Synthesis of cyclic enehydrazides by ring-closing metathesis

Article abstract of DOI:10.1055/s-2006-949464

A series of five- and six-membered unsaturated hydrazides were efficiently prepared from precursor dienehydrazides through a ring-closing metathesis (RCM) reaction. The parent compounds were easily obtained by sequential acylation and alkylation of approp

Full text of DOI:10.1055/s-2006-949464

3490
PAPER
Synthesis of Cyclic Enehydrazides by Ring-Closing Metathesis
Cyclic
E
nehyd
t
razide
s
é
via
R
ing-
C
p
losingMeta
h
thesis ane Lebrun, Axel Couture,* Eric Deniau, Pierre Grandclaudon
UMR 8009 ‘Chimie Organique et Macromoléculaire’, Laboratoire de Chimie Organique Physique, Université des Sciences et Technologies
de Lille, Bâtiment C3(2), 59655 Villeneuve d’Ascq Cedex, France
Fax +33(3)20336309; E-mail: axel.couture@univ-lille1.fr
Received 16 May 2006; revised 26 June 2006
the annulation of the dienic hydrazides 8–12 which could
Abstract: A series of five- and six-membered unsaturated hy-
be in turn assembled by sequential N-alkylation of enehy-
drazides were efficiently prepared from precursor dienehydrazides
drazides 13–16 and N-acylation of the appropriate hydra-
zines 17–19 (Table 1). For the key step of this synthetic
approach, which is based on inexpensive and readily ac-
cessible starting materials, only the commercially avail-
able Grubbs catalysts 1 and 2 were employed.
through a ring-closing metathesis (RCM) reaction. The parent com-
pounds were easily obtained by sequential acylation and alkylation
of appropriate hydrazines.
Key words: metathesis, ring closure, heterocycles, enehydrazides
The first facet of the synthesis was the preparation of the
diolefinic hydrazides 8a,b–10a,b. These highly conjugat-
ed precursors were easily synthesized as depicted in
Scheme 2 by treatment of the suitably substituted hydra-
zines 17–19 with acryloyl (20a; n = 0, R1 = H),
methacryloyl (20b; n = 0, R1 = Me) and but-3-enoyl chlo-
ride (21; n = 1, R1 = H), respectively. The mandatory in-
stallation of the second olefinic unit was readily accessed
by N-alkylation of the resulting enehydrazide 13–16 with
During the past decade the ring-closing metathesis (RCM)
reaction has emerged as a powerful synthetic tool for the
creation of carbon–carbon bonds and this annulation tech-
nique ranks henceforth highly in the hierarchy of synthetic
tactics for the elaboration of small-, medium- and large-
sized unsaturated heterocycles.1 The propulsion of the
RCM reaction to the forefront of contemporary organic
chemistry stems also mainly from the advent of an array
of efficient homogeneous ruthenium catalysts,2 the three
most common of which, 1–3, are shown in Figure 1.
Table 1 Compounds 4–19 Prepared
Compound(s) R1
R2
R3
Ph
m
–
–
–
–
–
–
–
–
–
–
1
1
1
1
1
1
2
2
1
n
–
–
–
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
1
M
N
17
–
Ph
M
N
Mes
Mes
Mes
Mes
Ph
PCy3
Ru
Ph
Cl
Cl
Cl
Cl
18
–
(CH2)5
Ru
O
Ru
Cl
Cl
PCy3
PCy3
19
–
(CH2)3CH(CH2OMe)
13a
13b
14a
14b
15a
15b
16
H
Ph
Ph
Ph
1
2
3
Figure 1 Common ruthenium catalysts used in RCM reactions
Me
H
Ph
(CH2)5
(CH2)5
In the case of nitrogen containing heterocycles, the syn-
thesis of five- and six-membered ring systems is well
documented3 as witnessed by the numerous total synthe-
ses of complex molecules, alkaloids4 and amino acid
derivatives5 that include this versatile technique as the
synthetic key step. Paradoxically, the synthesis of small-
and medium-sized azaheterocycles such as unsaturated
five- and six-membered hydrazides 4–7 has not been in-
vestigated in detail. The rising interest in these classes of
azacycles as putative pharmaceuticals, namely as potent
potassium channel activators,6 prompted us to develop a
synthetic sequence leading to this class of compounds via
an RCM approach.
