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DOI: 10.1055/s-2006-950262
Domino Ring-Closing Enyne-Metathesis-Cross-Metathesis Approach to 1-Phosphonylated Benzazepines
Publication History
Publication Date:
09 October 2006 (online)
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Abstract
A short approach was developed towards phosphonylated benzazepines. Aminophosphonates containing an ‘yne’ and an ‘ene’ moiety were synthesised via phosphonylation of the corresponding imines. The key step in the reaction sequence is a domino enyne-metathesis-cross-metathesis.
Key words
domino reactions - enynes - fused-ring systems - metathesis - phosphorus
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References and Notes
Synthesis of Derivatives 3 from 4; General Procedure
To a solution of 4 (1 equiv) in anhyd CH2Cl2 (15 mL) was added the alkene (5 equiv). This mixture was refluxed under N2 atmosphere and the second-generation Grubbs’ catalyst 2 (10 mol%) was added. The resulting solution was refluxed for 4 h. The residue was adsorbed onto silica gel and purified by flash chromatography.
Synthesis of Derivatives 3 from 5; General Procedure
To a solution of 5 (1 equiv) in anhyd CH2Cl2 (15 mL) was added the alkene (5 equiv). This mixture was refluxed under N2 atmosphere and the second-generation Grubbs’ catalyst 2 (10 mol%) was added. An additional amount of alkene (5 equiv) was added after 2 h and refluxing was continued for an additional 4 h. The residue was adsorbed onto silica gel and purified by flash chromatography.
Dimethyl 2-Benzyl-5-[(
E
)-2-phenylvinyl]-2,3-dihydro-1
H
-2-benzazepin-1-ylphosphonate: R
f
= 0.27 (EtOAc-MeCN, 8:2). IR: 1031 (PO), 1057 (PO), 1247 (P=O), 1600 (C=C) cm-1. 1H NMR (300 MHz, CDCl3): δ = 2.79 (dd, J = 7.2 Hz, J = 11.6 Hz, 1 H, NCH
AHBCH), 3.04 (dd, J = 7.2 Hz, J = 11.6 Hz, 1 H, NCHA
H
BCH), 3.50 (d, J = 10.5 Hz, 3 H, OCH3), 3.62 (d, J = 12.6 Hz, 1 H, NCH
AHBPh), 3.62 (d, J = 10.7 Hz, 3 H, OCH3), 4.06 (d, J = 12.6 Hz, 1 H, NCHA
H
BPh), 4.35 (d, J = 25.0 Hz, 1 H, CHP), 6.30 (t, J = 7.2 Hz, 1 H, NCH2CH), 6.67 (d, J = 16.2 Hz, 1 H, HC=CHPh), 7.00 (d, J = 16.2 Hz, 1 H, HC=CHPh), 7.16-7.47 (m, 13 H, 13 × ArCH), 7.53 (d, J = 7.2 Hz, 1 H, ArCH). 13C NMR (75 MHz, CDCl3): δ = 50.14 (d, J = 5.8 Hz), 53.04 (d, J = 10.4 Hz), 61.48 (d, J = 11.5 Hz), 64.71 (d, J = 171.9 Hz), 126.58, 127.42, 127.96, 128.05, 128.32, 128.43, 128.69, 129.42, 129.50, 129.76, 131.44, 131.61 (d, J = 10.4 Hz), 133.13, 137.45, 138.14 (d, J = 6.9 Hz), 138.63, 143.58. 31P NMR (121.5 MHz, CDCl3): δ = 26.30. MS (ESI): m/z (%) = 446.3 (M + H+, 100), 336.2 [M+ - P(O)(OMe)2, 50].
Dimethyl 2-Benzyl-5-(3-trimethylsilanyl-propenyl)-2,3-dihydro-1
H
-2-benzazepin-1-ylphosphonate: E/Z, 66:34. R
f
= 0.47 (hexane-EtOAc, 2:8). IR: 1033 (PO), 1059 (PO), 1248 (P=O), 1636 (C=C) cm-1. 13C NMR (75 MHz, CDCl3): δ = 127.28, 127.45, 127.67, 127.80, 127.93, 128.35, 129.21, 129.30, 129.39, 129.45, 129.91, 130.86; where it was possible to assign the chemical shift to a specific isomer, the assignments are given below. 31P NMR (121.5 MHz, CDCl3): δ = 26.33, 26.36. MS (ESI): m/z (%) = 456.2 (M + H+, 100), 346.3 [M+ - P(O)(OMe)2, 53].
