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H), 7.25–7.19 (m, 2 H), 6.90–6.84 (m, 4 H), 5.07 (s, 4 H), 4.61 (s, 4 H), mixture was stirred for 20 min. Methanesulfonyl chloride (58 μL,
4
(
.49 (pseudo-t, J = 1.9 Hz, 4 H), 4.24 (pseudo-t, J = 1.9 Hz, 4 H), 1.80 152 μmol) was then added at –10 °C, and the reaction was warmed
s, 2 H) ppm. 13C NMR (63 MHz, CDCl , 25°C): δ = 159.21, 140.63,
slowly to room temperature overnight. To the reaction mixture, LiBr
(133 mg, 1.5 mmol) was added, and the reaction was stirred at
room temperature for 2 h. After the completion of the reaction, the
mixture was poured onto water and extracted with EtOAc
3
1
1
36.85, 133.28, 129.12, 127.52, 127.30, 120.98, 114.04, 112.64,
00.12, 91.74, 82.85, 72.99, 71.47, 70.21, 65.21 ppm. HRMS (MALDI/
+
ESI): calcd. for C H FeO [M] 658.1802; found 658.1802.
42
34
4
(
2 × 50 mL). The organic phase was washed with water (2 × 50 mL)
Compound 21: An oven-dried 10 mL round-bottomed flask was
flushed with argon and charged with 20 (15 mg, 22.8 μmol) in
freshly distilled and deoxygenated THF (5 mL). To the mixture, NaH
and brine (50 mL), dried with MgSO , filtered, and concentrated
4
under reduced pressure. The crude product was purified by filtra-
tion through a silica gel plug with DCM/cyclohexane (1:5). The sol-
vent was removed under reduced pressure to afford 22 as an or-
ange oil, which solidified upon standing at 4 °C, yield 69 % (41 mg,
0
8
(60 % dispersion in mineral oil, 18.2 mg, 456 μmol) was added at
–10 °C, and the resulting suspension was stirred for 20 min. Meth-
anesulfonyl chloride (5.3 μL, 45.6 μmol) was then added at –10 °C.
The reaction mixture was warmed to room temperature overnight.
To the reaction mixture, LiBr (39.6 mg, 456 μmol) was added, and
the reaction was stirred at room temperature for 2 h. After the
reaction was finished, the reaction mixture was poured onto water
and extracted with EtOAc (2 × 50 mL). The organic phase was
washed with water (2 × 50 mL) and brine (50 mL), dried with
1
3
.052 mmol). H NMR (400 MHz, CDCl , 25°C): δ = 7.51 (d, J
=
3
H,H
.1 Hz, 4 H), 7.43–7.37 (m, 6 H), 7.26–7.20 (m, 2 H), 6.91–6.84 (m, 4
H), 5.08 (s, 4 H), 4.50 (pseudo-t, J = 1.9 Hz, 4 H), 4.45 (s, 4 H), 4.27
(
pseudo-t, J = 1.9 Hz, 4 H) ppm. 13C NMR (101 MHz, CDCl , 25°C):
3
δ = 159.21, 140.63, 136.58, 133.28, 129.12, 127.52, 127.30, 120.98,
14.04, 112.64, 100.12, 91.74, 82.85, 72.99, 71.47, 70.21, 65.21 ppm.
1
+
HRMS (MALDI/ESI): calcd. for C H Br FeO [M] 782.0113; found
7
42
32
2
2
MgSO , filtered, and concentrated under reduced pressure. The
4
82.0111.
