Copper(I) enolate complexes in α-arylation reactions: Synthesis, reactivity, and mechanism

Article abstract of DOI:10.1002/anie.201106719

Copper is all bound up: The copper-catalyzed α-arylation of carbonyl compounds occurs through oxidative addition of iodoarenes to the C-bound Cu ^I enolate species 1 to form an aryl-Cu^III intermediate (see scheme). Computational results provide insight into the origins of the relative reactivity of various Cu^I enolate complexes in the reactions with iodoarenes. Copyright

Full text of DOI:10.1002/anie.201106719

.
Angewandte
Communications
DOI: 10.1002/anie.201106719
Reaction Mechanisms
Copper(I) Enolate Complexes in a-Arylation Reactions: Synthesis,
Reactivity, and Mechanism**
Zheng Huang and John F. Hartwig*
The a-arylation of enolates has become a widely used method
to prepare a-aryl carboxylic acid and ketone derivatives that
comprise important classes of biologically active compounds.
Palladium-catalyzed a-arylation of carbonyl compounds has
been developed over the past decade, but the copper-
mediated a-arylation of activated methylene compounds
has been known for nearly a century [Eq. (1)].[1–2] Recently,
the selectivity and reactivity of CuI enolate complexes
containing or lacking phen ligands in reactions with different
iodoarenes, reactions with substrates that probe for aryl
radical intermediates, and DFT calculations all indicate that
the active species is a C-bound CuI enolate complex ligated by
a single phen unit, and that this intermediate reacts with the
iodoarene to generate a CuIII intermediate without the
intermediacy of aryl radicals. The relative reactivity of the
different enolates correlates with the energy differences
between the observed species and the reactive C-bound
enolates, along with the barriers to oxidative addition of ArI
to form aryl–CuIII enolate intermediates.
The syntheses of phen-ligated CuI complexes containing
the enolates from b-dicarbonyl compounds and cyanoacetate,
as well as the less stabilized enolates from a phenylesters, is
outlined in Scheme 1. Treatment of copper tert-butyloxide
with 2 equivalents of phen in benzene, with subsequent
addition of 2,4-pentanedione, ethyl acetoacetate, diethyl
malonate, dimethyl malonate, ethyl cyanoacetate, ethyl
phenylacetate, and methyl phenylacetate formed the CuI
complexes 1–7 in 59–82% yield.[8]
significant improvements in the scope and reaction conditions
of these copper-catalyzed Hurtley-type reactions have been
achieved using a combination of copper complexes with
ancillary ligands, such as 2-phenylphenol,[3] chelating Schiff
bases,[4] l-prolines,[5] and 2-picolinic acid.[6]
Despite the long history of Hurtley couplings, the
mechanism of this process has been little explored. Setsune
et al. proposed that the active copper species in the coupling
of aryl halides with diethyl malonate is a CuI enolate
generated in situ and that the CuI species reacts with the
aryl halide by electron transfer.[7] Buchwald et al. found that
CuI and 2-phenylphenol catalyzed the arylation of diethyl
malonate, but this system did not catalyze the arylation of the
cyclic isopropylidene malonate and 1,3-cyclopentanedione.
Accordingly, they proposed that a bidentate coordination
mode through two O atoms was required for the arylation
reactions to occur.[3] Thus, mechanistic proposals have been
made, but no explicit structural information on the copper
enolate complexes that could be intermediates in the Hurtley
couplings has been reported.
We report the synthesis of a series of CuI enolate
complexes supported by 1,10-phenanthroline (phen). Their
structures consist of an unusual combination of one cationic
CuI center ligated by two phen ligands and one free, anionic
enolate unit. Kinetic data on the stoichiometric reactions of
the CuI enolate complexes with iodobenzene, comparisons of
Scheme 1. Synthesis of CuI enolate complexes 1–7.
[*] Dr. Z. Huang, Prof. Dr. J. F. Hartwig[+]
Department of Chemistry
All complexes were characterized by IR and NMR
spectroscopy and elemental analysis, and complexes 1, 4, 5,
and 6 were characterized by single-crystal X-ray diffraction
University of Illinois Urbana-Champaign, Urbana, IL 61801 (USA)
[+] Current address: University of California, Department of Chemistry
718 Latimer Hall, Berkeley, CA 94720 (USA)
E-mail: jhartwig@berkeley.edu
1
(Figure 1).[9] The H NMR spectra and microanalytical data
for each complex showed that the complexes contain a 2:1:1
ratio of phen/Cu/enolate. The solid-state structures of 1, 4,
and 6 contain a cationic CuI center ligated by two phen ligands
and a free, unligated anionic enolate unit.[10] The sp2
[**] We thank the NIH (GM-58108) for support of this work.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201106719.