E-Isomer: 1H NMR (300 MHz, CDCl3): δ = 0.03 [s, 9 H, Si(CH3)3], 1.59 (d, J = 8.3 Hz, 2 H, CH2Si), 2.75 (dd, J = 7.0 Hz, J = 11.7 Hz, 1 H, NCH
AHBCH), 2.86 (dd, J = 7.0 Hz, J = 11.7 Hz, 1 H, NCHA
H
BCH), 3.49 (d, J = 10.5 Hz, 3 H, OCH3), 3.54 (d, J = 13.2 Hz, 1 H, NCH
AHBPh), 3.63 (d, J = 10.7 Hz, 3 H, OCH3), 4.08 (d, J = 13.2 Hz, 1 H, NCHA
H
BPh), 4.29 (d, J = 25.0 Hz, 1 H, CHP), 5.81 (dt, J = 8.3 Hz, J = 15.5 Hz, 1 H, HC=CHCH2), 5.99 (t, J = 7.0 Hz, 1 H, NCH2CH), 6.09 (d, J = 15.5 Hz, 1 H, HC=CHCH2), 7.25-7.46 (m, 18 H, 18 × ArCH). 13C NMR (75 MHz, CDCl3): δ = -1.67, 24.03, 50.12 (d, J = 6.9 Hz), 53.00 (d, J = 5.8 Hz), 53.07 (d, J = 5.8 Hz), 61.19 (d, J = 9.2 Hz), 64.41 (d, J = 168.4 Hz), 123.97, 131.04, 131.30 (d, J = 9.2 Hz), 132.92 (d, J = 2.3 Hz), 133.09 (d, J = 2.3 Hz), 138.83, 139.11 (d, J = 8.1 Hz), 139.79, 144.03.
Z-Isomer: 1H NMR (300 MHz, CDCl3): δ = 0.02 [s, 9 H, Si(CH3)3], 1.64 (d, J = 9.0 Hz, 2 H, CH2Si), 3.07 (dd, J = 6.4 Hz, J = 13.9 Hz, 1 H, NCH
AHBCH), 3.17 (dd, J = 6.4 Hz, J = 13.9 Hz, 1 H, NCHA
H
BCH), 3.54 (d, J = 13.4 Hz, 1 H, NCH
AHBPh), 3.54 (d, J = 10.4 Hz, 3 H, OCH3), 3.69 (d, J = 10.5 Hz, 3 H, OCH3), 4.04 (d, J = 13.4 Hz, 1 H, NCHA
H
BPh), 4.36 (d, J = 24.8 Hz, 1 H, CHP), 5.74 (dt, J = 9.0 Hz, J = 12.2 Hz, 1 H, HC=CHCH2), 6.01 (t, J = 6.4 Hz, 1 H, NCH2CH), 6.01 (d, J = 12.2 Hz, 1 H, HC=CHCH2), 7.25-7.46 (m, 18 H, 18 × ArCH). 13C NMR (75 MHz, CDCl3): δ = -1.40, 19.67, 51.27 (d, J = 8.1 Hz), 52.96 (d, J = 6.9 Hz), 53.34 (d, J = 6.9 Hz), 60.30 (d, J = 8.1 Hz), 64.84 (d, J = 166.1 Hz), 130.91 (d, J = 8.1 Hz), 138.87, 139.95 (d, J = 8.1 Hz).
Dimethyl 2-Benzyl-5-[(1
E
)-5-oxohex-1-enyl]-2,3-dihydro-1
H
-2-benzazepin-1-ylphosphonate: R
f
= 0.27 (EtOAc-MeCN, 8:2). IR: 1031 (PO), 1057 (PO), 1249 (P=O), 1713 (C=O) cm-1. 1H NMR (300 MHz, CDCl3): δ = 2.15 (s, 3 H, C=OCH3), 2.42 (dt, J = 6.8 Hz, J = 6.8 Hz, 2 H, CH
2CH2C=O), 2.56 (t, J = 6.8 Hz, 2 H, CH2CH
2C=O), 2.73 (dd, J = 7.1 Hz, J = 11.9 Hz, 1 H, NCH
AHBCH), 2.98 (dd, J = 7.1 Hz, J = 11.9 Hz, 1 H, NCHA
H
BCH), 3.47 (d, J = 10.5 Hz, 3 H, OCH3), 3.59 (d, J = 13.1 Hz, 1 H, NCH
AHBPh), 3.66 (d, J = 10.5 Hz, 3 H, OCH3), 4.01 (d, J = 13.1 Hz, 1 H, NCHA
H
BPh), 4.29 (d, J = 25.0 Hz, 1 H, CHP), 5.79 (dt, J = 6.8 Hz, J = 15.5 Hz, 1 H, HC=CHCH2), 6.08 (t, J = 7.1 Hz, 1 H, NCH2CH), 6.26 (d, J = 15.5 Hz, 1 H, HC=CHCH2), 7.23-7.41 (m, 9 H, 9 × ArCH). 13C NMR (75 MHz, CDCl3): δ = 27.16, 30.06, 43.17, 50.07 (d, J = 5.8 Hz), 52.92 (d, J = 6.9 Hz), 53.07 (d, J = 8.1 Hz), 61.41 (d, J = 10.4 Hz), 64.91 (d, J = 171.9 Hz), 126.38, 127.35, 127.82, 128.37, 129.16, 129.45, 131.47, 131.53 (d, J = 9.2 Hz), 131.76, 132.98, 138.49 (d, J = 6.9 Hz), 138.69, 143.06, 208.13. 31P NMR (121.5 MHz, CDCl3): δ = 26.22. MS (ESI): m/z (%) = 439.7 (M + H+, 10), 330 [M+ - P(O)(OMe)2, 100].