Me
H
(CH2)3CH(CH2OMe)
(CH2)3CH(CH2OMe)
Me
H
Ph
Ph
Ph
Ph
8a, 4a
H
Ph
8b, 4b
9a, 5a
9b, 5b
10a, 6a
10b, 6b
11a, 7a
11b, 7b
12
Me
H
Ph
(CH2)5
(CH2)5
Me
H
(CH2)3CH(CH2OMe)
(CH2)3CH(CH2OMe)
As outlined in the retrosynthetic Scheme 1, our straight-
forward strategy towards the azacycles 4–7 hinges upon
Me
H
Ph
Ph
Ph
Ph
Ph
Ph
SYNTHESIS 2006, No. 20, pp 3490–3494
1
7.
1
0
.
2
0
0
6
Me
H
Advanced online publication: 10.10.2006
DOI: 10.1055/s-2006-949464; Art ID: T08006SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Cyclic Enehydrazides via Ring-Closing Metathesis
3491
R1
R1
R1
R1
R1
NH2
Et3N, CH2Cl2, r.t.
n
NH2
N
n
n
n
n
N
+
R3
R2
m
m
R2
N
O
HN
N
O
N
N
O
HN
N
O
R3
Cl
O
N
R3
R3
R3
R3
R2
R2
R2
R2
17–19
20a,b n = 0
21 n = 1
13a,b–15a,b n = 0
16 n = 1
4–7
8–12
13–16
17–19
Scheme 1
1. NaH,
allyl bromide 22 (m = 1) and this operation delivered our
RCM precursors in excellent yields ranging from 52% to
75% (two steps, Table 2).
R1
DMF, reflux
R1
2.
Br
5 mol% 2
CH2Cl2
reflux, 24 h
m
n
n
22 m = 1
23 m = 2
m
m
With the acyclic dienehydrazides 8a,b–10a,b in hand we
then studied the outcome of the RCM reaction and, in or-
der to ensure the optimal formation of the target annulated
compounds, variation of the nature of the catalyst, the
amount of ruthenium catalyst, temperature profile and
time were screened. The diolefinic hydrazide 8a was cho-
sen as the starting material for our study. Results are pre-
sented in Table 2 where it can be seen that as expected the
Grubbs catalyst 2 performed significantly better than its
analogue 1. Best results were obtained by employing 5
mol% of this catalyst at reflux in CH2Cl2. These optimal
conditions were then used to perform the annulation reac-
tions of substrates 8b–10a,b in which the structural envi-
ronment of the non-acylated nitrogen has been changed. A
representative series of compounds which have been pre-
pared by this technique are presented in Table 2 where it
can be seen that this simple procedure affords very satis-
factory yields of the previously unknown cyclic enehy-
drazides 4a,b–6a,b.
N
N
O
N
N
O
R3
R3
R2
R2
8a,b–10a,b m = 1; n = 0
4a,b–6a,b m = 1; n = 0
7a,b m = 2; n = 0
11a,b
m = 2; n = 0
m = 1; n = 1
12
Me
O
R1
R1
O
N
N
N
N
N
O
N
R3
R3
Ph
Ph
R2
R2
4a,b–6a,b
24 (from 16 and 22)
instead of 12
7a,b
Scheme 2
to the six-membered terms of the series. Disappointingly,
initial attempts to assemble the diolefinic precursor 12 as
outlined in Scheme 2 met with no success. Thus when the
appropriate enehydrazide 16 was allowed to react with al-
The promising results obtained for the five-membered
enelactamic models prompted us to envisage an extension
Table 2 Reaction Conditions for the RCM Reaction
Entry
Substrate
Yield (%)a Reaction
time (h)
Temp (°C)
Annulated
compound
Catalyst 1
Catalyst 2
Yield (%) mol%
mol%
Yield (%)
1
2
8a
67
–
36
36
36
24
24
24
24
24
24
24
24
24
r.t.
