References and Notes
For reviews, see:
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Raymo FM.
Tomasulo M.
Chem. Eur.
J.
2006,
12:
3186
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Pischel U.
Angew.
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2007,
46:
4026
2 For a review, see: Cusido J.
Deniz E.
Raymo FM.
Eur. J. Org. Chem.
2009,
2031
3 For a review, see: Berkovic G.
Krongauz V.
Weiss V.
Chem. Rev.
2000,
100:
1741
4 For a review, see: Mayer G.
Heckel A.
Angew. Chem.
Int. Ed.
2006,
45:
4900
5 For a review, see: Moroder L.
Renner C.
ChemBioChem
2006,
7:
868
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Asanuma H.
Liang X.
Komiyama M.
ChemBioChem
2001,
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Nishioka H.
Liang X.
Asanuma H.
Chem.
Commun.
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Liang X.
Takenaka N.
Nishioka H.
Asanuma H.
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553
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Yamazawa A.
Liang X.
Asanuma H.
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Liang X.
Asanuma H.
Komiyama M.
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Yan Y.
Marriott G.
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Corrias B.
Fissi A.
Pieroni O.
Lenci F.
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Kocer A.
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Meijberg W.
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Asanuma H.
Shirasuka K.
Yoshida T.
Takarada T.
Liang X.
Komiyama M.
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Andersson J.
Li S.
Lincoln P.
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Deiters A.
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Beyer C.
Wagenknecht H.-A.
Synlett
2010,
1371
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Vomasta D.
Hogner C.
Branda N.
König B.
Angew. Chem.
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Jäschke A.
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2010,
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20 Compound 5:
Compound 4
¹9 (490 mg,
3.35 mmol) was dissolved in anhyd EtOH (50 mL), freshly distilled 3
¹9 (0.59 mL, 3.33
mmol) was added in one portion, and the reaction mixture was sonicated
at 35 kHz under Ar. After 53 min the solvent was removed under reduced
pressure. The crude product was purified by gradient flash chromatography
on silica gel (hexane-THF, 70:1 → 50:1) yielding 5 (762 mg, 76%) as a pale blue
foam; R
f
0.36
(hexane-THF, 50:1). ¹H NMR (600 MHz,
CDCl3): δ = 7.15-7.27 (m,
2 H, ArH), 7.20 (dt, 1 H, J = 1.2,
7.7 Hz, ArH), 7.09 (d, 1 H, J = 7.2
Hz, ArH), 6.87 (t, 1 H, J = 7.4
Hz, ArH), 6.83 (d, 1 H, J = 10.3
Hz, ArH), 6.67 (d, 1 H, J = 8.3
Hz, ArH), 6.55 (d, 1 H, J = 7.7 Hz,
ArH), 5.74 (d, 1 H, J = 10.2
Hz, ArH), 2.98 (s, 1 H, CºCH), 2.74 (s, 3 H, NMe), 1.31 (s, 3 H,
Me), 1.18 (s, 3 H, Me). ¹³C NMR (150
MHz, CDCl3): δ = 155.0, 148.1, 136.6, 133.7,
130.5, 128.8, 127.6, 121.5, 120.3, 119.3, 118.8, 115.2, 113.5, 106.9,
104.8, 83.6, 75.5, 51.9, 28.9, 25.9, 20.1. MS (CI, NH3): m/z (%) = 302.1
(100) [MH+]. HRMS (EI-MS): m/z [M+] calcd
for C21H19NO: 301.1467; found: 301.1465.
21 Compound 8:
Compound 6
¹9 (335 mg,
1.11 mmol) was dissolved in freshly distilled EtOH (10 mL) and anhyd
Et3N (200 µL, 1.43 mmol). Compound 7
¹9 (220 mg, 1.09 mmol) was
added and the reaction mixture was sonicated at 35 kHz under Ar.
