A. Boutros et al. / Tetrahedron 56 (2000) 2239±2246
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4-Quinolylmethyl phenoxyethanoate 8i. Yield: 92%. H
NMR 4.70 (2H, s), 5.62 (2H, s), 6.8±7.0 (3H, m), 7.15±7.25
(2H, m), 7.28 (1H, d, J4.5 Hz), 7.49 (1H, t, J7.5 Hz),
7.67 (1H, t, J7.5 Hz), 7.81 (1H, d, J8.5 Hz), 8.11 (1H, d,
J8.5 Hz), 8.81 (1H, d, J4.5 Hz). 13C NMR 63.0, 65.3,
114.6, 119.9, 121.8, 122.7, 125.8, 127.0, 129.3, 129.4,
130.3, 140.0, 148.2, 150.0, 157.7, 168.5. IR 1727. HRMS
calculated for C18H15NO3: 293.1052. Found: 293.1049.
148.3, 150.2, 173.2, 173.4. IR 1740. C27H31NO4 calculated:
C 74.80, H 7.21, N 3.23. Found: C 74.79, H 7.21, N 3.22.
Prop-2-enyl 4-quinolylmethyl decanedioate 8n. Yield:
90%. H NMR 1.10±1.40 (8H, m), 1.50±1.75 (4H, m),
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2.30 (2H, t, J7.5 Hz), 2.41 (2H, t, J7.5 Hz), 4.55 (2H,
d, J5.5 Hz), 5.20 (1H, dd, J10.5 and 1 Hz), 5.28 (1H, dd,
J17 and 1 Hz), 5.58 (2H, s), 5.89 (1H, ddt, J17, 10.5, and
5.5 Hz), 7.43 (1H, d, J4.5 Hz), 7.58 (1H, t, J7.5 Hz), 7.73
(1H, t, J7 Hz), 7.93 (1H, d, J8 Hz), 8.14 (1H, d, J8 Hz),
8.90 (1H, d, J4.5 Hz). 13C NMR 24.6, 28.7, 33.8, 62.1, 64.6,
117.7, 119.4, 122.7, 125.7, 126.7, 129.1, 129.9, 132.1, 140.9,
147.8, 149.9, 172.9, 173.0. IR 1732, 1736. HRMS calculated
for C23H29NO4: 383.2097. Found: 383.2087.
4-Quinolylmethyl 5-chloropentanoate 8j. Yield: 92%. 1H
NMR 1.65±1.90 (4H, m), 2.41 (2H, t, J7 Hz), 3.46 (2H, t,
J6 Hz), 5.53 (2H, s), 7.36 (1H, d, J4.5 Hz), 7.52 (1H, t,
J7.5 Hz), 7.67 (1H, t, J7.5 Hz), 7.87 (1H, d, J8.5 Hz),
8.08 (1H, d, J8.5 Hz), 8.84 (1H, d, J4.5 Hz). 13C NMR
22.0, 31.6, 33.1, 44.2, 62.4, 119.6, 122.8, 125.8, 126.9,
129.3, 130.1, 140.8, 147.9, 150.0, 172.5. IR 1732. HRMS
calculated for C15H16ClNO2: 277.0870. Found: 277.0870.
Preparation of di (4-QUI) diester 8o
To a CH2Cl2 (10 ml) solution of 4-quinolylmethanol 7
(318 mg, 2 mmol), DMAP (24 mg, 0.2 mmol) and Et3N
(340 ml, 2.4 mmol), sebacoyl chloride (240 ml, 1.1 mmol)
was added dropwise. After stirring at room temperature
during 24 h, the resulted mixture was diluted with 30 ml
of diethyl ether and washed with 2£30 ml water. The
aqueous phases were extracted with 2£20 ml of diethyl
ether and the combined ethereal phases were dried
(MgSO4) and concentrated. The crude product was puri®ed
by ¯ash chromatography (silica, heptane/ethyl acetate 6:4).
4-Quinolylmethyl 7-oxooctanoate 8k. Yield: 95%. 1H
NMR 1.15±1.40 (2H, m), 1.45±1.70 (4H, m), 2.08 (3H,
s), 2.30±2.50 (4H, m), 5.56 (2H, s), 7.40 (1H, d,
J4.5 Hz), 7.57 (1H, t, J7.5 Hz), 7.71 (1H, t,
J7.5 Hz), 7.92 (1H, d, J8 Hz), 8.12 (1H, d, J8.5 Hz),
8.87 (1H, d, J4.5 Hz). 13C NMR 23.1, 24.5, 28.4, 29.8,
33.8, 43.2, 62.3, 119.7, 122.9, 125.9, 126.9, 129.4, 130.1,
141.0, 148.0, 150.1, 173.0, 208.7. IR 1714, 1736. HRMS
calculated for C18H21NO3: 299.1522. Found: 299.1520.
