Syntheses of 1,2-amino alcohols and their applications for oxazaborolidine catalyzed enantioselective reduction of aromatic ketones

Article abstract of DOI:10.1071/CH06412

Six new chiral 1,2-amino alcohol derivatives have been synthesized starting from (1R,2R)-2-amino-1-phenylpropane-1,3-diol. Asymmetric reduction of aryl ketones with in-situ generated oxazaborolidine from these amino alcohol derivatives and BH₃?

Full text of DOI:10.1071/CH06412

Full Paper
CSIRO PUBLISHING
Aust. J. Chem. 2007, 60, 196–204
www.publish.csiro.au/journals/ajc
Syntheses of 1,2-Amino Alcohols and Their Applications
for Oxazaborolidine Catalyzed Enantioselective Reduction
of Aromatic Ketones
Namdev S. Vatmurge,A Braja G. Hazra,A,B and Vandana S. PoreA
AOrganic Chemistry Synthesis Division, National Chemical Laboratory, Pune 411008, India.
BCorresponding author. Email: bg.hazra@ncl.res.in
Six new chiral 1,2-amino alcohol derivatives have been synthesized starting from (1R,2R)-2-amino-1-phenylpropane-
1,3-diol. Asymmetric reduction of aryl ketones with in-situ generated oxazaborolidine from these amino alcohol
derivatives and BH3·Me2S afforded secondary alcohols with good yield and moderate to high enantiomeric excess.
Manuscript received: 1 November 2006.
Final version: 13 February 2007.
Introduction
similar types of chiral catalysts in which the primary alcohol at
C3 is protected as its O-tert-butyldiphenylsilyl (TBDPS) ether
2, or its O-tert-butyldimethylsilyl (TBDMS) ether 3, and to use
these bulky ethers for the enantioselective reduction of prochi-
ral ketones (Fig. 1). Again, for good optical yield, a tertiary
hydroxy[1–3] functionality is essential and we resorted to syn-
thesize C1 tertiary alcohols 4 and 5 and utilize these optically
active amino alcohols for the asymmetric reduction of ketones.
Sibi et al. used[11] borane and 10 mol% of an oxazaborolidine,
derived from cis-2-aminoindanol ligand. The primary amino
group of the parent amino indanol was modified to a secondary
amino group with 2-pyridylmethyl, 2-pyridylcarbonyl, and
2-pyridylsulfonylmoieties.Thesebifunctionalligandshavebeen
evaluated in the reduction of prochiral ketones with high chemi-
cal efficiency and fair to high enantioselectivity. Again, Martens
and coworkers[8] have developed acyclic and cyclic secondary
amino alcohols for the enantiocontrolled catalytic reduction of
alkyl aryl ketones in good ee.The work of Sibi et al.,[11] Martens
and coworkers,[8] and others[1] led us to transform the C2 pri-
mary amine to its secondary amino compound 6 and to observe
the enantioselectivity for the reduction of ketones.
It would also be highly interesting and thought provoking to
build the oxazaborolidine with the primary alcohol at C3 and
the amino group at C2. For this the secondary C1 hydroxy group
was protected as itsTBDMS ether to afford compound 7 and this
amino alcohol was applied for the asymmetric borane reduction
of alkyl aryl ketones. Oxazaborolidine generated from this type
of acyclic amino diol in which the secondary alcohol is protected
has not been previously reported. We report here the syntheses
of six new chiral amino alcohols 2–7, their use for the enantios-
elective reduction of aryl ketones, and the optical yields of the
derived secondary alcohols.
The design of an asymmetric transformation reaction is a great
challenge in organic chemistry, in particular, the development of
enantioselective homogeneous catalysts in which a small amount
of an optically active ligand can induce asymmetry for a given
reaction. Enantioselective oxazaborolidine-catalyzed borane
reduction of prochiral ketones to chiral secondary alcohols pro-
vides convenient access to a wide variety of optically active
secondary alcohols, which are valuable chiral building blocks for
the synthesis of natural products and bioactive compounds.[1–3]
Oxazaborolidines prepared from chiral amino alcohols[4] give
excellent enantiomeric excess (ee) values and often have wide
substrate scope. Itsuno and coworkers[5] have carried out pio-
neering work on the asymmetric reduction of alkyl aryl ketones
with the reagent prepared from (S)-(−)-2-amino-3-methyl-1,1-
diphenylbutan-1-ol and borane. The secondary alcohols were
obtained in 94–100% ee and in 100% chemical yields. The
catalytic behaviour of the more sterically hindered oxazaboro-
lidine based on (S)-(−)-2-diphenylhydroxymethylpyrrolidine
was introduced[6] in the borane reduction of ketones by Corey
et al. Optically active amino alcohols[7,8] have been documented
recently as catalysts for the enantioselective reduction of vari-
ous ketones. In 1987 Mandal et al.[9] carried out the asymmetric
reduction of alkyl aryl ketones with borane–methyl sulfide and
the reagent prepared from (1S,2S)-(+)-2-amino-3-methoxy-1-
phenylpropan-1-ol, which is the antipode of 1 with the primary
alcohol at C3 protected as its methyl ether.They obtained the cor-
responding secondary alcohols in 30–60% ee. Mandal’s work
prompted our inquisitiveness to protect the primary alcohol
at C3 with a bulkier group and to determine the ee of the
derived secondary alcohols. Very recently, Chen et al.[10] have
carried out enantioselective reduction of a meso-cyclic imide
to its cyclic n-acyl aminol in excellent ee. This is mediated
by a chiral oxazaborolidine catalyst derived from (1S,2S)-(+)-
threo-2-amino-1-(4-nitrophenyl)propane-1,3-diol. The catalyst
has the primary alcohol at C3, which is protected as its
O-triphenylmethyl ether, and there is a p-nitrophenyl moiety
at C1. Chen’s observation gave us the impetus to synthesize
Results and Discussion
Commercially available[12] and inexpensive chiral amino alco-
hol (1R,2R)-2-amino-1-phenylpropane-1,3-diol 1, a precursor
for the preparation of chloramphenicol, has been used by us for
the synthesis of all six new chiral auxiliaries.The amino alcohols
© CSIRO 2007
10.1071/CH06412
0004-9425/07/030196

Enantioselective Reduction of Aromatic Ketones
197
OH
2
OH
OH
3
1
Ph
OH
OTBDMS
OTBDPS
Ph
OTBDPS
OTBDMS
Ph
NH2
NH2
NH2
1
2
3
OH
Ph
Ph
Ph
Ph
HO
OTBDPS
HO
Ph
NH2
NH2
NHCH2Ph
4
5
6
OTBDMS
OH
Ph
NH2
7
Fig. 1. Amino alcohols 2–7 synthesized from 1.