After 2 h the solvent was removed under reduced pressure, the residue
was dissolved in CH2Cl2 and dried over anhyd
Na2SO4. The solvent was evaporated under reduced pressure,
and the residue was dried in vacuo and purified by gradient flash
chromatography on silica gel (hexane-EtOAc, 30:1 → 15:1)
to yield 8 (300 mg, 77%) as a
pale pink solid; R
f
0.49
(hexane-EtOAc, 19:1). ¹H NMR (300 MHz,
CDCl3): δ = 7.15-7.27 (m,
3 H, ArH), 7.09 (d, 1 H, J = 7.2
Hz, ArH), 6.87 (t, 1 H, J = 7.4
Hz, ArH), 6.80 (d, 1 H, J = 10.3
Hz, ArH), 6.61 (d, 1 H, J = 9.2
Hz, ArH), 6.55 (d, 1 H, J = 7.7 Hz,
ArH), 5.74 (d, 1 H, J = 10.2
Hz, ArH), 2.74 (s, 3 H, NMe), 1.32 (s, 3 H, 3-Me), 1.18 (s, 3 H,
3-Me). ¹³C NMR (75 MHz, CDCl3): δ = 153.6
(Cquat), 148.0 (Cquat), 136.5 (Cquat), 132.2
(+, CH), 129.1 (+, CH), 128.4 (+, CH),
127.7 (+, CH), 121.5 (+, CH), 120.7 (+,
CH), 120.6 (Cquat), 119.3 (+, CH), 116.9 (+,
CH), 111.8 (Cquat), 106.9 (+, CH), 104.5 (Cquat), 51.9
(Cquat), 28.9 (+, Me), 25.9 (+, Me),
20.1 (+, Me). MS (EI, 70 eV): m/z (%) = 357.0(100) [M+˙],
339.9 (47) [M+ - Me.].
HRMS (EI-MS): m/z [M+] calcd
for C19H18BrNO: 355.0572; found: 355.0570.
22
Chung-Shan Y.
Oberdorfer F.
Synlett
2010,
86
23 Compound 1:
Compound 5 (53 mg, 0.176 mmol), 9 (50 mg, 0.141 mmol), CuI (6 mg, 0.0315
mmol) and Pd(dppf)Cl2 (20 mg, 0.0245 mmol) were dissolved
in anhyd DMF (2.0 mL) and anhyd Et3N (100 µL,
0.717 mmol). The mixture was degassed and stirred at r.t. for 26
h. Then all was poured into an EtOAc-H2O mixture
(20 mL, 1:1). After separation, the aqueous phase was extracted
with CH2Cl2, and the combined organic layers
were dried over anhyd Na2SO4 and the solvent was
evaporated under reduced pressure. The residue was dried in vacuo
and purified by gradient flash chromatography on silica gel (CH2Cl2-MeOH,
10:1 → 5.1) to yield 1 (50 mg,
67%) as glistening green crystals; R
f
0.29 (CH2Cl2-MeOH,
10:1). ¹H NMR (600 MHz, MeOD): δ = 8.36
(s, 1 H, H-6), 7.27 (d, 1 H, J = 2.0
Hz), 7.23 (dd, 1 H,
J = 8.4
Hz), 7.10 (dt, 1 H, J = 7.6
Hz), 7.03 (d, 1 H, J = 7.2 Hz),
6.92 (d, 1 H, J = 10.3 Hz),
6.78 (t, 1 H, J = 7.1 Hz), 6.61 (d,
1 H, J = 8.4 Hz), 6.52 (d, 1
H, J = 7.8 Hz), 6.26 (t, 1 H,
J = 6.6 Hz, H-1′),
5.80 (d, 1 H, J = 10.3 Hz),
4.40-4.43 (m, 1 H, H-3′), 3.94 (q, 1 H, J = 3.3 Hz, H-4′),
3.83 (dd, 1 H, J = 3.0, 12.0
Hz, H-5′), 3.75 (dd, 1 H, J = 3.4,
12.0 Hz, H-5′), 2.70 (s, 3 H, NMe), 2.29-2.34
(m, 1 H, H-2′), 2.22-2.28 (m, 1 H, H-2′),
1.26 (s, 3 H, MeC), 1.14 (s, 3 H, Me). ¹³C
NMR (150 MHz, MeOD): δ = 164.4, 156.2, 151.2,
149.5, 144.5 (C6), 137.8, 134.2, 131.1, 130.0, 128.6, 122.4, 121.4,
120.5, 120.4, 116.0, 107.9, 106.3, 100.9, 93.9, 89.1 (C-4′),
87.0 (C-1′), 80.1, 72.0 (C-3′), 62.6 (C-5′),
52.9, 41.8 (C-2′), 29.2 (NMe), 26.3 (Me), 20.4 (Me), 9.3.
MS (ESI): m/z (%) = 528.2
(100) [MH+].
24
Stafforst T.
Hilvert D.
Chem. Commun.
2009,
287
25 Compound 12:
Compound 11 (2.50 g, 11.7 mmol) was dissolved
under argon atmosphere in anhyd THF (30 mL) and cooled to -78 ˚C.
A 2 M lithium diisopropylamide solution in THF-heptane-ethylbenzene
(8.79 mL, 17.6 mmol) was added dropwise and the mixture was stirred
for 1 h at 0 ˚C. After cooling down to -78 ˚C,
MeI (1.10 mL, 17.6 mmol) was added dropwise. The mixture was stirred
for 2 additional hours. Then H2O (30 mL) was added, the
phases were separated and the aqueous phase was extracted with EtOAc.
The combined organic layers were dried over anhyd Na2SO4 and
the solvent was evaporated under reduced pressure. The residue was
dried in vacuo and purified by flash chromatography on silica gel(hexanes)
to yield 12 (2.66 g, 99%) as a
white solid; R
f
0.57
(hexanes). ¹H NMR (300 MHz, CDCl3): δ = 7.78
(d, 1 H, J = 1.9 Hz, ArH), 7.59 (d,
1 H, J = 8.5 Hz, ArH), 7.34
(dd, 1 H, J = 8.5, 1.9 Hz, ArH),
6.90 (s, 1 H, ArH), 2.59 (d, 3 H, J = 1.2
Hz, Me).
¹³C NMR (75 MHz,
CDCl3): δ = 143.1 (Cquat),
142.2 (Cquat), 138.4 (Cquat), 126.5 (Carom),
125.3 (Carom), 123.4 (Carom), 121.0 (Carom),
118.2 (Carom), 16.3 (Me). MS (EI, 70 eV):
m/z (%) = 228.0(100) [M+],
147.1 (24) [M - Me].
26 Compound 13:
Compound 12 (969 mg, 4.3 mmol) and glutaryl
chloride (0.27 mL, 2.1 mmol) were dissolved under argon atmosphere
in anhyd CH2Cl2 (20 mL) and the solution was
cooled to 0 ˚C. Then AlCl3 (626 mg 4.7 mmol)
was added and the reaction mixture was stirred for 3 h at r.t. After completion
of the reaction, a mixture of ice and 1 M aq HCl was added. The
solution was let to be warmed to r.t., the phases were separated
and the aqueous phase was extracted with EtOAc. The combined organic
layers were dried over anhyd Na2SO4 and the
solvent was evaporated under reduced pressure. The residue was dried
in vacuo and purified by flash chromatography on silica gel (hexanes-EtOAc,
10:1) to yield 13 (896 mg, 74%)
as a white solid;
R
f
0.31 (hexanes-EtOAc,
10:1). ¹H NMR (400 MHz, CDCl3): δ = 8.36
(d, 2 H, J = 1.8 Hz, ArH), 7.57
(d, 2 H, J = 8.5 Hz, ArH), 7.42
(dd, 2 H, J = 8.5, 1.8 Hz, ArH),
3.06 (t, 4 H, J = 6.9 Hz, CH2),
2.77 (s, 6 H, Me), 2.27 (quin, 2 H, J = 7.0
Hz, CH2). ¹³C NMR (75 MHz,
CDCl3): δ = 168.6 (CO), 146.1 (Cquat),
142.9 (Cquat), 140.5 (Cquat), 136.5 (Cquat),
127.2 (Carom), 125.0 (Carom), 123.4 (Carom),
118.8 (Carom), 28.6 (CH2), 19.6 (CH2),
15.3 (Me). MS (EI, 70 eV): m/z (%) = 549.9 (14) [M+].
