Enantioselective synthesis of (S,S)-ethambutol using proline-catalyzed asymmetric α-aminooxylation and α-amination

Article abstract of DOI:10.1016/j.tetasy.2006.06.011

An efficient enantioselective synthesis of (S,S)-ethambutol, a tuberculostatic antibiotic, has been achieved in 99% ee via both proline-catalyzed α-aminooxylation and α-amination of n-butyraldehyde as the key step.

Full text of DOI:10.1016/j.tetasy.2006.06.011

Tetrahedron: Asymmetry 17 (2006) 1738–1742
Enantioselective synthesis of (S,S)-ethambutol using
proline-catalyzed asymmetric a-aminooxylation and a-amination
Shriram P. Kotkar and Arumugam Sudalai*
Chemical Engineering and Process Development Division, National Chemical Laboratory, Pashan Road, Pune 411 008, India
Received 15 May 2006; accepted 2 June 2006
Abstract—An efficient enantioselective synthesis of (S,S)-ethambutol, a tuberculostatic antibiotic, has been achieved in 99% ee via both
proline-catalyzed a-aminooxylation and a-amination of n-butyraldehyde as the key step.
ꢀ 2006 Elsevier Ltd. All rights reserved.
1. Introduction
around the world. In particular, organocatalytic asymmet-
ric synthesis has provided several new methods for obtain-
ing chiral compounds.7 In this connection, proline, an
abundant, inexpensive amino acid available in both enan-
tiomeric forms, has emerged as arguably the most practical
and versatile organocatalyst.8 Proline has also been found
to be an excellent asymmetric catalyst for a-functionaliza-
tion9,10 of carbonyl compounds. We envisaged O-protected
(S)-2-amino-1-butanol 7 as the precursor for an asymmet-
ric synthesis of ethambutol. Thus, we have achieved the
enantioselective synthesis of (S,S)-ethambutol by employ-
ing proline-catalyzed a-aminooxylation9 and a-amina-
tion10 of n-butyraldehyde; the results of which are
presented in this paper.
Ethambutol 1 [(S,S)-2,20-(ethylenediimino)-di-butanol] is
among the frontline antimycobacterial chemotherapeutic
agents, active against nearly all strains of Mycobacterium
tuberculosis and Mycobacterium kansasii as well as a num-
ber of strains of Mycobacterium avium.1 The biological
activity of ethambutol has been attributed to its inhibition
of mycobacterial arabinosyl transferases involved in bacte-
rial cell wall biosynthesis.2 Ethambutol is administered as
its (S,S)-enantiomer, which is 200–500 times more potent
than the (R,R)-enantiomer and the meso-isomer.3
The literature methods for the synthesis of (S,S)-etham-
butol involve resolution of racemic 2-amino-1-butanol,1,4
palladium catalyzed regio- and stereoselective epoxide
opening by pthalimide as the key step,5 and a chiral pool
approach by using L-methionine as a chiral material.3b
As a part of our research program aimed at developing ste-
reocontrolled synthesis of bioactive molecules,6 we report a
highly efficient synthesis of (S,S)-ethambutol 1 using both
proline-catalyzed a-aminooxylation9 and a-amination10 of
n-butyraldehyde (Schemes 1 and 2).
2.1. a-Aminooxylation approach
Firstly, a-aminooxylation9a of n-butyraldehyde was car-
ried out using nitrosobenzene and L-proline (25 mol %)
at ꢀ20 ꢁC to furnish an aminooxy aldehyde, which upon
in situ reduction with sodium borohydride afforded the
25
a-aminooxy alcohol 2 in 85% yield; ½aꢁD ¼ þ20:7 (c 1,
25
CHCl3) {lit.9e ½aꢁD ¼ þ20:5 (c 1, CHCl3)}. Alcohol 2
was then protected with TBSCl to give the corresponding
silyl ether 3 in 90% yield, which on hydrogenation over
Pd/C (10 mol %) furnished monoprotected diol 4 in 88%
yield. Tosylation of 4 using p-toluenesulfonyl chloride
and pyridine followed by displacement of tosyl group with
NaN3 in DMF gave the azido product 6 in 75% yield.
Subsequent catalytic hydrogenation of azide with Pd/C–
H2 (1 atm) afforded the protected amine 7 in 95% yield
(Scheme 1).
