1016/j.tetasy.2005.04.008

(1S,2S)-1-Amino-2-hydroxy-1,2,3,4-tetrahydronaphthalene, synthesized via a chemoenzymatic approach from naphthalene, has been successfully used as a chiral auxiliary in Reformatsky-type reactions between the corresponding α-bromoacyloxazolidinone and carbonyl compounds.

Full text of DOI:10.1016/j.tetasy.2005.04.008

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 16 (2005) 1913–1918
(1S,2S)-1-Amino-2-hydroxy-1,2,3,4-tetrahydronaphthalene: a
new chiral auxiliary for asymmetric Reformatsky reactions
Fulvia Orsini,* Guido Sello, Angelo Maria Manzo and Elvira Maria Lucci
Dipartimento di Chimica Organica e Industriale, Via Venezian 21, 20133 Milano, Italy
Received 19 January 2005; revised 14 April 2005; accepted 15 April 2005
Abstract—(1S,2S)-1-Amino-2-hydroxy-1,2,3,4-tetrahydronaphthalene, synthesized via a chemoenzymatic approach from naphtha-
lene, has been successfully used as a chiral auxiliary in Reformatsky-type reactions between the corresponding a-bromoacyloxazol-
idinone and carbonyl compounds.
ꢀ 2005 Elsevier Ltd. All rights reserved.
1. Introduction
of Dolastin,10 an anti-tumour agent, via a Co(0)-medi-
ated Reformatsky-type protocol developed in our labo-
ratory.11 Another metal, which has proven quite useful
is samarium (used as SmI2) for its remarkable stereo-
selectivity, achieved through chelation control of the
samarium intermediate in the transition state.12
It is widely recognized that chiral amino alcohols are
versatile reagents for the preparation of enantiopure
compounds. For this purpose they can be used directly
or derivatized to give, for example, chiral oxazolid-
inones, acetonides, hydroxyesters and hydroxyamides.1
It is also well known that amide-containing chiral auxil-
iaries often require harsh conditions in order to remove
them, thus limiting their usefulness and general applica-
bility. However it has been demonstrated that ester
derivatives of cis-1-p-tolylsulfonamido-2-indanol can
be successfully used in asymmetric synthesis.13
Many chiral amino alcohols have been used as back-
bones of chiral oxazolidinones. The latter have been
widely used as auxiliaries for a variety of asymmetric
transformations,1 such as C-alkylations,2 acylations,3
a-amination, aldol reactions,4 Michael additions5 and
Diels–Alder reactions.6 The methodologies have been
applied to the preparation of a variety of natural prod-
ucts7 as well as biologically and medicinally important
compounds. Some oxazolidinones also possess biologi-
cal activity on their own. The frequent use of oxazol-
idin-2-ones has prompted the investigation of several
methodologies of synthesis8 and acylation9 of these type
of molecules. N-Acyloxazolidinones are among the most
versatile chiral auxiliary systems, due to their ability to
form rigid chelates with metal ions, especially in the
presence of a bulk substituent in the 4-position.
Herein, we report some results concerning the use of
(1S,2S)-1-amino-2-hydroxy-1,2,3,4-tetrahydronaphthal-
ene 1 (Scheme 1), obtained via a chemoenzymatic
approach from the inexpensive and convenient naphtha-
lene (Scheme 1),14 as a chiral auxiliary in Reformatsky-
type reactions.
For this purpose, two different strategies were followed:
in the first, 1 was first converted to the chiral a-bromo-
acyloxazolidinone 3, while in the second, 1 was
Reformatsky-type reactions between a-bromoacyloxazol-
idinones and carbonyl compounds have been success-
fully performed with different metals and applied to
the construction of medicinally important compounds.
Such an example is the synthesis of the dolaproin unit
NH2
OH
OH
OH
a
b,c,d,e
1
Scheme 1. Reagents and conditions: (a) Escherichia coli
JM109(pVL13 + pMS13); (b) H2, Pd/C, MeOH; (c) triphosgene, triethylamine,
CH2Cl2, 0 ꢁC; (d) NaN3, DMF, 110 ꢁC; (e) H2, Pd/C, MeOH, 25 ꢁC.
*
Corresponding author. Tel.: +39 02 50314111; fax: +39 02
50314106; e-mail: fulvia.orsini@unimi.it
0957-4166/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2005.04.008

1914
F. Orsini et al. / Tetrahedron: Asymmetry 16 (2005) 1913–1918
O
ene.14 Reaction with triphosgene in methylene chloride
,
HN
in the presence of triethylamine at 0 ꢁC afforded oxazo-
lidinone 2 in 87% yield. N-Bromoacyloxazolidinone 3
was readily accessible in a reasonable yield (70%) by
reaction of the auxiliary 2 with butyllithium in toluene
at low temperature, followed by addition of bromo-
acetyl chloride. Bromoacetyl bromide was also tested,
but gave lower yields and unidentified side products.
O
b
a
2
O
O
NH2
Br
OH
N
O
We first tested the reaction of isobutyraldehyde with
chiral bromoacyloxazolidinone 3 at room temperature.