27 Compound 14:
To a suspension of zinc dust (301 mg, 4.6 mmol, stabilized, grading <63 µm)
in anhyd THF (50 mL) TiCl4 (0.26 mL, 2.3 mmol) was added
under argon atmosphere dropwise at 0 ˚C. The suspension
was heated to 40 ˚C and stirred for 1 h. Compound 13 (631 mg, 1.1 mmol) was added and the
mixture was stirred for 18 h. After cooling to r.t. the reaction
mixture was poured through a silica gel pallet and rinsed with hexanes.
The solvent was removed under reduced pressure and the residue was
dried in vacuo and purified by flash chromatography on silica gel(hexanes) to
yield 14 (328 mg, 55%) as a white
solid; R
f
0.25
(hexanes). ¹H NMR (300 MHz, CDCl3): δ = 7.64
(s, 2 H, ArH), 7.46 (d, 2 H, J = 8.4
Hz, ArH), 7.24 (s, 2 H, ArH), 2.88-3.02 (m, 4 H, CH2),
2.28 (quin, 2 H, J = 7.22 Hz,
CH2), 2.12 (s, 6 H, Me). ¹³C
NMR (75 MHz, CDCl3): δ = 140.9 (Cquat),
137.0 (Cquat), 136.8 (Cquat), 129.72 (Carom),
126.5 (Carom), 125.1 (Carom), 123.3 (Carom),
118.1 (Carom), 37.8 (CH2), 24.1 (CH2), 15.2
(Me). MS (EI, 70 eV): m/z (%) = 517.9 (100) [M+].
28 Compound 15:
Compound 14 (131 mg, 0.25 mmol), trimethylsilylacetylene
(72 µL, 0.51 mmol), anhyd Et3N (41 µL,
0.51 mmol), Pd(PPh3)4 (30 mg, 0.03 mmol) and
CuI (5 mg, 0.03 mmol) were dissolved in anhyd THF (3 mL) under argon.
The mixture was degassed and refluxed for 19 h. After cooling to
r.t. the solvent was removed under reduced pressure, the residue
was dried in vacuo and purified by flash chromatography on silica
gel(hexanes) to yield 15 (58 mg, 43%)
as a white solid; R
f
0.26
(hexanes). ¹H NMR (300 MHz, CDCl3): δ = 7.67
(s, 2 H, ArH), 7.54 (d, 1 H, J = 8.2 Hz,
ArH), 7.47 (d, 1 H, J = 8.0
Hz, ArH), 7.29 (s, 2 H, ArH), 2.83-3.12 (m, 4 H, CH2),
2.28 (quin, 2 H, J = 7.8 Hz,
CH2), 2.04 (s, 6 H, Me), 0.29 (s, 9 H, SiMe3). ¹³C
NMR (75 MHz, CDCl3): δ = 139.1 (Cquat),
138.6 (Cquat), 137.3 (Cquat), 136.7 (Cquat),
127.1 (Carom), 126.4 (Carom), 125.9 (Carom),
125.1 (Carom), 123.3 (Carom), 121.9 (Carom),
118.0 (Carom), 105.9 (CºC), 37.9 (CH2), 29.9
(CºC), 24.2 (CH2), 15.3 (Me), 0.3 (SiMe3).