2. Results and discussion
The field of asymmetric organocatalysis is rapidly develop-
ing and attracts an increasing number of research groups
*
Corresponding author. Tel.: +91 20 25902174; fax: +91 20 25902676;
email: a.sudalai@ncl.res.in
0957-4166/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2006.06.011

S. P. Kotkar, A. Sudalai / Tetrahedron: Asymmetry 17 (2006) 1738–1742
1739
OH
H
N
N
H
HO
1, (S,S)-Ethambutol
ONHPh
OR
OR
c
a
e
OTBS
d
CHO
2 R = H
4 R = H
b
3 R = TBS
5 R = Ts
N3
NH2
f
OTBS
OTBS
6
7
Scheme 1. Reagents and conditions: (a) PhNO, L-proline (25 mol %), ꢀ20 ꢁC, 24 h then MeOH, NaBH4, 85%; (b) TBSCl, imidazole, CH2Cl2, 3 h, 90%; (c)
H2 (1 atm), Pd/C (10%), Et3N, MeOH, 12 h, 88%; (d) p-TsCl, Py, 24 h, 95%; (e) NaN3, DMF, 60 ꢁC, 30 h, 75%; (f) H2 (1 atm), Pd–C (10%), Et3N, MeOH,
6 h, 95%.
Cbz
NH2
Cbz
a
N
Cbz
b
N
N
HO
N
OH
+
CHO
H
Cbz
9 R = H
c
8
7 R = TBS
Scheme 2. Reagents and conditions: (a) dibenzyl azodicarboxylate, D-proline (10 mol %), 0–20 ꢁC, 3 h then NaBH4, EtOH, 92%; (b) H2 (12 bar), Raney-
nickel, MeOH, AcOH, 70%; (c) TBSCl, imidazole, CH2Cl2, 0–20 ꢁC, 3 h, 85%.
2.2. a-Amination approach
and TBS deprotection were carried out in one-pot reaction
using lithium aluminum hydride at reflux conditions to give
(S,S)-ethambutol 1 in 80% yield and 99% ee (Scheme 3).
The physical and spectroscopic data were in full agreement
with the literature values.3b
In the second approach, a-amination of n-butyraldehyde
was carried out using List’s protocol.10a Thus, n-butyralde-
hyde was treated with dibenzyl azodicarboxylate in the
presence of D-proline (10 mol %) to furnish an aminoalde-
hyde, which upon in situ reduction with sodium boro-
hydride afforded the protected aminoalcohol 8 in 92%
yield. Aminoalcohol 8 was then hydrogenated using Raney-
nickel11 as a catalyst to give (S)-2-amino-1-butanol 9 in 70%
3. Conclusion
In conclusion, we have successfully applied proline-cata-
lyzed a-aminooxylation and a-amination strategies toward
the synthesis of (S,S)-ethambutol, which was obtained in
99% ee. The operationally simple reactions are rapid, and re-
quire a relatively low amount of an inexpensive and non-
toxic proline-catalyst that is available in both enantiomeric
forms. The high overall yields (35.7% via a-aminooxylation
and 43% via a-amination) and small number of steps renders
our approach a good alternative to the known methods.
25
25
yield; ½aꢁD ¼ þ10:1 (neat), {lit.12 ½aꢁD ¼ þ10 (neat) for 96%
ee}. Protection of the hydroxyl group in amino alcohol 9
with TBSCl afforded silyl ether 7 in 85% yield (Scheme 2).
Finally, protected aminoalcohol 7 was transformed into
(S,S)-ethambutol in two steps. Thus, amine 7 on treatment
with 0.5 equiv of oxalyl chloride and pyridine furnished
oxalyldiamide 10 in 98% yield. The reduction of diamide
OTBS
OH
H
N
O
O
NH
NH
10
NH2
a
b
N
H
OTBS
HO
7
OTBS
(
S,S)-ethambutol 1
Scheme 3. Reagents and conditions: (a) oxalyl chloride (0.5 equiv), Py, CH2Cl2, 12 h, 98%; (b) LAH, THF, reflux, 24 h, 80%.

