Co(I)-versus Ru(II)-Catalyzed [2+2+2] cycloadditions involving alkynyl halides

Article abstract of DOI:10.1016/j.jorganchem.2011.08.041

Alkynyl chlorides, bromides, and iodides have been tested as [2 + 2 + 2] cycloaddition partners using CpCo(CO)(dimethylfumarate) and Cp*Ru(cod)Cl as precatalysts. A series of cocyclizations between diynyl dihalides and alkynes, as well as intramolecular c

Full text of DOI:10.1016/j.jorganchem.2011.08.041

Journal of Organometallic Chemistry 696 (2011) 3906e3908
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Journal of Organometallic Chemistry
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Note
Co(I)- versus Ru(II)-Catalyzed [2þ2þ2] cycloadditions involving alkynyl halides
**
,
1
,
1
,
1
,
a,b,1,
*
Laura Iannazzoa , Naoko Koteraa , Max Malacriaa , Corinne Auberta , Vincent Gandon
a Institut Parisien de Chimie Moléculaire (UMR CNRS 7201)-FR 2769 UPMC univ Paris 06, C. 229, 4 place Jussieu, 75005 Paris, France
b ICMMO (UMR CNRS 8182), Université Paris-Sud 11, 91405 Orsay cedex, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Alkynyl chlorides, bromides, and iodides have been tested as [2 þ 2 þ 2] cycloaddition partners using
CpCo(CO)(dimethylfumarate) and Cp*Ru(cod)Cl as precatalysts. A series of cocyclizations between diynyl
dihalides and alkynes, as well as intramolecular cycloadditions of triynyl dihalides, has been carried out.
While this study confirmed the versatility of the ruthenium complex with all kinds of halides, the cheap
air-stable cobalt complex proved nonetheless efficient with alkynyl bromides.
Received 22 June 2011
Received in revised form
18 August 2011
Accepted 25 August 2011
Ó 2011 Elsevier B.V. All rights reserved.
Keywords:
Alkynes
Catalysis
Cobalt
Cycloadditions
Ruthenium
1. Introduction
the potential importance of this methodology for the synthesis of
complex molecules, we decided to study in detail the behavior of 1
The transition-metal-catalyzed [2 þ 2 þ 2] cycloaddition reaction
has become an increasingly popular way to form functionalizable
six-membered rings in the organic chemists’ community [1]. Ever
sincethe first total synthesis involving this reaction in 1980 [2], more
than 30 natural products have been prepared owing to this strategy
[3]. For instance, Nicolaou’s approach to Sporolide B relies on
a Ru(II)-catalyzed [2 þ 2 þ 2] cycloaddition between three alkyne
partners including an alkynyl chloride [4]. Alkynyl chlorides [4,5],
bromides [5,6], and iodides [6,7] have been only scarcely employed
in transition-metal-catalyzed [2 þ 2 þ 2] cycloadditions, and these
reactions have been strictly limited to the use of Cp*Ru(cod)Cl as
precatalyst. Due totheir higher tendency to insert intothe CeX bond
of alkynyl halides, materialized by the formation of homocoupling
products (i.e. 1,2-diynes) [5,8], cobalt-based catalysts are notably
absent in this chemistry. There is yet one exception in the bromide
series: we have recently synthesized the air-stable cobalt complex 1
which allowed the cyclization of a triyne into the corresponding 1,2-
dibromobenzene derivative in excellent yield (Scheme 1) [9]. Due to
toward alkynyl halides and to compare the results with those ob-
tained with Cp*Ru(cod)Cl. The comparison between cobalt and
ruthenium is particularly worthwhile since complex 1 is about 30
times cheaper than Cp*Ru(cod)Cl [10]. Besides, we have explored
a new type of cyclization between diynyl dichlorides and alkynes.
2. Results and discussion
We started our investigation by a brief examination of the reac-
tivity of monoalkynes. Because Ru-catalyzed cyclotrimerizations of
alkynyl chlorides and bromides have been previously described [5],
and because alkynyl chlorides are prone to homocoupling under
cobalt-catalysis [8], we focused on the reactivity of a bromide and an
iodide in the presence of 1 (Scheme 2). Homocoupling of iodide 2b
occurred highly selectively to afford 1,2-diyne 3 quantitatively. In
contrast, neither cyclotrimerization nor homocoupling took place
when using bromide 2a.
The fact that alkynyl bromides apparently do not autotrimerize
with 1 makes them potential candidates for cocyclization with
other alkyne partners. We first focused on diynyl dihalides and
compared cobalt with ruthenium catalysis (Table 1). In addition to
the halide, the nature of the tether Z (carbon-, oxygen-, nitrogen-
linkers) and of the R1 and R2 substituents (H, vinyl, aryl, alkyl, and
ester) at the alkyne was also varied. Two experimental conditions
were used: A (DCE, rt, 12 h) which are standard ones for Ru-
* Corresponding author. ICMMO (UMR CNRS 8182), Université Paris-Sud 11,
91405 Orsay cedex, France. Tel.: þ33 (0) 1 69 15 39 31; fax: þ33 (0) 1 69 15 47 47.
** Corresponding author. Tel.: þ33 (0) 1 44 27 70 68; fax: þ33 (0) 1 44 27 73 60.
E-mail addresses: corinne.aubert@upmc.fr (C. Aubert), vincent.gandon@u-psud.
fr (V. Gandon).
1
Tel.: þ33 (0) 1 44 27 70 68; fax: þ33 (0) 1 44 27 73 60.
0022-328X/$ e see front matter Ó 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2011.08.041