1028
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 1028 –1032

Angewandte
Chemie
Table 1: Reactions of copper enolate complexes with PhI.[a]
Complex
R1
R2
T [8C]
Yield [%][b]
1
2
3
4
5
6
7
MeCO
MeCO
EtCO2
MeCO2
CN
MeCO
EtCO2
EtCO2
MeCO2
EtCO2
EtCO2
MeCO2
60
60
25
25
25
25
25
0
63[c]
79
80
86
68
70
Ph
Ph
[a] Reaction conditions: 34.4 mm of complexes, [D6]DMSO. [b] The yield
was determined by 1H NMR spectroscopy using trimethoxybenzene as
an internal standard. [c] Reaction time: 22 h.
The reaction of diethyl malonate with 2 equivalents of PhI
in the presence of 2 equivalents of Cs2CO3 catalyzed by the
CuI diethyl malonate complex 3 (10 mol%) gave the diethyl
arylmalonate in 73% yield after 8 hours and in 95% yield
after 20 hours at 258C.[11] The similarity of this rate to that for
the stoichiometric reaction of 3 with PhI indicates that
complex 3 is kinetically competent to be an intermediate in
the catalytic process.
Figure 1. ORTEP diagrams of 1 (top left, C50–C51=1.400(3) ꢀ, C51–
C52=1.392(6) ꢀ, ]C50-C51-C52=128.3(5)8), 4 (top right, C27–
C26=1.400(3) ꢀ, C27–C28=1.398(3) ꢀ, ]C26-C27-C28=124.71(17)8),
5 (bottom left, C1–N1=1.151(4) ꢀ, C1–C2=1.396(5) ꢀ, C2–
C3=1.399(5) ꢀ, ]C1-C2-C3=119.9(4)8), and 6, (bottom right, C28–
C29=1.432(6) ꢀ, C27–C28=1.391(5) ꢀ, ]C27-C28-C29=126.3(4)8).
Thermal ellipsoids shown at 50% probability.
Kinetic data gained by 1H NMR spectroscopy on the
reactions of 3 with varying excess quantities of PhI and added
phen at 608C showed that the reaction is first order in 3, first
order in PhI, and inverse first order in phen (see the
Supporting Information for data). These data imply that the
reaction occurs by reversible dissociation of one phen from 3
and that the reactive CuI enolate species contains a 1:1:1 ratio
of phen/Cu/enolate. This complex could be the ionic species
[(phen)2Cu][Cu{CH(CO2Et)2}2] (A) or the neutral complex
[(phen)Cu{CH(CO2Et)2}] (B) [Eq. (2)].
carbanions in the enolates (C51 in 1, C27 in 4, C28 in 6) are
nearly trigonal planar, and, consistent with a conjugated
À
enolate, the C C bond distances are close to those in an
aromatic ring.
In contrast to the enolates in complexes 1, 4, and 6, the
cyanoester anion in 5 is bound to copper through the N atom
of the cyano group (Figure 1), and this binding creates an
unusual five-coordinate, trigonal bipyramidal, formally 20
I
À
valence electron Cu site. The Cu N bonds in the equatorial
plane (1.947(3) to 2.071(3) ꢀ) are considerably shorter than
those in the axial positions (2.368(3) and 2.411 ꢀ).
The conductivity of solutions containing the complexes
was used to assess the relationship between the solid-state and
solution structures. The conductivities of 1.0 mm solutions of
complexes 1–7 in DMSO solvent ranged from 18.8 to
24.5 WÀ1 cm2 molÀ1 versus 23.5 WÀ1 cm2 molÀ1 for [NBu4]-
[BPh4] and 0.3 WÀ1 cm2 molÀ1 for ferrocene. Thus, complexes
1–7 are all predominantly salts in DMSO, including complex
5, which adopts the neutral, five-coordinate structure in the
solid state.