Unfortunately, the diastereoselectivity of the reaction
proved unsatisfactory, giving both diastereomers in a
1.6/1 ratio. The reaction was then carried out at
À78 ꢁC with only one diastereoisomer isolated in about
80% yield. Other aldehydes were then used and the
results summarized in Scheme 3. The yields were
in general from reasonable to good15,16 and one
diastereoisomer was isolated at low temperature.
3
1
c
HNTs
HNTs
O
OH
Br
d
O
5
4
Scheme 2. Reagents and conditions: (a) Triphosgene, triethylamine,
CH2Cl2, 0 ꢁC; (b) BuLi, THF, À78 ꢁC; bromoacetyl chloride, triethyl-
amine, CH2Cl2, 25 ꢁC; (c) tosyl chloride, 2,4-di-methyl aminopyridine,
CH2Cl2, 25 ꢁC; (d) bromoacetyl chloride, triethylamine, CH2Cl2,
25 ꢁC.
The lowest yields were obtained with benzaldehyde,
which are more inclined to give pinacol coupling: a
problem that can be minimized by the stepwise addition
of organic reagents (bromoacyloxazolidinone first, fol-
lowed by benzaldehyde).
converted to the 1-p-tolylsulfonamido-2-(a-bromoacyl-
oxy)-derivative 5 (Scheme 2).
The depicted stereochemistry has been suggested assum-
ing that the stereochemistry of the Reformatsky adduct
can be determined by a chelate transition structure
involving a samarium enolate with the samarium atom
coordinated to the oxazolidinone carbonyl, as verified
in other cases17 (Scheme 4). This assumption has been
experimentally verified in cases 6, 8 and 10. Cleavage
2. Results and discussion
Amino alcohol 1 was synthesized in a few steps, in good
total yields (80%) and under mild neutral conditions
from the cis-diol obtained by bioconversion of naphthal-
O
OH
O
N
O
81%
O
OH
O
O
6
OH
N
O
O
Ph
N
a*
O
6
+
68%
b
O
O
a*
11
Br
N
d.r. = 1.6/1
7
O
a*
O
OH
O
O
OH
O
3
N
b
Ph
N
O
O
a*
a*
81%
7
+
8
O
12
OH
O
O
OH
O
d.r. = 1.6/1
N
Ph
N
O
O
60%
60%
9
10
Scheme 3. Reagents and conditions: (a) Bromoacyloxazolidinone (1 equiv), carbonyl compound, SmI2 (2 equiv), THF, À78 ꢁC; (b) bromo-
acyloxazolidinone (1 equiv), carbonyl compound, SmI2 (2 equiv), THF, 25 ꢁC (*—dr >99/1).

F. Orsini et al. / Tetrahedron: Asymmetry 16 (2005) 1913–1918
1915
O
O
H
O
O
CH2
R
N
N
I
H
HO
Sm
O
O
I
O
R
Scheme 4.
NHTs
NHTs
O
O
SmI2, THF
-78 °C
Br
CHO
+
O
O
OH
5
13
Scheme 5.
of the chiral auxiliary with lithium hydroxide18 afforded
chloride (18 mL) was added a solution of triphosgene
(0.89 g, 3 mmol) in methylene chloride, dropwise in
about 1 h at 0–10 ꢁC. The reaction was monitored by
thin layer chromatography (SiO2, chloroform–metha-
nol–isopropylamine 9.5:0.25:0.25). After 2 h, methanol
(3 mL) and water (5 mL) were added to the reaction
mixture, which was vigorously stirred for an additional
30 min, concentrated under reduced pressure, after
which was added 10 mL of water and stirred for a fur-
ther 10 min. The suspension was filtered on a buckner,
washed with 1 M hydrochloric acid (0.2 mL) and water
(0.8 mL), to afford pure oxazolidinone 2 in 87.5% total
yield (1.38 g, 7.54 mmol).
indeed the corresponding (R)-b-hydroxy acids.19
The second devised strategy involved the conversion of
the aminoalcohol 1 into the p-tolylsulfonamido deriva-
tive 5 in two steps with 50% total yield: treatment with
p-toluenesulfonyl chloride in dichloromethane in the
presence of 2,4-dimethylaminopyridine afforded deriva-
tive 4, which was subsequently reacted with a-bromo-
acetyl chloride in dichloromethane in the presence of
triethylamine. The Sm(II)-mediated Reformatsky-type
reaction with isobutyraldehyde, performed at À78 ꢁC,
afforded, however, a diastereoisomeric mixture of aldols
in almost equimolar amounts (Scheme 5).