Dimethyl 2-Benzyl-5-[(1
Z
)-5-oxohex-1-enyl]-2,3-dihydro-1
H
-2-benzazepin-1-ylphosphonate:
R
f
= 0.27 (EtOAc-MeCN, 8:2). IR: 1030 (PO), 1058 (PO), 1252 (P=O), 1714 (C=O) cm-1. 1H NMR (300 MHz, CDCl3): δ = 2.10 (s, 3 H, C=OCH3), 2.34-2.53 (m, 4 H, CH2CH2C=O), 3.01 (dd, J = 6.1 Hz, J = 13.8 Hz, 1 H, NCH
AHBCH), 3.29 (dd, J = 6.1 Hz, J = 13.8 Hz, 1 H, NCHA
H
BCH), 3.53 (d, J = 10.5 Hz, 3 H, OCH3), 3.66 (d, J = 13.2 Hz, 1 H, NCH
AHBPh), 3.71 (d, J = 10.4 Hz, 3 H, OCH3), 3.94 (d, J = 13.2 Hz, 1 H, NCHA
H
BPh), 4.36 (d, J = 24.8 Hz, 1 H, CHP), 5.61 (dt, J = 7.0 Hz, J = 11.4 Hz, 1 H, HC=CHCH2), 6.00 (t, J = 6.1 Hz, 1 H, NCH2CH), 6.13 (d, J = 11.4 Hz, 1 H, HC=CHCH2), 7.26-7.38 (m, 9 H, 9 × ArCH). 13C NMR (75 MHz, CDCl3): δ = 23.28, 29.90, 43.68, 50.87 (d, J = 6.9 Hz, 52.97 (d, J = 6.9 Hz, 53.29 (d, J = 8.1 Hz), 61.02 (d, J = 9.2 Hz), 65.75 (d, J = 167.3 Hz), 127.33, 127.70, 128.02, 128.37, 128.81, 129.16, 129.39, 131.16, 131.41 (d, J = 9.2 Hz), 131.59, 133.10, 138.74, 139.22 (d, J = 8.1 Hz), 139.53, 208.25. 31P NMR (121.5 MHz, CDCl3): δ = 25.89. MS (ESI): m/z (%) = 439.7 (M + H+, 13), 330 [M+ - P(O)(OMe)2, 100].
Dimethyl 2-(4-Bromobenzyl)-4-[(1
E
)-4-fenylvinyl]-2,3-dihydro-1
H
-2-benzazepin-1-ylphosphonate: R
f
= 0.20 (hexane-EtOAc, 4:6). IR: 1031 (PO), 1057 (PO), 1250 (P=O) cm-1. 1H NMR (300 MHz, CDCl3): δ = 3.52 (d, J = 13.6 Hz, 1 H, NCH
AHBPh), 3.65 (d, J = 10.7 Hz, 3 H, OCH3), 3.68 (d, J = 11.0 Hz, 3 H, OCH3), 3.75 (d, J = 13.5 Hz, 1 H, NCHA
H
BPh), 3.95 (d, J = 18.4 Hz, 1 H, NCH
AHBC), 4.37 (d, J = 18.4 Hz, 1 H, NCHA
H
BC), 4.47 (d, J = 27.5 Hz, 1 H, CHP), 6.46 (d, J = 16.4 Hz, 1 H, HC=CHPh), 6.68 (s, 1 H, C=CHC), 6.89 (d, J = 16.4 Hz, 1 H, HC=CHPh), 7.10-7.42 (m, 13 H, 13 × ArCH). 13C NMR (75 MHz, CDCl3): δ = 53.08 (d, J = 6.9 Hz), 53.65 (d, J = 4.6 Hz), 53.72 (d, J = 6.9 Hz), 57.07, 64.14 (d, J = 155.8 Hz), 121.25, 126.46, 127.33, 127.68, 128.06, 128.09, 128.92, 130.55, 130.92, 131.54, 132.31 (d, J = 4.6 Hz), 132.52, 132.83, 133.74, 136.28 (d, J = 8.1 Hz), 136.57, 137.33, 137.71, 139.27. 31P NMR (121.5 MHz, CDCl3): δ = 25.29. MS (ESI): m/z (%) = 524.03/526.3 (M + H+, 60), 414.2/416.2 [M+ - P(O)(OMe)2, 100].