1740
S. P. Kotkar, A. Sudalai / Tetrahedron: Asymmetry 17 (2006) 1738–1742
4. Experimental
drops of Et3N. The reaction mixture was then stirred in a
hydrogen atmosphere (1 atm of H2) for 12 h. After comple-
tion of the reaction (monitored by TLC), the reaction mix-
4.1. General information
ture was filtered through
a Celite pad and then
The solvents were purified and dried by standard procedures
before use. Melting points are uncorrected. Optical rota-
tions were measured using sodium D line on a JASCO-181
concentrated to near dryness. The crude product was then
purified by silica gel chromatography (pet. ether–EtOAc
25
95:5). Yield = 2.4 g, 88%. Colorless liquid; ½aꢁD ¼ ꢀ9:4 (c
1
digital polarimeter. H NMR and 13C NMR spectra were
1, CHCl3). IR (CHCl3) mmax 3569, 3018, 2859, 2957,
recorded on Brucker AC-200 spectrometer. Elemental ana-
lysis was carried out on a Carlo Erba CHNS-O analyzer.
2400, 1711, 1460, 1362, 1216, 1093, 927, 837, 669 cmꢀ1
.
1H NMR (CDCl3): d 0.06 (s, 6H), 0.89 (s, 9H), 0.94 (t,
J = 7.32 Hz, 3H), 1.44 (m, 2H), 2.42 (br s, 1H), 3.39–3.59
(m, 2H), 3.54 (m, 1H). 13C NMR (CDCl3): d ꢀ5.45, 9.85,
18.21, 25.69, 25.80, 66.85, 73.15 ppm. Elemental analysis:
C10H24O2Si required C, 58.77; H, 11.84. Found C, 58.66;
H, 12.05.
4.2. (R)-2-(N-Phenylaminooxy)butan-1-ol 2
To a CH3CN (60 mL) solution of n-butyraldehyde (4.5 mL,
50 mmol) and nitrosobenzene (2.67 g, 25 mmol) was added
L-proline (718 mg, 6.2 mmol, 25 mol %) at ꢀ20 ꢁC. The
reaction mixture was allowed to stir at the same tempera-
ture for 24 h followed by addition of MeOH (25 mL) and
NaBH4 (2.8 g, 75 mmol) to the reaction mixture, which
was stirred for 10 min. After addition of phosphate buffer,
the resulting mixture was extracted with EtOAc
(60 mL · 3) and the combined organic phases were dried
over Na2SO4. Purification by column chromatography
4.5. (R)-1-(tert-Butyldimethylsilyloxybutan-3-yl)4-methyl-
benzenesulfonate 5
To a solution of alcohol 4 (2.4 g, 11.7 mmol) in pyridine
(30 mL) kept at 0 ꢁC was added p-toluenesulfonyl chloride
(2.44 g, 12.8 mmol, 1.1 equiv) and the reaction mixture was
allowed to stir at 25 ꢁC for 24 h. After completion of the
reaction (monitored by TLC), pyridine was removed under
reduced pressure. To the residue was added water (30 mL)
and extracted with EtOAc (3 · 30 mL). The crude product
was then purified by silica gel chromatography (pet. ether–
with silica gel (pet. ether–EtOAc = 80:20) afforded amino-
25
oxy alcohol 2 (3.8 g, 85% yield); ½aꢁD ¼ þ20:7 (c 1, CHCl3)
25
{lit.9e ½aꢁD ¼ þ20:5 (c 1, CHCl3)}. IR (CHCl3) mmax 3375,
3012, 2933, 1955, 1689, 1605, 1596, 1483, 1298, 1217,
1
1070, 756 cmꢀ1. H NMR (CDCl3): d 1.01 (t, J = 6.9 Hz,
EtOAc = 97:3). Colorless liquid, yield = 4 g, 95%;
25
3 H), 1.4–1.79 (m, 2H), 3.81 (m, 2H), 3.98 (m, 1H), 6.93
½aꢁD ¼ þ17:0 (c 1, CHCl3). IR (CHCl3) mmax 3030, 2955,
(m, 3H), 7.25 (m, 2H), 7.4 (br s, 1H). 13C NMR (CDCl3):
2930, 1598, 1496, 1463, 1362, 1255, 1188, 1099, 915, 835,
1
d
10.17, 26.0, 64.43, 85.23, 114.66, 122.2, 128.92,
758, 665 cmꢀ1. H NMR (CDCl3): d ꢀ0.02 (s, 6H), 0.82
148.51 ppm. Elemental analysis: C10H25NO required C,
(s, 9H), 0.79 (t, J = 7.45 Hz, 3H), 1.63 (m, 2H), 2.42 (s,
3H), 3.61–3.65 (m, 2H), 4.38 (m, 1H), 7.29 (d,
J = 8.34 Hz, 2H), 7.77 (d, J = 8.35 Hz, 2H). 13C NMR
(CDCl3): d ꢀ5.62, 9.02, 18.14, 24.03, 25.69, 63.52, 73.12,
84.34, 127.70, 129.58, 134.42, 144.34. Elemental analysis:
C17H30O4SSi required C, 56.94; H, 8.43; S, 8.94. Found
C, 56.82; H, 8.38; S, 8.75.
