G. Papageorgiou, J. E. T. Corrie / Tetrahedron 63 (2007) 9668–9676
9673
J¼5.3 Hz, 1H), 4.44 (dd, J¼11.8 and 5.6 Hz, 2H), 4.37 (dd,
J¼11.7 and 5.0 Hz, 2H), 2.07 (s, 6H). Anal. Calcd for
C15H17NO5: C, 61.85; H, 5.88; N, 4.81. Found: C, 61.96;
H, 5.98; N, 4.73.
and evaporated to give crude 4-[1,3-di(tert-butyldimethylsi-
lyloxy)propan-2-yloxy]indoline (3.14 g, 75%) as a viscous
oil. 1H NMR (90 MHz) d 6.82 (t, J¼7.2 Hz 1H), 6.04–6.32
(m, 2H), 4.16–4.32 (m, 1H), 3.64–3.88 (m, 4H), 3.46 (t,
J¼7.2 Hz, 2H), 2.88 (t, J¼7.2 Hz, 2H), 2.04 (s, 1H), 0.88
(s, 18H), 0.04 (s, 12H). This material was dissolved in dry
MeCN (95 mL) and treated with 4-phthalimidobutanoic
acid (2.66 g, 11.4 mmol) and 1-(3-dimethylaminopropyl)-
3-ethylcarbodiimide hydrochloride (2.55 g, 13.3 mmol)
and the mixture was stirred at rt overnight. The solvent
was evaporated and the residue was taken up in EtOAc,
washed with 0.5 M aq HCl, saturated aq NaHCO3 and brine,
dried and evaporated. Flash chromatography [EtOAc–hex-
anes (1:4)/(2:3)/(1:1)] gave four products. The first
material eluted was 15 (1.69 g) as colourless crystals, mp
118–120 ꢀC (MeOH). This material was estimated by
1H NMR to contain w20% of 1-(4-phthalimidobutanoyl]-
4-[1-(tert-butyldimethylsilyloxy)propan-2-yloxy]indoline
16 (see below) and was not characterised further.
4.3. 1-[4-(tert-Butoxycarbonylamino)butanoyl]-
4-(1,3-diacetoxypropan-2-yloxy)indoline (10)
To a solution of 9 (0.55 g, 1.9 mmol) in acetic acid (15 mL)
was added portionwise NaBH3CN (0.47 g, 5.7 mmol), and
the mixture was stirred at rt for 1 h. The solvent was evapo-
rated and the residue was diluted with water, neutralised with
NaHCO3 and extracted with EtOAc. The combined organic
phases were washed with brine, dried and evaporated to give
crude 4-(1,3-diacetoxypropan-2-yloxy)indoline (0.56 g,
100%) as a viscous oil. 1H NMR (90 MHz) d 6.95 (t,
J¼7.2 Hz, 1H), 6.24–6.68 (m, 2H), 4.62 (quintet, J¼
5.4 Hz, 1H), 4.20–4.46 (m, 4H), 3.64 (s, 1H), 4.52 (t, J¼
7.2 Hz, 2H), 2.94 (t, J¼7.2 Hz, 2H), 2.06 (s, 6H). Without
further purification, this material was dissolved in dry
MeCN (20 mL) and treated with N-Boc-g-aminobutyric acid
(0.43 g, 2.1 mmol), followed by 1-(3-dimethylaminopropyl)-
3-ethylcarbodiimide hydrochloride (0.52 g, 2.7 mmol) and
the mixture was stirred at rt overnight. The solvent was
evaporated and the residue was taken up in EtOAc,
washed with dilute aq HCl, saturated aq NaHCO3 and
brine, dried and evaporated. Flash chromatography
[EtOAc–hexanes (3:2)] gave 10 (0.75 g, 82%) as a colour-
The second material eluted was 1-(4-phthalimidobutanoyl)-
4-[1-(tert-butyldimethylsilyloxy)propan-2-yloxy]indoline
16 (0.22 g, 6%) as colourless crystals, mp 94–96 ꢀC (Et2O–
hexanes). 1H NMR (500 MHz) d 7.81 (dd, J¼5.4 and 2.9 Hz,
2H), 7.71 (d, J¼8.2 Hz, 1H), 7.68 (dd, J¼5.4 and 2.9 Hz,
2H), 7.07 (t, J¼8.2 Hz, 1H), 6.51 (d, J¼8.2 Hz, 1H), 4.13–
4.19 (m, 1H), 4.02 (t, J¼8.5 Hz, 2H), 3.74–3.92 (m, 6H),
3.10 (t, J¼8.5 Hz, 2H), 2.47 (t, J¼7.1 Hz, 2H), 2.15 (quintet,
J¼7.1 Hz, 2H), 1.23 (d, J¼6.2 Hz, 3H), 0.90 (s, 9H), 0.10 (s,
3H), 0.08 (s, 3H). LRMS (ES+): calcd for (C29H38N2O5-
Si+H)+ 523, found 523. Anal. Calcd for C29H38N2O5-
Si+H2O: C, 64.64; H, 7.45; N, 5.18. Found: C, 64.70; H,
7.13; N, 5.12.
