J
A. Hausherr et al.
Paper
Synthesis
g, 42%) as yellow oil and 15 (0.180 g, 72%, d.r. 80:20) as light-yellow
oil. A separation of the diastereomers was not possible at this stage.
Preferred R-configuration is assumed by analogy.
H), 5.56 (t, J = 6.3 Hz, 1 H, 4-H), 5.67 (d, J = 7.4 Hz, 1 H, NH), 7.16–7.26
(m, 5 H, Ph, Tos), 7.35 (d, J = 6.6 Hz, 2 H, Ph), 7.69 (d, J = 8.1 Hz, 2 H,
Tos).
[α]D20 = –45.4 (c = 0.5, CHCl3).
13C NMR (CDCl3, 67.9 MHz): δ [(R,aR)-20] = 14.0 (q, Me), 21.4 (q, Tos-
Me), 22.6, 28.6, 29.1, 29.2, 29.3, 29.4, 31.3, 31.8 (8 t, CH2), 58.4 (d, C-
1), 111.7 (d, C-4), 127.2, 127.3, 127.5, 128.0, 129.3 (5 d, Ph, Tos), 132.7
(s, C-2), 137.7, 138.5, 142.9 (3 s, Ph, Tos), 188.6 (s, C-3); δ [(S,aR)-20] =
14.0 (q, Me), 21.4 (q, Tos-Me), 22.6, 28.8, 29.1, 29.2, 29.3, 29.4, 31.3,
31.8 (8 t, CH2), 59.5 (d, C-1), 111.7 (d, C-4), 127.2, 127.3, 127.5, 128.0,
129.3 (5 d, Ph, Tos), 132.7 (s, C-2), 137.7, 138.6, 142.9 (3 s, Ph, Tos),
188.6 (s, C-3); δ [(R,aS)-20] = 14.1 (q, Me), 21.5 (q, Tos-Me), 22.6, 28.7,
29.2, 29.3, 29.4, 29.5, 31.3, 31.8 (8 t, CH2), 59.2 (d, C-1), 110.2 (d, C-4),
127.0, 127.3, 127.4, 128.1, 129.3 (5 d, Ph, Tos), 132.1 (s, C-2), 137.6,
138.4, 142.9 (3 s, Ph, Tos), 188.5 (s, C-3).
1H NMR (CDCl3, 270 MHz): δ = 2.38 (s, 3 H, Tos-Me), 3.02, 3.09 (AB
part of ABX system, JAB = 13.8 Hz, JAX = 6.5 Hz, JBX = 5.2 Hz, 2 H, 1-H),
4.02–4.15 (m, 1 H, 2-H), 4.69 (d, J = 9.6 Hz, 1 H, NH), 5.03, 5.06 (AB
system, JAB = 11.8 Hz, JA,CH = 2.1 Hz, JB,CH = 2.1 Hz, 2 H, 5-H), 7.15–7.25
(m, 7 H, Ph, Tos), 7.64 (d, J = 8.3 Hz, 2 H, Tos); minor diastereomer:
δ = 2.38 (s, 3 H, Tos-Me), 2.98, 3.10 (AB part of ABX system,
JAB = 13.2 Hz, JAX = 5.9 Hz, JBX = 8.1 Hz, 2 H, 1-H), 4.02–4.15 (m, 1 H, 2-
H), 5.01 (s, 2 H, 5-H), 5.39 (d, J = 8.7 Hz, 1 H, NH), 7.15–7.25 (m, 7 H,
Ph, Tos), 7.66 (d, J = 8.3 Hz, 2 H, Tos).
13C NMR (CDCl3, 67.9 MHz): δ = 20.9 (q, Tos-Me), 39.4 (t, C-1), 54.8 (d,
C-2), 94.5 (t, C-5), 126.6, 127.1, 127.9, 129.4, 130.2 (5 d, Ph, Tos), 133.5
(s, C-3), 135.7, 137.6, 143.1 (3 s, Ph, Tos), 196.6 (s, C-4); minor diaste-
reomer: δ = 20.9 (q, Tos-Me), 40.5 (t, C-1), 57.9 (d, C-2), 92.4 (t, C-5),
126.3, 127.2, 127.9, 129.2, 129.7 (5 d, Ph, Tos), 131.1 (s, C-3), 135.7,
137.0, 143.1 (3 s, Ph, Tos), 196.2 (s, C-4).