4.2.1. (4S,5S)-Tetrahydronaphthalene-(1,2-d)-oxazolidin-
2-one 2. Colourless crystals, mp = 157 ꢁC (ethylace-
tate/n-hexane); [a]D = +14.0 (c 10, CHCl3); 1H NMR
(CDCl3): d 2.14 (1H, m), 2.45 (1H, m), 3.08 (1H, ddd,
J = 18.0, 18.0, 8.0 Hz), 3.18 (1H, ddd, J = 18.0, 9.0,
3.0 Hz), 4.20 (1H, ddd, J = 11.0, 11.0, 5.0 Hz), 4.6
(1H, d, J = 11.0 Hz), 6.6 (1H, s), 7.0–7.3 (4H); 13C
NMR (CDCl3): 23.62 (t), 26.39 (t), 60.30 (d), 81.17
(d), 122.89 (d), 126.39 (d), 127.67 (d), 128.70 (d),
133.67 (s), 134.71 (s), 161.81 (s); EI MS, m/z (%): 189
(59) (M+), 161 (100) (M+ÀCO), 144 (39) (M+ÀCOO),
129 (29) (M+ÀNHCOO). Anal. Calcd for C11H11NO2:
C, 69.84; H, 5.82. Found: C, 69.63; H, 5.88.
3. Conclusion
In conclusion, (1S,2S)-1-amino-2-hydroxy-1,2,3,4-tetra-
hydronaphthalene, previously converted to the corre-
sponding a-bromoacyloxazolidinone, can be efficiently
used as a chiral auxiliary in Reformatsky-type reactions
to afford b-hydroxy acids.
4. Experimental
4.1. General
4.3. Synthesis of the a-bromoacetyl-2-oxazolidinone 3
Reagent grade tetrahydrofuran was refluxed on LiAlH4
and distilled. Reagent grade dichloromethane was
heated under reflux over P2O5 and distilled. Triethyl-
amine was refluxed on calcium hydride and distilled.
Proton and carbon nuclear magnetic resonance (1H
and 13C NMR) were recorded at 300 MHz in CDCl3
solutions. Mass spectra were recorded with a VG7070
E9 instrument. Melting points were determined with a
capillary apparatus and are uncorrected.
To a solution of oxazolidinone 2 (1.382 g, 7.55 mmol) in
dry tetrahydrofuran (12 mL), at À78 ꢁC, a solution of
butyllithium (1.6 M in hexane, 5.2 mL) was added
dropwise in about 20 min. The resulting solution was
stirred at À78 ꢁC for an additional 30 min. a-Bromoace-
tyl chloride (0.340 mL) in tetrahydrofuran (2 mL) was
added dropwise in about 20 min. The reaction mixture
was allowed to reach room temperature in about 1 h.
A
solution of saturated monohydrogenphosphate
4.2. Synthesis of the oxazolidinone 2
(5 mL) was then added and the water phase extracted
(3 · 10 mL) with ethylacetate. The combined organic
extracts were dried over Na2SO4 and the solvent
removed under reduced pressure. The crude material
To a solution of amino alcohol 1 (1.43 g, 8.7 mmol) and
freshly distilled triethylamine (1.8 mL) in dry methylene

1916
F. Orsini et al. / Tetrahedron: Asymmetry 16 (2005) 1913–1918
was chromatographed on silica gel (eluting with ethyl-
acetate/n-hexane 2:8) and afforded a-bromoacetyl-2-
oxazolidinone 3 (70%) and starting oxazolidinone (20%).
m), 2.7–2.9 (2H, m), 2.98 (1H, ddd, J = 15.4, 8.8,
4.4 Hz), 3.18 (1H, ddd, J = 15.4, 6.6, 4.9 Hz), 3.25 (2H,
J = 6.2 Hz), 4.02 (1H, ddd, J = 11.1, 11.0, 8.4 Hz), 4.25
(1H, m), 4.83 (1H, d, J = 11.1 Hz), 7.01–7.3 (9H); 13C
NMR (CDCl3): 22.29 (t), 25.89 (t), 29.88 (t), 38.72 (t),
44.20 (d), 61.52 (d), 68.18 (d), 123.62 (d), 126.10 (d),
126.72 (d), 127.02 (d), 127.88 (d), 128.13 (d), 2 · 128.64
(d), 128.68 (d), 134.13 (s), 135.34 (s), 141.90 (s), 155.41
(s), 176.20 (s); MS, m/z (%): 365 (1) (M+), 347 (52)
(M+ÀH2O), 130 (100) (C10H10), 91 (100) (C6H5CH2).
Anal. Calcd for C22H23NO4: C, 72.33; H, 6.30. Found:
C, 72.63; H, 6.38.
4.3.1. N-(a-Bromoacetyl)-(4S,5S)-tetrahydronaphthalene-
(1,2-d)-oxazolidin-2-one 3. Colourless crystals, mp =
126 ꢁC (ethylacetate/n-hexane); [a]D = +272 (c 1,
1
CHCl3); H NMR (CDCl3): d 2.08 (1H, m), 2.40 (1H,
m), 3.02 (1H, ddd, J = 14.3, 9.2, 3.7 Hz), 3.18 (1H,
ddd, J = 14.3, 9.1, 4.0 Hz), 4.10 (1H, ddd, J = 11.2,
11.2, 8.0 Hz), 4.42 (1H, d, J = 12 Hz), 4.86 (1H, d,
J = 12 Hz), 4.88 (1H, d, J = 11.2 Hz), 7.0 (1H, dd,
J = 5.5, 1.8 Hz), 7.15–7.25 (3H). 13C NMR (CDCl3):
22.12 (t), 25.69 (t), 28.43 (t), 61.40 (d), 78.79 (d),
123.21 (d), 126.68 (d), 127.77 (d), 128.52 (d), 133.84
(s), 134.59 (s), 154.70 (s), 169.54 (s); EI MS, m/z (%):
311–309 (19) (M+), 230 (76) (M+ÀBr), 188 (82)
(M+ÀBrCH2CO), 144 (29) (188ÀCO2), 130 (100)