OH
OH
OH
OH
(a)
(b)
(c)
OR
OR
Ph
Ph
OH
Ph
Ph
OH
NHCbz
NHCbz
NH2
NH2
1
8
9 R ϭ TBDPS
10 R ϭ TBDMS
2 R ϭ TBDPS
3 R ϭ TBDMS
O
Ph
Ph
Ph
Ph
(d)
(e)
(f)
9 or 10
OR
HO
HO
OR
Ph
OR
NHCbz
NHCbz
NH2
11 R ϭ TBDPS
12 R ϭ TBDMS
13 R ϭ TBDPS
14 R ϭ TBDMS
4 R ϭ TBDPS
5 R ϭ TBDMS
Scheme 1. Reagents and conditions: (a) PhCH2OCOCl, Na2CO3, water–dioxan, 30◦C, 2 h, 99%; (b) compound
9: TBDPSCl, imidazole, DMF, 30◦C, 10 min, 92%; compound 10: TBDMSCl, imidazole, DMF, 25◦C, 0.5 h, 90%;
(c) H2/Pd–C, MeOH, 30◦C, 10 h, 75 psi, 98% for 2 and 99% for 3; (d) IBX, EtOAc, reflux, 5 h, 98% for 11 and
97% for 12; (e) bromobenzene, Mg, THF, 25◦C, 1 h, 84% for 13 and 87% for 14; (f) H2/Pd–C, MeOH, 30◦C, 10 h,
75 psi, 99% for 4 and 5.
2 and 3 were prepared from (1R,2R)-2-amino-1-phenylpropane-
1,3-diol 1 (Scheme 1). The amino group in compound 1 was
protected as its carbamate 8 and primary alcohol at C3 was then
converted into a TBDPS ether 9 or TBDMS ether 10. Deprotec-
tion of the carbamate by hydrogenation gave the required amino
alcohol derivatives 2 and 3 in excellent yield. Compounds 4
and 5 with tert-alcohol functionality were synthesized from the
primary amino and primary hydroxy protected alcohols 9 and
10. The secondary hydroxy group in compounds 9 and 10 were
subjected to oxidation with o-iodoxybenzoic acid (IBX)[13] in
ethyl acetate to afford ketones 11 and 12. The tertiary alcohols
13 and 14 were obtained on exposure of ketones 11 and 12 to
an excess of Grignard reagent prepared from bromobenzene in
tetrahydrofuran (THF). Lastly, deprotection of the carbamate by
hydrogenation gave the required amino alcohols 4 and 5. Both
compounds 4 and 5 were synthesized from 1 in five steps with
an overall yield of 74%.
sodium borohydride to give N-benzylated compound 15 with
an overall yield of 76% in two steps. The primary hydroxy
group in compound 15 was selectively converted into its
tert-butyldiphenylsilyl ether 6 in good yield.
Protection of the secondary hydroxy group at C1 in com-
pound 7 was carried out successfully as shown in Scheme 2.
Initially, both the primary and secondary hydroxy groups in
compound 8 were protected with TBDMSCl (2.4 mol) and imi-
dazole in N,N-dimethylformamide (DMF) to furnish compound
16. Selective deprotection of the primary O-TBDMS group with
camphorsulfonic acid (CSA)[14] in methanol afforded alcohol
17. Deprotection of the carbamate group by catalytic hydro-
genation gave amino alcohol 7 in four steps with an overall yield
of 92%.
It is well known[1–3] that the temperature and amount of
catalyst have important effects on the enantioselectivity of the
reduction. The application of catalysts 2–7 to the reduction of
acetophenone was investigated with respect to temperature and
catalyst concentration; the results are summarized in Tables 1
and 2.[15]
The secondary amino alcohol 6 has been synthesized
from amino diol 1 (Scheme 2). Compound 1 was converted
into an imine with benzaldehyde, which was reduced with

198
N. S. Vatmurge, B. G. Hazra, and V. S. Pore
OH
OH
(a)
(b)
OH
NHCH2Ph
1
8
Ph
OTBDPS
NHCH2Ph
6
Ph
15
OR
OR
OR
(c)
(d)
(e)
Ph
Ph
Ph
OH
OR
OH
NH2
NHCbz
NHCbz
7
17
16
R ϭ TBDMS
Scheme 2. Reagents and conditions: (a) (i) PhCHO, anhydrous MgSO4, CH2Cl2/MeOH
(3:1), reflux, 2 h; (ii) NaBH4, MeOH, 0–25◦C, 3 h, 76% in two steps; (b)TBDPSCl, imidazole,
DMF, 25◦C, 0.5 h, 83%; (c) TBDMSCl, imidazole, DMF, 30◦C, 13 h, 99%; (d) CSA, MeOH,
10 min, 20◦C, 96%; (e) H2/Pd–C, MeOH, 30◦C, 10 h, 75 psi, 98%.
Table 1. Effect of temperature on the enantioselectivity of reduction
Table 2. Effect of catalyst concentration on the enantioselectivity of
reduction
OH
O
OH
O
*
BH3·Me2S ϩ 10 mol% 2Ϫ7
BH3·Me2S ϩ catalyst
THF, 50°C
*
THF or toluene
Entry Catalyst Temp.
[◦C]
Time
eeC
Isolated
Configuration
Entry
Catalyst
Catalyst
[mol%]
eeA [%]
Isolated
yield [%]
Configuration
[min] [%] yield [%]
1
2
3
4
5
6
7
8
2
2
2
2
2
2
2
2
3
3
3
3
4
4
4
4
4
4
4
4
5
5
5
5
6
6
6
6
7
7
7
0
25
50
65B
30
5
11
46
81
79
8
14
11
9
78
88
89
89
88
89
88
85
83
90
89
90
81
90
89
87
89
89
88
86
84
89
90
89
81
87
86
87
85
92
91
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
R
R
R
1
2
3
4
5
6
7
8
2
2
2
2
2
4
4
4
4
4
7
7
7
7
7
2
5
7.5
10
20
2
67
75
79
81
81
45
72
80
88
88
48
58
61
63
63
88
90
90
89
88
90
92
91
89
88
91
89
90
92
90
S
S
S
S
S
S
S
S
S
S
R
R
R
R
R
65
4
25A
50A
75A
100A
0
55
10
5
5
3
7.5
10
20
2
9
67B
30
5
7
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
25
50
65
0
25
50
65
25A
50A
75A
100A
0
25
50
65
0
49
62
60
63
80
88
87
40
67
60
51
30
80
88
86
4
10
11
12
13
14
15
4
5
15B
35
5
7.5
10
20
4
50
10
5
ADetermined by comparison with standard specific rotation value.
