Full Paper
(
(
2
2
1
1
7
2
1
5
m, 5H), 6.78 (d, J=8.1 Hz, 1H), 4.92 (dd, J=20.3, 5.6 Hz, 2H), 4.55
d, J=31.3 Hz, 2H), 4.22 (d, J=23.6 Hz, 2H), 3.93 (d, J=21.7 Hz,
1H), 5.16 (s, 2H), 4.95 (s, 1H), 4.60 (s, 1H), 4.31 (s, 1H), 4.04–3.65
(m, 11H), 3.46 (d, J=20.8 Hz, 5H), 1.16–0.67 (m, 27H), 0.07 to
1
3
H), 3.84 (s, 6H), 3.80 (s, 3H), 3.71 (t, J=13.4 Hz, 2H), 3.51 ppm (s,
À0.13 ppm (m, 18H); C NMR (101 MHz, CDCl ): d=165.51, 150.58,
3
1
3
H); C NMR (101 MHz, (CD ) CO): d=150.80, 150.39, 148.63,
149.74, 149.25, 147.46, 137.25, 134.63, 132.38, 129.24, 128.48,
128.25, 128.03, 127.77, 127.48, 127.35, 122.22, 120.78, 120.63,
119.10, 117.37, 115.08, 113.35, 112.46, 111.44, 110.84, 84.87, 81.62,
78.00, 74.05, 71.06, 62.16, 61.08, 55.87, 55.68, 55.50, 25.82, 18.19,
À4.97, À5.06, À5.52, À5.53, À5.70, À5.72 ppm; IR (neat): n˜ =
3
2
47.89, 147.15, 145.91, 136.04, 132.92, 122.54, 121.07, 119.68,
19.56, 118.82, 118.28, 114.39, 112.46, 111.22, 110.48, 87.50, 87.05,
2.96, 72.78, 60.96, 55.41, 55.31 ppm; IR (neat): n˜ =3334.02,
965.98, 2927.42, 2885.36, 1476.29, 1374.64, 1311.55, 1157.32,
À1
+
122.27 cm
;
HRMS (DART-TOF): m/z calcd for C H O :
33 10
2955.46, 2923.92, 2853.61, 1753.20, 1591.96, 1462.27, 1251.96,
27
+
À1
17.20682 [M+H] ; found: 517.20780.
1115.26, 1024.12 cm
;
HRMS (DART-TOF): m/z calcd for
+
+
C H O Si : 931.50264 [MÀC H F O ] ; found: 931.49846.
52
79
9
3
10
8
3
2
(
1R,2R)-1-(4-(((5S,6S)-5-(4-(benzyloxy)-3-methoxyphenyl)-
,2,3,3,9,9,10,10-octamethyl-4,8-dioxa-3,9-disilaundecan-6-
yl)oxy)-3-methoxyphenyl)-3-((tert-butyldimethylsilyl)oxy)-2-(2-
methoxyphenoxy)propan-1-ol (20): To a solution of 16 (0.3 g,
.31 mmol) in THF/H O (4:1), was added sodium borohydride
(1R,2R)-1-(4-(((5S,6S)-5-(4-(Benzyloxy)-3-methoxyphenyl)-
2
2
,2,3,3,9,9,10,10-octamethyl-4,8-dioxa-3,9-disilaundecan-6-
yl)oxy)-3-methoxyphenyl)-3-((tert-butyldimethylsilyl)oxy)-2-(2-
methoxyphenoxy)propyl (S)-3,3,3-trifluoro-2-methoxy-2-phenyl-
propanoate (21b): By following the general procedure outlined
above for compound 21a, compound 20 (0.12 g, 0.13 mmol) was
converted into the ester 21b (0.12 g, 80%) as a colorless oil.
