Well-defined copper(I) amido complex and aryl iodides reacting to form aryl amines

Article abstract of DOI:10.1021/om101084e

The Cu^I complex (IPr)Cu(NHPh) {IPr = 1,3-bis(2,6- diisopropylphenyl)imidazol-2-ylidene} reacts with aryl iodides to form diaryl amine products and (IPr)Cu(I), which was confirmed by independent synthesis and characterization. For the reaction with iodobenzene, the products are diphenylamine and aniline. Protection of the hydrogen para to the iodo functionality with ortho-methyl groups results in quantitative conversion to diaryl amine. Combined computational and experimental studies suggest that C-N bond formation most likely occurs via an oxidative addition/reductive elimination sequence.

Full text of DOI:10.1021/om101084e

Organometallics 2011, 30, 55–57 55
DOI: 10.1021/om101084e
Well-Defined Copper(I) Amido Complex and Aryl Iodides Reacting
to Form Aryl Amines
†
Samuel A. Delp, Laurel A. Goj, Mark J. Pouy, Colleen Munro-Leighton, John P. Lee,
†,
‡
†
†
,
‡
,§
T. Brent Gunnoe,* Thomas R. Cundari,* and Jeffrey L. Petersen
^
†
Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695, United States,
Department of Chemistry, University of Virginia, Charlottesville, Virginia 22904, United States,
Department of Chemistry, University of North Texas, Denton, Texas 76203-5070, United States, and
C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, West Virginia 26506,
United States. Current address: Department of Chemistry, Rollins College, Winter Park,
Florida 32789, United States
‡
§
^
Received November 16, 2010
I
Summary: The Cu complex (IPr)Cu(NHPh) {IPr = 1,3-bis-
C-halide oxidative addition would form rarely observed
III 14-17
(
2,6-diisopropylphenyl)imidazol-2-ylidene} reacts with aryl
Cu intermediates. Taillefer et al. have recently studied
the role of a tetradentate nitrogen-based ligand on arylation
iodides to form diaryl amine products and (IPr)Cu(I), which
was confirmed by independent synthesis and characterization.
For the reaction with iodobenzene, the products are diphenyl-
amine and aniline. Protection of the hydrogen para to the iodo
functionality with ortho-methyl groups results in quantitative
conversion to diaryl amine. Combined computational and exper-
imental studies suggest that C-N bond formation most likely
occurs via an oxidative addition/reductive elimination sequence.
1
8
reactions; however, these studies did not identify Cu inter-
mediates in the catalytic cycle. In addition, Paine disclosed a
detailed comparison of homogeneous and heterogeneous
copper catalysts for transformations of Li amides that sug-
gests the formation of an unobserved “cuprous nucleophile
19
species, Ph NCu” that reacts with iodobenzene, but obser-
2
vation of Cu amido systems was not reported. A kinetic and
spectroscopic study of Cu-catalyzed amidation of aryl iodides,
a reaction that is potentially related to aryl amination, indi-
Copper-mediated Ullmann-type reactions are among the
oldest and most widely utilized catalytic processes available
to organic chemists. In recent years, there has been a resur-
gence of interest in such reactions, and several groups have
developed methods for aryl amination using Cu salts as
I
cated a Cu amidate as an intermediate. In these studies, the
I
Cu amidate was observed by NMR spectroscopy but not
2
0
isolated. Hartwig et al. have studied a range of Cu amidate
systems and concluded that amidation of aryl halides likely
1
-10
catalysts.
catalysts,
In contrast to the well-defined and tunable Pd
many systems for Cu catalysis involve mix-
1
1-13
21
occurs through C-X oxidative addition, and more recently
Giri and Hartwig have reported a mechanistic study of Cu
I
tures of Cu salts and ligands. Thus, studies based on the
reaction of isolable and well-defined Cu-amido complexes
with aryl halides have not been possible. By analogy with Pd-
based reactions, copper amido intermediates are possible;
however, catalytic cycles analogous to Pd that involve
2
2
amido complexes reacting with iodoarenes.
Although Cu amido complexes have been implicated in
Cu-catalyzed C-N bond formation, to our knowledge a
well-defined monomeric Cu amido complex has not been
previously demonstrated to react with an aryl halide to give
an amine product. In fact, isolation of monomeric Cu com-
plexes with a terminal amido ligand (i.e., amido is not part of
a chelate and is not bridging) is rare, with only three exam-
*
Corresponding authors. E-mail: tbg7h@virginia.edu; t@unt.edu.
1) Ley, S. V.; Thomas, A. W. Angew. Chem., Int. Ed. 2003, 42, 5400–
449.
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Herein, we report the conversion
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(
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D. F.; Wingad, R. L. Organometallics 2008, 27, 3196–3202.
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(
(
10) Kwong, F. Y.; Buchwald, S. L. Org. Lett. 2003, 5, 793–796.
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r 2010 American Chemical Society
Published on Web 12/06/2010
pubs.acs.org/Organometallics