2
For the study of temperature effect, the catalyst concentra-
tion was fixed (10 mol%) for all reactions. As shown in Table 1,
catalyst 2 at 50◦C in THF (entry 3) resulted in 81% ee. Neither
higher (65◦C, reflux temperature of THF), nor lower tempera-
ture (25 or 0◦C) was beneficial to the catalytic activities. The
reduction using catalyst 3 at 50◦C lead to low ee (62%, Table 1,
entry 11) as compared to catalyst 2 and this may be as a result of
the decrease in the bulk of the primary alcohol protecting group.
The best results (88% ee) were obtained for the reduction of ace-
tophenone with catalyst 4 and 5 at 50◦C (Table 1, entries 15 and
23). We have also used toluene as solvent for the enantioselective
reduction of acetophenone with catalysts 2 and 4 (Table 1, entries
5–8 and 17–20). The ee obtained for the secondary alcohol at
temperatures of 25, 50, 75, and 100◦C in toluene is less in com-
parison to THF. This may be caused by the polarity difference
28B
30
5
4
25B
30
5
25
50
65
0
25
50
7
7
2
42
63
53
4
17B
30
5
AToluene used as solvent.
BTime in hours.
CDetermined by comparison with standard specific rotation for (S)-
1-phenylethanol, [α]2D0 −45.50 (c 2.0 in MeOH).[15]

Enantioselective Reduction of Aromatic Ketones
199
Table 3. Asymmetric reduction of prochiral ketones catalyzed by 2–7
O
OH
BH3·Me2S ϩ 10 mol% catalyst
THF, 50°C (25°C for 7),
5 min
*
R1
R2
R1
R2
Entry
Ketone
Catalyst
eeA [%]
Isolated
Configuration
yield [%]
1
2
3
4
5
6
7
8
PhCOMe
PhCOMe
PhCOMe
PhCOMe
PhCOMe
PhCOMe
4-MePhCOMe
4-MePhCOMe
4-MePhCOMe
4-MePhCOMe
4-MePhCOMe
4-MePhCOMe
PhCOEt
2
3
4
5
6
7
2
3
4
5
6
7
2
3
4
5
6
7
2
3
4
5
6
7
2
3
4
5
6
7
2
3
4
5
6
7
81
62
88
88
7
63
72
63
75
83
2
62
71
69
86
88
4
69
71
51
59
87
5
57
46
54
43
46
2
57
36
70
92
94
1
88
89
89
90
86
92
91
87
90
92
89
92
89
91
91
89
90
92
88
90
90
91
89
90
87
90
86
86
89
88
90
93
93
92
91
92
S
S
S
S
S
R
S
S
S
S
S
R
S
S
S
S
S
R
S
S
S
S
S
R
R
R
R
R
R
S
S
S
S
S
S
R
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
PhCOEt
PhCOEt
PhCOEt
PhCOEt
PhCOEt
1,2,3,4-Tetrahydronaphthalen-1-one
1,2,3,4-Tetrahydronaphthalen-1-one
1,2,3,4-Tetrahydronaphthalen-1-one
1,2,3,4-Tetrahydronaphthalen-1-one
1,2,3,4-Tetrahydronaphthalen-1-one
1,2,3,4-Tetrahydronaphthalen-1-one
PhCOPri
PhCOPri
PhCOPri
PhCOPri
PhCOPri
PhCOPri
2-Acetylnaphthalene
2-Acetylnaphthalene
2-Acetylnaphthalene
2-Acetylnaphthalene
2-Acetylnaphthalene
2-Acetylnaphthalene
74
ADetermined by comparison with standard specific rotations, for (S)-1-(4-methylphenyl)ethanol [α]D25 −57.3
(c 0.190 in CHCl3),[16] for (S)-1-phenylpropanol [α]D25 −45.45 (c 5.15 in CHCl3),[17] for (S)-1,2,3,4-
tetrahydronaphth-1-ol [α]2D5 +32.65 (c 2.5 in CHCl3),[18] for (R)-2-methyl-1-phenylpropanol [α]2D5 +47.7 (c 6.8
in diethyl ether),[19] and for (R)-1-(naphthalen-2-yl)ethan-1-ol [α]D25 +55.8 (c 4.8 in CHCl3).[20]
between THF and toluene.∗ It should be noted that negligible
asymmetric induction was observed with catalyst 6. This may be
a result of the steric repulsion of the N-benzyl of the oxazaboroli-
dine, which prevents approach of the ketone towards borane and
favours direct reduction by BH3 (good isolated yield). In the
case of catalyst 7, maximum enantioselectivity (63% ee) was
obtained at 25◦C.
Having studied the optimum temperature, attention was
turned towards the optimum concentration of the catalyst.All the
reactions were carried out at the optimized temperature of 50◦C
(25◦C for catalyst 7) to study the effect of catalyst concentration
on enantioselectivity.As shown inTable 2, increasing the amount
of catalyst from 2 to 10 mol% improves the enantioselectivity
of the reactions. However, no obvious change in enantioselec-
tivity was observed on increasing the catalyst concentration to
20 mol%. Therefore, the best experimental conditions found for
the asymmetric reduction of acetophenone required the use of
10 mol% of catalyst at 50◦C (25◦C in case of catalyst 7). It is
worth mentioning here that with loadings of 7.5 and 10% of
catalysts 2 and 7, there is no significant change of optical and
chemical yields (1–2% change), hence a lower catalyst loading
of 7.5 mol% can also be used.
Thereductionofavarietyofprochiralketoneswasthenexam-
ined using the catalysts derived from chiral amino alcohols 2–7
under optimized temperature and catalyst concentration. The
results are summarized in Table 3.
∗ THF and toluene are expected to give different enantiomeric excesses under a similar range of temperatures. This is because of the very different polarity
between THF and toluene. We thank a referee for this point.

200
N. S. Vatmurge, B. G. Hazra, and V. S. Pore
OTBDMS
TBDMSO
Ph
O
Ph
Ph
H
Ph
Excess
BH3·Me2S
Ph
H
H
HO
Ar
ϩ
N
O
Ar
R
H
H2
B
HO
OTBDMS
[ A ]
N
H
B
R
B
O
R
Ϫ
Ph
NH2
(S)
BH3
H
O
5
Ar
TBDMSO
Ph
TBDMSO
Ph
H
H
H
N
H
N
H2
H2
H
B
B
R
B
O
B
Ar
R
O
H
Ph
Ph
O
O
A
Ar
A؅
Favoured
Less favoured
OTBDMS
OTBDMS
O
H
OTBDMS
H
O
H
Excess
BH3·Me2S
Ϫ
H
O
Ph
HO
Ar
R
Ph
Ar
R
B
H
OH
Ph
N
[ B ]
O
ϩ
N
B
BH2
R
NH2
H
Ar
H
(R)
BH3
7
OTBDMS
OTBDMS
H
H
H
H
H
H
O
O
R
Ar
R
Ph
Ph
B
N
B
N
O
O
H2B
H2B
Ar
H
H
B؅
B
Less favoured
Favoured
Fig. 2. Proposed models for oxazaborolidine reduction.