Although (S,aS)-20 could not be detected unambiguously in the major
fraction by 1H- and 13C NMR spectroscopy, its presence was proven by
the subsequent base-catalyzed cyclization to (2S,2R)-cis-31 of this
mixture (see below).
1,2:4,5-Di-O-isopropylidene-3-O-[1-phenyl-2-(p-toluenesulfon-
amido)tetradeca-3,4-dien-3-yl]-β-D-fructopyranose (23)
IR (film): 3430 (N–H), 3030, 2990, 2935 (C–H), 1965 (C=C=C), 1385,
1160 (TosN) cm–1
.
According to GP1, alkoxyallene 17 (0.960 g, 3.20 mmol, d.r. 15:85), n-
butyllithium (1.37 mL, 3.20 mmol of 2.34 M in hexanes) in THF (60
mL) and 13 (0.688 g, 1.60 mmol) provided (after 1 h at –80 °C, warm-
up to –30 °C within 3 h and stirring at –30 °C for 12 h) the crude
product mixture. Purification by column chromatography (alumina
III, hexanes/EtOAc 3:1) afforded allene 17 (0.666 g, 69%, d.r. 15:85) as
a yellow oil and 23 (0.907 g, 81%, d.r. 11:68:0:21) as a light-yellow oil.
The ratio of diastereomers was determined by analytical HPLC.
[α]D20 = –45.4 (c = 0.5, CHCl3).
MS (EI, 80 eV): m/z (%) = 571 (0.8) [M+], 570 (2) [M+ – H], 479 (5) [M+ –
H – Bn], 326 (9), [M+ – Bn – Tos], 155 (31) [Tos+], 91 (100) [Bn+].
1,2:4,5-Di-O-isopropylidene-3-O-[1-(p-toluenesulfonamido)-1-
phenyltrideca-2,3-dien-2-yl]-β-D-fructopyranose (20)
According to GP1, alkoxyallene 17 (0.930 g, 2.19 mmol, d.r. 75:25), n-
butyllithium (0.86 mL, 2.08 mmol of 2.42 M in hexanes) in THF (40
mL) and 4 (0.511 g, 1.97 mmol) provided, after 1 h at –80 °C and
warm-up to –30 °C within 1.5 h and stirring at –30 °C for 8 h, the
crude product mixture (1.84 g, d.r. 69:21:6:4) as a light-yellow oil. Pu-
rification by column chromatography (alumina III, hexanes/EtOAc
4.5:1) afforded allene 17 (0.087 g, 9%) as colorless oil and 20 (1.35 g,
99%, all four diastereomers) as a light-yellow oil.
According to GP1, alkoxyallene 17 (1.40 g, 3.30 mmol, d.r. 75:25), n-
butyllithium (1.36 mL, 3.30 mmol of 2.43 M in hexanes) in THF (60
mL) and 13 (0.708 g, 1.65 mmol) provided (after 1 h at –80 °C and
warm-up to –30 °C within 3 h and stirring at –30 °C for 12 h) the
crude product mixture. Purification by column chromatography (alu-
mina III, hexanes/EtOAc 3:1) afforded allene 17 (0.768 g, 55%) as a yel-
low oil and 23 (0.972 g, 85%, d.r. 54:22:21:3) as a light-yellow oil. The
ratio of diastereomers was determined by analytical HPLC.
1H NMR (CDCl3, 270 MHz): δ [(R,aS)-23] = 0.89 (t, J = 6.6 Hz, 3 H, Me),
0.95–1.60 (m, 16 H, CH2), 2.40 (s, 3 H, Tos-Me), 3.02–3.10 (m, 2 H, 1-
H), 3.95–4.10 (m, 1 H, 2-H), 5.07 (d, J = 8.6 Hz, 1 H, NH), 5.40 (td,
J = 6.7 Hz, J = 0.8 Hz, 1 H, 5-H), 7.15–7.25 (m, 7 H, Ph, Tos), 7.70 (d,
J = 8.3 Hz, 2 H, Tos); distinguishable signals of the other isomers,
δ [(S,aR)-23] = 5.24 (t, J = 6.6 Hz, 1 H, 5-H), 5.56 (d, J = 8.8 Hz, 1 H,
NH), δ [(R,aR)-23] = 2.38 (s, 3 H, Tos-Me), 4.41 (d, J = 9.6 Hz, 1 H, NH),
5.32 (t, J = 6.7 Hz, 1 H, 5-H), 7.64, 7.69 (2 d, J = 8.4 Hz, 2 H each, Tos);
the signals of (S,aS)-23 are hidden by those of the other diastereo-
mers.
