Full Paper
●
+
1
37.5, *159.3, 159.4 ppm. MS (ESI): m/z = 401 [M + Na] . HRMS
Butyldimethylsilyloxy)-3-[(4R,5S)-5-(4-methoxyphenyl)-2,2-di-
methyl-1,3-dioxolan-4-yl]propylcarbamate (16): To a solution of
LiAlH4 (0.625 g, 16.03 mmol) in THF (20 mL) at 0 °C was added
compound 14 (4.5 g, 10.68 mmol) in THF (20 mL) under nitrogen.
After the reaction mixture was stirred for 1 h at 0 °C, it was
+
(ESI): calcd. for C H O SiNa [M + Na] 401.2119; found 401.2131.
21 34 4
3
2
-(tert-Butyldimethylsilyloxy)-3-[(4R,5S)-5-(4-methoxyphenyl)-
,2-dimethyl-1,3-dioxolan-4-yl]propan-1-ol (13): To a solution of
compound 12 (7.2 g, 19.04 mmol) in dry THF (50 mL) under nitro-
gen was added BH ·DMS (2.6 mL, 28.5 mmol) at 0 °C. The reaction
mixture was stirred for 3 h, and then 10 % NaOH (8 mL) followed
by 30 % H O (6 mL) was added at 0 °C. The resulting suspension
quenched by the addition of H O (0.6 mL), 15 % aqueous NaOH
2
3
(
0.6 mL), and H O (1.8 mL). The precipitate was filtered through a
2
pad of Celite, and the filter cake was washed with hot ethyl acetate.
The filtrate was concentrated under reduced pressure to give the
crude amine. To a solution of the crude residue in MeOH (25 mL)
were added K CO (4.42 g, 32.06 mmol) and Troc-Cl (2.18 mL,
2
2
was stirred for an additional 1 h and extracted with ethyl acetate
2 × 20 mL). The organic layers were separated and combined. The
(
2
3
solvent was evaporated on a rotary evaporator to give the crude
compound. Purification by chromatography on a silica gel column
16.03 mmol) dropwise at 0 °C. After the reaction mixture was stirred
for 30 min at room temperature, it was concentrated under reduced
pressure and diluted with ethyl acetate (50 mL). The organic layer
(20 % ethyl acetate in hexane) gave compound 13 (5.95 g, 79 %
yield) as a thick syrup. IR: ν˜ = 1034, 1064, 1244, 1514, 1613, 2856,
max
was washed with brine, dried with anhydrous Na SO , and concen-
–1
1
●
2
4
2
930, 2954, 3457 cm . H NMR (300 MHz, CDCl ; * minor isomer,
3
trated under reduced pressure to give a mixture of 15 and 16 as a
thick syrup. Purification by chromatography on a silica gel column
major and minor isomer): δ = 0.01 (s, 3 H), 0.03 (s, 3 H) *0.08 (s, 6
H), *0.85 (s, 9 H), 0.89 (s, 9 H), *1.49 (s, 6 H), 1.51 (s, 3 H), 1.55 (s, 3
(
ethyl acetate/hexane, 0.4:9.6) afforded 15 (1.95 g) as a colorless
thick syrup followed by (ethyl acetate/hexane, 0.5:9.5) to give pure
6 (2.96 g) as a colorless thick syrup (combined yield: 4.91 g, 81 %).
●
H), *1.55–1.69 (m, 2 H), 1.69–1.93 (m, 2 H), 3.52–3.76 (m, 4 H),
●
●
3
.80 (s, 6 H), 3.88–3.09 (m, 4 H), *4.83 (d, J = 8.1 Hz 1 H), *6.87
1
(d, J = 1.8 Hz, 2 H), 6.90 (d, J = 1.8 Hz, 2 H), 7.30 (d, J = 2.4 Hz, 2
2
8
Data for 15: [α] = + 9.1, (c = 0.77, CHCl ). IR (neat): ν = 1036,
1
1
3
D
3
˜
max
H), *7.33 (d, J = 2.4 Hz, 2 H) ppm. C NMR (75 MHz, CDCl ; * minor
isomer, major and minor isomer): δ = –4.7, *–4.4, –4.3,* –4.2, *17.9,
3
064, 1243, 1514, 1740, 2856, 2929, 2953, 3349 cm–1. H NMR
1
●
(
500 MHz, CDCl ): δ = 0.08 (s, 3 H), 0.09 (s, 3 H), 0.89 (s, 9 H), 1.49
3
1
8.1, 25.8, *26.9, *27.1, 27.3, *36.3, 36.7, *55.1, 55.2, *58.4, 59.2, 69.0,
(s, 3 H), 1.55 (s, 3 H), 1.60 (m, 1 H), 1.87 (m, 1 H), 3.16–3.29 (m, 2 H),
● ●
*
69.4, 79.0, 85.2, *108.6, 108.7, 113.8, *113.9, *128.5, 128.7, 129.7,
3.81 (s, 3 H), 3.85–3.89 (m, 2 H), 4.69 (s, 2 H), 4.79 (d, J = 8.0 Hz, 1
+
*
130.3, 159.5, *159.6 ppm. MS (ESI): m/z = 419 [M + Na] . HRMS
H), 5.69 (br. s, 1 H), 6.89 (d, J = 8.6 Hz, 2 H), 7.30 (d, J = 8.6 Hz, 2
+
(ESI): calcd. for C H O SiNa [M + Na] 419.2224; found 419.2227.