The level of asymmetric induction was found to be influ-
enced by the nature of the substrate and catalyst. As seen from
Table 3, asymmetric reduction of aromatic ketones with chiral
amino alcohols gave fair to excellent ee (36–94%), except for
amino alcohol 6. Amino alcohol 6 gave very poor ee in all cases.
As expected, reduction with the bulky primary hydroxy protected
ether at C3 and 2-amino-1-diphenyl alcohols 4 and 5 proceeds
with very good to excellent optical yields (86–94%; Table 3,
entries 3, 4, 15, 16, 22, 33, 34). Reduction of ketones with the
oxazaborolidine formed with the C1 hydroxy-protected amino
diol 7 yielded the secondary alcohols in moderate ee (57–74%)
with an opposite configuration with respect to all other catalysts.
Steric bulk around the prochiral carbonyl group plays an
important role in the enantiomeric discrimination, as revealed by
the low ee observed in the reduction of isopropylphenyl ketone
with all six catalysts (Table 3, entries 25–30).
From the proposed model (Fig. 2) the configuration of the
obtained chiral alcohol can be deduced. However, catalyst 7
and isopropylphenyl ketone gave the (S)-configuration, and all
other catalysts 2–6 with isopropyl phenyl ketone gave the (R)-
configuration. These results are of some concern to us. This may
be caused by the isopropyl group in isopropylphenyl ketone
predominating over the phenyl, which changes the favoured
transition state to the less favoured transition state.
have been fully characterized and used for the enantioselec-
tive reduction of aromatic ketones. The secondary alcohols were
obtained in fair to excellent enantiomeric excesses (up to 94%)
for the reduction of all the aromatic ketones studied. The tert-
alcohol at C1 with a bulky O-protected group at C3 (4 and 5)
gave uniformly encouraging results in all cases. Moderate ee
was observed with the C3 primary alcohol 7. As the reactions
are rapid and high yielding, these chiral amino alcohols may be
used as an alternative to the existing amino alcohols.
Experimental
General
Commercially available reagents were used without further
purification. Air- and moisture-sensitive liquids and solutions
were transferred by syringe or stainless steel cannula. Organic
solutions were concentrated by rotary evaporation below 45◦C
at ∼20 mmHg. All non-aqueous reactions were carried out
under anhydrous conditions using flame-dried glassware under
an argon atmosphere in dry, freshly distilled solvents, unless
otherwise noted. All melting points were determined on aYanco
Micro melting point apparatus. Optical rotations were obtained
on a Bellingham and Stanly ADP-220 polarimeter. Reactions
were monitored by thin-layer chromatography (TLC) using silica
gel 60-F254 precoated TLC aluminium sheets, Merck, Germany,
and the spots were located using UV light as the visualiz-
ing agent or by spraying with ethanolic phosphomolybdic acid
Conclusions
1
Six new chiral amino alcohols 2–7 have been synthesized from
readily available (1R,2R)-2-amino-1-phenylpropane-1,3-diol 1
in excellent yields. The structures of these amino alcohols 2–7
(PMA) or ninhydrin solution followed by heating. H and 13C
NMR spectra were recorded on a Bruker AC-200 (200 MHz)
at 200.13 and 50.32 MHz, or on a Bruker MSL-300 at 300.13

Enantioselective Reduction of Aromatic Ketones
201
and 75.47 MHz, or on a Bruker DRX-500 spectrophotometer at
500.13 and 125.78 MHz, respectively. Chemical shifts are given
in δ values relative to tetramethylsilane as internal standard, and
J values are given in Hz. IR spectra were recorded on a Schi-
madzu 8400 series FTIR instrument and values are reported
in cm−1. Mass spectra were recorded by a LC-TOF-MS (API
QSTAR PULSAR) spectrometer, with samples introduced by the
infusion method using the electrospray ionization technique and
matrix-assisted laser desorption–ionization time-of-flight mass
spectrometry (MALDI-TOF-MS, Voyager DE STR Biospec-
trometry). Elemental analyses were performed with a CHNS-O
EA 1108-Elemental analyzer, Carloerba Instrument (Italy) or
Elementor Vario EL (Germany).
(1R,2R)-(−)-2-Amino-(N-benzyloxycarbonyl)-3-O-
(tert-butyldimethylsilyl)-1-phenylpropane-1,3-diol 10
Compound
8 (1.505 g, 5 mmol) and imidazole (0.85 g,
12.5 mmol) were dissolved in dry DMF (3.5 mL). To this solu-
tion tert-butyldimethylsilyl chloride (0.9 g, 6 mmol) was added
and the reaction mixture was stirred at 25◦C for 0.5 h. Ice
pieces were added and the reaction mixture was extracted
with diethyl ether (3 × 50 mL). The organic phase was washed
with water and brine, dried over anhydrous sodium sulfate,
and concentrated under reduced pressure. The crude product
was purified by column chromatography over silica gel using
ethyl acetate/petroleum spirits (8:92) as eluent to give com-
pound 10 as a white solid (1.877 g, 90%). mp 60–61◦C (ethyl
acetate/petroleum spirits). [α]D −60.16 (c 0.96 in CHCl3).
Found: C 66.5, H 8.4, N 3.3. C23H33NO4Si requires C 66.5, H
8.0, N 3.4%. δH (500 MHz, CDCl3) 7.37–7.26 (10H, m, ArH),
5.42 (1H, d, J 6.88, NHCbz), 5.05–4.99 (3H, m, PhCHOH,
PhCH2OCO), 4.71 (1H, br s, OH), 3.87 (2H, m, CH2OSi), 3.80
(1H, m, CHNHCbz), 0.92 (9H, s, C(CH3)3), 0.06 (3H, s, SiCH3).
δC (125 MHz, CDCl3) 156.58, 141.12, 136.51, 128.49, 128.35,
128.04, 127.95, 127.66, 126.03, 74.36, 66.76, 64.82, 57.07,
25.86, 18.19, −5.59. νmax (Nujol)/cm−1 3425 (–OH), 1701
(C=O), 1512, 1454, 1251. m/z (LCMS) 416.05 (M + 1).