(C10H10). Anal. Calcd for C13H12BrNO3: C, 50.32; H,
3.87. Found: C, 50.26; H, 3.87.
4.4.4. N-[(3R)-3-Hydroxy-4,4-dimethyl-pentanoyl]-(4S,5S)-
tetrahydronaphthalene-(1,2-d)-oxazolidin-2-one 8. Yield
81%, mp = 116–118 ꢁC (ethylacetate/n-hexane); [a]D =
+290.3 (c 0.75, CHCl3); 1H NMR (CDCl3): d 1.02
(9H, s), 2.06 (1H, dddd, J = 11.0, 11.0, 10.8, 4.3 Hz),
2.36 (1H, m), 2.98 (1H, ddd, J = 15.2, 8.7, 4.3 Hz),
3.04 (1H, dd, J = 13.6, 11.1 Hz), 3.15 (1H, ddd, J =
15.2, 10.8, 5.4 Hz), 3.36 (1H, dd, J = 13.6, 3.0 Hz), 3.88
(1H, dd, J = 11.1, 3.0 Hz), 4.03 (1H, ddd, J = 11.0,
10.8, 6.5 Hz), 4.84 (1H, d, J = 10.8 Hz), 7.05–7.15
(4H); 13C NMR (CDCl3): d 22.12 (t), 25.38 (t),
3 · 25.56 (q), 34.89 (s), 39.57 (t), 61.29 (d), 76.59 (d),
78.27 (d), 123.50 (d), 126.58 (d), 127.62 (d), 128.42 (d),
133.96 (s), 135.23 (s), 155.35 (s), 176.63 (s); MS m/z
(%): 299 (1) (M+ÀH2O), 273 (4) (M+ÀCO2), 260 (63)
(M+À(CH3)3C), 216 (32) (M+À(CH3)3CCH(OH)CH2),
130 (100) (C10H10). Anal. Calcd for C18H23NO4: C,
68.14; H, 7.26. Found: C, 68.45; H, 7.28.
4.4. Synthesis of b-hydroxyacyloxazolidinones 6–10
4.4.1. Typical procedure at À78 ꢁC. To a tetrahydrofu-
ran solution of samarium iodide (0.1 M, 1.25 mmol), the
bromoacyloxazolidinone 3 (0.175 g, 0.55 mmol) and the
aldehyde (0.55 mmol) in dry tetrahydrofuran (1 mL)
were added dropwise (30 min) at À78 ꢁC. The resulting
mixture was stirred at À78 ꢁC for 30 min and the colour
of the solution turned from deep blue to yellow.14 A di-
luted HCl solution (0.1 N, 9 mL) was then added and
the aqueous phase was extracted three times with ethyl-
acetate (3 · 5 mL). The combined organic extracts were
washed with water, dried (Na2SO4) and the solvent re-
moved under reduced pressure to afford the crude mate-
rial, which was purified by column chromatography
(SiO2; eluting with ethylacetate/n-hexane).
4.4.5. N-[(3R)-3-Hydroxy-4-ethyl-hexanoyl]-(4S,5S)-tet-
rahydronaphthalene-(1,2-d)-oxazolidin-2-one 9. Yield
60%, mp = 92–93 ꢁC (ethylacetate/n-hexane); [a]D =
1
+309.3 (c 1.1, CHCl3); H NMR (CDCl3): d 1.04 (3H,
d, J = 7.5 Hz), 1.04 (3H, d, J = 7.5 Hz), 1.3–1.6 (5H,
m), 2.05 (1H, dddd, J = 10.0, 10.0, 10.0, 4.0 Hz), 2.35
(2H, m), 2.98 (1H, ddd, J = 15.0, 10.0, 4.0 Hz), 3.15
(1H, dd, J = 15.0, 10.0, 4.4 Hz), 3.15 and 3.25 (2H,
4.4.2. N-[(3R)-3-Hydroxy-4-methyl-pentanoyl]-(4S,5S)-
tetrahydronaphthalene-(1,2-d)-oxazolidin-2-one 6. Yield
81%, colourless crystals, mp = 145–146 ꢁC (ethylacetate/
n-hexane); [a]D = +208.4 (c 1, CHCl3); 1H NMR
(CDCl3): d 1.02 (6H, d, J = 6.5 Hz), 1.81 (1H, mt, J =
6.5 Hz), 2.07 (1H, dddd, J = 11.0, 11.0, 10.8, 3.6 Hz),
2.37 (1H, m), 3.0 (1H, ddd, J = 17.5, 9.1, 3.6 Hz), 3.11
(1H, dd, J = 16.2, 6.0 Hz), 3.16 (1H, ddd, J = 17.5,
10.8, 5.4 Hz), 3.32 (1H, dd, J = 16.2, 2.2 Hz), 3.97 (1H,
m), 4.06 (1H, m), 4.85 (1H, d, J = 11.5), 7.05–7.42
(4H); 13C NMR (CDCl3): 13.44 (q), 17.68 (q), 18.46
(d), 22.06 (t), 25.70 (t), 33.75 (d), 41.43 (t), 73.73 (d),
78.29 (d), 126.53 (d), 126.54 (d), 127.63 (d), 128.46 (d),
133.95 (s), 135.17 (s), 155.33 (s), 176.43 (s); MS m/z
(%): 285 (1) (M+ÀH2O), 260 (10) (M+À(CH3)2CH),
216 (92) (M+À(CH3)2CHCH(OH)CH2), 188 (21)
(216ÀCO), 172 (11) (216ÀCO2), 130 (100) (C10H10).