Scheme 2 summarizes the rate constants for analogous
reactions of complexes 1–7 with 10 equivalents of PhI in the
presence of 12 equivalents of phen. The relative reactivity
follows the trend: 1, 2 < 3 < 4 < 5 < 6 ꢀ 7. These data show
To assess the potential of the enolate complexes 1–7 to be
intermediates in the a-arylation reactions, we investigated
their reactions with iodobenzene (PhI). These results are
summarized in Table 1. The malonate, cyanoester, and
phenylacetate complexes 3–7 reacted with PhI at 258C to
form the coupled products in 68–86% yield (100% conver-
sion) after 12 hours, whereas the ethyl acetoacetate complex 2
required over 22 hours at 608C for > 95% conversion and
formed the arylated product in 63% yield. The acetylacetone
complex 1 did not react with PhI to form the arylated product;
no reaction occurred at room temperature, and multiple
unidentified species formed at 608C.
Scheme 2. Rate of reactions of enolate complexes 1–7 with PhI.
[a]<5% conversion after 18 h at 608C.
Angew. Chem. Int. Ed. 2012, 51, 1028 –1032
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org 1029

.
Angewandte
Communications
that complexes of the more-electron-donating enolates react
with the iodoarenes faster than the complexes of the less-
electron-donating enolates.
reaction of a 1:1 mixture of o- and p-iodotoluene (10 equiv
each) with complex 3 (34.4 mm) formed two diethyl arylmal-
onates in a 95:5 ratio (entry 1). The reaction of o- and p-
iodotoluene with complex A or B, generated by treatment of
complex 3 (34.4 mm) with 1 equivalent of CuI, gave the
diethyl arylmalonates in a similar 97:3 ratio (entry 2). The
similarity of this ratio is consistent with our conclusion that
the species reacting with the iodoarene contains a 1:1:1 ratio
of phen, enolate, and copper, as drawn from kinetic data on
the reactions of isolated 3 in the presence of added phen.
Although attempts to generate enolate complexes lacking
any dative ligand did not lead to pure, isolable species (see the
Supporting Information for details), we did conduct stoichio-
metric reactions of the aryl iodides with the combination of
copper and alkali metal enolates. The reaction of o- and p-
iodotoluene with a 1:1 and 2:1 ratio of potassium diethyl
malonate to CuI (34.4 mm each) without phen, formed the
diethyl arylmalonates in an approximately 70:30 ratio and a
total yield of only 19% after 21 hours (Table 2, entry 3) and
53% after 23 hours (entry 4), respectively. The low selectivity
and the slow rate of these reactions in the absence of phen
further imply that the iodoarenes react with a phen-ligated
copper species during the reactions initiated with isolated
phen-ligated complexes. Moreover, the lower selectivity of
the enolate complex containing the putative [Cu{H-
(CO2Et)2}2]À anion (entry 4) implies that the active inter-
mediate in the reaction of 3 with iodoarenes is the neutral
phen-ligated copper enolate species B, rather than the anionic
[Cu{CH(CO2Et)2}2]À portion of the ionic species A.
The catalytic reactions of diethyl malonate with PhI in the
presence of 10 mol% of 3 were also inhibited by added phen.
Without added phen, this reaction formed the product in 73%
yield after 8 hours and in 95% yield after 20 hours at room
temperature. The same reaction conducted with 30 mol% of
added phen gave diethyl phenylmalonate in only 4% yield
after 8 hours and 11% yield after 20 hours (11% conversion).
The same reaction with a full equivalent of added phen gave
no detectable arylated product after 8 hours. These results are
consistent with the reversible dissociation of one phen ligand
from 3 to generate the active intermediate (A or B) in the
catalytic process.
To gain more direct information on the reactivity of the
species generated by dissociation of phen, we generated this
complex by treatment of the complex 3 (34.4 mm) with
1 equivalent of CuI in DMSO [Eq. (3)]. This reaction formed
[{(phen)CuI}2] and the ionic or neutral complex A or B
containing a 1:1 ratio of phen to enolate, as indicated by
1H NMR spectroscopy. The species containing a single phen
reacted with 2 equivalents of PhI to form diethyl phenyl-
malonate in 37% yield in less than 10 minutes at 258C and
62% yield with 100% conversion of the copper species after
1 hour,[12] whereas complex 3 reacted with PhI under analo-
gous reaction conditions to form the coupled product in only
23% yield after 78 minutes and 63% yield after 9 hours.