66.27; H, 8.34; N, 7.73. Found C, 66.15; H, 8.26; N, 7.80.
4.3. (R)-2-N-Phenylaminooxy(tert-butyl)dimethylsilane 3
To a solution of alcohol 2 (3.0 g, 16.5 mmol) dissolved in
dry CH2Cl2 (30 mL) was added imidazole (1.34 g,
19.8 mmol, 1.2 equiv) at 0 ꢁC. After stirring for 10 min,
TBDMSCl (2.73 g, 18.2 mmol, 1.2 equiv) was added and
the reaction mixture was stirred at 25 ꢁC for 3 h. After
completion of the reaction as monitored by TLC, the reac-
tion mixture was poured into water and extracted with
CH2Cl2 (3 · 30 mL). The combined organic phases were
washed with brine, dried (Na2SO4) and concentrated under
reduced pressure. The crude product was then purified by
column chromatography with silica gel (pet. ether–
4.6. ((S)-2-Azidobutoxy)(tert-butyl)dimethylsilane 6
To a solution of 5 (4.0 g, 11.1 mmol) in DMF (40 mL) was
added sodium azide (5.0 g, excess), and the reaction mix-
ture was allowed to stir at 60 ꢁC for 30 h. After completion
of the reaction (monitored by TLC), the reaction mixture
was poured into 50 mL water and extracted with diethyl
ether (3 · 50 mL) to give the crude product, which was
EtOAc = 98:2). Colorless liquid, yield = 4.4 g, 90%;
purified, by column chromatography (pet. ether) as a color-
25
25
½aꢁD ¼ þ42:35 (c 1, CHCl3). IR (neat) mmax 3412, 2929,
less liquid, yield = 1.91 g, 75%; ½aꢁD ¼ þ21:9 (c 1, CHCl3).
2856, 2360, 1718, 1600, 1471, 1255, 1097, 910, 775 cmꢀ1
.
1H NMR (CDCl3): d 0.07 (s, 6H), 0.89 (s, 9H), 0.96 (t,
J = 7.45 Hz, 3H), 1.45 (m, 2H), 3.24 (m, 1H), 3.63–3.69
(m, 2H). 13C NMR (CDCl3): d ꢀ5.59, 10.56, 18.19,
23.47, 25.75, 65.30, 65.98. Elemental analysis: C10H23N3O-
Si required C, 52.36; H, 10.11; N, 18.32. Found C, 56.25;
H, 10.10; N, 18.48.
1H NMR (CDCl3): d 0.09 (s, 6H), 0.94 (s, 9H), 1.01 (t,
J = 7.45 Hz, 3H), 1.61 (m, 2H), 3.77 (m, 2H), 3.78 (m,
1H), 6.97 (m, 2H), 7.24 (m, 2H), 7.25 (br s, 1H). 13C
NMR (CDCl3): d ꢀ5.42, 10.17, 18.30, 23.01, 25.87, 64.46,
85.25, 114.30, 121.55, 128.80, 149.09. Elemental analysis:
C16H29NO2Si required C, 65.03; H, 9.89; N, 4.74. Found
C, 65.1; H, 9.85; N, 4.78.
4.7. ((S)-2-Aminobutoxy)(tert-butyl)dimethylsilane 7
4.4. ((R)-2-Hydroxy)(tert-butyl)dimethylsilane 4
To the solution of azide 6 (1.9 g, 8.2 mmol) in MeOH
(15 mL) was added 10% Pd/C (100 mg) carefully followed
by addition of 5–6 drops of Et3N. The reaction mixture
was then stirred in a hydrogen atmosphere (1 atm of H2)
To a solution of 3 (4.0 g, 13.5 mmol) in MeOH was added
10% Pd/C (200 mg) carefully followed by addition of 5–6

S. P. Kotkar, A. Sudalai / Tetrahedron: Asymmetry 17 (2006) 1738–1742
1741
for 6 h. After completion of the reaction (monitored by
TLC), the reaction mixture was filtered through a Celite
pad, concentrated to near dryness to get amine 7 which
was purified by column chromatography with neutral
completion of the reaction, the solvent was removed under
reduced pressure and the crude product was then purified
by column chromatography on neutral Al2O3 (pet. ether–
EtOAc = 70:30) as colorless liquid (yield = 1.87 g, 85%)
25
Al2O3 (pet. ether–EtOAc = 70:30). Yield = 1.6 g, 95%.
