4302
N. Dieltiens et al. / Tetrahedron 64 (2008) 4295e4303
Rf¼0.11. C20H24NO3P: calcd C 67.21, H 6.77, N 3.92; found
PE/EtOAc (70/30) Rf¼0.08. C21H26NO4P: calcd C 65.11, H
C 67.21, H 6.80, N 3.91.
6.76, N 3.62; found C 65.11, H 6.81, N 3.64.
3.9. Synthesis of dimethyl 2-(benzyl)-1,2,3,6-tetrahydro-
2-benzazocin-1-ylphosphonates 2b,c: general procedure
3.8.2. Synthesis of dimethyl 2-(3-fluorobenzyl)-1,2,3,4-
tetrahydro-2-benzazocin-1-ylphosphonate (1e)
Yield: 70% (viscous oil).
In a flask of 10 mL, aminophosphonate 4b,c (0.24 mmol)
was refluxed in 5 mL of benzene. To this solution, the first
generation Grubbs’ catalyst (0.01 mmol) was added. After re-
fluxing for 8 h, again 0.03 equiv of the first generation Grubbs’
catalyst (0.006 mmol) was added. After refluxing the resulting
mixture for another 2 days, benzene was evaporated under
vacuum. The crude product was purified by chromatography.
1H NMR (CDCl3, 300 MHz) d: 2.02e2.08 (2H, m,
CH2CH2N), 2.40e2.49 (1H, m, CH2CHAHBN), 2.74e2.82
(1H, m, CH2CHAHBN), 3.28 (1H, d, J¼13.2 Hz, NCHAHB-
3
Car), 3.56 (3H, d, JHP¼10.5 Hz, CH3OP), 3.93 (3H, d,
3JHP¼10.5 Hz, CH3OP), 4.41 (1H, d, J¼13.2 Hz, NCHAHB-
2
Car), 4.47 (1H, d, JHP¼23.4 Hz, CHP), 6.06 (1H, dt,
J¼11.3 Hz, J¼8.0 Hz, CH]CHCH2), 6.69 (1H, d,
J¼11.3 Hz, CH]CHCH2), 6.92e6.98 (1H, m, CHar), 7.09e
7.15 (1H, m, CHar), 7.16e7.39 (4H, m, CHar), 7.69e7.75
(1H, m, CHar), 8.08e8.11 (1H, m, CHar). 13C NMR (CDCl3,
75 MHz) d: 23.23 (CH2CH2N), 44.46 (NCH2Car), 46.67 (d,
3.9.1. Synthesis of dimethyl 2-(3-fluorobenzyl)-1,2,3,6-
tetrahydro-2-benzazocin-1-ylphosphonate (2b)
Yield: 75% (viscous oil).
1H NMR (CDCl3, 300 MHz) d: 3.02e3.30 (2H, m,
NCHAHBCarþNCHAHBCH), 3.38 (1H, dd, J¼14.6 Hz,
J¼6.7 Hz, NCHAHBCH), 3.37e3.87 (5H, m, CH3OPþ
3JCP¼15.0 Hz, CH2CH2N), 52.41 (d, JCP¼6.9 Hz, CH3OP),
2
2
1
54.52 (d, JCP¼6.9 Hz, CH3OP), 59.59 (d, JCP¼172.0 Hz,
CHP), 114.90 (d, J¼23.1 Hz, CHar), 124.10 (d, J¼2.3 Hz,
CHar), 126.24 (d, J¼15.0 Hz, Cq,ar), 126.97 (CHar), 127.61
(CHar), 128.46 (d, J¼8.1 Hz, CHar), 128.61 (CHar), 129.46
(CH]CHCH2), 130.02 (d, J¼10.4 Hz, Cq,ar), 130.62 (d,
J¼4.6 Hz, CHar), 132.30 (d, J¼4.6 Hz, CHar), 133.40
(CH]CHCH2), 137.62 (d, J¼16.2 Hz, Cq,ar), 161.44 (d,
J¼245.8 Hz, Cq,ar). 31P NMR (CDCl3, 121 MHz) d: 24.62.
19F NMR (CDCl3, 282 MHz) d: ꢀ119.61. IR (NaCl, cmꢀ1):
1625 (C]C); 1246 (P]O); 1061, 1036 (PeO). MS (ESI,
pos mode) (%) m/z: 376 (MþHþ, 100). Chromatography:
PE/EtOAc (3/1) Rf¼0.05. C20H23FNO3P: calcd C 63.99, H
6.18, N 3.73; found C 63.98, H 6.16, N 3.72.