21
36
5
13
H) ppm. C NMR (100 MHz, CDCl ): δ = –4.37, –4.34, 18.1, 25.8,
3
{
3-Azido-1-[(4R,5S)-5-(4-methoxyphenyl)-2,2-dimethyl-1,3-diox-
27.0, 27.3, 33.6, 37.3, 55.2, 69.6, 74.3, 79.1, 84.9, 95.7, 108.8, 114.0,
+
olan-4-yl]propoxy}(tert-butyl)dimethylsilane (14): To a solution
of 13 (5.8 g, 14.60 mmol) and Et N (4.3 mL, 29.29 mmol) in dry
CH Cl (30 mL) in an ice bath was added methanesulfonyl chloride
(
was quenched by the addition of cold water, and the resulting mix-
ture was extracted with CH Cl (2 × 30 mL). The combined organic
layers were washed with water, dried with Na SO , and concen-
trated under reduced pressure to afford the corresponding mesyl
derivative as a yellow oil, which was carried onto the next step
without any further purification. To a stirred solution of the mesyl
128.7, 129.5, 154.3, 159.7 ppm. MS (ESI): m/z = 592 [M + Na] , 594
+
+
[(M + 2) + Na] , 596 [(M + 4) + Na] . HRMS (ESI): calcd. for
3
+
C
H
38Cl
NO
= –22.4 (c = 0.97, CHCl
1248, 1514, 1741, 2854, 2926, 3353 cm . H NMR (500 MHz, CDCl ):
3
Na [M + Na] 592.1426; found 592.1427. Data for 16:
2
2
24
3
6
2
6
1.69 mL, 21.90 mmol) dropwise. After 20 min at 0 °C, the reaction [α]
). IR (neat): ν˜max = 1037, 1065, 1141,
D
3
–
1 1
δ = 0.01 (s, 3 H), 0.02 (s, 3 H), 0.84 (s, 9 H), 1.48 (s, 3 H), 1.50 (s, 3
H), 1.52–1.81 (m, 2 H), 3.19–3.31 (m, 2 H), 3.80 (s, 3 H), 3.83–3.89
(m, 2 H), 4.70 (s, 2 H), 4.79 (d, J = 7.5 Hz, 1 H), 5.29 (br. s, 1 H), 6.88
(d, J = 8.4 Hz, 2 H), 7.30 (d, J = 8.4 Hz, 2 H) ppm. 13C NMR (100 MHz,
2
2
2
4
CDCl
): δ = –4.5, –4.3, 17.9, 25.7, 27.1, 33.0, 37.9, 55.2, 70.1, 74.3,
3
derivative in dry DMF (30 mL) was added NaN (2.98 g, 43.80 mmol)
at room temperature under nitrogen. The mixture was slowly
heated to 80 °C and stirred for 2 h. After this time, the mixture was
79.4, 84.6, 95.6, 108.7, 113.9, 128.5, 130.1, 154.2, 159.5 ppm. MS
3
+
+
+
(ESI): m/z = 592 [M + Na] , 594 [(M + 2) + Na] , 596 [(M + 4) + Na] .
+
HRMS (ESI): calcd. for C24H38Cl NO Na [M + Na] 592.1426; found
3 6
cooled to room temperature and poured into ice water (30 mL). 592.1424.
