Template Aggregative Activation: Metal Salt-reinforced Complex Bases in Arynic Synthesis

Article abstract of DOI:10.1039/a703090h

A substantial effect on the reactivity of a common complex base is observed by the addition of metal salts MX_n (M = Mg, Zn, Cu, Zr); a template effect of the new aggregates is proposed.

Full text of DOI:10.1039/a703090h

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334 J. CHEM. RESEARCH (S), 1997
J. Chem. Research (S),
Template Aggregative Activation: Metal Salt-reinforced
Complex Bases in Arynic Synthesis†
1
997, 334–335†
Yves Fort, St e´ phanie Christophe and Paul Caub e` re*
Laboratoire de Chimie Organique I, Unit e´ Associ e´ e au CNRS No 457, Facult e´ des Sciences,
UHP-Nancy 1, BP 239, F-54506 Vandœuvre les Nancy, France
A substantial effect on the reactivity of a common complex base is observed by the addition of metal salts MX
Zn, Cu, Zr); a template effect of the new aggregates is proposed.
n
(M = Mg,
We have previously showed that the complex bases NaNH2–
RONa (RONa was a sodium alkoxide or ketone enolate) are
expected that any addition of a metal salt to a given complex
base should lead to aggregates with modified properties. In
this way the insertion of a salt with cation-favouring template
effects ought to favour intermolecular reactions initiated on
the aggregates of the usual complex base. To verify this hypo-
1
useful reagents in organic synthesis. The behaviour of such
2
unimetal super bases stems from the formation of aggre-
3
gates whose properties are governed by the principles of
4
aggregative activation. According to these principles it was
thesis we studied the condensation of NaNH –cyclohexan-
2
one sodium enolate with bromobenzene. We have previously
O
5
Na+
showed that this complex base generates benzyne which con-
–
Br
denses with the enolate according to Scheme 1.
+
+
NaNH2 –
The expected consequence of a template effect was an
increase in the reaction rate and the overall yield as well as an
increase in the 2:3 ratio. The main results obtained with
optimised amounts of added salts are reported in Table 1.
According to our hypothesis, it appeared that under appro-
priate conditions the reaction rates were increased while the
O
Na+
Na+
–
–
O
2
:3 ratio curiously decreased. In the presence of a too large
excess of added salt (1.5 or 1 equiv. depending on the nature
of the salt) no reaction was observed and the starting bromo-
benzene was recovered. As far as overall yields and the 2:3
ratio were concerned, the best results were obtained with
path b
H2O
Na+
path a
H2O
MgBr
2
, CuCl and ZrCl . The condensation observed with
4
OH
O –
O
CuCl was rather surprising since cupric salts induce the oxi-
2
6
H2O
ring
dation and coupling of carbanions. No such reaction was
presently observed. The nature of the counteranion of the
salt seems to play a part as exemplified by the difference in
opening
2
3
reactivity observed between ZnCl
2
and ZnBr
2
. On the other
hand, steric effects could be partially responsible for the
Scheme 1
Table 1 Condensation of benzyne and cyclohexanone sodium enolate in the presence of
a
metal salt-reinforced complex bases (MCB)
c
Yield (%)
Total yield
b
c
Run
MX
n
Equiv.
t/h
2
3
2:3
(%)
1
2
3
4
5
6
7
8
9
None
MgBr
MgBr
—
7
40
48
64
53
53
40
42
42.5
60
64
54
53
33
64
67
19
22
37
30
27
28
38
36
41
34
27
30
30
33
28
28
28
12
24.5
1.08
1.6
2.37
1.9
1.4
1.11
1.02
1.25
2.22
2.13
1.8
1.6
1.17
2.3
2.4
1.58
0.9
77
78
91
81
91
76
83
76.5
87
94
84
86
61
92
95
31
56.5
2
2
0.1
0.2
0.1
0.2
0.1
0.2
0.1
0.2
0.5
0.2
0.1
0.2
0.1
0.2
0.2
0.5
0.5
1.5
1.5
3
ZnCl
ZnCl
2
2
ZnBr
ZnBr
CuCl
CuCl
CuCl
2
7.5
7
2
2.25
3
1
1
1
1
1
1
1
1
0
1
2
3
4
5
6
7
4
CuCl
2
6
CeCl
CeCl
3
3
3
4
ZrCl
ZrCl
4
1.5
2
4
(C
(C
5
H
5
)
)
2
ZrCl
ZrCl
2
3
2
5
H
5
2
2
a
2 n
MCB = NaNH (4 equiv.)–cyclohexanone enolate (2 equiv.)–MX (0.1–0.5 equiv.) prepared in
DME at 40 °C. All reactions were performed on a 25 mmol scale of bromobenzene at room
temperature. Reaction time after which no evolution was observed. Isolated yields.
b
c
lower reactivity observed with (C H ) ZrCl compared with
5
5
2
2
*
To receive any correspondence (e-mail: caubere@lcol.u-nancy.fr).
This is a Short Paper as defined in the Instructions for Authors,
ZrCl . Moreover, we also observed the formation of coupling
†
4
Section 5.0 [see J. Chem. Research (S), 1997, Issue 1]; there is there-
fore no corresponding material in J. Chem. Research (M).
products of the benzyne and cyclopentadienyl ligand which
accounts for the low yield of the arynic condensation.

