Domino ring-closing enyne-metathesis-cross-metathesis approach to 1-phosphonylated benzazepines

Article abstract of DOI:10.1055/s-2006-950262

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. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-950262

LETTER
2771
Domino Ring-Closing Enyne-Metathesis–Cross-Metathesis Approach to
1-Phosphonylated Benzazepines
1-Phosphonylated
i
Benza
z
c
epines olai Dieltiens, Christian V. Stevens*
Research Group SynBioc, Department of Organic Chemistry, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653,
9000 Ghent, Belgium
Fax +32(9)2646243; E-mail: chris.stevens@UGent.be
Received 8 August 2006
Scheme 1 shows the retrosynthetic analysis of the envis-
Abstract: A short approach was developed towards phosphon-
aged structures 3. Depending on the position of the alkene
ylated benzazepines. Aminophosphonates containing an ‘yne’ and
an ‘ene’ moiety were synthesised via phosphonylation of the
and alkyne moieties, an alkenyl group (R1 or R2) is intro-
duced at a different position. Starting from aminophos-
phonates 4 leads to derivatives 3 with a substituent at the
4-position (R1 = H) whereas starting from compounds 5
should lead to benzazepines bearing a substituent at the 5-
position (R2 = H). The main advantage of this strategy is
that the synthesis of the two pivotal compounds 4 and 5
provides access to a wide variety of benzazepines 3. Ami-
nophosphonate 4 was synthesised in four steps starting
from a-bromobenzaldehyde 6 (Scheme 2). In the first step
the aldehyde was converted into an alkene via a Wittig re-
action in good yield. Compound 7 was treated with 1.05
equivalents of BuLi at –78 °C and after stirring for one
hour 1.1 equivalents of DMF was added. Aldehyde 8 was
converted into the imine upon treatment with propargyl-
amine and MgSO4 in CH2Cl2, subsequently phosphony-
lated using dimethylphosphite in MeOH and isolated
using an acid-base extraction.13 The N-atom was protect-
ed using an appropriate electrophile and K2CO3 as a solid
base in refluxing acetone.
corresponding imines. The key step in the reaction sequence is a
domino enyne-metathesis–cross-metathesis.
Key words: domino reactions, enynes, fused-ring systems, meta-
thesis, phosphorus
Benzo-fused seven-membered-ring systems have re-
ceived a lot of attention over the years because of their
ubiquitous appearance in natural products and modern
pharmaceuticals.1 2,3-Dihydro-1H-benzo[c]azepines 1
have previously been prepared by electrocyclisation
reactions2 and ring-closing metathesis3–5 using the sec-
ond-generation Grubbs’ catalyst 2 (Figure 1).6
N
N
Mes
Mes
Cl
Cl
Ru CHPh
PCy3
N
R
1
2
R1
R2
Figure 1
alkene
alkene
N
N
Only a few papers, however, have been published in the
field of seven-membered aza-heterocyclic phosphonates,7
although some of these compounds show interesting bio-
logical properties, such as bone-resorption inhibitory ac-
tivity.8 To the best of our knowledge, the ring expansion
of nitro-substituted naphthalenes upon reaction with dim-
ethyl phosphite under basic conditions is the only synthe-
sis of 1H-2-benzazepine-1-ylphosphonates reported in the
literature.9 During our ongoing program to evaluate ring-
closing metathesis for the synthesis of aza-heterocyclic
phosphonates,10 we became interested in ring-closing
enyne metathesis for the construction of new 1H-2-benza-
zepine-1-ylphosphonates.11 Not only is ring-closing
enyne metathesis more atom-efficient than normal ring-
closing metathesis, it also provides the possibility of
immediately functionalising the intermediate diene by
cross-metathesis with an alkene.12
cat. 2
cat. 2
PG
PG
N
PG
P(O)(OMe)2
P(O)(OMe)2
(MeO)2(O)P
3
4
5
Scheme 1 Retrosynthetic analysis of 1H-2-benzazepine-1-ylphos-
phonates 3
The synthesis of the second building block, aminophos-
phonate 5, started from the commercially available
aldehyde 10 (Scheme 3). It was observed, however, that
treating this aldehyde with allylamine and MgSO4 in
CH2Cl2, in order to synthesise the imine, resulted in the
formation of a complex reaction mixture. Therefore, alde-
hyde 10 was converted into the desired aminophospho-
nate by a one-pot three-component coupling mediated by
LiClO4 and was further purified by column chromatogra-
phy.14
Upon evaluation of the enyne-metathesis–cross-metathe-
sis sequence between 5 and five equivalents of styrene
(Scheme 4) by 31P NMR spectroscopy, it was found that
after 30 minutes the starting compound was completely
SYNLETT 2006, No. 17, pp 2771–2776
Advanced online publication: 09.10.2006
DOI: 10.1055/s-2006-950262; Art ID: G26506ST
© Georg Thieme Verlag Stuttgart · New York
1
7
.1
0
.2
0
0
6

2772
N. Dieltiens, C. V. Stevens
LETTER
O
H
a
b
H
Br
Br
6
7
8
O
Br
c,d
e
NH
N
P(O)(OMe)2
P(O)(OMe)2
9
4
Figure 2 Conversion of aminophosphonate 5 into 11 and 12 as
Scheme 2 Reagents and conditions: (a) Ph3PCH3Br, t-BuOK, THF,
24 h (6, 91%); (b) BuLi, DMF, THF, –78 °C (7, 73%); (c) propargyl-
amine, MgSO4, CH2Cl2; (d) HP(O)(OMe)2, MeOH (9, 82%); (e) p-
bromobenzylbromide, K2CO3, acetone (4, 69%).