crude product was purified by silica gel FCC with DCM/cyclohexane
Compound 23: A 5 mL round-bottomed flask was dried with a
heat gun, purged with argon, and charged with vinylmagnesium
bromide (0.7
(
(
1:5) to elute the bisbromo adduct 22 (40 %), EtOAc/cyclohexane
1:5) was utilized to elute 21, and EtOAc/cyclohexane (1:1) was used
M solution in THF, 1.5 mL, 1.04 mmol; clear, light brown
to wash out the starting material 20 (21 %). The solvent was re-
solution) and CuI (10 mg, 52 umol), and the mixture was cooled to
–78 °C. To the stirred suspension, 22 (41 mg, 52 umol) in freshly
distilled and deoxygenated THF (5 mL) was added, and the mixture
was allowed to reach room temperature overnight. After the reac-
tion was complete, the suspension was poured onto a saturated
moved under reduced pressure to afford 21 as an orange solid,
1
yield 33 % (5.5 mg, 7.28 μmol). H NMR (600 MHz, CDCl , 25°C): δ =
3
3
7
7
5
.54–7.52 (m, 2 H), 7.51 (d, J = 8.1 Hz, 2 H), 7.41–7.38 (m, 4 H),
.37 (d, J = 8.0 Hz, 2 H), 7.25–7.21 (m, 2 H), 6.90–6.85 (m, 4 H),
H,H
3
H,H
.09 (s, 2 H), 5.08 (s, 2 H), 4.64 (s, 2 H), 4.49 (pseudo-t, J = 1.9 Hz, 2
aqueous NH Cl solution (100 mL) and extracted with EtOAc
H), 4.46 (pseudo-t, J = 1.8 Hz, 2 H), 4.44 (s, 2 H), 4.24 (pseudo-dt,
4
1
3
(2 × 50 mL). The combined organic phases were washed with water
J = 4.9, 1.9 Hz, 4 H) ppm. C NMR (151 MHz, CDCl , 25°C): δ =
3
(
2 × 50 mL) and brine (50 mL), dried with MgSO , and filtered, and
1
1
1
7
59.05, 158.94, 140.49, 137.43, 137.29, 136.47, 133.16, 133.16,
29.19, 128.99, 128.96, 127.40, 127.16, 120.95, 120.83, 113.96,
13.87, 112.58, 112.50, 91.76, 91.60, 82.65, 82.60, 72.87, 72.85, 71.26,
4
the volatiles were removed under reduced pressure. The crude
product was purified by silica gel FCC with DCM/cyclohexane (1:10).
The solvent was removed under reduced pressure to afford 23 as
1.23, 70.06, 69.87, 67.12, 67.02, 65.12, 33.27 ppm. HRMS (ESI-TOF):
1
+
an orange oil, yield 68 % (24 mg, 0.035 mmol). H NMR (400 MHz,
calcd. for C H BrFeO [M] 720.0959; found 720.0956.
42
33
3
3
CDCl , 25°C): δ = 7.47 (d, J
= 8.0 Hz, 4 H), 7.41 (dd, J = 7.5,
3
H,H
Ether-Bridged Macrocycle 1: An oven-dried 20 mL round-bot-
tomed microwave vial was flushed with argon, charged with NaH
3
1
1
.7 Hz, 2 H), 7.25–7.18 (m, 6 H), 6.94–6.84 (m, 4 H), 5.94 (ddt, J
=
H,H
3
3
6.9, J
= 10.2 Hz, J
= 6.7 Hz, 2 H), 5.13–5.01 (m, 8 H), 4.49
H,H
H,H
(60 % dispersion in mineral oil, 10 mg, 251 μmol), 21 (5.5 mg,
(
pseudo-t, J = 1.9 Hz, 4 H), 4.22 (pseudo-t, J = 1.9 Hz, 4 H), 3.37 (d,
7
.2 μmol), and freshly distilled and deoxygenated THF (15 mL). The
3
13
JH,H = 6.7 Hz, 4 H) ppm. C NMR (63 MHz, CDCl , 25°C): δ = 159.21,
3
suspension was heated to70 °C for 2 h, after which MALDI MS indi-
cated the complete consumption of the starting material. The reac-
tion mixture was cooled to room temperature, transferred to an
Erlenmeyer flask, and quenched by the dropwise addition of water
139.69, 137.37, 134.82, 133.18, 128.96, 128.73, 127.38, 120.77,
1
15.84, 113.97, 112.68, 91.68, 82.59, 72.80, 71.42, 70.32, 66.94,
+
39.94 ppm. HRMS (MALDI/ESI): calcd. for C H FeO [M] 678.2217;
46
38
2
found 678.2215.