To assess further the potential of the species containing a
1:1:1 ratio of phen/Cu/enolate to be the active intermediates
in the reactions of the isolated complexes with aryl halides,
the ratio of products from reactions of sterically distinct o-
and p-iodotoluenes with the CuI enolate complexes contain-
ing or lacking phen ligands was measured (Table 2). The
With an understanding of the structure of the starting
enolate complexes and the composition of the reactive
intermediate, we sought to distinguish between reaction
mechanisms involving electron transfer to generate aryl
radicals proposed previously[7] and mechanisms involving
the formation of CuIII intermediates by nonradical pathways
more akin to those deduced for reactions of complexes with
reactive anionic oxygen and nitrogen ligands.[13] To do so, we
studied the reaction of complex 3 with o-(allyloxy)iodoben-
zene [8; Eq. (4)]. The aryl radical of 8 is known to undergo
Table 2: Selectivity of CuI enolate complexes toward o- and p-iodo-
toluene.
Entry CuI enolate
t
Yield [%]
ortho-
substituted substituted
Ratio
para-
cyclization with a rate constant of 9.6 ꢁ 109 sÀ1 in DMSO to
form a [3-(2,3-dihydrobenzofuran)]methyl radical, which is
eventually converted into 2-methyldihydrobenzofuran (11).
The reaction of 3 with 8 in DMSO at 258C produced the
arylated molonate 9 in 59% yield and ethyl 2-aryl-2-
oxoacetate 10 in 14% yield after two days [Eq. (4)].[14] No
detectable amount of cyclized product 11 was observed by
GC/MS. The detection limit for product 11 by GC/MS was
product
product
1 h
3 h
45
73
2
3
2
2.4
6
95:5
95:5
97:3
72:28
69:31
70:30
69:31
1
2
3
3
A or B
K[CH(CO2Et)2] +
CuI
2K[CH(CO2Et)2] +
CuI
<5 min 62
1 h 6.2
21 h 13
2 h 23
23 h 37
10
16
4
1030
www.angewandte.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 1028 –1032

Angewandte
Chemie
determined to be less than 0.2% of the amount of 9. Thus, any
aryl radical formed from this process must react with the
copper enolate complex to form the arylmalonate 9 in less
than 2 ꢁ 10À13 s. Because this timescale is the lifetime of a
transition state, and the organic product would be required to
form by recombination of the free aryl radical with the copper
enolate in less than 2 ꢁ 10À13 s, free radicals that could be
formed by initial electron transfer are unlikely to be
intermediates in the reaction of copper malonate complexes
with aryl halides.
only 22.7 kcalmolÀ1 above the most stable species in this case
(Figure S1). The prohibitively large barrier calculated for
oxidative addition to the acetylacetonate complex is consis-
tent with our observation of the lack of reactivity of 1 with PhI
to form 3-phenyl acetylacetone. The 26.1 and 22.7 kcalmolÀ1
barriers computed for reaction of the malonate and phenyl-
acetate complexes, respectively, agree with the moderate rate
observed for the reaction of PhI with complex 4 and the faster
rate observed for the reaction of iodobenzene with complex 7
(see Scheme 2).[15]
To assess the potential intermediacy of the arylcopper(III)
complexes proposed to lie on the reaction pathway, we
computed the energies for oxidative addition of PhI to the
phen-ligated C-bound CuI complexes of acetylacetone,
dimethyl malonate, and methyl phenylacetate anions. These
three enolate complexes (1, 4, and 7) reacted with iodoarene
with the most diverse rates (see Scheme 2). The free energies
of activation (DG°) for oxidative addition of PhI to the C-
bound CuI complexes of the anions of acetylacetone, dimethyl
malonate, and methyl phenylacetate to form an aryl–CuIII
intermediate were calculated to be 27.2, 21.9, and 22.7 kcal
molÀ1, respectively, at 258C (see 1-TS1, 4-TS1, and 7-TS1 in
Figure S1 in the Supporting Information). These computa-
tional results imply that the CuIII species lie at energies that
are accessible under mild reaction conditions.