0
(
3
2
0.07 g, 1.78 mmol) portion-wise and the mixture was stirred for
h. Upon complete consumption of the starting material as moni-
tored by TLC, the reaction was quenched by the addition of satu-
rated NH Cl. The resulting suspension was extracted with Et O (3ꢂ
1
and concentrated in vacuo to provide the TBS protected diol inter-
mediate, which was used in the next step without further purifica-
tion. The crude TBS protected diol intermediate was dissolved in
anhydrous THF. To this solution was added TBSCl (0.075 g,
2
D
5
1
[
7
6
a] =À26.3 (c=1.00 in CHCl ); H NMR (400 MHz, CDCl ): d=
3
3
4
2
.50–7.25 (m, 9H), 7.19 (d, J=15.0 Hz, 2H), 7.03–6.77 (m, 10H),
.39 (d, J=7.0 Hz, 1H), 5.15 (s, 2H), 4.94 (d, J=5.9 Hz, 1H), 4.54 (d,
00 mL). The combined organic extracts were dried over MgSO4
J=6.8 Hz, 1H), 4.32 (d, J=13.7 Hz, 1H), 3.90–3.67 (m, 11H), 3.45 (d,
J=25.1 Hz, 5H), 0.94–0.76 (m, 27H), 0.03 to À0.10 ppm (m, 18H);
13
C NMR (101 MHz, CDCl ): d=165.59, 150.50, 149.77, 149.36,
3
1
1
7
1
2
49.23, 147.64, 147.45, 137.24, 134.61, 132.31, 129.25, 128.48,
28.45, 128.02, 127.78, 127.65, 127.35, 84.84, 81.80, 77.24, 74.10,
1.05, 62.29, 61.28, 55.87, 55.68, 55.35, 25.81, 25.79, 25.72, 18.21,
8.17, 18.15, À4.99, À5.12, À5.54, À5.69 ppm; IR (neat): n˜ =
0
.5 mmol) and imidazole (0.034 g, 0.5 mmol). The resulting solution
was stirred for 2 h. Upon complete consumption of the starting
material as monitored by TLC, the reaction was quenched by the
addition of saturated NH Cl. The organic phase was extracted with
4
953.18, 2856.16, 1752.08, 1592.71, 1500.82, 1462.87, 1248.45,
CH Cl (3ꢂ50 mL), dried over MgSO , and concentrated in vacuo.
2
2
4
À1
1118.76, 1017.11 cm
;
HRMS (DART-TOF): m/z calcd for
The crude compound was purified by column chromatography
hexane/EtOAc, 4:1) to afford asymmetric TBS protected intermedi-
+
+
C H O Si : 931.50264 [MÀC H F O ] ; found: 931.49818.
(
52 79
9
3
10
8
3
2
25
ate 20 (0.26 g, 90%) as a viscous oil. [a] =À14.0 (c=1.00 in
D
(1R,2R)-1-(4-(Benzyloxy)-3,5-dimethoxyphenyl)-3-((tert-butyldi-
methylsilyl)oxy)-2-(2-methoxy-4-methylphenoxy)propyl (R)-3,3,3-
trifluoro-2-methoxy-2-phenylpropanoate (19a): A stirred solution
of the TBS protected asymmetric alcohol 10 (0.07 g, 0.12 mmol) in
1
CHCl ); H NMR (400 MHz, CDCl ): d=7.44 (s, 2H), 7.39–7.19 (m,
3
3
5
4
H), 6.89 (d, J=38.7 Hz, 8H), 5.14 (s, 2H), 4.94 (d, J=5.4 Hz, 1H),
.84 (d, J=7.2 Hz, 1H), 4.25 (d, J=29.1 Hz, 2H), 4.11 (s, 1H), 3.88
(
3
d, J=4.0 Hz, 6H), 3.80 (s, 3H), 3.74 (s, 2H), 3.64 (d, J=5.8 Hz, 1H),
.43 (d, J=16.6 Hz, 1H), 0.89 (s, 9H), 0.83 (s, 18H), À0.07 ppm (d,
J=16.5 Hz, 18H); C NMR (101 MHz, CDCl ): d=150.68, 150.05,
49.15, 148.60, 147.35, 137.28, 134.66, 132.91, 128.46, 127.75,
27.36, 123.22, 121.22, 120.20, 119.62, 119.05, 115.60, 113.32,
anhydrous CH Cl2 (10 mL) was treated sequentially with TEA
2
(0.034 mL, 0.24 mmol) and (S)-3,3,3-trifluoro-2-methoxy-2-phenyl-
1
3
3
propanoyl chloride (0.033 g, 0.13 mmol). A catalytic amount of
DMAP was added and the resulting solution was stirred for 3 h.
Upon complete consumption of the starting material as monitored
1
1
111.91, 110.90, 110.86, 88.80, 84.96, 73.77, 71.05, 62.57, 62.19, 55.84,
by TLC, the reaction was quenched by addition of saturated NH Cl
4
5
5.76, 55.74, 25.90, 25.84, 25.77, 18.30, 18.20, 18.19, 1.83, À4.97,
and extracted with CH Cl (3ꢂ50 mL). The combined organic ex-
2
2
À5.04, À5.45, À5.53 ppm; IR (neat): n˜ =3050.10, 1976.95, 1262.74,
tracts were dried over MgSO4 and concentrated in vacuo. The
crude compound was purified by column chromatography
(hexane/EtOAc, 7:3) to afford ester 19a (0.08 g, 89%) as a colorless
À1
1
041.41, 712.5, 668.08 cm ; HRMS (DART-TOF): m/z calcd for
+
+
C H O Si : 931.50264 [MÀOH] ; found: 931.49949.