The mixture was extracted with diethyl ether (3 × 50 mL), and the
(
1S,2S,3R)-1-(4-Methoxyphenyl)-5-{[(2,2,2-trichloroethoxy)-
combined organic extracts were washed with brine, dried with an-
hydrous Na SO , and concentrated under reduced pressure. Purified
by chromatography on a silica gel column (ethyl acetate/hexane,
carbonyl]amino}pentane-1,2,3-triyl Triacetate (17): A solution of
compound 15 (0.5 g, 0.87 mmol) in 80 % aqueous AcOH (5 mL)
was stirred at room temperature for 8 h. The reaction mixture was
neutralized by the addition of an aqueous 30 % ammonia solution
dropwise at 0 °C. The resulting reaction mixture was concentrated
under reduced pressure, and the residue was purified by chroma-
tography on a silica gel column (ethyl acetate/hexane, 4:1) to give
the triol as a thick syrup. To the solution of the triol in CH Cl (5 mL)
were added Et N (0.74 mL, 5.27 mmol), acetic anhydride (0.40 mL,
3
%
was warmed to room temperature, stirred for 12 h, and diluted with
chloroform (30 mL). The resulting solution was washed with brine,
dried with anhydrous Na SO , and concentrated under reduced
pressure. The resulting residue was purified by chromatography on
a silica gel column (ethyl acetate/hexane, 1.2:8.8) to afford triacetate
2
4
1
1
.5:8.5) afforded 14 (4.74 g, 77 %) as a yellow oil. IR (neat): ν
=
˜
max
–
1 1
034, 1067, 1244, 1514, 1613, 2093, 2857, 2930, 2985 cm . H NMR
●
(300 MHz, CDCl ; * minor isomer, major and minor isomer): δ =
3
0
0
.01 (s, 3 H), 0.02 (s, 3 H) *0.04 (s, 3 H),* 0.08 (s, 3 H), *0.85 (s, 9 H),
.89 (s, 9 H), *1.39 (s, 3 H), 1.46 (s, 3 H), 1.49 (s, 3 H), *1.51 (s, 3 H),
●
●
●
●
2
2
1
.52–1.79 (m, 4 H), 3.17–3.37 (m, 4 H), 3.80 (s, 6 H), 3.81–3.88
●
3
(m, 2 H), 3.93–4.00 (m, 2 H), *4.69 (d, J = 8.4 Hz, 1 H), 4.75 (d, J =
.91 mmol), and 4-(dimethylamino)pyridine (DMAP, 0.01 g, 1 mol-
) at 0 °C. Upon completion of the addition, the reaction mixture
8
.4 Hz, 1 H), 6.85 (d, J = 8.4 Hz, 4 H), 7.26 (d, J = 8.4 Hz, 4 H) ppm.
1
3
●
C NMR (100 MHz, CDCl ; * minor isomer, major and minor iso-
3
mer): δ = –4.8, –4.7, *-4.2, *18.0, 18.1, 25.8, *27.0, *27.1, 27.3, *32.5,
●
●
3
2.8, *47.5, 47.6, 55.2, *68.0, 69.3, *78.7, 79.0, *84.9, 85.2, 108.6,
2
4
1
13.9, *114.0, 128.5, *128.8, *129.7, 130.0, 159.60, *159.67 ppm. MS
+
(
[
ESI): m/z = 444 [M + Na] . HRMS (ESI): calcd. for C H N O SiNa
M + Na] 444.2289; found 444.2277.
2
1 35 3 4
+
2
8
1
7 (0.33 g, 70 %) as a thick syrup; [α] = –82.9 (c = 0.18, CHCl ). IR
D
3
2
,2,2-Trichloroethyl (R)-3-(tert-Butyldimethylsilyloxy)-3- (neat): ν˜
= 770, 1032, 1219, 1515, 1742, 2852, 2922, 2955,
max
–
1 1
[
(4R,5S)-5-(4-methoxyphenyl)-2,2-dimethyl-1,3-dioxolan-4-yl]-
3369 cm . H NMR (500 MHz, CDCl ): δ = 1.67–1.86 (m, 2 H), 2.02
3
propylcarbamate (15) and 2,2,2-Trichloroethyl (S)-3-(tert-
(s, 3 H), 2.05 (s, 3 H), 2.06 (s, 3 H), 2.96 (m, 1 H), 3.37 (m, 1 H), 3.80
Eur. J. Org. Chem. 2016, 1693–1701
www.eurjoc.org
1699
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim