The Ni-mediated cyclocarbonylation of allyl halides and alkynes made catalytic. Evidence supporting the involvement of pseudoradical NiI species in the mechanism

Article abstract of DOI:10.1021/ja0525713

We report here on a highly efficient catalytic method to synthesize intermolecularly the cyclopentane skeleton from starting products as simple as allyl halides, alkynes, and carbon monoxide under very mild reaction conditions by means of a substoichiomet

Full text of DOI:10.1021/ja0525713

Published on Web 07/07/2005
The Ni-Mediated Cyclocarbonylation of Allyl Halides and Alkynes Made
I
Catalytic. Evidence Supporting the Involvement of Pseudoradical Ni Species
in the Mechanism
M. Llu ¨ı sa Nadal, Julia Bosch, Josep M. Vila, G u¨ nter Klein, Susagna Ricart, and Josep M. Moret o´ *
Laboratori de Cat a´ lisi Homogenea, Institut de Ci e` ncia de Materials de Barcelona,
(CSIC) Campus de la UAB, 08193 Bellaterra, Spain
Received April 20, 2005; E-mail: moreto@icmab.es
Among the different pentannulation methods, the metal-mediated
2 + 2 + 1] carbonylative cycloadditions represent the most
Scheme 1. Ni-Mediated Carbonylative Cycloaddition of Allyl
Halides and Alkynes
[
straightforward way to synthesize the cyclopentane skeleton since
three C-C bonds are formed in a single experimental operation.
The Pauson-Khand reaction, originally mediated by cobalt and
later found to undergo in the presence of other metal complexes,1
fits within this strategy. In a similar approach, we have studied the
scope and the selectivity arising from the cyclocarbonylation of
Scheme 2. Intramolecular Version (not optimized)
2
allyl halides and acetylenes mediated by nickel (a reaction which
3
4
has precedents in the work of G. P. Chiusoli and W. Oppolzer )
(Scheme 1).
The main advantages of this cycloaddition are its regio- and
of iron metal by ferrous bromide or other metals (Zn, Mg)14 led
only to allyl self-coupling to form 1,5-hexadiene, complete inactiv-
ity, or formation of metallic nickel, respectively, suggesting a fine
redox tuning for the cycloaddition reaction to be able to proceed.
The presence of substoichiometric amounts of a Lewis acid (iodine
stereoselectivity as well as the mild reaction conditions required.
However, the most promising feature compared with similar
5
processes is its efficiency in the intermolecular version. Thus, the
vast majority of the pentannulations of this kind so far reported
apply only to preformed enynes or strained olefins.
In our attempt to make the process catalytic in Ni, we introduced
3
or better AlBr ) was found to activate considerably the CO uptake.
The present methodology was successfully extended to other
alkynes and allyl halides of mechanistic significance as well as to
one intramolecular version (Scheme 2). The corresponding results
are collected in Table 1.
an excess of sodium ascorbate in the reaction mediated by
6
Ni(COD)
2
under CO, aimed at removing any hydrogen halide
7
I
generated in the reaction and also returning any Ni species to the
original Ni0 oxidation state of the mediator. Studies on the
As can be seen from the table, in most cases, the corresponding
2-(5-cyclopent-2-enonyl)acetic acid adducts were obtained with
yields ranging from good to excellent, improving those formerly
obtained under stoichiometric conditions. In addition, the regiose-
lectivities (controlled mainly by electronic effects) and stereose-
lectivities (arising from steric effects) were also improved. Again,
the identity of the products obtained when starting from two
positional allyl halide isomers and the similarity of the diastereo-
meric ratios (entries 10 and 11) point to the involvement of a π-allyl
species.
Remarkable is the high yield of cyclopentenone adduct versus
that from self-coupling when starting from an electrodeficient
conjugated allyl component (entry 12). Moreover, one carbonyl only
is inserted.2b For hindered allyl halides, such as prenyl bromide
and 3-bromocyclohexene, the reaction is slower, allowing further
insertion of an alkyne moiety into the transient acyl halide adduct
in preference to the initiation of a new cycle (entries 9 and 13)
giving 4a and 4b, respectively. The effect of steric hindrance was
even emphasized with bis(trimethylsilyl)acetylene, in which case
no CO uptake was recorded.
pernicious allyl self-coupling reaction, leading the mediator to
inactive Ni halides, had pointed to the intervention of Ni species
generated from the π-allyl intermediate by valence dismutation.8
II
I
However, the cycloaddition reaction was completely inhibited
I
under these conditions. We assumed, therefore, that Ni free-radical-
2a,c
like species were also responsible for the cyclocarbonylation
reaction. Alternatively, the catalytic species could thus be advan-
tageously prepared by a single electron reduction of a Ni(II) salt.
We chose the readily available phenylacetylene and allyl bromide
as model substrate and tried different reductants compatible with
9
acetone, the best solvent for this reaction. We were pleased to
record high turnovers in the presence of finely divided iron (up to
40). Unexpectedly, most of the excess of iron was consumed during
the process. As a consequence, an oxidative workup to free the
product from iron was necessary after the reaction was completed.
Thus, we assigned a dual role to the iron: to generate the reduced
I
catalytic Ni species and to be an efficient terminating agent. An
EPR spectrum of a sample taken after the initial reduction revealed
I
the presence of Ni evidenced by the three signals recorded at g )
.246, 2.113, and 2.005.10 Another sample was taken shortly after
2
the substrate had been added and CO uptake had started. In it, the
three former signals had collapsed to a sharp single one at g )
2
.001 (∆Hpp ∼ 13 G). Although this value matches well with those
11
for organic free radicals, the high regio- and stereoselectivity of
the resulting products rather supports the intervention of a free allyl
ligand in a Ni(II) EPR-silent complex.12 While any nickel halide
or even Ni(acac)
similar results, the absence of any nickel source or the replacement
in the presence of an excess of iodide ion13 gave
For practical purposes, turnovers of up to 20 with a high yield
in cyclopentenone derivatives have been achieved in acetone as
2
10476
9
J. AM. CHEM. SOC. 2005, 127, 10476-10477
10.1021/ja0525713 CCC: $30.25 © 2005 American Chemical Society