Anal. Calcd for C17H21NO4: C, 67.33; H, 6.93. Found:
C, 67.63; H, 6.98.
ABX system, JAB = 15.0 Hz, JAX = 5.0 Hz, JBX
=
2.5 Hz), 4.0 (1H, ddd, J = 10.0, 10.0, 6.0 Hz), 4.23
(1H, ddd, J = 10.0, 5.0, 2.5 Hz), 4.83 (1H, d,
J = 10.0 Hz), 7.1–7.3 (4H); 13C NMR: 2 · 11.82 (q),
20.86 (t), 21.32 (t), 21.78 (t), 21.99 (t), 25.48 (t), 46.75
(d), 61.22 (d), 70.12 (d), 78.20 (d), 123.73 (d), 126.76
(d), 127.04 (d), 128.35 (d), 133.99 (s), 135.20 (s),
155.31 (s), 176.45 (s); MS, m/z (%): 313 (5)
(M+ÀH2O), 260 (54) (331ÀCH3CH2CHCH2CH3), 216
(30) (260ÀCH(OH)CH2), 172 (7) (216ÀCO2), 130
(100) (C10H10). Anal. Calcd for C19H25NO4: C, 68.88;
H, 7.55. Found: C, 68.55; H, 7.67.
4.4.6. N-[(3R)-3-Hydroxy-3-phenyl-pentanoyl]-(4S,5S)-tet-
rahydronaphthalene-(1,2-d)-oxazolidin-2-one 10. Yield
60%, mp = 156–157 ꢁC (ethylacetate/n-hexane); [a]D =
1
+284.0 (c 1, CHCl3); H NMR (CDCl3): d 2.05 (1H,
dddd, J = 10.0, 10.0, 10.0, 4.8 Hz), 2.48 (1H, ddd,
J = 15.0, 10.0, 4.8 Hz), 3.15 (1H, ddd, J = 17.5, 10.0,
5.0 Hz), 3.28 (1H, m), 3.48 and 3.55 (2H, ABX system,
JAB = 15.0 Hz, JAX = 9.0 Hz, JBX = 5.0 Hz), 4.02 (1H,
ddd, J = 10.0, 10.0, 5.3 Hz), 4.85 (1H, d, J = 10.0 Hz),
5.35 (1H, dd, J = 9.0, 5.0 Hz), 7.01–7.25 (9H); 13C
4.4.3. N-[(3S)-3-Hydroxy-5-phenyl-pentanoyl]-(4S,5S)-
tetrahydronaphthalene-(1,2-d)-oxazolidin-2-one 7. Yield
68%, colourless crystals, mp = 155–156 ꢁC (ethylacetate/
n-hexane); [a]D = +271.1 (c 1.66, CHCl3); 1H NMR
(CDCl3): d 1.85–1.95 (2H, m), 2.05 (1H, m), 2.4 (1H,

F. Orsini et al. / Tetrahedron: Asymmetry 16 (2005) 1913–1918
1917
NMR (CDCl3): 21.50 (t), 24.14 (t), 46.04 (t), 61.18
(d), 71.03 (d), 78.32 (d), 123.38 (d), 2 · 125.83 (d),
126.44 (d), 127.54 (d), 127.88 (d), 128.36 (d), 2 · 128.50
(d), 133.89 (s), 135.05 (s), 142.81 (s), 155.20 (s), 174.88;
MS, m/z (%): 337 (80) (M+), 231 (16) (M+ÀPhCHO),
187 (33) (231ÀCO2), 130 (100) (C10H10). Anal. Calcd
for C20H19NO4: C, 71.22; H, 5.64. Found: C, 71.35; H,
5.68.
eluting with n-hexane/ethylacetate 1:1). After 1 h, the
reaction mixture was quenched with sodium bicarbonate
and extracted with ethylacetate (3 · 2 mL). The com-
bined organic extracts were dried over Na2SO4 and the
solvent removed under reduced pressure to give
0.015 g of crude oxazolidinone. The aqueous layer was
acidified with HCl and then extracted with 3 mL portion
of methylene chloride. The combined organic extracts
were dried over Na2SO4 and the solvent removed under
reduced pressure to give (R)-3-hydroxy-3-phenyl prop-
ionic acid19 (13.2 mg, 79.5%): [a]D = +21.5 (c 2, MeOH);
1H NMR (CDCl3 + D2O): d 2.78 and 2.82 (2H, ABX
system, JAB = 16.0; JAX = 9.0; JBX = 4.0 Hz), 5.18 (1H,
dd, J = 9.0, 4.0 Hz), 7.2–7.5 (5H, aromatic protons).
