Full Paper
doi.org/10.1002/ejoc.202001229
EurJOC
European Journal of Organic Chemistry
0.48 μL (0.27 mmol, 1.7 equiv.) tert-butylhydroperoxide (5.5
M
, in n-
(C-3′,ds), 65.0–64.9 (m, C-5′, ds), 55.9–55.8, 55.7, 55.5, 55.5, 55.4–
55.3, 54.1–55.1 (OMe, ds), 23.4–22.9 (CH3, ds); 31P-NMR (242 MHz,
[D4]MeOD): δ = –11.6 (d, 2JP, P = 19.2 Hz, P-α), –11.7 (d, 2JP, P = 20.8 Hz,
decan) were added. Yield: 89 mg (96 μmol, 60 %) as a yellow cotton.
Yield was calculated with two ammonium counterions. 1H-NMR
(600 MHz, D2O): δ = 8.40 (s, 1 H, H-Ar), 8.14 (s, 1 H, H-Ar), 7.40 (s,1
H, H-Ar), 7.38 (s,1 H, H-Ar), 6.80 (s,1 H, H-Ar), 6.73 (s, 1 H, H-Ar), 5.86
2
2
P-α), –14.1 (d, JP, P = 17.9 Hz, P-γ), –15.5 (d, JP, P = 16.9 Hz, P-γ),
–23.3 to –23.8 (m, P-ꢀ); IR (ATR): ν = [cm–1] = 3175, 1642, 1580,
˜
3
(d, JH,H = 5.3 Hz, 1 H, H-1′), 5.27–5.18 (m, 4 H, Ph-CH2), 4.54 (pt,
1518, 1453, 1379, 1272, 1218, 1172, 1127, 1077, 922, 874, 816, 794,
1 H, H-2′), 4.46 (pt, 1 H, H-3′), 4.38–4.33 (m, 1 H, H-5′a), 4.33–4.30 711, 642; HRMS (ESI–): m/z calcd. for C30H38N7O21P3– + H+: 926.1412,
(m, 1 H, H-4), 4.28–4.22 (m, 1 H, H-5′), 3.82 (s, 6 H,2 × OMe), 3.77 (s,
6 H,2 × OMe); 13C-NMR (150 MHz, D2O): δ = 152.7 (C-Ar), 152.6,
(C-Ar), 152.1 (C-Ar), 148.4 (C-Ar), 147.4 (C-Ar), 140.5 (C-Ar), 138.5 (d,
3JC,P = 12 Hz, C-Ar), 119.1 (C-Ar), 117.8 (C-Ar), 110.5 (C-Ar), 110.4 (C-
Ar), 107.5 (C-Ar), 107.5 (C-Ar), 87.1 (C-1′), 83.6 (C-4′), 74.5 (C-2′),69.3
(C-3′), 66.8 (Ph-CH2), 64.8 (C-5′), 56.2, 56.2, 55.9 (OMe); 31P-NMR
found 926.1443.
γ-Bis-O-(1-(4-methoxy-2-nitro-5-octanoxyphenyl)ethyl)ATP
(17): The synthesis was done according to general procedure 4b;
0.16 g (0.23 mmol, 1.0 equiv.) of H-phosphonate 11 was activated
with 62 mg (0.46 mmol, 2.0 equiv.) N-chlorosuccinimide and 0.23 g
(0.20 mmol 0.8 equiv.) ADP 24 was added. Yield: 53 mg (46 μmol,
23 %) as a yellow cotton in a mixture of four diastereomers. The
yield was calculated with two ammonium counterions. 1H-NMR
(600 MHz, [D4]MeOD): δ = 8.63, 8.62, 8.62, 8.60 (s, 1 H, H-Ar, ds.),
8.19, 8.18 (s, 1 H, H-Ar, ds.), 7.40–7.36 (m, 2 H, H-Ar), 7.06–6.93 (m,
2 H, H-Ar), 6.16–6.06 (m, 2 H, H-1′, Ph-CH-P, ds.), 4.69–4.64 (m, 1 H,
H-2′), 4.55–4.51 (m, 1 H, H-4′), 4.35–4.23 (m, 3 H, H-3′, 5′), 4.00–3.91
(m, 4 H, 2 × CH2), 3.91, 3.89, 3.87 (s, 6 H, 2 × OMe, ds.), 1.85–1.77
(m, 4 H, 2 × CH2), 1.64–1.53 (m, 6 H, 2 × CH3), 1.52–1.44 (m, 4 H,
2 × CH2), 1.42–1.27 (m, 16 H, 8 × CH2), 0.94–0.88 (m, 6 H, 2 × CH3);
13C-NMR (150 MHz, [D4]MeOD): δ = 155.1, 155.1, 154.9 (C-Ar, ds),
153.4 (C-Ar, ds), 149.6, 149.2 (C-Ar, ds), 148.0 (C-Ar), 137.9 (C-Ar), 131.