(1R,2R)-(−)-2-Amino-(N-benzyloxycarbonyl)-
1-phenylpropane-1,3-diol 8
To the solution of 1 (1.002 g, 6 mmol) in water–dioxan (20 mL,
1:1) was added sodium carbonate (0.320 g, 3 mmol). The reac-
tion mixture was stirred for 10 min at 30◦C. To this mixture
benzyl chloroformate (0.95 mL, 6.6 mmol) was added and the
reaction mixture was stirred at 30◦C for 2 h. Dioxan was removed
under reduced pressure, 5 mL of water was added, and the reac-
tion mixture was extracted with ethyl acetate (3 × 50 mL). The
ethyl acetate extract was washed with water and brine, dried over
anhydrous sodium sulfate, and concentrated under reduced pres-
sure to afford compound 8 as a white solid. The crude product
was chromatographed on silica gel (methanol/dichloromethane,
5:95) to give pure product 8 (1.780 g, 99%). mp 105–106◦C
(ethyl acetate/petroleum spirits). [α]D −68.12 (c 0.69 in CHCl3).
Found: C 67.4, H 6.3, N 4.8. C17H19O4N requires C 67.8, H 6.4,
N 4.7%. δH (300 MHz, CDCl3) 7.29 (10H, m, ArH), 5.55 (1H,
d, J 6, NH, exchangeable with D2O), 4.96 (3H, m, PhCH2OCO,
PhCHOH), 3.85 (1H, m, CHNHCbz), 3.72 (2H, m, CH2O).
δC (125 MHz, CDCl3) 156.92, 141.03, 136.27, 128.44, 128.29,
128.02, 127.86, 127.77, 125.98, 73.67, 66.85, 63.49, 57.63. νmax
(Nujol)/cm−1 3429 (–OH), 1667, 1512, 1454, 1377, 1255. m/z
(LCMS) 319.05 (M + H2O), 302.05 (M + 1).
(1R,2R)-(−)-2-Amino-3-O-(tert-butyldiphenylsilyl)-
1-phenylpropane-1,3-diol 2
To a solution of 9 (1.5 g, 12.8 mmol) in methanol (25 mL)
was added Pd–C catalyst (0.150 g, 10%) and hydrogenation
was carried out using a Parr apparatus at 75 psi pressure, at
30◦C for 10 h. The reaction mixture was filtered and the fil-
trate was concentrated under reduced pressure to obtain (1R,2R)-
2-amino-1-phenyl-3-O-tert-butyldiphenylsilylpropane-1,3-diol
2 (1.109 g, 98%) as a gummy material. [α]D −11.23 (c 1.25 in
CHCl3). Found: C 74.3, H 7.9, N 3.2. C25H31NO2Si requires
C 74.0, H 7.7, N 3.5%. δH (200 MHz, CDCl3) 7.61 (5H,
m, ArH), 7.37 (10H, m, PhSiPh), 4.60 (1H, d, J 5.48, OCHPh),
3.61 (2H, m, CH2OSi), 2.92 (1H, m, CHNH2), 1.05 (9H,
s, C(CH3)3). δC (50 MHz, CDCl3) 142.25, 135.41, 132.98,
132.91, 129.64, 128.09, 127.62, 127.21, 126.18, 73.43, 65.49,
58.47, 26.79, 19.11. νmax (CHCl3)/cm−1 3396, 1471, 1427,
1215. m/z (MALDI–TOF) 406.38 (M + 1).
(1R,2R)-(−)-2-Amino-(N-benzyloxycarbonyl)-3-O-(tert-
butyldiphenylsilyl)-1-phenylpropane-1,3-diol 9
Compound 8 (3.01 g, 10 mmol) and imidazole (1.7 g, 25 mmol)
were dissolved in dry DMF (8 mL). To this solution tert-
butyldiphenylsilyl chloride (2.86 mL, 11 mmol) was added and
the reaction mixture was stirred at 30◦C for 10 min. Ice pieces
were added and the reaction mixture was extracted with diethyl
ether (3 × 60 mL). The organic phase was washed with water
and brine, dried over anhydrous sodium sulfate, and concen-
trated under reduced pressure. The crude product was puri-
fied by column chromatography over silica gel using ethyl
acetate/petroleum spirits (12:88) as eluent to obtain compound
9 as a gummy material (4.964 g, 92%). [α]D −32.38 (c 1.05
in CHCl3). Found: C 73.1, H 6.9, N 2.8. C33H37NO4Si requires
C73.4, H6.9, N2.6%. δH (200 MHz, CDCl3)7.58–7.21(20H, m,
ArH), 5.33 (1H, d, J 9.39, CHNHCbz, exchangeable with D2O),
5.02 (1H, m, PhCHOH), 4.93 (2H, s, PhCH2OCO), 3.84 (1H,
m, CHNHCbz), 3.73 (2H, m, CH2OSi), 3.17 (1H, s, OH), 1.02
(9H, s, C(CH3)3). δC (50 MHz, CDCl3) 156.40, 141.03, 136.33,
135.44, 132.54, 129.86, 128.31, 128.20, 127.76, 127.51, 125.96,
66.56, 64.65, 57.33, 26.79, 19.07. νmax (CHCl3)/cm−1 3436
(–OH), 1718 (C=O), 1500, 1404, 1215. m/z (MALDI–TOF)
562.37 (M + Na).
(1R,2R)-(−)-2-Amino-3-O-(tert-butyldimethylsilyl)-
1-phenylpropane-1,3-diol 3
Compound 3 was synthesized following the experimental pro-
cedure described for compound 2 and was obtained as a gummy
material (99% yield). [α]D −20.63 (c 2 in CHCl3). Found: C
64.1, H 9.6, N 5.1. C15H27NO2Si requires C64.0, H 9. 7, N 5.0%.
δH (300 MHz, CDCl3) 7.26–7.17 (5H, m, ArH), 4.66 (1H, d, J
4.40, PhCHOH), 3.64 (1H, dd, J 9.53, 3.66, CH2OSi), 3.57 (1H,
dd, J9.53, 3.66, CH2OSi), 2.96–2.93(1H, m, CHNH2), 2.29(3H,
br s, OH + NH2), 0.91 (9H, s, C(CH3)3), 0.06 (6H, s, SiCH3). δC
(75 MHz, CDCl3) 142.13, 128.15, 127.39, 126.32, 73.55, 64.24,
58.41, 25.73, 18.04, −5.68. νmax (CHCl3)/cm−1 3371 (–OH, –
NH2), 1577, 1492, 1463, 1255, 1215. m/z(MALDI–TOF)282.51
(M + 1).