4a
4a
4a
4a
4a
4b
5a
5b
6a
6b
7a
7b
5
5
–
–
20
–
–
–
–
–
–
–
–
–
–
–
–
5
3
5
5
5
5
5
5
5
–
8a
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
–
3
8a
–
15
–
–
4
8a
–
82
55
76
73
78
84
80
72
78
5
8a
–
–
6
8b
73
75
69
70
66
52
56
–
7
9a
–
8
9b
–
9
10a
10b
11a
11b
–
10
11
12
–
–
–
Synthesis 2006, No. 20, 3490–3494 © Thieme Stuttgart · New York

3492
S. Lebrun et al.
PAPER
lyl bromide 22 under basic conditions the isomerized di- nyl bromide 23. These compounds were then subjected to
enehydrazide 24 was solely obtained, probably due to the previously defined RCM reaction conditions and we were
high degree of conjugation of the final compound. Alter- pleased to observe that the annulated compound 7a,b
natively, the structurally modified diolefinic precursors were obtained in a very satisfactory yield (Table 2). The
11a,b were synthesized as portrayed in Scheme 2 by N- analytical and spectral data of the hydrazides prepared are
alkylation of the suitable enehydrazides 13a,b with bute- given in Table 3.
Table 3 Spectroscopic and Physical Data of Hydrazides Prepared
Producta,b Yield (%)c Mp (°C) 1H NMR (CDCl3/TMS) d, J (Hz)
13C NMR (CDCl3/TMS) d
13a
91
159–160d 5.69 (d, J = 10.2, 1 Hvin), 5.78 (d, J = 10.2, 1 Hvin), 6.21 (ddd, J = 2.3, 119.5, 119.6, 123.0, 123.7, 125.5,
10.2, 16.9, 1 Hvin), 6.38 (d, J = 16.9, 1 Hvin), 6.51 (d, J = 16.9, 1 Hvin), 128.0, 128.8, 129.2, 129.4, 131.1,
6.78 (ddd, J = 2.3, 10.2, 16.9, 1 Hvin), 6.96–7.35 (m, 20 Harom), 7.76 145.7, 146.3, 164.9, 170.3e
(br s, 1 H, NH), 8.56 (br s, 1 H, NH)e
13b
14a
93
87
173–174 2.00 (s, 3 H, CH3), 5.42 (s, 1 Hvin), 5.80 (s, 1 Hvin), 6.88–7.31 (m, 10 18.8, 119.4, 120.8, 122.9, 129.1,
Harom), 8.42 (br s, 1 H, NH)
138.5, 145.8, 167.6
130–131
22.9, 23.2, 25.2, 25.6, 56.8, 58.0,
126.7, 126.9, 128.4, 129.7, 163.0,
168.0e
1.52–1.68 (m, 12 Hc-hex), 2.78–2.86 (m, 8 Hc-hex), 5.54 (dd, J = 1.6,
10.3, 1 Hvin), 5.63 (dd, J = 1.9, 10.4, 1 Hvin), 6.05 (dd, J = 10.3, 16.9,
1 Hvin), 6.26 (dd, J = 1.6, 16.9, 1 Hvin), 6.34 (dd, J = 1.9, 17.4, 1 Hvin),
6.85 (br s, 1 H, NH), 6.92 (dd, J = 10.4, 17.4, 1 Hvin), 7.20 (br s, 1 H,