9 (C-Ar), 110.5, 110.1, 110.1 (C-Ar, ds), 108.6, 108.3 (C-Ar, ds), 91.2 (C-
1′), 83.7 (C-4′), 76.5 (C-2′), 73.9 (Ph-CH-O), 71.0 (C-3′), 70.0–69.9 (m,
C-5′), 65.9 (CH2), 56.7, 56.6, 56.5 (OMe, ds); 33.0, 30.6–30.1, 27.3–
2
2
(242 MHz, D2O): δ = –11.9 (d, JP, P = 20.5 Hz, P-α), –13.3 (d, JP, P
=
16.9 Hz, P-γ), –24.0 to –24.3 (m, P-ꢀ); IR (ATR): ν = [cm–1] = 3141,
˜
1679, 1521, 1327, 1275, 1218, 1169, 1127, 1066, 1019, 924, 813, 753,
710, 604; HRMS (ESI–): m/z calcd. for C28H33N7O21P3–: 896.0948,
found 896.0648.
γ-Bis(5-methoxy-2-nitro-4-octanoxybenzyl)ATP (15): The synthe-
sis was done according to general procedure 4; 0.16 g (0.21 mmol,
1.5 equiv.) of phosphoramidite 8 and 0.13 g (0.14 mmol, 1.0 equiv.)
ADP 24 were dissolved in 10 mL dry CH3CN and 0.85 mL
(0.21 mmol, 1.5 equiv.) DCI-activator solution (0.25
M
in CH3CN) and
0.44 μL (0.24 mmol, 1.7 equiv.) tert-butylhydroperoxide (5.5
M, in n-
decan) were added. Yield: 50 mg (45 μmol, 38 %) as a yellow cotton.
The yield was calculated with two ammonium counterions. 1H-NMR
(600 MHz, [D4]MeOD): δ = 8.65 (s, 1 H, H-Ar), 8.20 (s, 1 H, H-Ar), 7.55
(s, 1 H, H-Ar), 7.54, (s, 1 H, H-Ar), 7.25 (s, 1 H, H-Ar), 7.24(s, 1 H, H-
3
3
27.0, 23.7 (CH2), 24.7 (d, JC,P = 4.5 Hz, CH3), 24.6 (d, JC,P = 4.4 Hz,
3
3
CH3), 23.8 (d, JC,P = 4.3 Hz, CH3), 14.5 (CH3); 31P-NMR (242 MHz,
Ar), 5.99 (d, JH,H = 4.2 Hz, 1 H, H-1′), 5.57–5.46 (m, Ph-CH2), 4.50–
3
4.45 (m, 2 H, H-2′, 3′), 4.40–4.36 (m, 1 H, H-5′a), 4.30 (ddd, JH,H
=
[D4]MeOD): δ = –11.5 to –11.9 (m, P-α), –13.5 to –13.6 (m, P-γ),
2
2
2
2
11.5, JH,P = 6.0, JH,H = 2.4 1 H, H-5′b), 4.24–4.21 (m, 1 H, H-4′),
–15.5 (d, JP, P = 15.4 Hz, P-γ), –17.2 (d, JP, P = 16.5 Hz, P-γ), –23.4 to
–23.9 (m, P-ꢀ); IR (ATR): ν = [cm–1] = 3191, 2926, 2854, 1580, 1519,
4.00–3.97 (m, 4 H, 2 × CH2), 3.91 (s, 3 H, OMe), 3.90 (s, 3 H, OMe),
˜
3
