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δ = 172.0, 140.1, 135.7, 134.3, 129.7, 117.9, 113.8, 112.5, 45.1,
33.3 ppm. HRMS (ESI+): calcd. for C20H17N4O4 377.1250 [M + H]+;
found 377.1242.
136.2, 145.1, 149.7, 150.3, 173.3 ppm. IR (neat): νmax = 755, 946,
˜
1056, 1158, 1171, 1211, 1243, 1328, 1435, 1728, 2942 cm–1. HRMS
(ESI+): calcd. for C20H17N6O4 405.1311 [M + H]+; found 405.1320.
6-Chloro-2-(dichloromethyl)-2,3-dihydroimidazo[1,2-a]pyridin-
2-ol Hydrochloride (5c): A similar procedure to that used for the
synthesis of 5a was followed. The product was obtained by filtration
Acknowledgments
1
Financial support from the Centre National de la Recherche
Scientifique (CNRS) is gratefully acknowledged. We gratefully
acknowledge the International Associated Laboratory (LIA:
NATPROCHEMLAB) between the Centre National de la Recher-
che Scientifique (CNRS, ICSN, France) and the Vietnam Academy
of Science and Technology (Institute of Marine Biochemistry,
VAST, Vietnam), which supports the project.
in virtually quantitative yield as a yellow solid (30 mmol scale). H
NMR (300 MHz, CD3OD): δ = 8.50 (d, J = 2.2 Hz, 1 H), 8.15 (dd, J =
9.7, 2.2 Hz, 1 H), 7.19 (d, J = 9.7 Hz, 1 H), 6.36 (s, 1 H), 5.04 (d, J =
14.9 Hz, 1 H), 4.72 (d, J = 14.9 Hz, 1 H) ppm. 13C NMR (75 MHz,
CD3OD): δ = 154.8, 147.5, 136.8, 122.9, 111.4, 93.5, 75.6, 61.8 ppm.
HRMS (ESI+): calcd. for C8H8Cl3N2O 252.9702 [M + H]+; found
252.9718.
6-Chloroimidazo[1,2-a]pyridine-2-carbaldehyde (6c): A similar
procedure to that used for the synthesis of 6a was followed. The
product was obtained by filtration as a brown-yellow solid. We
noted that the product was first obtained as a mixture of aldehyde
and hydrate, but finally transformed into the pure aldehyde on stor-
age at room temp. 1H NMR (300 MHz, CDCl3): δ = 10.14 (s, 1 H),
8.26 (d, J = 1.9 Hz, 1 H), 8.15 (s, 1 H), 7.64 (d, J = 9.7 Hz, 1 H), 7.26
(dd, J = 9.7, 1.9 Hz, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 187.8,
144.5, 144.2, 128.5, 124.5, 123.0, 119.8, 115.7 ppm. HRMS (ESI+):
calcd. for C8H6ClN2O 181.0169 [M + H]+; found 181.0177.
Keywords: Natural products · Dimerization ·
Photochemistry · Cyclization · Synthetic methods
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(E)-3-(6-Chloroimidazo[1,2-a]pyridin-2-yl)acrylic Acid [(E)-7c]: A
similar procedure to that used for the synthesis of 7a was followed
(130 °C, 1 h). The product (1023 mg) was obtained as a yellow solid
1
in 92 % yield (5 mmol scale). H NMR (300 MHz, CD3OD): δ = 8.60
(d, J = 2.2 Hz, 1 H), 8.10 (s, 1 H), 7.68 (d, J = 15.7 Hz, 1 H), 7.54 (d,
J = 9.7 Hz, 1 H), 7.37 (dd, J = 9.7, 2.2 Hz, 1 H), 6.71 (d, J = 15.7 Hz,
1 H) ppm. 13C NMR (75 MHz, CD3OD): δ = 170.2, 145.9, 142.8, 137.0,
129.6, 126.4, 122.6, 121.7, 118.2, 116.8 ppm. HRMS (ESI+): calcd. for
C10H8ClN2O2 223.0274 [M + H]+; found 223.0265.
[2+2] Photodimerization Reaction of a Suspension of (E)-7c in
Cyclohexane — 3-(6-Chloro-1,8a-dihydroimidazo[1,2-a]pyridin-
2-yl)-4-(6-chloroimidazo[1,2-a]pyridin-2-yl)cyclobutane-1,2-di-
carboxylic Acid (8c): A slurry of acid (E)-7c (100 mg) in cyclohex-
ane (5 mL) was irradiated and stirred under Ar for 24 h in a 17 mL
Pyrex tube. The reaction mixture was concentrated in vacuo to pro-
vide crude diacid 8c, which was purified by dissolving in hot meth-
anol and filtering through a short pad of silica gel. The filtrate was
concentrated to give pure 8c as a pale-yellow solid (95 mg, 95 %).
1H NMR (300 MHz, CD3OD): δ = 8.38 (d, J = 2.2 Hz, 2 H), 7.55 (s, 2
H), 7.32 (d, J = 9.7 Hz, 2 H), 7.16 (dd, J = 9.7, 2.2 Hz, 2 H), 4.45 (dd,
J = 6.2, 1.7 Hz, 2 H), 4.07 (dd, J = 6.2, 1.7 Hz, 2 H) ppm. 13C NMR
(125 MHz, [D6]CD3OD + 1 drop of TFA): δ = 174.0, 141.1, 140.8,
129.8, 125.5, 122.3, 114.3, 112.7, 43.4, 37.5 ppm. HRMS (ESI+): calcd.
for C20H15Cl2N4O4 445.0470 [M + H]+; found 445.0482.
Photocyclization of 9a into 13: Diester 9a (239 mg, 0.59 mmol,
1 equiv.) and iodine (75 mg, 0.29 mmol, 0.5 equiv.) were dissolved
in DMSO (88 mL). The resulting solution was stirred at room temp.
for 15 min and then poured into nine quartz tubes. Propylene oxide
(400 μL) was added to each tube. The reaction mixtures were then
irradiated at 365 nm and stirred under argon for 24 h. The com-
bined reaction mixtures were concentrated under vacuum. The
crude mixture was purified by rapid filtration through a silica gel
pad (eluent: CH2Cl2/MeOH, 95:5 then 9:1) to provide 140 mg of
compound 13 as a yellow solid in 59 % yield. M.p. >300 °C (degrad.)
1H NMR (500 MHz, CD3OD/CDCl3, 5:1): δ = 3.76 (s, 6 H), 3.83 (d, J =
5.1 Hz, 2 H), 4.50 (d, J = 5.1 Hz, 2 H), 7.19 (dd, J = 6.9, 4.1 Hz, 2 H),
8.52 (d, J = 4.2 Hz, 2 H), 9.07 (dd, J = 6.9 Hz, 2 H) ppm. 13C NMR
(125 MHz, CD3OD/CDCl3, 5:1): δ = 37.4, 48.5, 52.9, 111.2, 114.4,
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