L. Iannazzo et al. / Journal of Organometallic Chemistry 696 (2011) 3906e3908
3907
catalyzed [2 þ 2 þ 2] cycloadditions, and B (toluene, reflux, 12 h)
which are typical for Co-catalyzed cyclizations. The cocyclization of
diynyl dichlorides with alkynes was not studied before in any
metal series. With such substrates, Cp*Ru(cod)Cl proved to be the
best precatalyst (Entries 1e16). Excellent yields of cycloadducts 5-7
and 8 were reached using either A or B (Entries 3, 8, 11, 15, and 16).
With 1, conditions A did not allow the cocyclization to take place
(Entries 1, 5, 9, and 13) and the diyne could be recovered in part
[11]. On the other hand, the expected products could be obtained
using conditions B, yet in low to moderate yields (Entries 2, 6, 10,
14).
CO2Me
Co
OC
Br
O
O
O
MeO2C 1 (10 mol%)
O
Toluene, reflux, 10 h
91%
Br
Br
Br
Scheme 1. Co(I)-catalyzed cyclization of a brominated triyne.
1 (10 mol%)
We next examined the case of diynyl dibromides (Entries
17e28). Although conditions A still proved unproductive with 1
(Entry 17), conditions B provided the expected cycloadduct 9 in 86%
yield (Entry 18). Of particular interest, 1 outperformed Cp*Ru(cod)
Cl which led to 79 and 69% yield of 9 under conditions A and B
respectively (Entries 19 and 20). To explore the scope of the Co-
catalyzed reaction, various combinations of diynyl dibromides
and alkynes were tested (Entries 21e28). Provided 1,6-diynes are
used, the products could be isolated in each of the seven cases, in
40e88% yield. In contrast, no cocyclization took place when using
the 1,7-diyne 4e (Entry 26).
Lastly, the superiority of Cp*Ru(cod)Cl in achieving the cocycli-
zation of diynyl diiodides with alkynes was clearly evidenced when
using 4h and 1-hexyne (Entries 29e32). With cobalt, homocou-
pling ensued to give tetrayne 18 in 38% yield (Entry 30), whereas 17
was isolated quantitatively with ruthenium (Entry 32). In order to
verify whether the compatibility of 1 toward alkynyl bromides was
inherent in its structure, some reactions of 4c were carried out
using the typical precatalysts CpCo(CO)2 and CpCo(C2H4)2 [12]. In
each case, 4c could be recovered in part, and no trace of cycloadduct
could be detected among the degradation products.
MeO
X
toluene, reflux, 12 h
2a (X = Br)
2b (X = I)
MeO
OMe
3
X = Br, no reaction
X = I, 100%
Scheme 2. Homocoupling of iodoalkyne 2a.
Table 1
Cocyclizations of diynes and alkynes.
E
E
X
X
R1
R1
R2
X
[M] (10 mol%)
Con d. A o r B
or
Z
+
Z
X
R2
(5 equiv)
4a-h
5-17
O
Co = 1; Ru = Cp*Ru(cod)Cl;
A: DCE, rt, 12 h;
The same conclusions could be reached in the triynyl dihalide
series (Table 2). With chlorides and iodides, only ruthenium gave
satisfactory yields of the expected tricyclic products (Entries 6 and
14). On the other hand, with bromides, complex 1 led to a slightly
better result than Cp*Ru(cod)Cl (Entry 8). Again, the use of
diox =
C
E
E
18
B: toluene, reflux, 12 h; E = CO2Me
O
Entry Diyne
Z
X
R1 R2
CO2Me
[M] Cond. Product Yield (%)
1
2
3
4
5
6
7
8
4a
4a
4a
4a
4a
4a
4a
4a
4a
4a
4a
4a
4b
4b
4b
4b
4c
4c
4c
4c
4c
4c
4c
4c
4d
4e
4f
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
diox
diox
diox
diox
CE2
CE2
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Br
Br
Br
Br
Br
Br
Br
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Co
Co
Ru
Ru
Co
Co
Ru
Ru
Co
Co
Ru
Ru
Co
Co
Ru
Ru
Co
Co
Ru
Ru
Co
A
B
A
B
A
B
A
B
A
B
A
B
A
B
A
B
A
B
A
B
B
B
B
B
B
B
B
B
A
B
A
B
e
0
20
87
65
0
18
90
97
0
10
93
82
0
52
100
100
0
86
79
69
70
53
48
40
50
0
46
88
0
38
33
100
CO2Me
CO2Me
CO2Me
Ph
5
5
5
e
Table 2
Cyclizations of triynes.
X
Z
Z
Z
Ph
Ph
Ph
6
6
6
[M] (10 mol%)
Cond. A or B
Z
9
CH2OMe
CH2OMe
CH2OMe
CH2OMe
C4H9
C4H9
C4H9
C4H9
C4H9
e
X
X
X
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
7
7
7
4i-l
19-22
Co = 1; Ru = Cp*Ru(cod)Cl;
A: DCE, rt, 12 h; B: toluene, reflux, 12 h
e
8
8
8
Entry
Triyne
Z
X
[M]
Cond.
Product
Yield (%)
1
2
3
4
5
6
7
8
4i
4i
4i
4i
4j
O
O
O
O
NTs
NTs
O
O
O
O
O
O
O
Cl
Cl
Cl
Cl
Cl
Cl
Br
Br
Br
Br
I
Co
Co
Ru
Ru
Co
Ru
Co
Co
Ru
Ru
Co
Co
Ru
Ru
A
B
A
B
B
A
A
B
A
B
A
B
A
B
e
0a
5
47
45
35
100
0a
91
83
76
0a
e
19
19
19
20
20
e
C4H9
C4H9
C4H9
9
9
9
10
11
12
13
14
e
CE2
CE2
CE2
CE2
CE2
CE2
CH2
Ph
4j
C(Me)]CH2 Co
4k
4k
4k
4k
4l
4l
4l
4l
p-MeOPh
Br Et Et
Co
Co
Co
Co
Co
Co
Co
Co
Ru
Ru
21
21
21
e
9
Br
H
H
H
H
H
H
H
H
C4H9
C4H9
C4H9
C4H9
C4H9
C4H9
C4H9
C4H9
10
11
12
13
14
(CH2)2 Br
O
Br
Br
I
I
I
15
16
e
I
I
I
22
22
22
5
4g
4h
4h
4h
4h
NTs
CE2
CE2
CE2
CE2
32b
100
O
18
17
17
Italics represents the optimal conditions.
a
I
No reaction.
60% reported with 15 mol% Ru in 24 h, see [6].
b
Italics represents the optimal conditions.

3908
L. Iannazzo et al. / Journal of Organometallic Chemistry 696 (2011) 3906e3908
CpCo(CO)2 and CpCo(C2H4)2 did not allow the formation of the
cyclization product.
Appendix. Supplementary material
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.jorganchem.2011.08.041.
3. Conclusion
References
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choice for [2 þ 2 þ 2] cycloaddition of alkynyl chlorides and iodides.
However, cobalt complexes may, under certain conditions, qualify as
precatalyst for [2 þ 2 þ 2] cycloaddition of alkynyl bromides. This
feature is highly dependent on the nature of the ligands at Co.
Mechanistic studies are underway to shed light on that matter.
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[10] Complex 1 is prepared in one step in a 100% yield from CpCo(CO)2 which
costs w 3 V/mmol while Cp*Ru(cod)Cl is worth w 100 V/mmol.
[11] Although the structure of the side products could not be ascertained, we
suspect a substantial amount of homocoupling.
Acknowledgments
[12] For a monograph on CpCo(C2H4)2, see V. Gandon, C. Aubert, e-EROS (2008).
doi:10.1002/047084289X.rn00943.pub2.
L. I. is thankful to UPMC for PhD grant.