5
6
Organometallics, Vol. 30, No. 1, 2011
Delp et al.
I
a
of a fully characterized monomeric Cu -anilido complex
and aryl iodides to amine products.
Scheme 1. DFT-calculated ΔG’s (kcal/mol, 298 K)
We recently reported the preparation, isolation, and full
characterization (including solid-state structure) of the mono-
meric anilido complex (IPr)Cu(NHPh) (1) [IPr=1,3-bis-
2
7
(
2,6-diisopropylphenyl)imidazol-2-ylidene]. The stoichio-
metric reaction of 1 with 5 equiv of PhI in C D (120 ꢀC, 4 h)
6
6
leads to the formation of diphenylamine (∼60%), aniline
(
(
∼40%), (IPr)Cu(I) (2) (60%), and a second uncharacterized
IPr)Cu system in ∼40% yield (eq 1). Performing this reac-
tion with PhI-d produces Ph NH-d (determined by GC/MS
5
2
5
analysis). Multiple attempts to characterize the second Cu com-
plex from the reaction of (IPr)Cu(NHPh) (1) and PhI were
unsuccessful. We independently prepared and fully charac-
terized complex 2, including a solid-state X-ray structure
I
(Supporting Information), by reaction of free IPr and Cu
iodide. In contrast to the reaction with iodobenzene, heating
a
OA = oxidative addition, NS = nucleophilic substitution, ts =
transition state.
30
cleaved (regardless of the specific mechanism). We sus-
pected that the iodide functionality might be providing elec-
tronic activation for the para-C-H bond of iodobenzene. To
test this possibility, we reacted complex 1 with 10 equiv
of 1-iodo-3,5-dimethylbenzene, for which the C-H bond
para to the iodide functionality is sterically protected by the
methyl groups. This stoichiometric reaction cleanly produces
complex 1 and PhOTs (OTs = tosylate) to 120 ꢀC in C D for
6
6
2
0 h results in no apparent formation of diphenylamine.
Complex 1 can be heated in C D at 120 ꢀC for at least 24 h
6
6
without evidence of aniline production. Thus, the produc-
tion of aniline from 1 and PhI is not likely due to thermal
decomposition.
(IPr)Cu(I) (2) and the corresponding aryl amine without
production of aniline (eq 2).
The reaction of complex 1 and 1-iodo-3,5-dimethylbenzene
to produce only diaryl amine (and no aniline) suggests that
steric protection of the iodo functionality should increase the
production of aniline. Indeed, the reaction of (IPr)Cu(NHPh) (1)
and 10 equiv of 1-iodo-2,6-dimethylbenzene produces ani-
line without observation of diaryl amine (eq 3).
We posit that an initial Cu-Namido bond homolysis to give
aniline radical is unlikely for formation of aniline from the
reaction of 1 with iodobenzene. No evidence of diphenylhy-
drazine is observed, which forms with a rate constant of 1.5 ꢀ
9
-1 -1
28
1
0 M
s
from the aminyl radical in water. In addition,
previous computational studies of complex 1 reveal that the
Cu-Namido BDE is 87 kcal/mol, and experimental studies
2
4
support the calculated strong Cu-N bond. Furthermore,
if Cu-N bond homolysis were responsible for aniline pro-
duction, we anticipate that reaction of 1 with 1-iodo-3,5-
dimethylbenzene would produce some aniline; however, ani-
line is not observed in this reaction (see below). Finally, we
attempted to trap the putative aniline radical. Given the
N-H BDE of aniline of 92 kcal/mol and the C-H BDE of
2
9
1
,4-cyclohexadiene (CHD) of 76.5 kcal/mol, the formation
of aniline radical in the presence of CHD should give aniline
and benzene. Heating 1 in C D to 120 ꢀC in the presence of
Of primary interest is the mechanism for (IPr)Cu(NHPh)
þ ArI f (IPr)Cu(I) þ diarylamine. As a probe of possible
pathways, we studied the conversion of 1 and PhI using DFT
with the parent NHC ligand at 298 K. Several different path-
ways were studied (see Supporting Information), with two emerg-
ing as most likely from calculated energetics (Scheme 1).
Utilizing a benzene solvation model, calculations indicate
6
6
5
protio benzene after 4 h.
equiv of CHD does not produce free aniline or additional
The production of aniline (40%) from the reaction of 1 and
PhI suggests the possibility that an aromatic C-H bond is
(
25) Munro-Leighton, C.; Blue, E. D.; Gunnoe, T. B. J. Am. Chem.
Soc. 2006, 128, 1446–1447.
26) Mankad, N. P.; Antholine, W. E.; Sziliagyi, R. K.; Peters, J. C.
J. Am. Chem. Soc. 2009, 131, 3878–3880.
27) Goj, L. A.; Blue, E. D.; Munro-Leighton, C.; Gunnoe, T. B.;
Petersen, J. L. Inorg. Chem. 2005, 44, 8647–8649.
28) Ingold, K. U. Rate Constants for Free Radical Reactions in
I
that PhI coordination to complex (NHC)Cu (NHPh) is ender-
gonic by 0.7 kcal/mol. An oxidative addition (OA) to form
(
III
(NHC)Cu (I)(Ph)(NHPh) was calculated to occur with
‡
(
ΔGOA = 25.6 kcal/mol relative to separated PhI and
I
‡
(
2
NHC)Cu (NHPh), which is similar to the calculated ΔG of
(
2
5kcal/molfor a Cu amidate system. This leads to an ender-
1
Solution. In Free Radicals; Kochi, J. K., Ed.; John Wiley & Sons: New
York, 1973; Vol. I, p 56.
III
gonic Cu product with ΔGOA = 6.2 kcal/mol for the most
stable geometric isomer. Reductive elimination of Ph NH
(
29) Gao, Y. D.; DeYonker, N. J.; Garrett, E. C.; Wilson, A. K.;
Cundari, T. R.; Marshall, P. J. Phys. Chem. A 2009, 113, 6955–6963.
30) Ribas, X.; Xifra, R.; Parella, T.; Poater, A.; Sola, M.; Llobet, A.
Angew. Chem., Int. Ed. 2006, 45, 2941–2944.
2
III
from (NHC)Cu (I)(Ph)(NHPh) to give (NHC)Cu(I) and
(
‡
free Ph NH is calculated to have a small ΔG of 11 kcal/mol.
2