The same protocol applied to b-hydroxyacyloxazolid-
inone 6 gave (R)-3-hydroxy-4-methylpentanoic acid;19
4.5. Synthesis of b-hydroxyacyloxazolidinones 6, 7, 11 and 12
4.5.1. Typical procedure at room temperature. To a tet-
rahydrofuran solution of samarium iodide (0.1 M,
1.25 mmol), bromoacyloxazolidinone
3
(0.175 g,
0.55 mmol) and isobutyraldehyde (0.175 g, 0.55 mmol)
in tetrahydrofuran (1 mL) were added dropwise
(30 min) at room temperature. The reaction was moni-
tored in thin layer chromatography (SiO2; eluting with
ethylacetate/n-hexane 3:7), stirred at room temperature
for an additional 90 min, and then worked up as de-
scribed above for the reactions performed at low tem-
perature. The crude material was purified by column
chromatography (SiO2; eluting with ethylacetate/n-hex-
ane 3:7) and afforded the diastereoisomeric aldols 6
and 11 in 1.6:1 ratio.
1
[a]D = +39.8 (c 1, CHCl3); H NMR (CDCl3 + D2O): d
0.94 (6H, d, J = 6.5 Hz), 1.72 (1H, m), 2.44 and 2.53
(2H, ABX system, JAB = 16.2; JAX = 3.0; JBX = 9.7 Hz),
3.81 (1H, m). The protocol was applied to b-hydroxy-
acyloxazolidinone 8 and afforded (R)-3-hydroxy-4,4-di-
1
methyl pentanoic acid19: [a]D = +50.5 (c 1, CHCl3); H
NMR (CDCl3 + D2O): d 0.95 (9H, s), 2.45 and 2.62
(ABX system, JAB = 16.0; JAX = 9.5; JBX = 3.0 Hz),
3.78 (1H, m).
4.5.2. N-[(3S)-3-Hydroxy-5-methyl-pentanoyl]-(4S,5S)-
tetrahydronaphthalene-(1,2-d)-oxazolidin-2-one 11. [a]D =
+150.5 (c 0.6, CHCl3); H NMR (CDCl3): d 1.0 (3H, d,
4.7. Synthesis of p-toluenesulfonylamide 4
1
To a solution of amino alcohol 1 (0.3 g, 1.84 mmol) and
2,4-dimethylaminopyridine (0.03 g) in methylene chlo-
ride (10 mL), a solution of p-toluenesulfonyl chloride
(0.35 g) in methylene chloride (3 mL) was added drop-
wise in about 30 min. The reaction was monitored by
thin layer chromatography (SiO2; ethylacetate/n-hexane
3:7) and stirred for 24 h at room temperature. Water
(2 mL) was added and the aqueous phase extracted with
dichloromethane (3 · 5 mL). The combined organic ex-
tracts were dried over Na2SO4 and the solvent removed
under reduced pressure. The crude material was crystal-
lized from dichloromethane–hexane and afforded pure 4
in 60% yields.
J = 5.6 Hz), 1.02 (3H, d, J = 5.6 Hz), 1.82 (1H, m), 2.06
(1H, m), 2.38 (1H, m), 3.0 (1H, ddd, J = 16.0, 10.0,
2.5 Hz), 3.08–3.35 (2H, dd, J = 15.0, 1.5, 10.0 Hz), 3.18
(1H, ddd, J = 16.0, 11.0, 5.0 Hz), 4.0 (1H, m), 4.01 (1H,
m), 4.85 (1H, d, J = 10.5 Hz), 7.01–8 (1H, d,
J = 8.8 Hz), 7.1–7.25 (3H); MS, m/z: 285 (1) (M+ÀH2O),
260 (10) (M+À(CH3)2CH), 216 (92) (M+À(CH3)2CH-
CH(OH)CH2), 188 (21) (216ÀCO), 172 (11) (216ÀCO2),
130 (100) (C10H10).