(50 mL). The organic phase was eluted with ethyl acetate, washed
Macrocycle 2: An oven-dried 50 mL Schlenk flask was purged with
argon and charged with a solution of 23 (20 mg, 295 μmol) in
freshly distilled dichloroethane (27 mL) and a solution of the first-
generation Grubbs catalyst (3.46 mg, 15 mol-%) in dichloroethane
with water (2 × 50 mL) and brine (50 mL), dried with MgSO , fil-
4
tered, and concentrated under reduced pressure. The crude product
was purified by silica gel column chromatography with EtOAc/cy-
clohexane (1:3). The solvent was removed under reduced pressure
(3 mL). The reaction mixture was degassed with bubbling argon for
to afford the ether-bridged derivative 1 as an orange oil, yield 70 %
15 min. Then, the flask was closed with a rubber septum, and the
1
(
3.4 mg, 7.62 μmol). H NMR (600 MHz, CDCl , 25°C): δ = 7.67 (d,
3
mixture was heated to 70 °C for 16 h. After the reaction was com-
plete, the mixture was cooled to room temperature and diluted
with EtOAc (50 mL). The crude mixture was concentrated and puri-
fied by silica gel FCC with DCM/cyclohexane (1:10). The solvent was
removed under reduced pressure to provide the macrocycle 2 as
an orange solid (a mixture of E and Z isomers, 73:27), yield 57 %
3
JH,H = 7.9 Hz, 4 H), 7.50–7.44 (m, 6 H), 7.35–7.28 (m, 2 H), 7.01 (dd,
3J = 8.3, J = 1.1 Hz, 2 H), 6.96 (td, J = 7.5, J = 1.0 Hz,
4
3
4
H,H
H,H
H,H
H,H
2
H), 5.14 (s, 4 H), 4.61 (pseudo-t, J = 1.8 Hz, 4 H), 4.58 (s, 4 H), 4.30
1
3
(pseudo-t, J = 1.8 Hz, 4 H) ppm. C NMR (151 MHz, CDCl , 25°C):
3
δ = 159.22, 137.78, 136.60, 132.65, 129.04, 128.00, 127.21, 120.94,
14.02, 112.19, 92.06, 82.67, 72.52, 72.41, 70.62, 70.03, 65.82 ppm.
1
1
13
(
11 mg, 0.017 mmol). The HSQC resolved H– C spectra is shown
+
HRMS (MALDI/ESI): calcd. for C H FeO [M] 640.1696; found
4
2
32
3
1
in Figure S17. H NMR (600 MHz, CDCl , 25°C): δ = 7.57–7.52 (m, 4
3
6
40.1696.
H, overlapping signals of E/Z), 7.47–7.42 (m, 2 H, overlapping signals
Compound 22: A 5 mL round-bottomed flask was dried with a heat of E/Z), 7.32–7.25 (m, 4 H, overlapping signals of E/Z), 7.02–6.97 (m,
gun, flushed with argon, and charged with 20 (50 mg, 756 umol) 2 H, overlapping signals of E/Z), 6.97–6.90 (m, 2 H, overlapping sig-
in freshly distilled and deoxygenated THF (5 mL). NaH (60 % disper-
nals of E/Z), 5.73–5.65 (m, 2 H, overlapping signals of E/Z), 5.16–
sion in mineral oil, 152 mg, 37 mmol) was added, and the reaction
5.13 (m, 4 H, overlapping signals of E/Z), 4.63 (pseudo-t, J = 1.8 Hz,
Eur. J. Org. Chem. 2016, 2187–2199
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2197
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