Photo-Triggered Click Reaction
A R T I C L E S
2-{2-[(9-Butoxy-1-oxo-6,7-dihydro-1H-dibenzo[a,e]cyclopro-
pa[c] [8]annulen-4-yl)oxy] ethoxy}ethyl {2-[2-(2-{[5-(2-oxohexahy-
dro-1H-thieno[3,4-d]imidazol-4-yl)pentanoyl]amino} ethoxy)etho-
xy]ethyl}carbamate (2b). A solution of cyclopropenone acetal 9
(0.21 g, 0.312 mmol) in DMF (2 mL) was added to a solution of
Et3N (0.18 g, 1.75 mmol) and N-biotinyl-3,6-dioxaoctane-1,8-
diamine9 (0.13 g, 0.35 mmol) in DMF (35 mL) at r.t. The reaction
mixture was stirred for 18 h and then most of the solvent was
evaporated under reduced pressure. The residue was passed through
a short column of silica gel (CH2Cl2:MeOH 25:1 + 1.5% of Et3N)
to provide crude 10 (0.275 g) that was used in the next step without
further purification. A suspension of crude cyclopropenone acetal
10 (0.199 g) and Amberlyst 15 (0.10 g) in Me2CO (10 mL) was
stirred for 60 min at r.t. Solids were removed by filtration, the
solvent was evaporated under reduced pressure, and the residue
was purified by silica gel column chromatography (CH2Cl2:MeOH,
10:1) to provide cyclopropenone 2b (17 mg) as an amorphous solid.
1H NMR: δ 7.65 (dd, J ) 8.4, 3.0 Hz, 2 H), 6.93-6.87 (m, 4 H),
6.66 (s, b, 1 H), 6.25, (s, b, 1 H) 5.61 (m, b, 1 H) 5.39 (s, b, 1 H)
4.48 (m, b, 1 H), 4.30-4.24 (m, 4 H), 4.21 (t, J ) 5.0 Hz, 2 H),
4.05 (t, J ) 7.5 Hz, 2 H), 3.88 (t, J ) 5.5 Hz, 2 H), 3.78 (m, 2 H),
3.60 (s, 4 H), 3.44 (q, J ) 6.5 Hz, 2 H), 3.40-3.30 (m, 4 H),
3.18-3.1 (m, 3 H), 2.27 (dd, J ) 16.0, 6.0 Hz, 1 H), 2.73 (d, J )
16.0 Hz, 1 H), 2.62 (d, J ) 14.0 Hz, 2 H), 2.20 (t, J ) 9.0 Hz, 2
H), 2.19-2.02 (m, 4 H), 1.81 (p, J ) 8.5 Hz, 2 H), 1.74-1.60 (m,
4 H), 1.51 (six, J ) 9.0 Hz, 2 H), 1.46-1.4 (m, 2 H), 1.36 (t, J )
9 Hz, 2 H), 1.00 (t, J ) 9.5 Hz, 3 H); 13C NMR: 173.4, 163.8,
162.2, 161.5, 156.5, 153.8, 147.86, 147.83, 142.5, 141.9, 135.85,
135.76, 116.71, 116.4, 116.28, 116.14, 112.39, 112.34, 70.13, 70.07,
69.99, 69.88, 69.4, 68.0, 67.7, 63.9, 62.8, 60.2, 55.5, 45.8, 40.8,
40.5, 39.1, 37.20, 37.15, 35.8, 31.1, 28.13, 28.07, 25.5, 19.2, 13.8,
8.6; MS calcd for C41H56N4O9S (M+-CO+Na) 803.3666, ESI-
HRMS found 803.3677.
126.9, 112.1, 121.9, 117.0, 116.97, 116.94, 112.15, 112.11, 112.00,
111.0, 110.3, 70.1, 69.1, 68.5, 68.0, 67.8, 36.9, 36.7, 31.5, 19.5,
14.2, 14.0.