C O M M U N I C A T I O N S
Table 1. Catalytic Carbonylative Cycloaddition of Alkynes
tance when the amount of iron decreases (at high turnovers).
Spectroscopic data from the dry crude product and its reactivity
toward aldehydes suggest an iron enolate as the most reasonable
outgoing reaction product from iron.15 The EPR spectrum also gave
a
(R1CtCR2) and Allyl Halides under a CO Atmosphere
III
an account of the presence of some Fe , but no signal ascribable
to a free organic radical could be detected.
In conclusion, we report here a highly efficient catalytic method
to synthesize intermolecularly the cyclopentane skeleton starting
from products as simple as allyl halides, alkynes, and carbon
monoxide under very mild reaction conditions by means of a
stoichiometric amount of iron, acetone, and a catalytic amount of
Ni halide.
R
1
R
2
R
3
(R
5
)
R
4
product (yield, %)
method
1
Ph
Si(Me)3
Me
Me
CH2OMe
Et
Bu
Si(Me)3
Ph
Ph
Ph
H
H
H(H)
H(H)
H(H)
H
H
H
H
H
H
H
H
3a (95)
3b (68)
3c (78)
3d (87)
3e (60)
3f (80)
3g (82)
-
a
a
a
a
a
a
b
a
a
a
b
b
a
2
3
4
5
6
7
8
9
1
1
1
1
CO2Et
CH2OMe H(H)
H
Et
H(H)
H(H)
H(H)
H(H)
H -(CH2)3-
Me(H)
H(H)
Acknowledgment. We acknowledge the financial support from
the Spanish Ministry of Science and Technology (Project PPQ2001-
H
Si(Me)3
1545), and the CIRIT (Grant No. 2001SG300362). We also
H
H
H
H
H
4a (28)
3h (92)
b
acknowledge Dr. Jose Vidal Gancedo and Dr. Anna Roig for their
helpful EPR and M o¨ ssbauer assistance, respectively.
0
1
2
3
H
Me
H
c
3h (90)
d
Ph
Ph
CO2Me
Me(Me)
3a (73)
Supporting Information Available: Synthesis and characterization.
This material is available free of charge via the Internet at http://
pubs.acs.org.
H
4b (19)
a
General conditions: (a) alkyne (5 mmol), allyl halide (5.8 mmol), I2
0.5 mmol) in 2 mL of CH2Cl2 slowly added onto 10 µM iron powder (5
mmol), NiI2 (0.25 mmol), NaI (0.50 mmol) in 2 mL of acetone, under a
CO atmosphere, room temperature, and atmospheric pressure; (b) NiBr2
and AlCl3 replace NiI2 and I2, respectively (see Supporting Information).
(
References
(1) For Pauson-Khand reactions, see: (a) Geis, O.; Schmalz, H. G. Angew.
Chem., Int. Ed. 1998, 37, 911-915. (b) Gibson, S. E.; Stevenazzi, A.
Angew. Chem., Int. Ed. 2003, 42, 1800-1810. (c) For Ni-catalyzed
Pauson-Khand-type reactions, see: Zhang, M.; Buchwald, S. L. J. Org.
Chem. 1996, 61, 4498-4499.
b
c
d
2a
Mixture of two diastereomers (95:5). Major isomer: (R,R) and (S,S) pair.2a
Mixture of two diastereomers (90:10). Major isomer: (R,R) and (S,S) pair.
As the corresponding methyl ester.
(
2) (a) Camps, F.; Coll, J.; Moret o´ , J. M.; Torras, J. J. Org. Chem. 1989, 54,
1969-1978. (b) Camps, F.; Moret o´ , J. M.; Pag e` s, Ll. Tetrahedron 1992,
Scheme 3. Proposed Ni Catalytic Cyclocarbonylation
48, 3147-3162. (c) Pag e` s, Ll.; Llebar ´ı a, A.; Camps, F.; Molins, E.;
Miravitlles, C.; Moret o´ , J. M. J. Am. Chem. Soc. 1992, 114, 10449-
1
1