(2R)-2-Amino-(N-benzyloxycarbonyl)-3-O-(tert-
butyldiphenylsilyl)-1-oxo-1-phenylpropan-3-ol 11
To the solution of carbamate alcohol 9 (10 g, 18.53 mmol) in
ethyl acetate (60 mL) was added o-iodoxybenzoic acid (15.56 g,
55.58 mmol). The reaction mixture was refluxed for 5 h and

202
N. S. Vatmurge, B. G. Hazra, and V. S. Pore
then it was filtered. The filtrate was concentrated under reduced
pressure. The crude material was chromatographed on silica gel
(ethyl acetate/petroleum spirits, 5:95) to obtain pure compound
11 (9.803 g, 98%) as a thick oil. [α]D −42.05 (c 1.28 in CHCl3).
Found: C 73.6, H 6.9, N 2.7. C33H35NO4Si requires C 73.7,
H 6.6, N 2.6%. δH (200 MHz, CDCl3) 7.92 (2H, d, J 8.33, ArH),
7.65–7.15 (18H, m, ArH), 6.05 (1H, d, J 8, NHCbz), 5.45–5.38
(1H, m, CHNHCbz), 5.13 (2H, s, PhCH2OCO), 3.99 (2H, d, J
3.67, CH2OSi), 0.90 (9H, s, –C(CH3)3). δC (100 MHz, CDCl3)
196.12, 155.73, 136.33, 135.35, 134.87, 133.42, 132.53, 132.43,
129.68, 129.55, 128.64, 128.46, 128.40, 127.97, 127.87, 127.64,
127.52, 66.73, 64.87, 57.44, 26.44, 18.99. νmax (CHCl3)/cm−1
3423 (–NH), 1685 (NH–COO), 1718 (PhCO–). m/z (LCMS)
538.73 (M + 1).
(2R)-2-Amino-(N-benzyloxycarbonyl)-3-O-(tert-
butyldimethylsilyl)-1,1-diphenylpropane-1,3-diol 14
Compound 14 was synthesized following the experimental pro-
cedure described for compound 13 to give a thick oil, 87% yield.
[α]D 34.64 (c 2.42 in CHCl3). Found: C 71.1, H 7.2, N 3.0.
C29H37NO4Si requires C 70.8, H 7.6, N 2.9%. δH (200 MHz,
CDCl3) 7.56–7.21 (15H, m, ArH), 5.78 (1H, d, J 8.71, NHCbz),
5.12 (2H, s, PhCH2OCO), 4.78–4.72 (1H, m, CHNHCbz), 3.94
(1H, dd, J 10.61, 2.15, CH2OSi), 3.75 (1H, dd, J 10.61, 2.15,
CH2OSi), 0.90 (9H, s, C(CH3)3), 0.00 (3H, s, SiCH3), −0.07
(3H, s, SiCH3). δC (50 MHz, CDCl3) 156.02, 145.43, 144.28,
136.50, 128.34, 128.30, 128.15, 127.81, 127.51, 126.81, 126.69,
125.11, 124.88, 81.14, 66.44, 64.62, 55.13, 25.63, 17.91, −6.01,
−6.11. νmax (CHCl3)/cm−1 3434 (–OH), 1710 (C=O). m/z
(LCMS) 514.63 (M + Na).
(2R)-2-Amino-(N-benzyloxycarbonyl)-3-O-(tert-
butyldimethylsilyl)-1-oxo-1-phenylpropan-3-ol 12
(2R)-2-Amino-3-O-(tert-butyldiphenylsilyl)-
1,1-diphenylpropane-1,3-diol 4
Compound 12 was synthesized following the experimental pro-
cedure described for compound 11. Colourless oil, 97% yield.
[α]D −36.43 (c 2.64 in CHCl3). Found: C 67.3, H 7.3, N 3.5.
C23H31NO4Si requires C 66.8, H 7.6, N 3.4%. δH (200 MHz,
CDCl3) 7.94 (2H, d, J 6, ArH), 7.57–7.37 (8H, m, ArH), 5.98
(1H, d, J 7.71, NHCbz), 5.44–5.36 (1H, m, CHNHCbz), 5.15
(2H, s, PhCH2OCO), 4.02–3.90 (2H, m, CH2OSi), 0.75 (9H,
s, –C(CH3)3), −0.13 (3H, s, SiCH3), −0.17 (3H, s, SiCH3).
δC (50 MHz, CDCl3) 197.00, 155.74, 136.28, 135.07, 133.37,
128.53, 128.45, 128.37, 127.97, 127.92, 66.75, 66.12, 64.12,
57.61, 25.47, 17.93, −5.91, −6.00. νmax (CHCl3)/cm−1 3427
(–NH), 1689 (NH–COO), 1716 (PhC=O). m/z (LCMS) 414.44
(M + 1), 436.35 (M + Na).
Compound 4 was prepared using the same approach to 2 to give
a gummy material, 99% yield. [α]D 39.42 (c 1.37 in CHCl3).
Found: C 77.4, H 7.3, N 3.0. C31H35NO2Si requires C 77.3, H
7.3, N 2.9%. δH (200 MHz, CDCl3) 7.62–7.14 (20H, m, ArH),
4.80(1H, s, OH), 3.93(1H, m, CHNHCbz), 3.73(1H, dd, J10.36,
6.57, CH2OSi), 3.62 (1H, dd, J 10.35, 3.15, CH2OSi), 1.64 (2H,
s, NH2), 1.04 (9H, s, C(CH3)3). δC (100 MHz, CDCl3) 144.56,
146.66, 135.50, 135.32, 132.69, 132.66, 129.81, 129.67, 128.37,
128.07, 127.74, 127.66, 126.62, 126.40, 125.44, 125.01, 78.61,
65.25, 57.48, 26.80, 19.06. νmax (CHCl3)/cm−1 3448 (–OH).
m/z (LCMS) 482.87 (M + 1).
(2R)-2-Amino-3-O-(tert-butyldimethylsilyl)-
1,1-diphenylpropane-1,3-diol 5
(2R)-2-Amino-(N-benzyloxycarbonyl)-3-O-(tert-
butyldiphenylsilyl)-1,1-diphenylpropane-1,3-diol 13
Compound 5 was synthesized following the experimental proce-
dure described for compound 2 to give a gummy material, 99%
yield. [α]D 79.23 (c 2.6 in CHCl3). Found: C 70.7, H 8.8, N 3.9.