NH)e
14b
15a
90
85
118–119 1.32-1.36 (m, 2 Hc-hex), 1.61–1.64 (m, 4 Hc-hex), 1.89 (s, 3 H, CH3),
18.8, 23.2, 25.3, 56.8, 119.1, 139.7,
2.71–2.75 (m, 4 Hc-hex), 5.22 (s, 1 Hvin), 5.55 (s, 1 Hvin), 6.83 (br s, 1 166.2
H, NH)
96–97
20.9, 21.4, 25.8, 26.6, 55.4, 57.1,
1.66–2.15 (m, 8 H), 2.58–2.66 (m, 1 H), 2.73–2.83 (m, 1 H), 3.01–
3.09 (m, 1 H), 3.18–3.25 (m, 1 H), 3.30 (s, 3 H, OCH3), 3.34 (s, 3 H,
OCH3), 3.38–3.51 (m, 6 H), 5.65–5.73 (m, 2 Hvin), 6.13 (dd, J = 10.4,
59.0, 59.2, 64.5, 65.5, 73.4, 74.8,
126.9, 127.4, 128.3, 129.5, 164.5,
169.3e
16.9, 1 Hvin), 6.32–6.43 (m, 2 Hvin), 6.61 (br s, 1 H, NH), 6.83 (br s, 1
e
H, NH), 6.95 (dd, J = 10.4, 16.4, 1 Hvin
)
15b
16
81
70
111–112 1.46–2.05 (m, 7 H), 2.73–2.81 (m, 1 H), 3.08–3.35 (m, 7 H), 5.26 (s, 18.7, 21.3, 26.3, 55.2, 59.2, 64.0,
1 Hvin), 5.58 (s, 1 Hvin), 7.04 (br s, 1 H, NH)
75.1, 119.1, 139.9, 167.4
85–86
72–73
36.4, 39.6, 118.9, 119.4, 119.9,
122.9, 123.8, 129.2, 129.5, 130.3,
130.5, 145.8, 146.0, 169.9, 176.5e
3.05 (d, J = 6.0, 2 H, CH2), 3.22 (d, J = 6.0, 2 H, CH2), 5.04–5.31 (m,
4 Hvin), 5.83–6.018 (m, 2 Hvin), 6.99–7.36 (m, 20 Harom), 7.84 (br s, 1
H, NH), 8.38 (br s, 1 H, NH)e
8a
80
4.33 (dt, J = 1.1, 6.7, 2 H, NCH2), 5.02–5.11 (m, 2 Hvin), 5.69 (dd,
50.5, 119.1, 119.2, 123.3, 127.1,
J = 2.2, 10.1, 1 Hvin), 5.75–5.89 (m, 1 Hvin), 6.51 (dd, J = 2.2, 16.9, 1 129.4, 130.2, 132.3, 144.4, 169.0
Hvin), 6.71 (dd, J = 10.1, 16.9, 1 Hvin), 7.03–7.16 (m, 6 Harom), 7.27–
7.34 (m, 4 Harom
)
8b
9a
81
78
oil
oil
1.62 (s, 3 H, CH3), 4.19 (d, J = 6.4, 2 H, NCH2), 4.88–5.12 (m, 4
20.3, 51.3, 117.1, 119.2, 119.5,
123.0, 129.2, 132.5, 140.1, 144.5,
174.2
Hvin), 5.72–5.88 (m, 1 Hvin), 6.89–7.18 (m, 10 Harom
)
1.51–1.72 (m, 6 Hc-hex), 2.56–2.75 (m, 4 Hc-hex), 4.01 (d, J = 5.5, 2 H, 23.3, 26.0, 42.0, 54.1, 116.7, 127.1,
NCH2), 5.05 (d, J = 10.2, 1 Hvin), 5.13 (d, J = 17.3, 1 Hvin), 5.54 (dd, 127.8, 134.8, 167.6
J = 1.6, 10.2, 1 Hvin), 5.86 (m, 1 Hvin), 6.28 (dd, J = 1.6, 17.3, 1 Hvin),
7.12 (dd, J = 10.2, 17.3, 1 Hvin
)
9b
75
79
53–54
oil
