Bronk and Thayumanavan
reaction mixture was cooled to -78 °C. To the stirring reaction
used. The reaction was refluxed for 72 h. The crude product
was purified using 50% CH2Cl2 in hexanes as the eluent.
Yield: 260 mg (80%). 1H NMR (400 MHz, CD2Cl2): δ 7.42-
7.34 (m, 8 H), 7.26-7.11 (m, 4 H), 7.09-6.91 (m, 29 H), 6.89-
6.82 (m, 12 H), 6.74-6.64 (m, 3 H), 6.26-6.25 (d, J ) 2.0 Hz,
2 H), 6.24-6.23 (m, 1 H), 4.82 (s, 4 H), 4.55 (s, 2 H), 3.96-
3.91 (m, 12 H), 1.81-1.74 (p, J ) 7.0 Hz, 12 H), 1.48-1.44 (m,
12 H), 1.36-1.32 (m, 48 H), 0.93-0.86 (m, 18 H). 13C NMR
(100 MHz, CD2Cl2): δ 164.9, 162.5, 160.7, 156.5, 155.9, 149.7,
149.6, 149.2, 148.7, 148.2, 147.5, 146.9, 143.2, 141.0, 140.4,
138.2, 134.7, 132.7, 130.4, 129.8, 129.6, 127.9, 127.2, 126.9,
124.6, 123.8, 122.6, 122.2, 121.7, 121.1, 121.0, 119.2, 115.7,
115.6, 109.3, 104.5, 97.7, 70.3, 68.2, 65.0, 32.2, 29.8, 29.7, 29.6,
26.4, 23.1, 14.3. MALDI-ToF (m/z): 2104.47 (M+ + Na calcd
for C140H166FN5O9 2104.8).
Syn th esis of 3-Mer Br om id e (20a ). The 3-mer alcohol 19a
(1.09 g, 0.52 mmol), CBr4 (173 mg, 0.52 mmol), Ph3P (137 mg,
0.52 mmol), and THF (60 mL) were used. The crude product
was purified using 35% CH2Cl2 in hexanes as the eluent.
Yield: 970 mg (87%). 1H NMR (400 MHz, CD2Cl2): δ 7.30-
7.22 (m, 7 H), 7.08-7.03 (m, 6 H), 6.98-6.72 (m, 43 H), 6.10-
6.09 (d, J ) 2.1 Hz, 2 H), 6.06-6.05 (t, J ) 2.3 Hz, 1 H), 4.71
(s, 4 H), 4.26 (s, 2 H), 3.84-3.81 (t, J ) 6.5 Hz, 12 H), 2.21 (s,
3 H), 1.71-1.64 (m, 12 H), 1.38-1.33 (m, 12 H), 1.25-1.21
(m, 48 H), 0.81-0.79 (m, 18 H). 13C NMR (100 MHz, CD2Cl2):
δ 160.4, 149.6, 148.2, 146.8, 144.6, 139.1, 133.9, 130.2, 129.7,
127.1, 125.8, 124.1, 123.6, 123.3, 123.0, 115.5, 103.1, 96.7, 70.1,
68.5, 33.9, 32.1, 29.6, 29.5, 29.4, 26.3, 22.9, 20.8, 14.1. MALDI-
ToF (m/z): 2152.03 (M+ calcd for C142H170BrN5O8 2152.2).
Syn th esis of 3-Mer Br om id e (20b). The 3-mer alcohol 19b
(220 mg, 0.11 mmol), CBr4 (35 mg, 0.11 mmol), Ph3P (28 mg,
0.11 mmol), and THF (10 mL) were used. The crude product
was purified using 40% CH2Cl2 in hexanes as the eluent.
Yield: 190 mg (84%). 1H NMR (400 MHz, CD2Cl2): δ 7.82-
7.36 (m, 8 H), 7.23-6.68 (m, 48 H), 6.27-6.25 (m, 3 H), 4.82
(s, 4 H), 4.38 (s, 2 H), 3.95-3.92 (t, J ) 6.3 Hz, 12 H), 1.81-
1.74 (quin, J ) 7.0 Hz, 12 H), 1.49-1.44 (m, 12 H), 1.37-1.32
(m, 48 H), 0.93-0.90 (m, 18 H). 13C NMR (100 MHz, CD2Cl2):
δ 162.5, 160.8, 149.4, 149.3, 149.0, 147.6, 139.6, 130.7, 130.6,
130.1, 125.4, 124.9, 124.4, 123.5, 119.6, 115.7, 111.0, 109.8,
109.6, 104.6, 98.0, 70.4, 68.6, 32.2, 29.8, 29.7, 29.6, 23.1, 14.3.
MALDI-ToF (m/z) 2080.58 (M+ - Br calcd for C141H167BrFN5O8
2078.8).
Syn th esis of 7-Mer Alcoh ol (21a ). Compound 1a (41 mg,
0.13 mmol), the 3-mer bromide 20a (550 mg, 0.26 mmol), 18-
crown-6 (34 mg, 0.13 mmol), K2CO3 (141 mg, 1.02 mmol), and
THF (40 mL) were used. The reaction was refluxed for 72 h.