2-{2-[(9-Butoxy-5,6-didehydro-11,12-dihydrodibenzo[a,e][8]an-
nulen-2-yl)oxy]ethoxy}Ethyl{2-[2-(2-{[5-(2-Oxohexahydro-1H-thieno-
[3,4-d]imidazol-4-yl)pentanoyl]amino}ethoxy)ethoxy]ethyl}carba-
mate (3b). A solution of carbonate 13 (0.15 g, 0.28 mmol) in DMF
(2 mL) was added to a solution of Et3N (0.5 g, 4.95 mmol) and
N-biotinyl-3,6-dioxaoctane-1,8-diamine9 (0.01 g, 0.28 mmol) in
DMF (10 mL) The reaction mixture was stirred for 18 h at ambient
temperature and then the solvents were evaporated under reduced
pressure, and the residue purified by silica gel chromatography
(CH2Cl2:MeOH 30:1) to provide 3b (0.164 g, 75%). 1H NMR: 7.19
(d, J ) 8.4 Hz, 2H), 6.88 (dd, J ) 9.5, 2.5 Hz, 2H), 6.76 (td, J )
8.2, 2.5, 2H), 6.74 - 6.65 (m, 1H), 6.54 (s, b, 1H), 5.74 (s, b, 1H),
5.60 (s, b 1 H), 4.49 - 4.43 (m, 1H), 4.29-4.22 (m, 3H), 4.16 -
4.10 (m, 2H), 3.97 (t, J ) 6.5, 2H), 3.87 - 3.81 (m, 2H), 3.76 (m,
2H), 3.59-3.48 (m, 10H), 3.42 (m, 2H), 3.37 - 3.12 (m, 2H), 3.21
- 3.09 (m, 4H), 2.86 (dd, J ) 12.6, 4.7 Hz, 1H), 2.72 (d, J ) 12.7,
1H), 2.42 (d, J ) 10.9, 2H), 2.21 (t, J ) 7.4, 4H), 1.81-1.56 (m,
6H), 1.48 (six, J ) 7.4 Hz, 2H), 1.44-1.36 (m, 2H), 1.32 (t, J )
7.4 Hz, 1H), 0.98 (t, J ) 7.4, 3H); 13C NMR: 173.4, 164.1, 158.7,
158.1, 156.5, 154.8, 126.66, 126.63, 116.80, 116.72, 116.59, 115.8,
111.91, 111.83, 110.67, 110.14, 70.09, 70.04, 69.95, 69.90, 69.80,
69.54, 67.78, 67.52, 63.88, 61.80, 60.2, 55.6, 45.6, 40.8, 40.5, 39.1,
36.63, 36.61, 35.9, 31.3, 28.22, 28.08, 25.6, 19.2, 13.8, 8.5. MS
calcd for C41H56N4O9S (M+ + Na) 803.3666, ESI-HRMS found
803.3672.
General Procedure for Preparative Photolyses of Cycloprope-
nones 2: 3,9-Dibutoxy-5,6-didehydro-11,12-dihydrodibenzo[a,e]-
[8]annulen-2-yl (3c). A solution of cyclopropenone 2c (0.20 g, 0.532
mmol) in MeOH (20 mL, 2.72 × 10-2M) was irradiated (4 × 350
nm) for 20 min at r.t. The solvent was evaporated under reduced
pressure, and the residue was purified by silica gel column
chromatography (Hex:EtOAc 1:20) to provide 3c (0.160 g, 86%)
2-{2-[(9-Butoxy-5,6-didehydro-11,12-dihydrodibenzo[a,e][8]an-
nulen-2-yl)oxy]ethoxy} Ethanol (12). A solution of cyclopropenone
6 (0.54 g, 1.35 mmol) in MeOH:THF (1:1, v:v, 60 mL) was
irradiated with 350 nm lamps for 20 min. The solution was
concentrated under reduced pressure to 10 mL, and 1 M aqueous
NaOH solution (1.68 mL, 1.68 mmol) was added to the mixture
and stirring was continued for 30 min. Ethyl acetate was added,
and the organic layer was separated, washed with water, brine, dried
(MgSO4), filtered and the filtrate was concentrated in Vacuo. The
residue was purified by silica gel column chromatography (EtOAc:
Hex 1:1.5) to provide 12 (0.375 g, 73%) as an amorphous white
1
as a slightly yellow oil. H NMR: 7.19 (d, J ) 8.4 Hz, 2 H), 6.87
(d, J ) 2.4 Hz, 2 H), 6.75 (dd, J ) 8.4, 2.4 Hz, 2 H), 3.97 (t, J )
6.4 Hz, 4 H), 3.18 (d, J ) 11.2 Hz, 2 H), 2.44 (d, J ) 11.2 Hz, 2
H), 1.77 (p, J ) 7.2 Hz, 4 H), 1.52 (six, J ) 7.2 Hz, 4 H), 0.98 (t,
J ) 7.2 Hz, 6 H); 13C NMR: 158.9, 155.1, 126.9, 116.9, 116.2,
112.0, 110.6, 68.0, 36.9, 31.5, 19.5, 14.1.
General Procedure for the Preparation of Triazoles 4. A
solution of 3c (0.5 mmol) and appropriate organic azide (0.75 mmol)
in MeOH was stirred for 18 h at r.t. The solvent was evaporated
under reduced pressure, and the excess of azide was removed by
silica gel column chromatography.
1
solid. H NMR: δ 7.20 (dd, J ) 8.4, 0.8 Hz, 2 H), 6.87 (dd, J )
11.2 Hz, 2.0, 2 H), 6.75 (td, J ) 8.0, 2.4 Hz, 2 H), 4.15 (t, J ) 4.4
Hz, 2 H), 3.97 (t, J ) 6.0 Hz, 2 H), 3.87 (t, J ) 4.4 Hz, 2 H), 3.76
(s, b, 2 H), 3.68 (d, J ) 4.4 Hz, 2 H), 3.17 (d, J ) 11.2 Hz, 2 H),
2.43 (d, J ) 10.4 Hz, 2 H), 1.77 (p, J ) 7.2 Hz, 2 H), 1.50 (six,
J ) 7.2 Hz, 4 H), 0.98 (t, J ) 7.2 Hz, 6 H); 13C NMR: 158.9,
158.3, 155.1, 126.99, 126.84, 117.05, 116.93, 116.10, 112.08,
112.05, 110.91, 110.39, 72.8, 69.8, 68.0, 67.7, 62.0, 36.94, 36.77,
31.5, 19.5, 14.1, 14.01. MS calcd for C24H28O4 (M+) 380.1988,
EI-HRMS found 380.1982.