½aꢁD ¼ þ9:5 (c 1, CHCl3).
25
½aꢁD ¼ þ9:7 (c 1, CHCl3). IR (neat) mmax 3355, 2952,
4.11. (S,S)-N1,N2-Bis(1-tert-butyldimethylsilyloxybutan-3-
yl)oxamide 10
2927, 2856, 1739, 1589, 1471, 1253, 1103, 837, 775,
1
667 cmꢀ1. H NMR (CDCl3): d 0.03 (s, 6H), 0.87 (s, 9H),
0.91 (t, J = 7.33 Hz, 3H), 1.34 (m, 2H), 1.78 (br s, 2H),
2.70 (m, 1H), 3.27–3.59 (m, 2H). 13C NMR (CDCl3): d
ꢀ5.48, ꢀ3.56, 10.46, 18.23, 25.84, 54.33. Elemental analy-
sis: C10H25NOSi required C, 59.05; H, 12.39; N, 6.89.
Found C, 59.2; H, 12.44; N, 6.88.
To a solution of amine 7 (1.21 g, 6 mmol) in dry CH2Cl2
(10 mL), pyridine (1.04 g, 13.2 mmol) was added and the
reaction mixture was cooled to 0 ꢁC, followed by dropwise
addition of oxalyl chloride (378 mg, 3 mmol, 0.5 equiv dis-
solved in CH2Cl2). On stirring the reaction mixture at
25 ꢁC overnight, it was quenched with water (10 mL) and
was extracted with EtOAc (20 mL · 3). The crude product
was purified by column chromatography over silica gel
4.8. (S)-2-(1,2-Dibenzyloxycarbonylhydrazinyl)-1-butanol 8
A mixture of dibenzyl azodicarboxylate (90%, 8.25 g,
25 mmol, 1 equiv) and D-proline (287 mg, 2.49 mmol,
10 mol %) in CH3CN (200 mL) was taken and cooled to
0 ꢁC, n-butyraldehyde (2.7 g, 37.5 mmol, 1.5 equiv) was
added to it and the reaction mixture was allowed to stir
at the same temperature for 2 h and then warmed to
20 ꢁC within 1 h. After the reaction mixture became color-
less it was cooled to 0 ꢁC, treated with EtOH (150 mL) and
NaBH4 (1.2 g), and was stirred for 5 min at 0 ꢁC. The reac-
tion mixture was worked up by adding half-concentrated
aq ammonium chloride solution and extracted with ethyl
acetate (100 mL · 3). The combined organic layers were
dried (Na2SO4), filtered, and concentrated under reduced
pressure. The crude product was purified by silica gel col-
umn chromatography (pet. ether–ethyl acetate = 85:15),
(pet. ether) as a white solid, mp 86 ꢁC; yield = 2.6 g, quan-
25
titative; ½aꢁD ¼ ꢀ60:3 (c 1, CHCl3) for a-aminooxylation and
25
½aꢁD ¼ ꢀ59:8 (c 1, CHCl3) for a-amination approach.
IR (CHCl3) mmax 3629, 3547, 2985, 2086, 1888, 1739,
1507, 1458, 1374, 1241, 1047, 917, 846, 607 cmꢀ1 1H
.
NMR (CDCl3): d 0.03 (s, 12H), 0.88 (s, 18H), 0.90 (t,
J = 7.3 Hz, 6H), 1.57 (m, 2H), 3.61 (m, 1H), 3.63 (br s,
2H). 13C NMR (CDCl3): d ꢀ5.60, 10.40, 18.17, 24.11,
25.78, 52.70, 63.73, 159.47. Elemental analysis:
C22H48N2O4Si2 required C, 57.34; H, 10.50; N, 6.08.
Found C, 57.48; H, 10.66; N, 6.24.