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Ethyl 4-quinolylmethyl butanedioate 8l. Yield: 88%. H
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Di(4-quinolylmethyl) decanedioate 8o. Yield: 85%. H
NMR 1.16 (3H, t, J7 Hz), 2.55±2.80 (4H, m), 4.06 (2H, q,
J7 Hz), 5.56 (2H, s), 7.40 (1H, d, J4.5 Hz), 7.53 (1H, t,
J7.5 Hz), 7.68 (1H, t, J7.5 Hz), 7.87 (1H, d, J8.5 Hz),
8.10 (1H, d, J8.5 Hz), 8.85 (1H, d, J4.5 Hz). 13C NMR
14.0, 28.88, 28.91, 60.7, 62.6, 119.6, 122.8, 125.8, 127.0,
129.4, 129.9, 140.9, 147.7, 149.9, 171.8, 172.0. IR 1731,
1733. HRMS calculated for C16H17NO4: 287.1158. Found:
287.1147.
NMR 1.15±1.45 (8H, m), 1.55±1.75 (4H, m), 2.40 (4H, t,
J7.5 Hz), 5.58 (4H, s), 7.42 (2H, d, J4.5 Hz), 7.59 (2H, t,
J7.5 Hz), 7.73 (2H, t, J7.5 Hz), 7.93 (2H, d, J8 Hz), 8.13
(2H, d, J8.5 Hz), 8.89 (2H, d, J4.5 Hz). 13C NMR 24.8,
28.9, 34.1, 62.3, 119.7, 122.9, 125.9, 127.0, 129.4, 130.1,
141.1, 148.0, 150.1, 173.2. IR 1736. C30H32N2O4 calculated:
C 74.35, H 6.66, N 5.78. Found: C 74.30, H 6.68, N 5.73.
Preparation of 1-NAP ester of N-Boc-l-Phe-OH 15
Preparation of 4-QUI esters 8m and 8n
To a CH2Cl2 (75 ml) solution of N-Boc-l-Phe-OH 14
(1.33 g, 5 mmol) and 1-naphthylmethanol (0.79 g,
5 mmol) was added at 08C a CH2Cl2 (10 ml) solution of
DCC (1.25 g, 6 mmol). After stirring at 08C during 2 h,
the reaction mixture was ®ltered and the solvent evaporated.
The crude product was puri®ed by ¯ash chromatography
(silica, heptane/ethyl acetate 6:4) to give 15 (1.82 g, 4.5 mmol).
To a CH2Cl2 (10 ml) solution of 4-quinolylmethanol 7
(159 mg, 1 mmol), DMAP (24 mg, 0.2 mmol) and Et3N
(340 ml, 2.4 mmol), sebacoyl chloride (240 ml, 1.1 mmol)
was added dropwise. After stirring at room temperature
during 4 h, benzyl (for 8m) or allyl (for 8n) alcohol
(1 mmol) was added dropwise. The resulted mixture was
stirred at room temperature during 24 h, when diluted
with 30 ml of diethyl ether and washed with 2£30 ml
water. The aqueous phases were extracted with 2£20 ml
of diethyl ether and the combined ethereal phases were
dried (MgSO4) and concentrated. The crude product was
puri®ed by ¯ash chromatography (silica, heptane/ethyl
acetate 6/4).
(2S) 1-Naphthylmethyl 2-[N-(1,1-dimethylethyl)oxycar-
bonyl]amino-3-phenylpropanoate 15. Yield: 90%.
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[a]2D0213.78 (c 1.56, methanol). H NMR 1.39 (9H, s),
3.03 (2H, m), 4.60±4.70 (1H, m), 4.99 (1H, d, J8 Hz),
5.60 (2H, AB signal, J12.5 Hz), 6.85±7.10 (2H, m),
7.10±7.30 (3H, m), 7.45±7.65 (4H, m), 7.80±8.05 (3H, m).
13C NMR 28.2, 38.1, 54.4, 65.2, 79.8, 123.4, 125.1, 125.9,
126.6, 126.8, 127.8, 128.3, 128.6, 129.2, 129.4, 130.7, 131.5,
133.6, 135.7, 155.0, 171.7. IR 3366, 1724, 1690. HRMS
calculated for C25H27NO4: 405.1940. Found: 405.1940.
Phenylmethyl 4-quinolylmethyl decanedioate 8m. Yield:
85%. 1H NMR 1.10±1.40 (8H, m), 1.50±1.75 (4H, m), 2.32
(2H, t, J7.5 Hz), 2.41 (2H, t, J7.5 Hz), 5.09 (2H, s), 5.58
(2H, s), 7.25±7.40 (5H, m), 7.43 (1H, d, J4.5 Hz), 7.59
(1H, t, J7.5 Hz), 7.73 (1H, t, J7.5 Hz), 7.94 (1H, d,
J8 Hz), 8.14 (1H, d, J8.5 Hz), 8.90 (1H, d, J4.5 Hz).
13C NMR 24.9, 29.0, 34.2, 34.3, 62.4, 66.0, 119.8, 123.0,
126.1, 127.0, 128.1, 128.5, 129.4, 130.3, 136.3, 141.2,
Deprotection reactions
A typical procedure is as follows: compound 8 or 15
(1 mmol) in 1 ml of DMSO was added under argon to a
mixture of Pd(dba)2 (11.5 mg, 0.02 mmol) and dppe