4.5.3. N-[(3R)-3-Hydroxy-5-phenyl-pentanoyl]-(4S,5S)-
tetrahydronaphthalene-(1,2-d)-oxazolidin-2-one 12. Col-
1
ourless syrup; [a]D = +177.8 (c 0.55, CHCl3); H NMR
(CDCl3): d 1.8–1.95 (2H), 2.06 (1H, dddd, J = 11.0,
11.0, 10.8, 4.3 Hz), 2.37 (1H, m), 2.7–2.85 (2H), 2.99
(1H, ddd, J = 15.2, 8.7, 4.3 Hz), 3.14 (1H, dd, J = 17.6,
9.4 Hz), 3.18 (1H, ddd, J = 15.2, 10.8, 5.4 Hz), 3.43
(1H, dd, J = 17.6, 2.7 Hz), 4.02 (1H, dd, J = 11.0, 10.5,
6.9 Hz), 4.23 (1H, m), 4.83 (1H, d, J = 10.5 Hz); 13C
NMR (CDCl3): d 22.30 (t), 25.90 (t), 29.88 (t), 32.00
(t), 38.30 (t), 44.11 (d), 61.60 (d), 67.28 (d), 123.64
(d), 126.11 (d), 126.77 (d), 127.87 (d), 128.65 (d),
2 · 128.66 (d), 2 · 128.67 (d), 134.12 (s), 135.26 (s),
141.87 (s), 155.42 (s), 175.94 (s); MS m/z (%): 347 (40)
(M+ÀH2O), 130 (88) (C10H10), 91 (100) (C6H5CH2).
4.7.1. (1S,2S)-1-p-Tolylsulfonamido-2-hydroxy-1,2,3,4-
tetrahydronaphthalene 4. Mp = 139–140 ꢁC (ethylace-
tate/n-hexane); [a]D = +33.8 (c 1, CHCl3); 1H NMR
(CDCl3): d 1.90 (1H, m), 2.18 (1H, m), 2.48 (3H, s),
2.86 (2H, m), 3.96 (1H, m), 4.29 (1H, dd, J = 6.8,
6.7 Hz), 4.68 (1H, d, J = 6.8 Hz), 6.74 (1H, d,
J = 6.5 Hz), 7.0–7.1 (3H), 7.40 (2H, d, J = 7.3 Hz),
7.90 (2H, d, J = 7.3 Hz); EI MS, m/z (%): 299 (1)
(M+ÀH2O), 162 (98) (M+ÀCH3C6H5SO2), 146 (59)
(M+ÀCH3C6H5SO2NH2), 118 (100) (M+ÀCH3C6H5-
SO2NH2ÀCO). Anal. Calcd for C17H19NO3S: C,
64.35; H, 5.99. Found: C, 64.75; H, 5.68.
4.6. Removal of the chiral auxiliary in b-hydroxyacyl-
oxazolidinones 6, 8 and 10
4.8. Synthesis of 2-(bromoacyloxy)-p-toluenesulfonyl-
amide 5
4.6.1. Typical procedure. An aqueous solution
(0.3 mL) of lithium hydroxide (5 mg, 0.2 mmol) was
added at 0 ꢁC to aldol adduct 10 (0.033 g, 0.1 mmol)
in THF (1.5 mL). The resulting mixture was stirred at
0 ꢁC, and the reaction monitored by TLC (silica gel,
To a solution of 4 (0.188 g, 0.59 mmol) and dry triethyl-
amine (0.14 mL) in methylene chloride (7 mL), a solu-
tion of a-bromoacetyl chloride (0.05 g) in dry
methylene chloride (1 mL) was added dropwise in
about 30 min. The reaction was monitored by thin layer

1918
F. Orsini et al. / Tetrahedron: Asymmetry 16 (2005) 1913–1918
chromatography (SiO2; ethylacetate/n-hexane 4:6) and
stirred for 15 h at room temperature. Water (3 mL) was
added and the aqueous phase extracted with dichloro-
methane (3 · 5 mL). The combined organic extracts
were dried over Na2SO4 and the solvent removed under
reduced pressure. The crude material was chromato-
graphed (SiO2; ethylacetate/n-hexane 4:6) and afforded
pure 5 in 80% yields.
code no. RBAU017KFW—COFIN 2002, Project code
no. 2002058141-007).
References
1. Review: Ager, D. J.; Prakash, I.; Schaad, R. Aldrichim.
Acta 1997, 30, 3–11; See also: Senanayake, C. H. Aldri-
chim. Acta 1998, 31, 1–15.
4.8.1.
(1S,2S)-1-p-Tolylsulfonamido-2-(a-bromoacetyl)-
2. Evans, D. A.; Ennis, M. D.; Mathre, D. J. J. Am. Chem.
Soc. 1981, 104, 1737–1739.
3. Evans, D. A.; Bartroli, J.; Shih, T. L. J. Am. Chem. Soc.
1981, 103, 2127–2129.
4. Evans, D. A.; Ennis, M. D.; Le, T. J. Am. Chem. Soc.
1984, 106, 1154–1156.
5. Cai, C.; Soloshonok, V. A.; Hruby, V. J. J. Org. Chem.
2001, 66, 1339–1350.