C21H31NO2Si requires C 70.5, H 8.7, N 3.9%. δH (200 MHz,
CDCl3) 7.60–7.16 (10H, m, ArH), 3.92 (1H, t, J 9.09, CHNH2),
3.60 (2H, d, J 4.55, CH2OSi), 0.86 (9H, s, C(CH3)3), −0.02 (3H,
s, SiCH3), −0.05 (3H, s, SiCH3). δC (50 MHz, CDCl3) 145.95,
144.99, 128.37, 128.07, 126.64, 126.46, 125.48, 125.03, 79.09,
64.45, 57.08, 25.73, 18.01, −5.67, −5.80. νmax (CHCl3)/cm−1
3438 (–OH), 3400 (NH2). m/z (LCMS) 359.14 (M + 2).
Magnesium turnings (2.5 g, 103 mmol) were placed in a flame-
dried two-necked round bottom flask fitted with a reflux con-
denser. The flask was cooled to room temperature by flushing
with argon gas. Dry THF (50 mL) was added by syringe under
an argon atmosphere. Freshly distilled bromobenzene (5.41 mL,
51.45 mmol) was added at such a rate that a mild reflux of
THF resulted. The reaction between bromobenzene and mag-
nesium is exothermic and dropwise addition of bromobenzene
took 15 min. The contents were further stirred for 15 min. The
N-carbamate ketone 11 (9.258 g, 17.15 mmol) in dry THF
(30 mL) was added dropwise by syringe over 20 min at 25◦C.The
whole reaction mixture was further stirred at 25◦C for 1 h. The
reaction was quenched with saturated ammonium chloride. THF
was removed completely and the residue was extracted with ethyl
acetate (3 × 100 mL). The combined extract was washed wither
water and brine, dried over anhydrous sodium sulfate, and con-
centrated under reduced pressure. The crude material was puri-
fied on flash silica gel with a mixture of ethyl acetate/petroleum
spirits (4:96) to obtain a white solid 13 (8.9 g) in 84% yield,
mp 58◦C (dichloromethane/petroleum spirits). [α]D 9 (c 1.26 in
CHCl3). Found: C 75.9, H 7.0, N 2.5. C39H41NO4Si requires C
76.1, H 6.7, N 2.3%. δH (200 MHz, CDCl3) 7.61–7.20 (25H, m,
ArH), 5.90 (1H, d, J 8.59, NHCbz), 5.05 (2H, s, PhCH2OCO),
4.77–4.73 (1H, m, CHNHCbz), 3.85 (2H, d, J 26, CH2OSi), 1.01
(9H, s, C(CH3)3). δC (50 MHz, CDCl3) 155.93, 145.47, 144.23,
136.53, 135.35, 135.14, 131.46, 131.25, 130.02, 129.81, 128.50,
128.42, 128.21, 127.87, 127.72, 127.57, 126.91, 126.76, 125.07,
81.16, 66.50, 65.64, 55.46, 26.59, 18.90. νmax (CHCl3)/cm−1
3438 (–OH), 1712 (C=O). m/z (LCMS) 638.50 (M + Na).
(1R,2R)-(−)-2-Amino-(N-benzyl)-1-phenylpropane-
1,3-diol 15
Compound 1 (1.67 g, 10 mmol) was dissolved in dichloro-
methane/methanol (20 mL, 4/1), to which benzaldehyde
(1.11 mL, 11 mmol) and anhydrous MgSO4 (1.5 g) were added.
The reaction mixture was refluxed for 2 h, filtered through
Celite, and concentrated under reduced pressure to afford crude
imine product (2.27 g). The solution of crude imine in methanol
(15 mL) was cooled (0◦C) and to it was added NaBH4 (0.637 g,
20 mmol). The reaction mixture was then allowed to warm to
30◦C and stirred for a further 3 h. The methanol was evap-
orated under reduced pressure, the product was dissolved in
dichloromethane (20 mL), 2 N HCl (10 mL) was added, and
the resulting mixture was stirred for 10 min. The reaction mix-
ture was neutralized with aqueous Na2CO3 and extracted with
dichloromethane (3 × 30 mL). The organic extract was washed
with water and brine, dried over anhydrous sodium sulfate,
and concentrated under reduced pressure to yield crude prod-
uct 15. This was purified by column chromatography on silica

Enantioselective Reduction of Aromatic Ketones
203
gel (methanol/dichloromethane, 5:95) to give a yellowish solid
15 (1.955 g, 76%). mp 75–76◦C (ethyl acetate/petroleum spir-
its). [α]D −87.48 (c 2 in CHCl3). Found C 74.7, H 8.0,
N 5.4. C16H19NO2 requires C 74.7, H 7.4, N 5.4%. δH
(200 MHz, CDCl3) 7.34 (10H, m, ArH), 4.65 (1H, d, J 7.43,
PhCHOH), 3.80 (1H, d, J 12.91, NHCH2Ph), 3.66 (1H, d, J 12,
NHCH2Ph), 3.66 (1H, dd, J 11.34, 3.91, CH2OH), 3.48 (1H,
dd, J 10.96, 3.52, CH2OH), 2.80 (1H, m, CHNH), 2.55 (3H,
br s, OH + NH). δC (75 MHz, CDCl3) 136.27, 141.21, 127.45,
127.02, 126.78, 126.13, 126.07, 125.43, 70.26, 63.18, 57.53,
49.63. νmax (CHCl3)/cm−1 3380(–OH), 1602, 1494, 1454, 1217.
m/z (MALDI–TOF) 257.34 (M + 1).
reaction mixture was stirred for 10 min at 20◦C. Ice pieces
were added and the methanol was evaporated on a rotary
evaporator. The mixture was then extracted with ethyl acetate
(3 × 60 mL).The combined extracts were washed with water and
brine, dried over anhydrous sodium sulfate, and concentrated on
the rotary evaporator. The crude product was chromatographed
on silica gel using ethyl acetate/petroleum spirits (30:70) as
eluent to furnish compound 17 as a colourless oil (7.716 g,
96%). [α]D −46.65 (c 2.92 in CHCl3). Found: C 66.2, H 7.9,
N 3.6. C23H33NO4Si requires C 66.5, H 8.0, N 3.4%. δH
(200 MHz, CDCl3) 7.33–7.31 (10H, m, ArH), 5.20 (1H, d, J
8.09, NHCbz), 5.02 (2H, s, PhCH2OCO), 4.97 (1H, d, J 3.41,
PhCHO), 3.89–3.77 (1H, m, CHNHCbz), 3.70 (2H, d, J 5.81,
CH2OH), 0.91 (9H, s, C(CH3)3), 0.06 (3H, s, SiCH3), −0.14
(3H, s, SiCH3). δC (100 MHz, CDCl3) 156.52, 141.54, 136.31,
128.33, 128.00, 127.87, 127.41, 126.15, 72.93, 66.62, 62.25,
59.09, 25.70, 18.00, −4.80, −5.36. νmax (CHCl3)/cm−1 3434.98
(–OH), 1708 (C=O). m/z (LCMS) 416.26 (M + 1), 438.24
(M + Na).