The crude product was purified using 10% ethyl acetate in
hexanes as the eluent. Yield: 450 mg (79%). 1H NMR (400
MHz, CD2Cl2): δ 7.33-7.31 (d, J ) 7.6 Hz, 15 H), 7.16-7.11
(m, 9 H), 7.03-6.78 (m, 96 H), 6.16 (d, J ) 2.1 Hz, 4 H), 6.15
(d, J ) 2.0 Hz, 2 H), 6.11-6.08 (m, 3 H), 4.75 (s, 8 H), 4.67 (s,
4 H), 4.48-4.47 (d, J ) 5.5 Hz, 2 H), 3.91-3.88 (m, 24 H),
2.36 (m, 9 H), 1.79-1.71 (m, 24 H), 1.45-1.43 (m, 24 H), 1.40-
1.30 (m, 96 H), 0.91-0.87 (m, 36 H). 13C NMR (100 MHz, CD2-
Cl2): δ 160.4, 130.1, 129.4, 127.1, 125.6, 123.3, 115.5, 102.9,
68.5, 32.1, 29.6, 29.5, 29.4, 26.3, 22.9, 14.1. MALDI-ToF (m/
z): 4483.96 (M+ + Na calcd for C304H357N11O19 4488.7).
t
mixture was added a 1.7 M solution of BuLi (11.5 mL, 19.6
mmol) and the mixture was allowed to stir for 15 min. This
was followed by the addition of dry DMF (2.42 mL, 31.2 mmol)
and allowed to stir for 30 min. The reaction mixture was then
removed from the bath and allowed to stir at room temperature
for 18 h. Water was added to the reaction mixture. The
aqueous layer was extracted with ether, and the organic layer
was concentrated under reduced pressure to afford the crude
reaction mixture, which was purified by column chromatog-
raphy (SiO2, 35% CH2Cl2 in hexanes) to afford 5.43 g (68%
1
yield) of product 16. H NMR (400 MHz, CD2Cl2): δ 9.87 (s, 1
H), 7.48-7.45 (m, 3 H), 7.41-7.35 (m, 4 H), 7.31-7.28 (m, 1
H), 7.12-7.05 (m, 7 H), 6.95-6.87 (m, 5 H), 6.85-6.83 (d, J )
9.0 Hz, 4 H), 3.98-3.92 (m, 6 H), 1.83-1.74 (m, 6 H), 1.48-
1.43 (m, 6 H), 1.39-1.31 (m, 24 H), 0.92-0.89 (m, 9 H). 13C
NMR (100 MHz, CD2Cl2): δ 192.4, 156.8, 149.3, 146.2, 156.8,
139.7, 137.8, 135.6, 129.9, 128.0, 127.3, 124.1, 122.5, 121.7,
115.7, 115.4, 68.5, 32.1, 29.6, 29.6, 29.5, 29.4, 26.3, 22.9, 14.1.
MALDI-ToF (m/z): 901.25 (M+ calcd for C61H75 N2O4 900.6).
Syn th esis of 17. In a round-bottom flask, 16 (5.30 g, 5.89
mmol) was dissolved in ethanol (300 mL). To this solution was
added NaBH4 (0.27 g, 7.06 mmol), and the mixture was
allowed to stir under N2 for 13 h. Water was added to the
reaction mixture. The aqueous layer was extracted with CH2-
Cl2, and the organic layer was concentrated under reduced
pressure to afford the crude reaction mixture, which was
purified by column chromatography (SiO2, 70% CH2Cl2 in
hexanes) to afford 5.31 g (97% yield) of 17. 1H NMR (400 MHz,
CD2Cl2): δ 7.43-7.38 (m, 4 H), 7.24-7.20 (t, J ) 7.8 Hz, 1 H),
7.09-7.04 (m, 9 H), 6.99-6.94 (m, 4 H), 6.88-6.83 (m, 6 H),
4.56-4.55 (d, J ) 5.7 Hz, 2 H), 3.97-3.93 (m, 6 H), 1.91-1.88
(t, J ) 5.9 Hz, 1 H), 1.84-1.76 (m, 6 H), 1.65-1.45 (m, 6 H),
1.41-1.31 (m, 24 H), 0.95-0.91 (m, 9 H). 13C NMR (100 MHz,
CD2Cl2): δ 156.3, 155.8, 148.6, 148.0, 147.0, 142.6, 140.9, 140.5,
134.4, 132.6, 129.4, 128.9, 127.7, 127.0, 126.8, 123.3, 121.9,
121.1, 120.9, 120.4, 115.5, 115.4, 68.5, 65.1, 32.1, 29.6, 29.6,
29.5, 26.3, 22.9, 14.2. MALDI-ToF (m/z): 906.07 (M+ calcd for
C
61H79 N2O4 902.6).