Dimethyl 2-(4-Bromobenzyl)-4-[(1
E
)-4-bromobut-1-enyl]-2,3-dihydro-1
H
-2-benzazepin-1-ylphosphonate: R
f
= 0.29 (hexane-EtOAc, 4:6). IR: 1031 (PO), 1058 (PO), 1252 (P=O) cm-1. 1H NMR (300 MHz, CDCl3): δ = 2.67 (q, J = 7.0 Hz, 2 H, CH
2CH2Br), 3.40 (t, J = 7.0 Hz, 2 H, CH2Br), 3.46 (d, J = 13.5 Hz, 1 H, NCH
AHBPh), 3.63 (d, J = 10.7 Hz, 3 H, OCH3), 3.68 (d, J = 10.8 Hz, 3 H, OCH3), 3.71 (d, J = 13.5 Hz, 1 H, NCHA
H
BPh), 3.79 (d, J = 18.6 Hz, 1 H, NCH
AHBC), 4.22 (d, J = 18.6 Hz, 1 H, NCHA
H
BC), 4.38 (d, J = 27.8 Hz, 1 H, CHP), 5.54 (dt, J = 7.0 Hz, J = 15.8 Hz, 1 H, HC=CHCH2), 6.23 (d, J = 15.8 Hz, 1 H, HC=CHCH2), 6.49 (s, 1 H, C=CHC), 7.10-7.46 (m, 8 H, 8 × ArCH). 13C NMR (75 MHz, CDCl3): δ = 32.39, 36.61, 53.07 (d, J = 6.9 Hz), 53.68 (d, J = 5.8 Hz), 53.68, 57.01, 63.98 (d, J = 154.6 Hz), 121.19, 125.74, 127.21, 128.02, 130.48, 130.89, 131.50, 132.67, 133.62 (d, J = 2.3 Hz), 136.20 (d, J = 6.9 Hz), 136.57, 137.68, 138.67. 31P NMR (121.5 MHz, CDCl3): δ = 25.24. MS (ESI): m/z (%) = 554.0/556.0/558.0 (M + H+, 35), 444.0/446.0/448.0 [M+ - P(O)(OMe)2, 100].
Dimethyl 2-(4-Bromobenzyl)-4-[(1
E
)-hex-1-enyl]-2,3-dihydro-1
H
-2-benzazepin-1-ylphosphonate: R
f
= 0.27 (hexane-EtOAc, 4:6). IR: 1031 (PO), 1058 (PO), 1253 (P=O) cm-1. 1H NMR (300 MHz, CDCl3): δ = 0.90 (t, J = 7.0 Hz, 3 H, CH3), 1.25-1.43 (m, 4 H, CH2CH2CH3), 2.11 (q, J = 6.9 Hz, 2 H, HC=CHCH
2), 3.46 (d, J = 12.4 Hz, 1 H, NCH
AHBPh), 3.64 (d, J = 10.7 Hz, 3 H, OCH3), 3.68 (d, J = 12.1 Hz, 3 H, OCH3), 3.72 (d, J = 12.4 Hz, 1 H, NCHA
H
BPh), 3.80 (d, J = 18.4 Hz, 1 H, NCH
AHBC), 4.19 (d, J = 18.4 Hz, 1 H, NCHA
H
BC), 4.39 (d, J = 27.5 Hz, 1 H, CHP), 5.60 (dt, J = 6.9 Hz, J = 16.0 Hz, 1 H, HC=CHCH2), 6.13 (d, J = 16.0 Hz, 1 H, HC=CHCH2), 6.44 (s, 1 H, C=CHC), 7.11-7.40 (m, 8 H, 8 × ArCH). 13C NMR (75 MHz, CDCl3): δ = 14.06, 22.35, 31.63, 33.08, 53.00 (d, J = 6.9 Hz), 53.73 (d, J = 8.1 Hz), 53.83 (d, J = 6.9 Hz), 56.80, 63.97 (d, J = 155.8 Hz), 121.18, 126.83, 127.97, 129.85, 130.52, 130.98, 131.45, 133.22, 132.38, 133.64, 136.54 (d, J = 6.9 Hz), 137.76, 139.32. 31P NMR (121.5 MHz, CDCl3): δ = 25.29. MS (ESI): m/z (%) =504.6/506.2 (M + H+, 60), 394.2/396.3 [M+ - P(O)(OMe)2, 100].