1,2,3,4-tetrahydronaphthalene 5. Mp = 132–133 ꢁC (ethy-
l- acetate/n-hexane); [a]D = +35.1 (c 1, CHCl3); H NMR
1
(CDCl3): d 2.07 (2H, m), 2.49 (3H, s), 2.88 (2H, m),
3.50 (1H, d, J = 14.3 Hz), 3.81 (1H, d, J = 14.3 Hz),
4.6 (1H, dd, J = 6.8, 6.8 Hz), 4.7 (1H, d, J = 6.8 Hz),
5.17 (1H, m), 7.0–7.1 (4H), 7.4 (2H, d, J = 7.7 Hz), 7.82
(2H, d, J = 7.7 Hz); EI MS, m/z (%): 439–437 (1) (M+),
299 (8) (M+, –BrCH2COOH), 144 (100) (299ÀCH3C6H5-
SO2), 128 (36) (299ÀCH3C6H5SO2NH2). Anal. Calcd
for C19H20BrNO4S: C, 52.05; H, 4.57. Found: C, 52.25;
H, 4.37.
6. Evans, D. A.; Chapman, K. T.; Bisaha, J. J. Am. Chem.
Soc. 1988, 110, 1238–1256.
7. (a) Park, C. H.; Britelli, D. R.; Wang, C. L. J.; Marsh, F.
D.; Gregory, W. A.; Wuonola, M. A.; McRipley, R. J.;
Eberly, V. S.; Slee, A. M.; Forbes, M. J. Med. Chem. 1992,
35, 1156–1165; (b) Grega, K. C.; Barbachyn, M. R.;
Brickner, S. J.; Mizsak, S. A. J. Org. Chem. 1995, 60,
5255–5261.
4.9. Synthesis of b-hydroxyesters 13
8. Review: Ager, D. J.; Prakash, I.; Schaad, R. Chem. Rev.
1996, 96, 835–876.
A solution of 5 (0.172 g, 0.39 mmol) and isobutyralde-
hyde (0.58 mmol, 0.053 mL) in dry tetrahydrofurane
(1 mL) was added dropwise in about 30 min at
À78 ꢁC, to a tetrahydrofuran solution of samarium
iodide (0.1 M, 0.89 mmol). The reaction was monitored
in thin layer chromatography (SiO2; eluting with ethyl-
acetate/n-hexane 3:7) and stirred at À78 ꢁC for an addi-
tional 2.5 h. A diluted HCl solution (0.1 M, 9 mL) was
then added and the aqueous phase extracted three times
with ethylacetate (3 · 5 mL). The combined organic ex-
tracts were washed with water, dried over Na2SO4 and
the solvent removed under reduced pressure to afford
the crude material, which was purified by column chro-
matography (SiO2; eluting with ethylacetate/n-hexane)
and afforded the mixture of the two diastereoisomers
in 50% yields. 1H NMR (CDCl3): d 0.88 (3H, d,
J = 6.7 Hz), 0.92 (3H, d, J = 6.7 Hz), 1.6 (1H, m), 2.0–
2.3 (4H, m), 2.47 (3H, s), 2.86 (2H, m), 3.65 (0.5H, m,
CHOH of one diastereoisomer), 3.7 (0.5H, m, CHOH
of the other diastereoisomer), 4.58 (1H, dd, J = 7.3,
7.2 Hz), 4.8 (1H, d, J = 7.3 Hz), 5.2 (1H, m), 6.95–7.1
(4H), 7.36 (2H, d, J = 7.33 Hz), 7.85 (2H, d,
J = 7.33 Hz); MS, m/z: 431 (M+).
9. (a) Ager, D. J.; Prakash, I.; Schaad, R. Synthesis 1996,
1283–1285; (b) Prashad, M.; Kim, H. Y.; Har, D.; Repic,
O.; Blacklock, T. J. Tetrahedron Lett. 1998, 39, 9369–9372.
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8640–8642.
11. Orsini, F.; Pelizzoni, F.; Pulici, M.; Vallarino, L. M.
J. Org. Chem. 1994, 59, 1–3.
12. Molander, G. A.; Harris, C. Chem. Rev. 1996, 96, 307–
338; Fukuzawa, S.-i.; Matsuzawa, H.; Yoshimitsu, S.-i.
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118, 2527–2528; (b) Ghosh, A. K.; Fidanze, S.; Onischi,
M. J.; Hussai, K. A. Tetrahedron Lett. 1997, 38, 7171–
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Tetrahedron 1995, 36, 6811–6814.
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2001, 12, 2961–2969.
15. Sometimes with commercial samarium iodide, the colour
changed during the addition of the organic reagents and
an excess had to be added to complete the reaction.
16. In some runs, when the colour of the solution turned
yellow before the end of the reaction and no more
samarium was added, a significant amount of a-iodoacyl-
oxazolidinone was isolated.
17. Fukuzawa, S.-i.; Matsuzawa, H.; Yoshimitsu, S.-i. J. Org.
Chem. 2000, 65, 1702–1706.
18. Nicolas, E.; Russell, K. C.; Hruby, V. J. J. Org. Chem.
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Acknowledgements
UniversitaÕ degli Studi di Milano and MIUR (Ministero
dellÕ Istruzione, dellÕ UniversitaÕ e della Ricerca) are
acknowledged for financial support (FIRB: Project
19. Palomo, C.; Oiarbide, M.; Aizpurua, J. M.; Gonzales, A.;
Garcia, J. M.; Landa, C.; Odriozola, I.; Linden, A. J. Org.
Chem. 1999, 64, 8193–8200.