1
less viscous oil. H NMR (500 MHz) d 7.85 (d, J¼8.1 Hz,
1H), 7.14 (t, J¼8.1 Hz, 1H), 6.68 (d, J¼8.1 Hz, 1H), 4.83
(br s, 1H), 4.69 (quintet, J¼5.3 Hz, 1H), 4.27–4.38 (m, 4H),
4.05 (t, J¼8.4 Hz, 2H), 3.16–3.23 (m, 2H), 3.10 (t,
J¼8.4 Hz, 2H), 2.46 (t, J¼7 Hz, 2H), 2.07 (s, 6H), 1.92 (quin-
tet, J¼6.6 Hz, 2H), 1.42 (s, 9H). HRMS (FAB): calcd for
(C24H34N2O8+H)+ 479.2394, found 479.2393.
The third material eluted was 1-(4-phthalimidobutanoyl)-
4-[1-acetoxy-3-(tert-butyldimethylsilyloxy)propan-2-yl-
oxy]indoline 17 (0.15 g, 4%) as colourless viscous oil. H
1
4.4. 4-[1,3-Di(tert-butyldimethylsilyloxy)propan-2-
yloxy]indole (14)
NMR (500 MHz) d 7.81 (dd, J¼5.4 and 2.9 Hz, 2H), 7.67–
7.74 (m, 3H), 7.07 (t, J¼8.2 Hz, 1H), 6.63 (d, J¼8.2 Hz,
1H), 4.52 (quintet, J¼5.2 Hz, 1H), 4.28–4.36 (m, 2H),
4.01 (t, J¼8.5 Hz, 2H), 3.77–3.85 (m, 4H), 3.08 (t,
J¼8.5 Hz, 2H), 2.47 (t, J¼7.1 Hz, 2H), 2.15 (quintet,
J¼7.1 Hz, 2H), 2.04 (s, 3H), 0.90 (s, 9H), 0.05 (s, 3H),
0.04 (s, 3H). HRMS (ES+): calcd for (C31H40N2O7Si+H)+
581.2678, found 581.2668.
Crude 8 (2.63 g), prepared as described in Section 4.2, was
dissolved in dry CH2Cl2 (250 mL) and treated with imid-
azole (2.45 g, 36 mmol) and tert-butyldimethylsilyl chloride
(4.52 g, 30 mmol) and the mixture was stirred at rt under ni-
trogen overnight. The precipitated colourless solid was fil-
tered off and washed with CH2Cl2. The filtrate was washed
successively with 0.5 M aq HCl, 0.5 M aq NaOH and brine,
dried and evaporated to give 14 (4.13 g, 79%) as a colourless
viscous oil. 1H NMR (500 MHz) d 8.11 (br s, 1H), 6.99–7.12
(m, 3H), 6.61–6.67 (m, 2H), 4.51 (quintet, J¼5 Hz, 1H),
3.86–3.95 (m, 4H), 0.89 (s, 18H), 0.07 (s, 6H), 0.03 (s,
6H). HRMS (ES+): calcd for (C23H41NO3Si2+H)+
436.2698, found 436.2718.
The fourth material eluted was 1-(4-phthalimidobutanoyl)-
4-[1-(tert-butyldimethylsilyloxy)-3-hydroxypropan-2-yloxy]-
indoline 18 (0.48 g, 13%) as colourless crystals, mp 74–76 ꢀC
(EtOAc–hexanes). 1H NMR (500 MHz) d 7.82 (dd, J¼5.4 and
2.9 Hz, 2H), 7.73 (d, J¼8.2 Hz, 1H), 7.68 (dd, J¼5.4 and
2.9 Hz, 2H), 7.07 (t, J¼8.2 Hz, 1H), 6.62 (d, J¼
8.2 Hz, 1H), 4.41 (quintet, J¼5 Hz, 1H), 4.03 (t, J¼8.5 Hz,
2H), 3.80–3.95 (m, 6H), 3.10 (t, J¼8.5 Hz, 2H), 2.48 (t,
J¼7.1 Hz, 2H), 2.10–2.19 (m, 3H), 0.90 (s, 9H), 0.07 (s,
3H), 0.06 (s, 3H). Anal. Calcd for C29H38N2O6Si: C, 64.66;
H, 7.11; N, 5.20. Found: C, 64.44; H, 7.10; N, 5.06.
4.5. 1-(4-Phthalimidobutanoyl)-4-[1,3-di(tert-
butyldimethylsilyloxy)propan-2-yloxy]indoline (15)
and related compounds (16–18)
NaBH3CN (1.79 g, 28.5 mmol) was added portionwise to
a solution of 14 (4.13 g, 9.5 mmol) in acetic acid (90 mL)
and the mixture was stirred at rt for 1 h. The solvent was
evaporated and the residue was diluted with water, neutral-
ised with solid NaHCO3 and extracted with EtOAc. The
combined organic phases were washed with brine, dried
4.6. 1-(4-Azidobutanoyl)-4-(1,3-diacetoxypropan-2-
yloxy)indoline (23)
Crude 8 (1.47 g, 5 mmol), prepared as described in Section
4.2, was dissolved in dry MeCN (40 mL) and treated with