MS (EI, 70 eV): m/z (%) = 536.0(100) [M+].
29 Compound 16:
Compound 15 (35 mg, 0.07 mmol) was dissolved
in anhyd MeOH (3 mL) and K2CO3 (27 mg, 0.19 mmol)
was added. The reaction mixture was stirred for 18 h at 40 ˚C.
After cooling to r.t. MeOH was removed under reduced pressure. The
residue was dried in vacuo and purified by flash chromatography
on silica gel (hexanes) to yield 16 (30
mg, 99%) as a white solid; R
f
0.65 (hexanes-EtOAc,
20:1) ¹H NMR (300 MHz, CDCl3): δ = 7.71
(s, 2 H, ArH), 7.57 (d, 2 H, J = 8.0
Hz, ArH), 7.46 (d, 1 H, J = 7.5 Hz,
ArH), 7.28 (s, 1 H, ArH), 3.07 (s, 1 H, CºCH), 2.84-3.01 (m,
4 H, CH2), 2.28 (quin, 2 H, J = 8.0
Hz, CH2), 2.02 (s, 6 H, Me). ¹³C
NMR (75 MHz, CDCl3): δ = 146.8 (Cquat),
139.2 (Cquat), 137.2 (Cquat), 136.9 (Cquat),
126.9 (Carom), 126.4 (Carom), 125.1 (Carom),
123.3 (Carom), 122.0 (Carom), 118.1 (Carom),
117.6 (Carom), 76.5 (CºC), 37.8 (CH2), 29.9
(CºC), 24.1 (CH2), 15.2 (Me). MS (EI, 70 eV): m/z (%) = 461.9 (100) [M+].
30 Compound 2:
Compound 16 (126 mg, 0.27 mmol), 9 (97 mg, 0.27 mmol), anhyd Et3N
(45 µL, 0.54 mmol), Pd(PPh3)4 (63 mg,
0.05 mmol) und CuI (11 mg, 0.05 mmol) were dissolved in anhyd DMF
(10 mL). The mixture was degassed and stirred for 18 h at 60 ˚C.
After cooling to r.t. the solvent was removed under reduced pressure,
the residue was dried in vacuo and purified by flash chromatography
on silica gel (CH2Cl2-MeOH, 25:1)
to yield 2 (121 mg, 65%) as a
light yellow foam; R
f
0.40 (CH2Cl2-MeOH,
10:1). ¹H NMR (300 MHz, MeOD): δ = 8.37
(s, 1 H, NH), 7.72 (s, 2 H, ArH), 7.58-7.68 (m, 1 H, C=CH),
7.55 (d, 1 H, J = 8.2 Hz, ArH), 7.46
(d, 1 H, J = 6.8 Hz, ArH), 6.95-7.29
(m, 2 H, ArH), 6.26 (t, 1 H, J = 6.2
Hz, 1′-H), 4.28-4.50 (m, 1 H, 3′-H),
3.88-4.03 (m, 1 H, 4′-H), 3.78-3.87 (m,
1 H, 5′-H), 3.66-3.78 (m, 1 H, 5′-H),
2.19-2.61 (m, 4 H, CH2), 2.00-2.48
(m, 9 H, 2′-H, CH2, Me), 1.95 (s, 1 H, 2′-H). ¹³C
NMR (75 MHz, MeOD): δ = 151.2 (CO), 144.7 (C=C),
140.4 (CO), 139.8 (Cquat), 138.6 (Cquat),
138.5 (Cquat), 138.1 (Cquat), 131.3 (Cquat),
127.3 (Carom), 126.0 (Carom), 124.3 (Carom),
122.9 (Carom), 118.9 (Carom), 94.5 (CºC),
89.2 (4′-C), 87.1 (1′-C), 72.1 (3′-C),
62.6 (5′-C), 41.8 (2′-C), 38.6 (CH2),
25.0 (CH2), 15.1 (Me). MS (FAB): m/z (%) = 689.1 (6) [M+].