1.80 (p, 3JH,H = 7.6 Hz, 4 H, 2 × CH2), 1.49 (p, JH,H = 7.1 Hz, 4 H, 2 ×
1442, 1379, 1329, 1271, 1217, 1175, 1104, 1079, 994, 871, 818, 757,
3
720, 624, 492; HRMS (ESI–): m/z calcd. for C44H65N7O21P3
:
–
CH2), 1.42–1.27 (m, 16 H, 8 × CH2), 0.91 (t, JH,H = 6.9 Hz, 6 H, 2 ×
CH3); 13C-NMR (150 MHz, [D4]MeOD): δ = 155.5 (C-Ar), 153.6 (C-Ar),
149.2 (C-Ar), 147.6 (C-Ar), 140.7 (C-Ar), 138.7 (C-Ar), 126.8 (C-Ar),
111.8 (C-Ar), 111.7 (C-Ar), 110.8 (C-Ar), 110.0 (C-Ar), 90.0 (C-1′), 85.4
(d, 3JC,P = 9.6 Hz, C-4′), 76.6 (C-2′), 71.1 (C-3′), 70.5 (d, 2JC,P = 9.6 Hz,
1120.3452, found 1120.3397.
4-(Hydroxymethyl)-phenyldecanoate (19): The synthesis of com-
pound 7 was performed as described in the literature. The analytical
data is in accordance with the literature.[25]
2
Ph-CH2), 68.0 (CH2), 65.4 (d, JC,P = 4.1 Hz, C-5′), 57.2, 56.8 (2 ×
OMe), 33.0, 30.5, 30.4, 30.1, 27.1, 23.7 (6 × CH2), 14.5 (CH3); 31P-NMR
O-(1-(4,5-Dimethoxy-2-nitrophenyl)ethyl)-bis(N,N-diisopropyl-
amin)phosphoramidite (20): Under anhydrous conditions a solu-
tion containing 0.30 g (1.3 mmol, 1.2 equiv.) of alcohol 4 and
0.45 mL (0.33 g, 3.3 mmol, 3.0 equiv.) anhydrous triethylamine in
10 mL anhydrous THF were added dropwise to an ice-cold solution
of 0.29 g (1.1 mmol, 1.0 equiv.) bis(N,N-diisopropylamino)-chloro-
phosphine in 10 mL anhydrous THF over a period of 30 minutes.
The resulting mixture was stirred at room temperature for 18 h. The
precipitate was removed and the filtrate was concentrated to dry-
2
(262 MHz, [D4]MeOD): δ = –11.8 (d, JP, P = 20.4 Hz, P-α), –13.3 (d,
2
2
2JP, P = 16.8 Hz, P-γ), –20.4 (dd, JP, P = 20.4 Hz, JP, P = 16.5 Hz, P-ꢀ);
IR (ATR): ν = [cm–1] = 3191, 2924, 2854, 1578, 1520, 1463, 1326,
˜
1275, 1217, 1128, 1067, 991, 872, 811, 754, 639; HRMS (ESI–): m/z
calcd. for C42H61N7O21P3–: 1092.3139, found 1092.3075.