1.35–1.49 (m, 6 Hc-hex), 1.92 (s, 3 H, CH3), 2.58–2.73 (m, 4 Hc-hex),
3.95 (d, J = 6.0, 2 H, NCH2), 4.90 (s, 1 Hvin), 5.02 (s, 1 Hvin), 5.05 (dd, 116.5, 134.7, 143.8, 173.8
J = 1.2, 10.2, 1 Hvin), 5.14 (dd, J = 1.6, 17.2, 1 Hvin), 5.86 (m, 1 Hvin
20.1, 23.3, 25.8, 41.7, 53.8, 113.6,
)
10a
1.55–1.78 (m, 4 H), 2.81–2.95 (m, 2 H), 3.05–3.22 (m, 6 H, 3 HSMP
+
20.6, 25.8, 42.6, 51.1, 58.3, 58.6,
73.1, 115.9, 126.3, 127.4, 134.0,
OCH3), 3.92–4.01 (m, 2 H), 5.04 (d, J = 10.2, 1 Hvin), 5.12 (d,
J = 17.3, 1 Hvin), 5.54 (dd, J = 1.6, 10.2, 1 Hvin), 5.81–5.88 (m, 1 Hvin), 168.1
6.26 (dd, J = 1.6, 17.3, 1 Hvin), 7.07 (dd, J = 10.2, 17.3, 1 Hvin
)
Synthesis 2006, No. 20, 3490–3494 © Thieme Stuttgart · New York

PAPER
Cyclic Enehydrazides via Ring-Closing Metathesis
3493
Table 3 Spectroscopic and Physical Data of Hydrazides Prepared (continued)
Producta,b Yield (%)c Mp (°C) 1H NMR (CDCl3/TMS) d, J (Hz)
13C NMR (CDCl3/TMS) d
10b
72
oil
1.56–1.83 (m, 7 H, 4 H + CH3), 2.83–2.89 (m, 2 H), 3.06–3.25 (m, 6 H, 20.4, 21.3, 26.3, 45.4, 51.5, 58.7,
3 HSMP + OCH3), 3.78 (d, J = 16.5, 1 H), 4.03 (d, J = 16.5, 1 H), 4.72 (s, 73.9, 110.4, 126.6, 127.9, 141.5,
1 Hvin), 4.75 (s, 1 Hvin), 5.53 (dd, J = 2.3, 10.4, 1 Hvin), 6.26 (dd, J = 2.3, 168.8
17.3, 1 Hvin), 7.13 (dd, J = 10.4, 17.3, 1 Hvin
)
11a
57
oil
2.22–2.26 (m, 2 H, CH2), 3.81 (dd, J = 5.5, 10.4, 2 H, NCH2), 4.91– 32.3, 47.7, 116.6, 119.1, 123.3,
4.97 (m, 2 Hvin), 5.67–5.72 (m, 2 Hvin), 6.51 (dd, J = 2.1, 16.9, 1 Hvin), 127.2, 129.5, 130.1, 134.9, 144.5,
6.73 (dd, J = 10.1, 16.9, 1 Hvin), 7.04–7.18 (m, 6 Harom), 7.24–7.35 (m, 169.2
4 Harom
)
11b
24
55
80
oil
oil
1.78 (s, 3 H, CH3), 2.27–2.35 (m, 2 H, CH2), 3.72–3.78 (m, 2 H,
20.4, 32.3, 48.6, 116.6, 117.2, 119.4,
NCH2), 4.94–5.05 (m, 3 Hvin), 5.18–5.26 (m, 1 Hvin), 5.61–5.74 (m, 1 123.2, 129.3, 134.9, 140.3, 144.9,
Hvin), 7.04–7.18 (m, 6 Harom), 7.23–7.35 (m, 4 Harom 170.2
)
1.72 (d, J = 6.9, 3 H, CH3), 4.21 (d, J = 6.7, 2 H, NCH2), 4.88–4.92 18.3, 50.4, 118.9, 119.2, 121.1,
(m, 2 Hl), 5.64–5.77 (m, 1 Hvin), 6.30 (d, J = 15.2, 1 Hvin), 6.94–6.98 123.0, 129.3, 132.5, 144.3, 144.5,