The calculated barriers for reductive elimination of a-aryl
carbonyl compounds from the C-bound CuIII acetylacetone,
dimethyl malonate, and methyl phenylacetate complexes are
3.5, 4.1, and 6.3 kcalmolÀ1, respectively (see 1-TS2, 4-TS2, and
7-TS2 in Figure S1 in the Supporting Information). These data
À
indicate that the reductive elimination to form the C C bond
from copper complexes of these stabilized anions is much
À
faster than reductive elimination to form the same type of C
C bond from known arylpalladium(II) enolate complexes.[16]
In summary, studies on isolated, phen-ligated enolate
complexes of 1,3-dicarbonyl compounds and phenylacetates
strongly indicate that the C-bound CuI enolate complex
ligated by a single phen lies on the pathway for the reaction of
copper enolates with iodoarenes (Scheme 3). The most stable
CuI enolate complex containing two phen ligands reversibly
dissociates one phen ligand to form the O,O-bound (or O-
bound) enolate species B1 containing one phen ligand. We
propose that this complex equilibrates with the C-bound
isomer B2 and that oxidative addition of the iodoarene occurs
to the C-bound isomer to form a CuIII enolate intermediate,
which undergoes facile reductive elimination to release the
arylated product and [{(phen)CuI}2]. Among the enolate
complexes studied, the phenylacetate complex, for which the
C-bound enolate is computed to be more stable than the
alternative O-bound form, and for which the enolate is the
most strongly electron donating, is the most reactive toward
oxidative addition of iodoarenes. The acetylacetone complex,
for which the O,O-chelating mode is calculated to be more
favorable than the C-bound form and for which the enolate is
the most weakly electron donating, is the least reactive
toward addition of iodoarenes. The intermediacy of the phen-
ligated enolate, the equilibration of species containing a free
enolate anion and a C-bound enolate, and reaction by
pathways lacking aryl radicals all contradict prior assertions
about the mechanism of copper-catalyzed couplings of
enolates[3,7] and require revisions of previous mechanistic
proposals.
However, the copper enolate complexes containing a
single phen ligand could exist in the O,O-bound (or O-bound)
form B1 or in the C-bound form B2 (Scheme 3; also see
Scheme 3. Proposed catalytic cycle with complex 3. Oxidative addition
to the C-bound enolate is shown. Oxidative addition to an O-bound
isomer, followed by rearrangement to the C-bound CuIII intermediate is
less likely, but not ruled out by our data.
Table S5 in the Supporting Information). Thus, we computed
the relative free energies of the C-bound species and the O-
bound forms (Table S5). The O,O-bound structures contain-
ing the anions of acetylacetone and dimethyl malonate are
computed to lie at energies that are lower than those of the C-
bound CuI structures by 12.5 and 4.2 kcalmolÀ1, respectively
(see 1-O,O and 4-O,O in Figure S1). Thus, the transition state
for oxidative addition to the C-bound isomers of the
complexes of acetyl acetonate and dimethyl malonate
anions are predicted to lie 39.7 kcalmolÀ1 and 26.1 kcalmolÀ1
above the energies of the most stable species containing a
1:1:1 ratio of enolate, phen, and copper. In contrast, the more
stable CuI complex containing the anion of methyl phenyl-
acetate is computed to be the C-bound form. Thus, the barrier
for oxidative addition of PhI to the C-bond enolate containing
a 1:1:1 ratio of enolate, phen, and copper is predicted to be
Received: September 22, 2011
Revised: October 18, 2011
Published online: December 8, 2011
Keywords: copper · cross-coupling · kinetics ·
.
reaction mechanism · structure elucidation
[1] W. R. H. Hurtley, J. Chem. Soc. 1929, 1870.
[2] a) F. Monnier, M. Taillefer, Angew. Chem. 2009, 121, 7088;
Angew. Chem. Int. Ed. 2009, 48, 6954; b) K. Okuro, M. Furuune,
M. Miura, M. Nomura, J. Org. Chem. 1993, 58, 7606.
Angew. Chem. Int. Ed. 2012, 51, 1028 –1032
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
1031

.
Angewandte
Communications
[3] E. J. Hennessy, S. L. Buchwald, Org. Lett. 2002, 4, 269.
[4] H. J. Cristau, P. P. Cellier, J. F. Spindler, M. Taillefer, Chem. Eur.
J. 2004, 10, 5607.
[5] a) X. A. Xie, Y. Chen, D. W. Ma, J. Am. Chem. Soc. 2006, 128,
16050; b) X. Xie, G. Cai, D. Ma, Org. Lett. 2005, 7, 4693; c) Y. W.
Jiang, N. Wu, H. H. Wu, M. Y. He, Synlett 2005, 2731.
[6] S. F. Yip, H. Y. Cheung, Z. Zhou, F. Y. Kwong, Org. Lett. 2007, 9,
3469.