followed by 31P NMR spectroscopy
by-product 11 is formed after cycloreversion which can
react in three different ways: 1) conversion to 13 via 15;
2) conversion to 13 by reaction with the methylidene car-
bene and production of ethylene or 3) conversion to 12
after reaction with the alkylidene carbene via 16. During
the course of the reaction, the alkene is consumed in two
different ways. The first is incorporation in the end prod-
uct. The second, the alkene sink (Scheme 5), is an unpro-
ductive pathway in which the alkene is dimerised with
regeneration of the methylidene carbene and production
of ethylene. This explains the fact that adding an extra
amount of alkene speeds up the conversion of 11 to 12
since the dimerised alkene remains relatively inert in the
reaction mixture.17 In all cases, however, about 10% of 11
remained present which was removed by flash chroma-
tography.
a
H
N
Bn
O
P(O)(OMe)2
10
5
Scheme 3 Reagents and conditions: (a) LiClO4, allylbenzylamine,
P(OMe)3, Et2O (5, 68%).
consumed. At this point, most of the product present was
compound 11 (11/12 = 60:40). Following the course of the
reaction further revealed that conversion of 11 to 12
proceeds very slowly. The addition of an extra five equiv-
alents of styrene, however, had a very positive effect on
the conversion rate (Figure 2). This can be explained by
looking at the complete reaction cycle of this conversion
(Scheme 5). In the first step vinylic carbene 13 is formed.
When working under Mori’s conditions,15 this carbene
would react with ethylene to produce 11.16 In the absence
of ethylene, however, 13 can react with the alkene in two
different ways: with the R group pointing away from the
metallic centre (14) or with the R group towards the
metallic centre (15).
Upon evaluation of the enyne-metathesis–cross-metathe-
sis sequence between 4 and styrene, it was found that in
this case it is not necessary to add an extra amount of alk-
ene. This seems to prove that in this case the formation of
metallacyclobutanes of type 14 are favoured, immediately
leading to the final products.
Table 1 provides an overview of the synthesised 2-benz-
azepine-1-ylphosphonates.18 In only two cases an E/Z
mixture was observed (Table 1, entries 2 and 3), in all oth-
er cases the E-form was obtained exclusively. With both
substrates the reaction failed using allyl cyanide, which is
probably due to the fact that this is a quite electron-poor
alkene.12a
In the first case the desired end product 12 is produced af-
ter the cycloreversion. In the second case the unwanted
Ph
In summary we have developed a new and efficient entry
to an interesting class of benzo-fused phosphonoazepines.
The reaction sequence starts with the synthesis of imines,
which are phosphonylated using dimethylphosphite in
MeOH. Using a domino enyne-metathesis–cross-meta-
thesis, these substrates are cyclised and functionalised in
the presence of a terminal alkene under the action of the
second-generation Grubbs catalyst.