3
CarCH2CH), 3.96 (3H, d, JHP¼10.5 Hz, CH3OP), 3.98e4.16
2
(1H, m, NCHAHBCar), 4.96 (1H, d, JHP¼24.5 Hz, CHP),
5.47e5.58 (1H, m, CH]CH), 6.12 (1H, dt, J¼10.5 Hz,
J¼7.7 Hz, CH]CH), 6.92e8.02 (8H, m, CHar). 13C NMR
(CDCl3, 75 MHz) d: 34.71 (CarCH2CH), 45.58 (br, NCH2Car),
2
49.97 (br, CHCH2N), 52.56 (d, JCP¼6.9 Hz, CH3OP), 54.63
2
(d, JCP¼6.9 Hz, CH3OP), 60.27 (d, 1J¼161.5 Hz, CHP),
115.18 (d, JCP¼21.9 Hz, CHar), 124.01 (d, JCP¼3.5 Hz,
CHar), 125.95 (d, J¼15.0 Hz, Cq,ar), 126.40 (CHar), 126.92
(CH]CH), 128.54 (CHar), 128.60 (d, J¼9.2 Hz, CHar),
129.10 (CHar), 129.39 (br, CHar), 131.67 (br, Cq,ar), 132.12
(br, CHar), 135.94 (CH]CH), 141.80 (br, Cq,ar), 161.49 (d,
J¼245.8, Cq,ar). 31P NMR (CDCl3, 121 MHz) d: 24.55. 19F
NMR (CDCl3, 282 MHz) d: ꢀ119.61. IR (NaCl, cmꢀ1):
1657 (C]C); 1248 (P]O); 1058, 1034 (PeO). MS (ESI,
pos mode) (%) m/z: 376 (MþHþ, 100). Chromatography:
PE/EtOAc (3/1) Rf¼0.06. C20H23FNO3P: calcd C 63.99, H
6.18, N 3.73; found C 64.05, H 6.23, N 3.72.
3.8.3. Synthesis of dimethyl 2-(3-methoxybenzyl)-1,2,3,4-
tetrahydro-2-benzazocin-1-ylphosphonate (1f)
Yield: 72% (yellow-brown oil).
1H NMR (CDCl3, 300 MHz) d: 1.97e2.04 (2H, m,
CH2CH2N), 2.40e2.48 (1H, m, CH2CHAHBN), 2.79e2.85
4
(1H, m, CH2CHAHBN), 2.93 (1H, dd, J¼13.2 Hz, JHP
¼
3
1.1 Hz, NCHAHBCar), 3.56 (3H, d, JHP¼10.5 Hz, CH3OP),
3.9.2. Synthesis of dimethyl 2-(3-methoxybenzyl)-1,2,3,6-
tetrahydro-2-benzazocin-1-ylphosphonate (2c)
3
3.78 (CH3O), 3.97 (3H, d, JHP¼10.2 Hz, CH3OP), 4.49
2
(1H, d, JHP¼26.4 Hz, CHP), 4.61 (1H, d, J¼13.2 Hz,
Yield: 75% (viscous oil).
NCHAHBCar), 6.05 (1H, dt, J¼11.3 Hz, J¼7.8 Hz,
CH]CHCH2), 6.68 (1H, d, J¼11.3 Hz, CH]CHCH2),
6.75e7.04 (3H, m, CHar), 7.16e7.37 (4H, m, CHar), 8.05e
8.09 (1H, m, CHar). 13C NMR (CDCl3, 75 MHz) d: 23.21
1H NMR (CDCl3, 300 MHz) d: 2.67e2.84 (1H, m,
NCHAHBCar), 3.05e3.30 (1H, m, NCHAHBCH), 3.40 (1H,
dd, J¼14.9 Hz, J¼6.3 Hz, NCHAHBCH), 3.46e3.96 (5H, m,
CH3OPþCarCH2CH), 3.78 (3H, s, CH3O), 4.02 (3H,
3JHP¼10.5 Hz, CH3OP), 4.07e4.25 (1H, m, NCHAHBCar),
4.91e5.09 (1H, m, CHP), 5.40e5.49 (1H, m, CH]CH),
6.11 (1H, dt, J¼9.9 Hz, J¼8.3 Hz, CH]CH), 6.75e6.79
(1H, m, CHar), 6.91e6.97 (2H, m, CHar), 7.15e7.28 (5H, m,
CHar). 13C NMR (CDCl3, 75 MHz) d: 34.57 (CarCH2CH),
3
(CH2CH2N), 46.40 (d, JCP¼15.0 Hz, CH2CH2N), 52.49 (d,
2JCP¼6.9 Hz, CH3OP), 52.51 (d, JCP¼6.9 Hz, CH3OP),
2
3
54.47 (d, JCP¼8.1 Hz, NCH2Car), 55.20 (CH3O), 59.78 (d,
1JCP¼171.9 Hz, CHP), 112.55 (CHar), 114.76 (CHar), 121.80
(CHar), 127.01 (CHar), 127.65 (CHar), 128.66 (CHar), 129.10
(CH]CHCH2), 129.53 (CHar), 130.22 (d, JCP¼9.2 Hz,
Cq,ar), 130.73 (d, JCP¼4.6 Hz, CHar), 133.42 (CH]CHCH2),
137.71 (d, JCP¼15.0 Hz, Cq,ar), 141.40 (Cq,ar), 159.64 (Cq,ar).
31P NMR (CDCl3, 121 MHz) d: 24.91. IR (NaCl, cmꢀ1):
1600 (C]C); 1261 (P]O); 1061, 1037 (PeO). MS (ESI,
pos mode) (%) m/z: 388 (MþHþ, 100). Chromatography:
2
49.81 (br, NCH2CH), 52.44 (d, JCP¼6.9 Hz, CH3OP), 52.70
2
(NCH2Car), 54.81 (d, JCP¼6.9 Hz, CH3OP), 55.20 (CH3O),
1
63.51 (d, JCP¼175.4 Hz, CHP), 112.73 (CHar), 114.60
(CHar), 121.73 (CHar), 126.32 (CHar), 126.99 (CH]CH),
128.46 (CHar), 129.07 (CHar), 129.27 (br, CHar), 130.70 (br,
CHar), 132.09 (d, J¼9.2 Hz, Cq,ar), 135.74 (CH]CH),