γ-Bis-O-(1-(4,5-dimethoxy-2-nitrophenyl)ethyl)ATP (16): The
synthesis was done according to general procedure 5; 0.20 g
(0.40 mmol, 1.0 equiv.) of H-phosphonate 11 was activated with
0.11 g (0.80 mmol, 2.0 equiv.) N-chlorosuccinimide and 0.31 g ness in vacuo. The remaining residue was purified on silica gel (PE/
(0.30 mmol 0.8 equiv.) ADP 24 was added. Yield: 0.14 g (0.15 μmol, EtOAc, 5:1 + 5 % TEA). Yield: 0.44 g (0.97 mmol, 88 %) as a yellow
49 %) as a yellow cotton in a mixture of four diastereomers. The
yield was calculated with two ammonium counterions. 1H-NMR
(600 MHz, [D4]MeOD): δ = 8.65, 8.64, 8.63, 8.61, (s, 1 H, H-Ar, ds.),
solid. Rf = 0.50 (PE/EtOAc, 5:1 + 5 % TEA); 1H-NMR (300 MHz, CDCl3):
3
δ = 7.56 (s, 1 H, H-Ar), 7.39 (s, 1 H, H-Ar), 5.51 (dq, JH,P = 12.4 Hz,
3JH,H = 6.2 Hz, 1 H, Ph-CH-O), 3.96 (s, 3 H, OMe), 3.93 (s, 3 H, OMe),
3
8.20, 8.19, 8.19 (s, 1 H, H-Ar, ds.), 7.43–7.29 (m, 2 H, H-Ar), 7.16–7.04 3.63–3.39 (m, 4 H, PNC-H), 1.53 (d, JH,H = 6.2 Hz, 3 H, CH3), 1.20
(m, 2 H, H-Ar), 6.15–6.02 (m, 2 H, H-1′, Ph-CH-P), 4.65–4.59 (m, 1 H,
(4 × d, 3JH,H = 6.6 Hz, 6 H, CH3); 13C-NMR (75 MHz, CDCl3): δ = 153.7
H-2′), 4.53–4.49 (m, 1 H, H-4′), 4.36–4.30 (m, 2 H, H-3′, 5′a), 4.29– (C-Ar), 147.5 (C-Ar), 139.4 (C-Ar), 138.1 (d, 3JC,P = 2.1 Hz, C-Ar), 109.6
4.21 (m, 1 H, H-5′b), 3.90, 3.88, 3.87, 3.83 (s, 12 H, OMe, ds.), 1.66– (C-Ar), 107.4 (C-Ar), 66.9 (d, 2JC,P = 17.7 Hz, Ph-CH2-P), 56.4, 56.3 (2 ×
1.51 (m, 6 H, 2 × CH3); 13C-NMR (150 MHz, D2O): δ = 154.1, 153.9,
OMe), 44.9, 44.7 (d, JC,P = 12.6 Hz, PNC), 25.2 (d, JC,P = 3.6 Hz,
153.7 (C-Ar, ds), 148.2, 148.2, 148.0, 147.9 (C-Ar, ds), 138.3, 138.1, CH3), 24.5–24.3 (m, CH3); 31P-NMR (162 MHz, CDCl3): δ = 148.8; IR
137.9 (C-Ar, ds), 132.7–132.6, 132.5–132.4, 132.1–131.9 (3 × m, C-Ar,
(ATR): ν = [cm–1] = 2966, 2929, 2868, 1519, 1497, 1462, 1452, 1438,
ds), 108.7, 108.7, 108.3, 107.6, 107.2, 107.1, 107.0, 106.8 (C-Ar, ds), 1319, 1272, 1219, 1184, 1114, 1099, 1051, 951, 916, 873, 794, 759,
88.1, 88.0, 87.9 (C-1′, ds), 84.1, 84.1 (C-4′, ds), 75.2, 75.1, 75.1 (C-2′,
672, 525; HRMS (ESI–): m/z calcd. for C22H40N3O5P + H+: 474.2733,
ds), 73.6–73.4, 73.0–72.8, 72.8–72.7 (3 × m, Ph-CH-O), 70.3, 70.2, 70.1 found 474.2730.
2
3
˜
Eur. J. Org. Chem. 2020, 6776–6789
6787
© 2020 The Authors. European Journal of Organic Chemistry
published by Wiley-VCH GmbH