styrene
+
Bn
N
2 (10 mol%)
∆, CH2Cl2
Bn
P(O)(OMe)2
N
N
Bn
(MeO)2(O)P
(MeO)2(O)P
5
11
12
Scheme 4 Conversion of aminophosphonate 5 into 11 and 12
Synlett 2006, No. 17, 2771–2776 © Thieme Stuttgart · New York

LETTER
1-Phosphonylated Benzazepines
2773
R
R
Ru
Ru
N
R
+
Ru
R
N
N
R
PG
PG
PG
(MeO)2(O)P
(MeO)2(O)P
(MeO)2(O)P
12
13
14
R
R
Ru
R
R
R
Ru
Ru
R
Ru
"Alkene sink"
R
Ru
Ru
N
R
N
PG
N
(MeO)2(O)P
PG
PG
11
(MeO)2(O)P
(MeO)2(O)P
15
16
Scheme 5
Table 1 Overview of the Synthesised 1H-2-Benzazepine-1-ylphosphonates18
Entry
Enyne
Alkene
Product
Yield (%) (E/Z)
1
5
78 (100:0)
N
Bn
(MeO)2(O)P
Si
2
5
74 (66:34)
Si
N
Bn
(MeO)2(O)P
O
3
5
68 (67:33)
O
N
Bn
(MeO)2(O)P
Synlett 2006, No. 17, 2771–2776 © Thieme Stuttgart · New York

2774
N. Dieltiens, C. V. Stevens
LETTER
Table 1 Overview of the Synthesised 1H-2-Benzazepine-1-ylphosphonates18 (continued)
Entry
Enyne
Alkene
Product
Yield (%) (E/Z)
4
4
69 (100:0)
N
Br
(MeO)2(O)P
Br
5
4
50 (100:0)
Br
N
Br
(MeO)2(O)P
6
4
70 (100:0)
N
Br
(MeO)2(O)P
(5) For a review on the use of Fisher carbene complexes for
heterocyclisation, see: Barluenga, J.; Martinez, S. Arkivoc
2006, (vii), 129.
Acknowledgment
Financial support from the BOF (Bijzonder Onderzoeksfonds
Universiteit Gent, Research Fund Ghent University) is gratefully
acknowledged. The authors thank their fellow researchers of the
Synbioc group for their fine-tuning of this manuscript.
(6) Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett.
1999, 1, 953.
(7) Moonen, K.; Laureyn, I.; Stevens, C. V. Chem. Rev. 2004,
104, 6177.
(8) Gaffar, A. US 5753633, 1998; Chem. Abstr. 1998, 129,
8161.
References and Notes
(9) Danikiewicz, W.; Makosza, M. J. Org. Chem. 1991, 56,
1283.
(1) Horton, D. A.; Bourne, G. T.; Smythe, M. L. Chem. Rev.
2003, 103, 893.
(10) (a) Dieltiens, N.; Stevens, C. V.; De Vos, D.; Allaert, B.;
Drozdzak, R.; Verpoort, F. Tetrahedron Lett. 2004, 45,
8995. (b) Dieltiens, N.; Stevens, C. V.; Allaert, B.; Verpoort,
F. Arkivoc 2005, (i), 92. (c) Moonen, K.; Dieltiens, N.;
Stevens, C. V. J. Org. Chem. 2006, 71, 4006. (d) Dieltiens,
N.; Moonen, K.; Stevens, C. V. Chem. Eur. J. 2006, in press.
(11) For recent reviews on enyne metathesis, see: (a) Poulson,
C. S.; Madson, R. Synthesis 2003, 1. (b) Diver, S. T.;
Giessert, A. J. Chem. Rev. 2004, 104, 1317. (c) Maifeld, S.
V.; Lee, D. Chem. Eur. J. 2005, 11, 6118.
(12) (a) Royer, F.; Vilain, C.; Elkaïm, L.; Grimaud, L. Org. Lett.
2003, 5, 2007. (b) Lee, H.-Y.; Kim, H. Y.; Tae, H.; Kim, B.
G.; Lee, J. Org. Lett. 2003, 5, 3439. (c) Imhof, S.; Blechert,
S. Synlett 2003, 609. (d) Kitamura, T.; Sato, Y.; Mori, M.
Tetrahedron 2004, 60, 9649.
(2) (a) Arany, A.; Groundwater, P. W.; Nyerges, M.
Tetrahedron Lett. 1998, 39, 3267. (b) Arany, A.; Bendell,
D.; Groundwater, P. W.; Garnett, I.; Nyerges, M. J. Chem.
Soc., Perkin Trans. 1 1999, 2605. (c) Gerdes, K.; Sagar, P.;
Fröhlich, R.; Wibbeling, B.; Würthwein, E.-U. Eur. J. Org.
Chem. 2004, 3465. (d) Sajitz, M.; Fröhlich, R.; Salorinne,
K.; Würthwein, E.-U. Synthesis 2006, 2183.
(3) (a) Van Otterlo, W. A. L.; Pathak, R.; de Koning, C. B.