(m, 1 Hvin), 7.02–7.09 (m, 6 Harom), 7.15–7.26 (m, 4 Harom
)
169.0
4a
4b
5a
5b
6a
82
76
73
78
84
84–85
oil
4.25 (t, J = 1.9, 2 H, NCH2), 6.33 (td, J = 1.9, 6.5, 1 Hvin), 7.05–7.12 50.6, 119.6, 123.3, 127.8, 129.5,
(m, 6 Harom), 7.17 (td, J = 1.9, 6.5, 1 Hvin), 7.26–7.34 (m, 4 Harom 142.7, 144.6, 169.1
)
2.08 (s, 3 H, CH3), 4.20 (br s, 2 H, NCH2), 6.87 (br s, 1 Hvin), 7.07– 11.8, 48.8, 119.6, 123.2, 129.4,
7.18 (m, 6 Harom), 7.25–7.41 (m, 4 Harom
)
135.3, 144.7, 169.9
oil
1.55–1.72 (m, 6 Hc-hex), 2.75–2.89 (m, 4 Hc-hex), 3.99 (br s, 2 H,
23.2, 25.9, 48.4, 53.4, 128.5, 141.0,
169.5
NCH2), 6.06 (br s, 1 Hvin), 6.92 (br s, 1 Hvin
)
75–76
oil
1.33–1.42 (m, 2 Hc-hex), 1.55–1.64 (m, 4 Hc-hex), 1.80 (s, 3 H, CH3),
11.5, 23.3, 25.9, 47.0, 53.1, 133.4,
136.0, 169.6
2.98 (t, J = 5.3, 4 Hc-hex), 3.84 (br s, 2 H, NCH2), 6.52 (br s, 1 Hvin
)
1.53–2.06 (m, 4 H), 3.08–3.41 (m, 6 H, 3 HSMP + OCH3), 3.52–3.60 21.2, 25.9, 50.7, 51.3, 58.4, 59.9,
(m, 2 H), 4.05 (d, J = 1.6, 2 H, NCH2), 6.03 (d, J = 6.4, 1 Hvin), 6.96 74.9, 127.7, 141.1, 169.1
(dt, J = 1.6, 6.4, 1 Hvin
)
6b
7a
80
72
oil
1.39–2.03 (m, 7 H, 4 H + CH3), 3.04–3.30 (m, 7 H, 4 HSMP + OCH3), 11.4, 21.9, 26.5, 49.6, 51.8, 58.9,
3.51–3.59 (m, 1 H), 3.93 (br s, 2 H, NCH2), 6.51 (br s, 1 Hvin 60.6, 75.2, 134.0, 135.7, 169.7
)
71–72
2.53 (ddt, J = 1.8, 4.2, 7.2, 2 H, CH2), 3.71 (d, J = 7.2, 2 H, NCH2), 25.3, 47.4, 119.4, 122.9, 125.5,
5.94 (dt, J = 1.8, 9.8, 1 Hvin), 6.57 (dt, J = 4.2, 9.8, 1 Hvin), 6.91–7.08 129.3, 129.5, 140.3, 144.1, 163.6
(m, 6 Harom), 7.16–7.24 (m, 4 Harom
)
7b
75
79–80
1.94 (q, J = 1.6, 3 H, CH3), 2.54–2.61 (m, 2 H, CH2), 3.82 (t, J = 7.1, 17.2, 24.8, 48.0, 119.4, 122.7, 129.2,
2 H, NCH2), 6.41 (dd, J = 4.2, 5.7, 1 Hvin), 7.00–7.03 (m, 2 Harom), 132.0, 134.5, 144.2, 164.9
7.05–7.13 (m, 4 Harom), 7.22–7.29 (m, 4 Harom
)
a Satisfactory microanalyses obtained: C 0.29, H 0.26, N 0.31.
b IR (KBr): 1660–1674 (C=O), 1628–1637 (C=C) cm–1. For 13a,b–15a,b, 16; IR (KBr): 3197–3240 (N–H) cm–1.
c Yield of purified product.
d Lit.8 mp 158 °C.
e Mixture of two rotamers (1:1).