4.12. (S,S)-Ethambutol 1
which furnished a white solid, mp = 65 ꢁC, yield = 8.6 g,
25
To a solution of lithium aluminum hydride (1.2 g,
30 mmol) in dry THF at 0 ꢁC was added amide 10 (in
THF) (2.5 g, 5.4 mmol) carefully. The mixture was
refluxed for 24 h. After completion (TLC), the reaction
mixture was quenched by 10% NaOH (2 mL) and water
(2 mL). The precipitate formed was filtered off and washed
with EtOAc (3 · 10 mL). The combined organic layers
were concentrated under reduced pressure, dried
(Na2SO4), and recrystallized (ethyl acetate/hexane) to fur-
92%; ½aꢁD ¼ þ14:3 (c 1, CHCl3). IR (Nujol) mmax: 3550,
3261, 2954, 2875, 1720, 1681, 1537, 1456, 1377, 1263,
1
1062 cmꢀ1. H NMR (CDCl3): d 0.81 (m, 3H), 1.36 (m,
2H), 3.46 (m, 2H), 4.5 (br s, 1H), 5.15 (m, 4H), 6.53 (s,
1H), 7.35 (m, 10H). 13C NMR (CDCl3): d 10.36, 20.82,
61.74, 61.78, 68.02, 68.08, 128.08, 135.06, 157.28. Elemen-
tal analysis: C20H24N2O5 required C, 64.50; H, 6.50; N,
7.52. Found C, 64.52; H, 6.45; N, 7.44.
nish ethambutol as a white solid (mp = 88 ꢁC, lit.12 mp
4.9. (S)-2-Aminobutan-1-ol 9
25
87.5–88.8 ꢁC). Yield = 0.87 g, 80%; ½aꢁD ¼ þ13:6 (c 2,
25
H2O) (99% ee) for a-aminooxylation and ½aꢁD ¼ þ13:4
Alcohol 8 (6.0 g, 16 mmol) was dissolved in MeOH
(40 mL), AcOH (10 drops) and treated with Raney nickel
(10.0 g, excess) for 24 h under 12 bar of hydrogen.
The reaction mixture was filtered over Celite and concen-
(c 2, H2O) (97% ee) for a-amination approach {lit.13
25
½aꢁD ¼ þ13:7 (c 2, H2O)}. IR (CHCl3) mmax: 3465, 2984,
1567, 1447, 1374, 1242, 1047, 758 cmꢀ1
.
1H NMR
(CDCl3): d 0.92 (t, J = 7.55 Hz, 6 H), 1.42 (m, 4H), 2.55
(m, 2H), 2.71 (m, 2H), 2.84 (m, 2H), 2.99 (br s, 2H),
3.34 (dd, J = 7.23, 10.88, 2H), 3.59 (dd, J = 3.74, 10.97,
2H). 13C NMR (CDCl3): d 10.33, 23.96, 46.52, 60.42,
62.99. Elemental analysis: C10H24N2O2 required C,
58.79; H, 11.84; N, 13.71. Found C, 58.85; H, 11.74; N,
13.55.
trated to give the corresponding aminoalcohol 9 as a color-
25
less liquid (1.0 g, 70%); ½aꢁD ¼ þ12:3 (c 2, EtOH), {lit.4b
25
½aꢁD ¼ þ12:5 (c 2, EtOH)}. IR (CHCl3) mmax 3450, 3560,
1
2960, 1650, 1420, 1060 cmꢀ1. H NMR (CDCl3): d 0.95
(t, J = 7.58 Hz, 3H), 1.44 (m, 2H), 3.40 (m, 1H), 3.57 (m,
1H), 4.07 (br s, 2H). 13C NMR (CDCl3): d 9.92, 25.87,
66.11, 73.60; MS (m/z, % RI) 89 (M+), 71, 60, 58, 56, 41.
4.10. ((S)-2-Aminobutoxy)(tert-butyl)dimethylsilane 7
Acknowledgements
To a solution of amino alcohol 5 (1.0 g, 11.2 mmol) dis-
solved in dry CH2Cl2 (50 mL) kept at 0 ꢁC was added imid-
azole (0.916 g, 13.4 mmol, 1.2 equiv) after stirring for
10 min, TBSCl (1.8 g, 12.3 mmol, 1.1 equiv) was added
and the reaction mixture was stirred at 25 ꢁC for 3 h. After
S.P.K. thanks CSIR, New Delhi, for the award of
research fellowships. The authors are thankful to Dr. B.
D. Kulkarni, Head, CEPD, for his support and
encouragement.

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S. P. Kotkar, A. Sudalai / Tetrahedron: Asymmetry 17 (2006) 1738–1742
Sudalai, A. Tetrahedron: Asymmetry 2004, 15, 3111; (f)
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