Synlett 2003, 1859. (b) Toda, N.; Tago, K.; Marumoto, S.;
Takami, K.; Ori, M.; Yamada, N.; Koyama, K.; Naruto, S.;
Abe, K.; Yamazaki, R.; Hara, T.; Aoyagi, A.; Abe, Y.;
Kaneko, T.; Kogen, H. Bioorg. Med. Chem. 2003, 11, 4389.
(4) For recent reviews on ring-closing metathesis, see:
(a) Schrock, R. R.; Hoveyda, A. H. Angew. Chem. Int. Ed.
2003, 42, 4592. (b) Grubbs, R. H. Tetrahedron 2004, 60,
7117. (c) Deiters, A.; Martin, F. Chem. Rev. 2004, 104,
2199. (d) Nicolaou, K. C.; Bulger, P. G.; Sarlah, D. Angew.
Chem. Int. Ed. 2005, 44, 4490. (e) Dragutan, I.; Dragutan,
V.; Filip, P. Arkivoc 2005, (x), 105.
(13) Van Meenen, E.; Moonen, K.; Acke, D.; Stevens, C. V.
Arkivoc 2006, (i), 31.
(14) Azizi, N.; Saidi, M. R. Tetrahedron 2003, 59, 5329.
(15) Mori, M.; Sakakibara, N.; Kinoshita, A. J. Org. Chem. 1998,
63, 6082.
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LETTER
1-Phosphonylated Benzazepines
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(16) Lloyd-Jones, G. C.; Margue, R. G.; de Vries, J. G. Angew.
Chem. Int. Ed. 2005, 44, 7442.
(17) For a general model for selectivity in cross-metathesis, see:
Chatterjee, A. K.; Choi, T. L.; Sanders, D. P.; Grubbs, R. H.
J. Am. Chem. Soc. 2003, 125, 11360.
(18) 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.
J = 13.9 Hz, 1 H, NCHAHBCH), 3.54 (d, J = 13.4 Hz, 1 H,
NCHAHBPh), 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,
NCHAHBPh), 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): d = –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-[(1E)-5-oxohex-1-enyl]-2,3-
dihydro-1H-2-benzazepin-1-ylphosphonate: Rf = 0.27
(EtOAc–MeCN, 8:2). IR: 1031 (PO), 1057 (PO), 1249
(P=O), 1713 (C=O) cm–1. 1H NMR (300 MHz, CDCl3): d =
2.15 (s, 3 H, C=OCH3), 2.42 (dt, J = 6.8 Hz, J = 6.8 Hz, 2
H, CH2CH2C=O), 2.56 (t, J = 6.8 Hz, 2 H, CH2CH2C=O),
2.73 (dd, J = 7.1 Hz, J = 11.9 Hz, 1 H, NCHAHBCH), 2.98
(dd, J = 7.1 Hz, J = 11.9 Hz, 1 H, NCHAHBCH), 3.47 (d, J =
10.5 Hz, 3 H, OCH3), 3.59 (d, J = 13.1 Hz, 1 H,
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-
1H-2-benzazepin-1-ylphosphonate: Rf = 0.27 (EtOAc–
MeCN, 8:2). IR: 1031 (PO), 1057 (PO), 1247 (P=O), 1600
(C=C) cm–1. 1H NMR (300 MHz, CDCl3): d = 2.79 (dd, J =
7.2 Hz, J = 11.6 Hz, 1 H, NCHAHBCH), 3.04 (dd, J = 7.2 Hz,
J = 11.6 Hz, 1 H, NCHAHBCH), 3.50 (d, J = 10.5 Hz, 3 H,
OCH3), 3.62 (d, J = 12.6 Hz, 1 H, NCHAHBPh), 3.62 (d, J =
10.7 Hz, 3 H, OCH3), 4.06 (d, J = 12.6 Hz, 1 H,
NCHAHBPh), 3.66 (d, J = 10.5 Hz, 3 H, OCH3), 4.01 (d, J =
13.1 Hz, 1 H, NCHAHBPh), 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): d = 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): d = 26.22. MS (ESI):
m/z (%) = 439.7 (M + H+, 10), 330 [M+ – P(O)(OMe)2, 100].
Dimethyl 2-Benzyl-5-[(1Z)-5-oxohex-1-enyl]-2,3-
dihydro-1H-2-benzazepin-1-ylphosphonate:
NCHAHBPh), 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): d = 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): d = 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-1H-2-benzazepin-1-ylphosphonate: E/Z, 66:34.