In summary we have developed a short and efficient syn- tion including, but not limited to epoxidation and dihy-
thetic strategy towards a variety of hitherto unknown sub- droxylation. Applications of this strategy to natural
stituted cyclic enehydrazides based on inexpensive and product synthesis are underway and will be reported in
readily available precursors. In contrast to structurally re- due course.
lated N-containing substrates, where it has been shown
that the efficacy of ring-closing metathesis is highly de-
Melting point determinations were carried out on a Reichert-
pendent upon the nature of the N-connected group,7 the
present method which makes use of the most popular me-
tathesis reagents 1 and 2 tolerates the presence of diverse-
ly substituted hydrazido groups. The synthetic sequence
gives rise to a number of a,b-unsaturated lactam-type
compounds which can be regarded as versatile building
blocks for further synthetic planning, e.g. functionaliza-
Thermopan apparatus and are uncorrected. 1H and 13C NMR spectra
were measured at 300 MHz and 75 MHz, respectively, on a Bruker
AM 300 spectrometer as solutions in CDCl3 with TMS as internal
standard. Elemental analyses were determined by the CNRS mi-
croanalysis center. For flash chromatography, silica gel 60 M
(230400 mesh ASTM) was used. All solvents were dried and dis-
tilled according to standard procedures.
Synthesis 2006, No. 20, 3490–3494 © Thieme Stuttgart · New York

3494
S. Lebrun et al.
PAPER
Hydrazides 13a,b–15a,b, 16; General Procedure
(2) Grubbs, R. H. In Handbook of Metathesis, Vol. 1-3; Wiley-
VCH: Weinheim, 2003.
A solution of acryloyl chloride (20a; 1.99 g, 22 mmol), methacryl-
oyl chloride (20b; 2.30 g, 22 mmol) or but-3-enoyl chloride (21;
2.01 g, 22 mmol) in anhyd CH2Cl2 (5 mL) was added dropwise un-
der argon to a cooled (0 °C) solution of hydrazine 17–19 (0.02 mol)
and Et3N (0.03 mol) in anhyd CH2Cl2 (20 mL). The mixture was
stirred at r.t. for 4 h, filtered and the filtrate was washed with H2O
(2 × 20 mL) and then dried (MgSO4). Evaporation of the solvent in
vacuo left a residue which was purified by column chromatography
using EtOAc as eluent (for 14a,b and 15a,b) or EtOAc–hexanes
(30:70) as eluent (for 13a,b and 16) (Table 3).
(3) For reviews, see: (a) Martin, S. F.; Chen, H.-J.; Courtney, A.
K.; Liao, Y.; Pätzel, M.; Ramser, M. N.; Wagman, A. S.
Tetrahedron 1996, 52, 7251. (b) Campagne, J.-M.; Ghosez,
L. Tetrahedron Lett. 1998, 39, 6175. (c) Nadin, A. J. Chem.
Soc., Perkin Trans. 1 1998, 3493. (d) Mitchinson, A.;
Nadin, A. J. Chem. Soc., Perkin Trans. 1 1999, 2553.
(e) Mitchinson, A.; Nadin, A. J. Chem. Soc., Perkin Trans. 1
2000, 2862. (f) Briot, A.; Bujard, M.; Gouverneur, V.;
Nolan, S. P.; Mioskowski, C. Org. Lett. 2000, 2, 1517.
(g) Gonzáles-Pérez, P.; Pérez-Serrano, L.; Casarrubios, L.;
Domínguez, G.; Pérez-Castells, J. Tetrahedron Lett. 2002,
43, 4765. (h) Felpin, F.-X.; Lebreton, J. Eur. J. Org. Chem.
2003, 3693. (i) Gille, S.; Ferry, A.; Billard, T.; Langlois, B.
R. J. Org. Chem. 2003, 68, 8932. (j) Declerck, V.; Ribière,
P.; Martinez, J.; Lamaty, F. J. Org. Chem. 2004, 69, 8372.
(4) (a) Arisawa, M.; Takezawa, E.; Nishida, A.; Mori, M.;
Nakagawa, M. Synlett 1997, 1179. (b) Paolucci, C.;
Musiani, L.; Venturelli, F.; Fava, A. Synthesis 1997, 1415.