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J. CHEM. RESEARCH (S), 1997 335
Table 2 Condensation of benzyne and cyclooctanone sodium enolate in the presence of metal
a
salt-reinforced complex bases (MCB)
Yield (%)
Total yield
b
c
d
d
c
Run
MX
n
Equiv.
t/h
4
5
6
4/(5ǹ6)
(%)
1
2
3
None
MgBr
—
0.2
0.2
1.5
2
1.5
37
67
72
21
11
9
42
22
19
37:63
67:33
72:28
54
55
57
2
ZrCl
4
a
2 n
MCB = NaNH (4 equiv.)–cyclooctanone enolate (2 equiv.)–MX (0.2 equiv.) prepared in THF at
4
0 °C. All reactions were performed on a 25 mmol scale of bromobenzene at room temperature.
b
c
d
Reaction time after which no evolution was observed. Isolated yields. Yields determined by
1
GC analysis using internal standard method. The (5ǹ6) ratios were confirmed by H NMR.
8
Na+
O
ing to a previously reported procedure. All products were purified
by flash chromatography and characterized by analytical and spec-
–
OH
Br
1
13
tral data ( H NMR, C NMR, IR, MS). These data were consistent
i, MXn
ii, H2O
5
+
NaNH2 –
with those of authentic samples. GC analyses were carried out
with a Shimadzu GC-8A instrument equipped with a 15 m HP1
column.
4
General Procedure.sCyclohexanone (20 mmol) in DME (10 ml)
was added dropwise to a stirred suspension of NaNH (60 mmol) in
2
+
DME (10 ml) under nitrogen and the mixture was heated at 40 °C
for 2 h. Dry metal salt (2–10 mmol) was then added at once and the
heating was continued for 0.5 h. The obtained metal salt-rein-
forced complex base (MCB) was allowed to warm to room tem-
perature and bromobenzene (25 mmol) in DME (10 ml) was drop-
wise added. The reaction was monitored by GC analysis of small
aliquots using the tetradecane as internal standard. After comple-
tion, the reaction medium was poured on ice (100 ml) and the
products were obtained after classical work-up and separation by
flash chromatography.
O
O
+
6
5
Scheme 2
We next examined the condensation of benzyne and
cyclooctanone sodium enolate which was previously found to
Received, 6th May 1997; Accepted, 29th May 1997
Paper E/7/03090H
be not very efficient for the synthesis of benzocyclobutenol
5
(
4). Indeed, the major products obtained with a classical
complex base prepared in THF were the phenylcyclooctan-
References and notes
one 5 and the benzocyclodecanone 6 (Scheme 2 and Table 2,
7
run 1). We found that the addition of a catalytic amount of
1 See for example: M. A. Zouaoui, A. Mouaddib, B. Jamart-
Gr ´e goire, S. Ianelli, M. Nardelli and P. Caub `e re, J. Org. Chem.,
1991, 56, 4078 and references cited therein.
ZrCl or MgBr (0.2 equiv.) led to a complete inversion of
4
2
selectivity.
2
3
P. Caub `e re, Chem. Rev., 1993, 93, 2317.
In conclusion, these results confirm that the insertion of a
coordinating cation into the complex base aggregates may
improve the reactivity and selectivity of these reagents.
P. Palmas, P. Tekely, B. Jamart-Gr ´e goire, P. Caub `e re and D.
Canet, J. Am. Chem. Soc., 1994, 116, 11 604.
P. Caub `e re, Rev. Heteroatom. Chem., 1991, 4, 78.
P. Caub `e re, N. Derozier and B. Loubinoux, Bull. Soc. Chim. Fr.,
1971, 302.
4
5
Experimental
Merck sodamide powder was used. THF freshly distilled from
benzophenone–sodium couple and 1,2-dimethoxyethane (DME)
distilled over sodium and stored over sodium were used. Commer-
cially available (Aldrich) cyclohexanone, cyclooctanone and bro-
mobenzene were used after standard distillation. Metal salts
6 See for example: Y. Ito, T. Konaike and T. Saegusa, J. Am. Chem.
Soc., 1975, 97, 2912.
7 P. Caub `e re, G. Guillaumet and M. S. Mourad, Tetrahedron, 1973,
29, 1857. In the present work, yields of compounds 5 and 6 were
1
determined by GC analyses and the 5:6 ratio was confirmed by H
NMR analyses.
[
ZnCl
chased from Aldrich and used after drying under vacuum (20
mmHg) at 100 °C for 16 h. Anhydrous MgBr was prepared accord-
2
, CuCl, CuCl
2
, CeCl
3
, ZrCl
4
and (C
5
H
5
)
2
ZrCl
2
] were pur-
8 J. J. Brunet, L. Mordenti and P. Caub `e re, J. Org. Chem., 1978, 43,
2
4804.