13C NMR (CDCl3, 67.9 MHz): δ [(R,aS)-23] = 14.1 (q, Me), 21.4 (q, Tos-
Me), 22.6, 29.2, 29.3, 29.5, 30.9, 31.0, 31.1, 31.8 (8 t, CH2), 40.1 (t, C-1),
56.9 (d, C-2), 110.1 (d, C-5), 126.4, 127.0, 127.9, 129.4, 129.9 (5 d, Ph,
Tos), 131.3 (s, C-3), 136.6, 137.9, 142.9 (3 s, Ph, Tos), 188.6 (s, C-4);
distinguishable signals of the other isomers, δ [(R,aR)-23] = 39.1 (t,
C-1), 53.9 (d, C-2), 111.5 (d, C-5), 126.8, 127.1, 129.2, 129.6, 130.5 (5
d, Ph, Tos), 132.1 (s, C-3), 135.3, 137.4, 142.6 (3 s, Ph, Tos), 187.8 (s,
C-4); δ [(S,aR)-23 and (S,aS)-23] = 40.1, 40.6 (2 t, C-1), 111.1, 111.3 (2
d, C-5).
Data obtained from this mixture:
IR (film): 3280 (N–H), 3030–2855 (C–H), 1965 (C=C=C) cm–1
.
MS (EI, 80 eV): m/z (%) = 683 (3) [M+], 668 (10) [M+ – Me], 556 (16)
[M+ – C9H19], 260 (46) [C12H20O6+], 185 (74), 91 (100) [Bn+].
HRMS (EI, 80 eV): m/z [M+] calcd for C38H53NO8S: 683.3492; found:
683.3447.
The four diastereomers of 20 were partially separated by HPLC (hex-
anes/EtOAc 4:1).
Fraction 1: (R,aR/S,aR/S,aS)-20 (0.922 g, 68%, d.r. 87:9:4, determined
by HPLC) as a colorless oil.
Optical rotation: [α]D20 = –72.4 (c = 0.9, CHCl3).
Fraction 2: (R,aS)-20 (0.308 g, 23%) as a light-yellow oil.
Optical rotation: [α]D20 = –42.7 (c = 1.2, CHCl3).
1H NMR (CDCl3, 270 MHz): δ [(R,aR)-20] = 0.90 (t, J = 6.4 Hz, 3 H, Me),
1.15–1.40, 1.80–1.90 (2 m, 14 H, 2 H, CH2), 2.39 (s, 3 H, Tos-Me), 5.02
(d, J = 7.7 Hz, 1 H, 1-H), 5.61 (d, J = 7.7 Hz, 1 H, NH), 5.73 (dt,
J = 6.6 Hz, J = 1.0 Hz, 1 H, 4-H), 7.18–7.26, 7.32–7.38 (2 m, 7 H, Ph,
Tos), 7.69 (d, J = 8.1 Hz, 2 H, Tos); δ [(S,aR)-20] = 0.90 (t, J = 6.4 Hz, 3 H,
Me), 1.15–1.40, 1.80–1.90 (2 m, 14 H, 2 H, CH2), 2.41 (s, 3 H, Tos-Me),
5.07 (d, J = 7.5 Hz, 1 H, 1-H), 5.59 (t, J = 6.6 Hz, 1 H, 4-H), 5.83 (d,
J = 7.5 Hz, 1 H, NH), 7.16–7.43 (m, 7 H, Ph, Tos), 7.68 (d, J = 8.3 Hz, 2 H,
Tos); δ [(R,aS)-20] = 0.88 (t, J = 6.6 Hz, 3 H, Me), 1.15–1.40, 1.90–2.00
(2 m, 14 H, 2 H, CH2), 2.40 (s, 3 H, Tos-Me), 5.00 (d, J = 7.4 Hz, 1 H, 1-
IR (film): 3285 (N–H), 3060–2855 (C–H), 1965 (C=C=C), 1380, 1160
(TosN) cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–N