(c) Dyatkin, A. B. Tetrahedron Lett. 1997, 38, 2065.
(d) White, J. D.; Hrnciar, P.; Yokochi, A. F. T. J. Am. Chem.
Soc. 1998, 120, 7359. (e) Ahn, J.-B.; Yun, C.-S.; Kim, K.
H.; Ha, D.-C. J. Org. Chem. 2000, 65, 9249. (f) White, J.
D.; Hrnciar, P. J. Org. Chem. 2000, 65, 9129.
(5) For representative examples, see: (a) Hammer, K.;
Undheim, K. Tetrahedron: Asymmetry 1998, 9, 2359.
(b) Clark, J. S.; Middleton, M. D. Org. Lett. 2002, 4, 765.
(c) Martín, R.; Alcón, M.; Pericás, M. A.; Riera, A. J. Org.
Chem. 2002, 67, 6896.
(6) Matsumoto, Y.; Tsuzuki, R.; Matsuhisa, A.; Takayama, K.;
Yoden, T.; Uchida, W.; Asano, M.; Fujita, S.; Yanagisawa,
I.; Fujikura, T. Chem. Pharm. Bull. 1996, 44, 103.
(7) (a) Rutjes, F. P. J. T.; Schoemaker, H. E. Tetrahedron Lett.
1997, 38, 677. (b) Maier, M. E.; Lapeva, T. Synlett 1998,
891.
Diolefinic Hydrazides 8a,b–10a,b, 11a,b, 24; General Procedure
A solution of hydrazides 13a,b–15a,b or 16 (9 mmol) in anhyd
DMF (3 mL) was added dropwise at 0 °C under argon to a stirred
suspension of NaH (24 mg, 10 mmol) in anhyd DMF (10 mL). The
mixture was then stirred at r.t. for 30 min and allyl bromide (22;
1.21 g, 10 mmol for 8a,b–10a,b and 24) or 4-bromobut-1-ene (23;
1.35 g, 10 mmol, for 11a,b) was slowly added. The mixture was
subsequently refluxed for 5 h and, after cooling, was diluted with
H2O (10 mL) and CH2Cl2 (20 mL). The organic layer was separated
and the aqueous layer was extracted with CH2Cl2 (2 × 20 mL). The
combined organic layers were washed with brine (20 mL) and dried
(MgSO4). After evaporation of the solvent under vacuum the oily
residue was purified by column chromatography using EtOAc as
eluent (for 9a,b and 10a,b) or EtOAc–hexanes (20:80) as eluent (for
8a,b, 11a,b and 24) (Tables 2 and 3).
Cyclic Enehydrazides 4a,b–7a,b; General Procedure
A solution of diolefinic hydrazides 8a,b–11a,b (0.5 mmol) and sec-
ond-generation Grubbs catalyst (5% mol, 21 mg, 0.025 mmol) in
CH2Cl2 (10 mL) was carefully degassed by three freeze-thaw cycles
and then refluxed for 24 h. Evaporation of the solvent in vacuo left
a residue which was purified by column chromatography using ac-
etone–hexanes (60:40) as eluent (for 5a,b and 6a,b) or EtOAc–hex-
anes (30:70) as eluent (for 4a,b and 7a,b) (Tables 2 and 3).
(8) Bar, D.; Marcincal-Lefebvre, A. Bull. Soc. Chim. Fr. 1976,
1207.
References
(1) For reviews, see: (a) Philips, A. J.; Abell, A. D.
Aldrichimica Acta 1999, 32, 75. (b) Schultz-Fademrecht,
C.; Deshmukh, P. H.; Malagu, K.; Procopiou, P. A.; Barrett,
A. G. M. Tetrahedron 2004, 60, 7515. (c) Dieters, A.;
Martin, S. F. Chem. Rev. 2004, 104, 2199.
Synthesis 2006, No. 20, 3490–3494 © Thieme Stuttgart · New York