[7] a) J.-i. Setsune, T. Ueda, K. Shikata, K. Matsukawa, T. Iida, T.
Kitao, Tetrahedron 1986, 42, 2647; b) J.-i. Setsune, K. Matsu-
kawa, T. Kitao, Tetrahedron Lett. 1982, 23, 663; c) J. Setsune, K.
Matsukawa, H. Wakemoto, T. Kitao, Chem. Lett. 1981, 367.
[8] Complex 1 has been synthesized by a different method, but its
structure remained unknown. R. Nast, W.-H. Lepel, Chem. Ber.
1969, 102, 3224.
Huffman, S. S. Stahl, Dalton Trans. 2011, 40, 8959; c) A. Casitas,
N. Ioannidis, G. Mitrikas, M. Costas, X. Ribas, Dalton Trans.
2011, 40, 8796; d) H.-Z. Yu, Y.-Y. Jiang, Y. Fu, L. Liu, J. Am.
Chem. Soc. 2010, 132, 18078; e) J. W. Tye, Z. Weng, R. Giri, J. F.
Hartwig, Angew. Chem. 2010, 122, 2231; Angew. Chem. Int. Ed.
2010, 49, 2185; f) R. Giri, J. F. Hartwig, J. Am. Chem. Soc. 2010,
132, 15860; g) A. E. King, L. M. Huffman, A. Casitas, M. Costas,
X. Ribas, S. S. Stahl, J. Am. Chem. Soc. 2010, 132, 12068; h) L. M.
Huffman, S. S. Stahl, J. Am. Chem. Soc. 2008, 130, 9196; i) J. W.
Tye, Z. Weng, A. M. Johns, C. D. Incarvito, J. F. Hartwig, J. Am.
Chem. Soc. 2008, 130, 9971; j) S.-L. Zhang, L. Liu, Y. Fu, Q.-X.
Guo, Organometallics 2007, 26, 4546.
[14] Compound 10 was likely formed through the oxidation of 9.
P. M. Allen, U. Hess, C. S. Foote, M. M. Baizer, Synth. Commun.
1982, 12, 123.
[9] CCDC 844995 (1), 844996 (4), 844997 (5), and 844998 (6)
contain the supplementary crystallographic data for this paper.
These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_
request/cif.
[15] These isolable species are the ionic complexes 1, 4 and 7, rather
than the neutral complexes on which we are able to conduct
meaningful calculations. The relative stability of these ionic
species and the neutral species [(phen)Cu(enolate)] is difficult to
evaluate by computational methods because the ions can exist as
contact, solvent-separated, or fully solvated ion pairs. At the
same time, the acidity of the carbonyl compounds in DMSO
(acetylacetone = 13.3, dimethyl malonate = 15.9 and methyl
phenylacetate ꢀ 22) shows clearly that the enolate from acetyl-
acetone is more stable than that from dimethyl malonate, which
is more stable than that from methyl phenylacetate. Thus the
energy difference between the observed ionic enolate complex
and the neutral species should follow the trend, acetylacetone >
dimethyl malonate > methyl phenylacetate. These energy differ-
ences would further increase the difference of free-energy
barriers between reactions of PhI with the complexes 1, 4 and 7.
Thus, the relative computed barriers would remain consistent
with the observed reactivity of these enolate complexes with PhI.
[16] D. A. Culkin, J. F. Hartwig, Acc. Chem. Res. 2003, 36, 234.
[10] Related bis(phen)-ligated CuI nitrophenylmethane and nitro-
methane complexes in which the enolate moieties were pro-
posed to be present as the free anions were reported previously,
but their structures were not defined by X-ray diffraction. N.
Marsich, A. Camus, J. Inorg. Nucl. Chem. 1977, 39, 275.
[11] The catalytic reaction with PhBr as the electrophile gave no
product under the same reaction conditions, but formed the
diethyl arylmalonate in 86% yield after 15 h at 808C.
[12] Full conversion of the species B into diethyl phenylmalonate and
free diethyl malonate after 1 h. The latter was presumably
formed by protonation of B with the trace amount of water in the
DMSO.
[13] a) L. M. Huffman, A. Casitas, M. Font, M. Canta, M. Costas, X.
Ribas, S. S. Stahl, Chem. Eur. J. 2011, 17, 10643; b) L. M.
1032
www.angewandte.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 1028 –1032