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