(1R,2R)-(−)-2-Amino-(N-benzyl)-3-(tert-
butyldiphenylsilyl)-1-phenylpropane-1,3-diol 6
To a solution of 15 (0.877 g, 3.4 mmol) and imidazole (0.578,
8.5 mmol) in dry DMF (5 mL) was added tert-butyldiphenylsilyl
chloride (0.97 mL, 3.74 mmol) at 25◦C, and the reaction mix-
ture stirred for 0.5 h. The reaction was quenched with crushed
ice and the mixture extracted with diethyl ether (3 × 40 mL).
The organic layer was washed with water and brine, dried over
anhydrous sodium sulfate, and concentrated under reduced pres-
sure. The residue was purified using a silica gel column with
a mixture of ethyl acetate/petroleum spirits (2:98) as eluent to
give compound 6 as colourless oil (1.452 g, 86%). [α]D −46.17
(c 1 in CHCl3). Found C 77.3, H 7.8, N 2.6. C32H37NO2Si
requires C 77.5, H 7.5, N 2.8%. δH (200 MHz, CDCl3) 7.62–
7.24 (20H, m, ArH), 4.61 (1H, d, J 7.83, PhCHOH), 3.77–3.42
(4H, m, CH2OSi, NHCH2Ph), 2.66 (1H, m, CHNH), 1.08 (9H, s,
C(CH3)3). δC (75 MHz, CDCl3) 132.88, 132.79, 129.77, 128.46,
128.15, 127.72, 127.48, 127.42, 126.81, 71.93, 64.55, 60.86,
51.21, 26.92, 19.17. νmax (CHCl3)/cm−1 3421 (–OH), 1469,
1454, 1427, 1217. m/z (MALDI–TOF) 496.05 (M + 1).
(1R,2R)-(−)-2-Amino-1-O-(tert-butyldimethylsilyl)-1-
phenylpropane-1,3-diol 7
Compound 7 was synthesized following the experimental pro-
cedure described for compound 2. Yield 98%. mp 80◦C (ethyl
acetate/petroleum spirits). [α]D −60.71 (c 1.12 in CHCl3).
Found: C 64.3, H 9.6, N 5.2. C15H27NO2Si requires C 64.0, H
9.7, N 5.0%. δH (200 MHz, CDCl3) 7.32 (5H, s,ArH), 5.45 (br s,
NH2 and OH), 4.80 (1H, d, J 7.45, PhCH), 3.63 (1H, dd, J 11.87,
3.28, CH2OH), 3.52 (1H, dd, J 11.88, 6.82, CH2OH), 3.36–3.27
(1H, m, CHNH2), 0.86 (9H, s, C(CH3)3), 0.09 (3H, s, SiCH3),
−0.23 (3H, s, SiCH3). δC (125 MHz, CDCl3) 140.02, 128.38,
128.24, 126.74, 73.41, 59.78, 59.71, 59.70, 25.70, 17.84, −4.73,
−4.89. νmax (Nujol)/cm−1 3402. m/z (LCMS) 282.41 (M + 1).
(1R,2R)-(−)-2-Amino-(N-benzyloxycarbonyl)-1,3-O-(di-
General Procedure for the Asymmetric Reduction
of Ketones
tert-butyldimethylsilyl)-1-phenylpropane-1,3-diol 16
Compound 8 (5.117 g, 17 mmol) and imidazole (5.780 g,
85 mmol) were dissolved in dry DMF (18 mL). To this solution
tert-butyldimethylsilyl chloride (6.120 g, 40.8 mmol) was added
and the reaction mixture was stirred at 30◦C for 13 h. Ice pieces
were added and the reaction mixture was extracted with diethyl
ether (3 × 70 mL).The organic phase was washed with water and
brine, dried over anhydrous sodium sulfate, and concentrated
under reduced pressure. The crude product was purified on sil-
ica gel by column chromatography using ethyl acetate/petroleum
spirits (4:96) as eluent to give compound 16 as a colourless oil
(8.9 g, 99%). [α]D −45.57 (c 1.62 in CHCl3). Found: C 65.7,
H 8.7, N 3.0. C29H47NO4Si2 requires C 65.7, H 8.9, N 2.6%.
δH (200 MHz, CDCl3) 7.31–7.25 (10H, m, ArH), 5.13 (1H,
d, J 8.84, NHCbz), 5.03 (1H, d, J 2.90, PhCH), 5.00 (2H, s,
PhCH2OCO), 3.76–3.67 (1H, m, CHNHCbz), 3.57 (2H, d, J
6.32, CH2OSi), 0.93 (9H, s, C(CH3)3), 0.89 (9H, s, C(CH3)3),
0.09 (3H, s, SiCH3), 0.07 (3H, s, SiCH3), 0.04 (3H, s, SiCH3),
−0.15 (3H, s, SiCH3). δC (125 MHz, CDCl3) 155.99, 142.19,
136.60, 128.39, 127.95, 127.26, 126.16, 71.73, 66.45, 61.55,
58.97, 25.79, 18.13, 18.05, −5.47, −4.67, −5.28, −5.34. νmax
(CHCl3)/cm−1 3446 (–NH), 1726 (C=O). m/z (LCMS) 530.46
(M + 1), 552.45 (M + Na).
To a solution of amino alcohol 2–7 (0.2 mmol) in dryTHF (3 mL)
was added 10 M borane–dimethyl sulfide complex (0.23 mL,
2.3 mmol), and the reaction mixture was stirred under an argon
atmosphere at 25◦C for 10 min. The reaction temperature was
increased to 50◦C and a solution of ketone (2 mmol) in dry THF
(3 mL) was added dropwise over 15 min. The reaction mixture
was then stirred for a further 5 min. The reaction was quenched
byadding2MHCl(5 mL), andthemixtureextractedwithdiethyl
ether (3 × 20 mL). The organic layer was washed with water and
brine, dried over anhydrous sodium sulfate, and concentrated
under reduced pressure. The residue was purified on a silica gel
column with ethyl acetate/petroleum spirits as eluent to give the
chiral secondary alcohols.
Acknowledgments
Namdev S. Vatmurge thanks CSIR, New Delhi, for the award of a Junior
Research Fellowship. B. G. Hazra is thankful to CSIR, New Delhi, for the
Award of Emeritus Scientist Scheme.
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