Rf = 0.47 (hexane–EtOAc, 2:8). IR: 1033 (PO), 1059 (PO),
1248 (P=O), 1636 (C=C) cm–1. 13C NMR (75 MHz, CDCl3):
d = 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): d = 26.33, 26.36. MS (ESI): m/z (%) = 456.2 (M +
H+, 100), 346.3 [M+ – P(O)(OMe)2, 53].
Rf = 0.27 (EtOAc–MeCN, 8:2). IR: 1030 (PO), 1058 (PO),
1252 (P=O), 1714 (C=O) cm–1. 1H NMR (300 MHz, CDCl3):
d = 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,
NCHAHBCH), 3.29 (dd, J = 6.1 Hz, J = 13.8 Hz, 1 H,
NCHAHBCH), 3.53 (d, J = 10.5 Hz, 3 H, OCH3), 3.66 (d, J =
13.2 Hz, 1 H, NCHAHBPh), 3.71 (d, J = 10.4 Hz, 3 H,
OCH3), 3.94 (d, J = 13.2 Hz, 1 H, NCHAHBPh), 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): d = 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): d = 25.89. MS (ESI): m/z (%) = 439.7 (M +
H+, 13), 330 [M+ – P(O)(OMe)2, 100].
Dimethyl 2-(4-Bromobenzyl)-4-[(1E)-4-fenylvinyl]-2,3-
dihydro-1H-2-benzazepin-1-ylphosphonate: Rf = 0.20
(hexane–EtOAc, 4:6). IR: 1031 (PO), 1057 (PO), 1250
(P=O) cm–1. 1H NMR (300 MHz, CDCl3): d = 3.52 (d, J =
13.6 Hz, 1 H, NCHAHBPh), 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, NCHAHBPh), 3.95 (d, J = 18.4 Hz, 1 H,
E-Isomer: 1H NMR (300 MHz, CDCl3): d = 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, NCHAHBCH), 2.86 (dd, J = 7.0 Hz,
J = 11.7 Hz, 1 H, NCHAHBCH), 3.49 (d, J = 10.5 Hz, 3 H,
OCH3), 3.54 (d, J = 13.2 Hz, 1 H, NCHAHBPh), 3.63 (d, J =
10.7 Hz, 3 H, OCH3), 4.08 (d, J = 13.2 Hz, 1 H,
NCHAHBPh), 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): d = –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.
NCHAHBC), 4.37 (d, J = 18.4 Hz, 1 H, NCHAHBC), 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): d = 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,
Z-Isomer: 1H NMR (300 MHz, CDCl3): d = 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, NCHAHBCH), 3.17 (dd, J = 6.4 Hz,
Synlett 2006, No. 17, 2771–2776 © Thieme Stuttgart · New York

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LETTER
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): d =
25.29. MS (ESI): m/z (%) = 524.03/526.3 (M + H+, 60),
414.2/416.2 [M+ – P(O)(OMe)2, 100].
d = 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-[(1E)-hex-1-enyl]-2,3-
dihydro-1H-2-benzazepin-1-ylphosphonate: Rf = 0.27
(hexane–EtOAc, 4:6). IR: 1031 (PO), 1058 (PO), 1253
(P=O) cm–1. 1H NMR (300 MHz, CDCl3): d = 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=CHCH2), 3.46 (d, J = 12.4 Hz, 1 H,
NCHAHBPh), 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,
NCHAHBPh), 3.80 (d, J = 18.4 Hz, 1 H, NCHAHBC), 4.19 (d,
J = 18.4 Hz, 1 H, NCHAHBC), 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): d = 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):
d = 25.29. MS (ESI): m/z (%) =504.6/506.2 (M + H+, 60),
394.2/396.3 [M+ – P(O)(OMe)2, 100].
Dimethyl 2-(4-Bromobenzyl)-4-[(1E)-4-bromobut-1-
enyl]-2,3-dihydro-1H-2-benzazepin-1-ylphosphonate:
Rf = 0.29 (hexane–EtOAc, 4:6). IR: 1031 (PO), 1058 (PO),
1252 (P=O) cm–1. 1H NMR (300 MHz, CDCl3): d = 2.67 (q,
J = 7.0 Hz, 2 H, CH2CH2Br), 3.40 (t, J = 7.0 Hz, 2 H,
CH2Br), 3.46 (d, J = 13.5 Hz, 1 H, NCHAHBPh), 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, NCHAHBPh), 3.79 (d, J = 18.6 Hz, 1 H,
NCHAHBC), 4.22 (d, J = 18.6 Hz, 1 H, NCHAHBC), 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). 13
C
NMR (75 MHz, CDCl3): d = 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):
Synlett 2006, No. 17, 2771–2776 © Thieme Stuttgart · New York