Syn th esis of 18. Compound 17 (2.00 g, 2.22 mmol), Ph3P
(0.58 g, 2.22 mmol), CBr4 (0.73 g, 2.22 mmol), and THF (100
mL) were used. The crude product was purified using 20% CH2-
Cl2 in hexanes as the eluent. Yield: 2.00 g (93%). 1H NMR
(400 MHz, CD2Cl2): δ 7.45-7.38 (m, 4 H), 7.21-7.17 (t, J )
7.9 Hz, 1 H), 7.10-7.06 (m, 9 H), 6.98-6.95 (m, 3 H), 6.90-
6.83 (m, 7 H), 4.41 (s, 2 H), 3.98-3.93 (m, 6 H), 1.83-1.75 (m,
6 H), 1.49-1.44 (m, 6 H), 1.39-1.32 (m, 24 H), 0.93-0.89 (m,
9 H). 13C NMR (100 MHz, CD2Cl2): δ 156.5, 146.6, 139.1, 129.6,
127.8, 127.2, 123.7, 122.5, 122.2, 115.6, 68.5, 34.0, 32.1, 29.6,
29.5, 29.4, 26.3, 22.9, 14.1. MALDI-ToF (m/z): 966.55 (M+ calcd
for C61H77 BrN2O3 964.5).
Syn th esis of 3-Mer Alcoh ol (19a ). Compounds 1a (180
mg, 0.56 mmol) and 18 (1.08 g, 1.12 mmol), 18-crown-6 (148
mg, 0.56 mmol), K2CO3 (464 mg, 3.36 mmol), and THF (60 mL)
were used. The reaction was refluxed for 60 h. The crude
product was purified using 45% CH2Cl2 in hexanes as the
1
eluent. Yield: 920 mg (79%). H NMR (400 MHz, CD2Cl2): δ
7.42-7.38 (t, J ) 9.2 Hz, 8 H), 7.24-7.19 (d of t, J ab ) 7.8 Hz,
J ac ) 1.9 Hz, 2 H), 7.10-7.04 (m, 22 H), 7.01-6.95 (m, 12 H),
6.88-6.85 (m, 12 H), 6.25 (d, J ) 2.0 Hz, 2 H), 6.19-6.18 (t, J
) 2.0 Hz, 1 H), 4.82 (s, 4 H), 4.54 (s, 2 H), 3.98-3.95 (t, J )
6.5 Hz, 12 H), 2.34 (s, 3 H), 1.88-1.79 (m, 12 H), 1.53-1.48
(m, 12 H), 1.39-1.37 (m, 48 H), 0.98-0.95 (m, 18 H). 13C NMR
(100 MHz, CD2Cl2): δ 160.5, 156.3, 155.8, 150.0, 148.5, 148.1,
148.0, 146.8, 145.1, 142.7, 141.0, 140.4, 138.3, 134.6, 133.5,
132.6, 130.2, 129.5, 127.7, 127.1, 126.8, 125.6, 123.4, 122.7,
122.1, 121.6, 121.3, 121.0, 120.9, 115.6, 115.5, 102.9, 96.3, 70.1,
68.5, 65.0, 32.1, 29.7, 29.6, 29.5, 26.4, 23.0, 14.2. MALDI-ToF
(m/z): 2087.56 (M+ calcd for C142H171N5O9 2090.3).
Syn th esis of 7-Mer Alcoh ol (21b). Compound 1b (23 mg,
0.070 mmol), the 3-mer bromide 20a (300 mg, 0.14 mmol), 18-
crown-6 (17 mg, 0.070 mmol), K2CO3 (58 mg, 0.42 mmol), and
THF (25 mL) were used. The reaction was refluxed for 36 h.
The crude product was purified using 10% ethyl acetate in
hexanes as the eluent. Yield: 247 mg (79%). 1H NMR (400
MHz, CD2Cl2): δ 7.35-7.32 (t, J ) 8.4 Hz, 16 H), 7.24-7.09
(m, 10 H), 7.04-6.94 (m, 46 H), 6.93-6.88 (m, 22 H), 6.83-
6.62 (m, 26 H), 6.28-6.13 (m, 9 H), 4.76 (s, 8 H), 4.72 (s, 4 H),
4.53 (s, 2 H), 3.94-3.89 (m, 24 H), 2.28 (s, 6 H), 1.81-1.74 (m,
24 H), 1.47-1.45 (m, 24 H), 1.36-1.32 (m, 96 H), 0.94-0.90
(m, 36 H). 13C NMR (100 MHz, CD2Cl2): δ 160.8, 160.5, 156.4,
155.9, 149.9, 148.2, 148.1, 146.9, 145.0, 141.0, 140.4, 138.3,
138.2, 134.2, 133.7, 132.7, 130.3, 129.6, 127.8, 127.2, 126.9,
Syn th esis of 3-Mer Alcoh ol (19b). Compounds 1b (51 mg,
0.16 mmol) and 18 (300 mg, 0.31 mmol), 18-crown-6 (41 mg,
0.16 mmol), K2CO3 (85 mg, 0.62 mmol), and THF (25 mL) were
5566 J . Org. Chem., Vol. 68, No. 14, 2003