0461. (d) Garcia-G o´ mez, G.; Moret o´ , J. M. Chem.sEur. J. 2001, 7,
503-1509.
(
(
3) Chiusoli, G. P.; Cassar, L. Angew. Chem. 1967, 79, 177-186.
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(
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(
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Acta 1999, 296/1, 94-102.
(
7) Protonolysis or “substitutive reduction” is one of the concurrent processes
responsible for Ni oxidation: Chiusoli, G. P.; Bottaccio, G.; Cameroni,
A. Chim. Ind. (Milan) 1962, 44, 131-135.
(
8) (a) Kochi, J. K. Pure Appl. Chem. 1980, 52, 571-605. (b) Dayrit, F. M.;
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(
(
(
(
10) (a) Farmer, P. J.; Reibenspies, J. H.; Lindahl, P. A.; Darensbourg, M. Y.
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Tetrahedron 1994, 50, 4001-4008.
the solvent of choice following a probable catalytic cycle, in which
the key step would be the transfer of the cycloadduct from the nickel
to the iron (Scheme 3). With higher turnovers, the amount of
products in which the alkyne has further inserted on the side chain
12) In some Ni complexes with a formally odd oxidation state for the metal,
the unpaired electron is fully localized on the ligand, and the complex is
Ni-silent. See, for instance: Kreisman, P.; Marsh, R.; Preer, J. R.; Gray,
H. B. J. Am. Chem. Soc. 1968, 90, 1067-1068.
(
mixture of stereoisomers) becomes relevant. In connection with
(
13) Although, initially, an excess of iodide was added only to solubilize the
Ni salt as tetraiodonickelate, the presence of iodide has proven to activate
the reaction and is liable to operate as well as an efficient allyl activator
and/or a stabilizing ligand. Without it, the reaction proceeds sluggishly.
this finding is the oxidation of iron. With long reaction times, the
iron is completely consumed. However, when the reaction was
stopped just after the substrate had been added, iron was consumed
up to around 0.5 equiv only.
We could not isolate any product derived from reduction of the
adduct or the solvent. Thus, we conclude that iron is, in part,
scavenging the acyl halide released from the reaction cycle,
preventing it, in this way, from undergoing further alkyne insertion.
This would be the reason this concurrent process acquires impor-
(14) Ikeda, S.; Sanuki, R.; Miyachi, H.; Miyashita, H.; Taniguchi, M.;
Odashima, K. J. Am. Chem. Soc 2004, 126, 10331-10338.
-1
(
15) Besides a strong and broad peak at 3376 cm , the dry crude product
shows strong peaks at 1684, 1595, and 1463 cm- in the IR spectrum not
present in the final adduct. The M o¨ ssbauer spectrum accounts for at least
1
8
5% of the dissolved iron as Fe(II). The reflux of the crude product in
THF with an excess of paraformaldehyde gave 40% of 3-hydroxy-2-[5-
2-phenylcyclopent-2-enonyl)]propionic acid (one single isomer).
(
JA0525713
J. AM. CHEM. SOC.
9
VOL. 127, NO. 30, 2005 10477