HRMS (ESI): m/z [M + H+] calcd
for C34H30BrN2O5S2:
691.0759; found: 691.0766.
31 Compound 17:
Compound 2 (50 mg, 0.07 mmol), dimethoxytrityl
chloride (37 mg, 0.11 mmol) and anhyd Et3N (10 µL,
0.12 mmol) were dissolved in anhyd pyridine (2 mL) under argon atmosphere.
The solution was stirred for 18 h at 40 ˚C. The solvent
was removed, the residue was dried in vacuo and purified by flash
chromatography on silica gel (CH2Cl2-MeOH,
100:3 + 0.1% Et3N) to yield 17 (62 mg, 90%) as a light yellow
foam; R
f
0.61
(CH2Cl2-MeOH, 10:1). ¹H
NMR (300 MHz, DMSO): δ = 8.05 (s, 1 H, NH), 7.70
(d, 2 H, J = 8.2 Hz, ArHbt),
7.63 (s, 1 H, C=CH), 7.43 (d, 2 H, J =7.4
Hz, ArHbt), 7.18-7.37 (m, 8 H, ArHDMT),
7.14 (d, 2 H, J = 7.3 Hz, ArHbt),
6.75-6.96 (m, 5 H, ArHDMT), 6.16 (t, 1 H, J = 6.7 Hz, 1′-H),
4.26-4.34 (m, 1 H, 3′-H), 3.93-398 (m,
1 H, 4′-H), 3.66-3.80 (m, 2 H, 5′-H), 3.61
(d, 6 H, J = 2.5 Hz, CH3,DMT),
2.79-2.93 (m, 4 H, CH2), 2.06-2.37
(m, 9 H, 2′-H, CH2, Me), 1.95-2.03
(m, 1 H, 2′-H). ¹³C NMR (75
MHz, acetone): δ = 163.9 (Cquat), 161.9 (Cquat),
159.6 (Cquat), 157.7 (Cquat), 150.4 (CO),
146.0 (Cquat), 143.1 (C=C), 140.3 (CO), 139.0
(Cquat), 138.1 (Cquat), 137.9 (Cquat),
136.6 (Cquat), 131.0 (Carom), 128.9 (Carom),
127.6 (Carom), 127.1 (Carom), 126.0 (Carom),
122.7 (Carom), 114.1 (CºC), 87.7 (4′-C), 86.6
(1′-C), 64.8 (5′-C), 58.4 (3′-C), 55.4 (2′-C),
46.4 (5′-C), 41.9 (s), 38.3 (CH2), 24.4 (CH2),
15.4 (Me), 8.9 (Me). MS (ESI): m/z (%) = 1015.2 (4)[(M + Na)+].
32 Compound 18:
Compound 17 (62 mg, 0.06 mmol), diisopropylethylamine
(36 µL, 0.16 mmol) and 2-cyano-ethyldiisopropylphosphoramidite
(27 µL, 0.16 mmol) were dissolved in anhyd CH2Cl2 (3
mL). The solution was stirred at r.t. for 40 min. The product was
purified by flash chromatography on silica gel (CH2Cl2-MeOH,
100:4 + 0.1% Et3N) and additionally
lyophilized out of benzene to yield 18 (74
mg, 99%) as a light yellow foam; R
f
0.85, 0.91 (CH2Cl2-MeOH,
25:1). ³¹P NMR (101 MHz, DMSO): δ = 150.6 [P(III),
37%], 16.3 [P(V), 63%].
MS (MALDI): m/z (%) = 1191.3
(28) [M+].
33
DNA 1: MS
(MALDI): m/z (%) = 5950.0(100) [(M + DMT)+],
5647.9 (38) [M+], 2974.6 (17) [(M + DMT)²+/2], 2823.6
(7) [M²+/2].