1-Phenyl-6,11-dibutoxy-8,9-dihydro-1H-dibenzo[3,4:7,8]cyclooc-
ta[1,2-d][1,2,3]triazoles (4a, R ) Ph). 1H NMR: δ 7.53 (d, J ) 8.8
Hz, 1 H), 7.39 (s, 5 H), 6.85 (d, J ) 2.4 Hz, 1 H), 6.79 (dd, J )
8.4, 2.4 Hz, 1 H), 6.74 (d, J ) 2.4 Hz, 1 H), 6.62 (d, J ) 8.8 Hz,
1 H), 6.51 (dd, J ) 8.4, 2.8 Hz, 1 H), 3.94 (t, J ) 6.4 Hz, 2 H),
3.89 (t, J ) 6.4 Hz, 2 H), 3.50-3.30 (m, 2 H), 3.17-2.92 (m, 2
H), 1.78-1.68 (m, 4 H), 1.46 (sep, J ) 7.2 Hz, 4 H), 0.96 (t, J )
7.2 Hz, 3 H), 0.95 (t, J ) 7.2 Hz, 3 H); 13C NMR: 159.9, 159.2,
147.0, 142.5, 139.7, 137.0, 133.6, 133.0, 131.8, 129.5, 128.8, 124.8,
122.5, 118.8, 116.5, 115.8, 112.8, 112.6, 67.81, 67.77, 36.2, 34.2,
31.5, 19.47, 19.45, 14.10, 14.07.
2-{2-[(9-Butoxy-5,6-didehydro-11,12-dihydrodibenzo[a,e][8]an-
nulen-2-yl)oxy]ethoxy} Ethyl 3-Nitrophenyl Carbonate (13). A
solution of pyridine (0.20 g, 2.60 mmol) in CH2Cl2 (∼1 mL) was
added to 12 (0.24 g, 0.63 mmol) and 4-nitrophenyl chloroformate
(0.20 g, 1.00 mmol) in CH2Cl2 (5 mL), and the reaction mixture
was stirred for 3 h. The solvent was evaporated under reduced
pressure, and the residue was purified by silica gel column
chromatography (Hex:EtOAc 4:1) to provide 13 (0.34 g, 99%) as
an oil. 1H NMR: δ 8.25 (d, J ) 8.8 Hz, 2 H), 7.36 (d, J ) 9.2 Hz,
2 H), 7.19 (d, J ) 8.8 Hz, 2 H), 6.89 (dd, J ) 14.0, 2.4 Hz, 2 H),
6.79-6.75 (m, 2 H), 4.47 (t, J ) 4.4 Hz, 2 H), 4.18 (t, J ) 4.4 Hz,
2 H), 3.97 (t, J ) 6.6 Hz, 2 H), 3.92-3.88 (m, 4 H), 3.17 (d, J )
10.8 Hz, 2 H), 2.42 (d, J ) 10.8 Hz, 2 H), 1.77 (p, J ) 7.2 Hz, 2
H), 1.49 (six, J ) 7.2 Hz, 4 H), 0.98 (t, J ) 7.2 Hz, 6 H); 13C
NMR: 158.9, 158.3, 155.7, 155.13, 155.08, 152.7, 145.6, 127.0,
6,11-Dibutoxy-1-butyl-8,9-dihydro-1H-dibenzo[3,4:7,8]cyclooc-
1
ta[1,2-d][1,2,3]triazole (4a, R ) n-Bu). H NMR: δ 7.43 (d, J )
8.4 Hz, 1 H), 7.06 (d, J ) 8.4 Hz, 1 H), 6.87 (d, J ) 2.4 Hz, 1 H),
6.78 (dd, J ) 8.4, 2.4 Hz, 1 H), 6.75 (dd, J ) 8.4, 2.4 Hz, 1 H)
6.67 (d, J ) 2.4 Hz, 1 H), 4.42-4.24 (m, 2 H), 3.96 (t, J ) 6.4
Hz, 2 H), 3.93 (t, J ) 6.8 Hz, 2 H), 3.40-3.32 (m, 1 H), 3.14-2.98
(m, 2 H), 2.88-2.78 (m, 1 H), 1.86-1.68 (m, 6 H), 1.54-1.41
(m, 4 H), 1.34-1.18 (m, 2 H), 0.98 (t, J ) 7.6 Hz, 3 H), 0.95 (t,
J ) 7.2 Hz, 3 H), 0.85 (t, J ) 7.2 Hz, 3 H); 13C NMR: 160.1,
158.9, 146.6, 143.3, 139.2, 133.6, 133.2, 130.2, 122.8, 118.9, 116.6,
9
J. AM. CHEM. SOC. VOL. 131, NO. 43, 2009 15775