5
2
79
9
3
2
D
5
1
oil. [a] =À21.9 (c=1.00 in CHCl ); H NMR (400 MHz, CDCl ): d=
3
3
(1R,2R)-1-(4-(((5S,6S)-5-(4-(Benzyloxy)-3-methoxyphenyl)-
7
3
6
2
3
0
.48 (d, J=7.1 Hz, 2H), 7.40 (d, J=7.8 Hz, 2H), 7.33 (d, J=7.9 Hz,
H), 7.21 (t, J=7.7 Hz, 2H), 6.81 (d, J=8.1 Hz, 1H), 6.69 (s, 1H),
.63 (d, J=8.8 Hz, 1H), 6.52 (s, 2H), 6.28 (d, J=7.6 Hz, 1H), 5.02 (s,
H), 4.46 (d, J=14.4 Hz, 1H), 3.76 (s, 3H), 3.72 (d, J=3.6 Hz, 1H),
.69 (s, 6H), 3.53 (s, 3H), 3.42 (dd, J=11.3, 3.1 Hz, 1H), 2.30 (s, 3H),
2
,2,3,3,9,9,10,10-octamethyl-4,8-dioxa-3,9-disilaundecan-6-
yl)oxy)-3-methoxyphenyl)-3-((tert-butyldimethylsilyl)oxy)-2-(2-
methoxyphenoxy)propyl (R)-3,3,3-trifluoro-2-methoxy-2-phenyl-
propanoate (21a): A stirred solution of TBS protected asymmetric
epoxy alcohol 20 (0.12 g, 0.13 mmol) in anhydrous CH Cl (10 mL)
2
2
13
.87 (s, 9H), À0.06 ppm (d, J=13.7 Hz, 6H); C NMR (101 MHz,
was treated sequentially with triethylamine (0.035 mL, 0.26 mmol)
and (S)-3,3,3-trifluoro-2-methoxy-2-phenylpropanoyl chloride
0.049 g, 0.13 mmol). A catalytic amount of DMAP was added and
CDCl ): d=165.57, 153.27, 150.28, 144.93, 137.69, 136.83, 132.28,
3
1
32.07, 131.50, 129.30, 128.50, 128.08, 127.85, 127.43, 120.94,
(
117.38, 113.46, 104.87, 81.67, 77.89, 74.87, 60.84, 55.89, 55.69,
the resulting solution was stirred for 3 h. Upon complete consump-
tion of the starting material as monitored by TLC, the reaction was
quenched by addition of saturated NH Cl and extracted with
CH Cl (3ꢂ50 mL). The combined organic extracts were dried over
MgSO and concentrated in vacuo. The crude compound was puri-
5
2
1
5.62, 25.83, 21.05, 18.24, À5.67 ppm; IR (neat): n˜ =2955.46,
229.96, 2853.81, 1750.92, 1591.96, 1504.33, 1458.76, 1223.92,
4
À1
+
122.27, 1010.10 cm ; HRMS (DART-TOF): m/z calcd for C H O Si
3
2
43
6
2
2
+
:
551.28234 [MÀC H F O ] ; found: 551.28255.
10
8
3
2
4
fied by column chromatography (hexane/EtOAc, 4:1) to afford
(1R,2R)-1-(4-(Benzyloxy)-3,5-dimethoxyphenyl)-3-((tert-butyldi-
25
ester 21a (0.12 g, 80%) as a colorless oil. [a] =À2.1 (c=1.00 in
methylsilyl)oxy)-2-(2-methoxy-4-methylphenoxy)propyl (S)-3,3,3-
trifluoro-2-methoxy-2-phenylpropanoate (19b): By following the
general procedure for 19a, compound 10 (0.07 g, 0.12 mmol) was
D
1
CHCl ); H NMR (400 MHz, CDCl ): d=7.55–7.26 (m, 8H), 7.24–7.09
3
3
(
m, 3H), 6.89 (ddd, J=35.0, 21.4, 11.5 Hz, 9H), 6.32 (d, J=8.0 Hz,
&
&
Chem. Eur. J. 2016, 22, 1 – 13
10
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!