Communication
Organometallics, Vol. 30, No. 1, 2011 57
A second plausible mechanism that involves a nucleophilic
substitution (NS) of iodide by the anilido ligand has a cal-
An initial electron transfer from 1 to aryl iodide to gen-
II
erate Cu and a radical anion, followed by iodide elimination
‡
þ
culated ΔGNS in benzene of 29.9 kcal/mol relative to sepa-
rated PhI and (NHC)Cu (NHPh). The NS transition state
and combination of phenyl radical with [(IPr)Cu(NHPh)] ,
cannot at this point be definitively eliminated from con-
I
I
leads to a product (NHC)Cu (I)(NHPh ) whose formation is
31
sideration. However, the reaction of 1 with AgOTf rapidly
produces diphenylhydrazine and (IPr)Cu(OTf). Thus, the
2
I
exergonic by 34.6 kcal/mol. The (NHC)Cu (I)(NHPh ) in-
2
‡
II
combination of phenyl radical with Cu would need to
occur via a rapid recombination event.
termediate easily rearranges (calculated ΔG = 0.7 kcal/mol)
to place the iodo ligand trans to the NHC ligand and disso-
ciate NHPh , which is calculated to be a further 4.6 kcal/mol
2
The fully characterized Cu complex 1 reacts with aryl iodides
to give aryl amine products, which provides direct evidence
that a Cu amido can react with aryl halide to produce aryl-
amine. Although more detailed experiments are required
to provide complete details, our preliminary experimental/
computational studies suggest a pathway that involves oxi-
dative addition to form a Cu(III) intermediate to be the most
reasonable route.
exergonic. Variations of this NS pathway were calculated to be
1
9
higher energy transformations (see Supporting Information).
‡
The calculated ΔG for conversion of (NHC)Cu(NHPh)
and PhI to (NHC)Cu(I) and Ph NH by an OA pathway is
25.6 kcal/mol. While the calculated activation barrier for the
NS route is not substantially greater than the OA route, a
2
‡
ΔΔG of 4.3 kcal/mol is sufficiently large to suggest the OA
pathway. Also, given that OTs is typically a good leaving
group for nucleophilic substitutions, the failure of complex 1
to react with PhOTs provides further evidence against the NS
mechanism. Although formation of a byproduct in the trans-
Acknowledgment. T.B.G. (CHE-0848693) and T.R.C.
CHE-0701247) acknowledge the National Science Foun-
dation for financial support. T.B.G. thanks Professor Bill
Myers and Diana Lovan (University of Richmond) for
assistance with mass spectrometry.
(
formation of 1 and PhI to 2 and Ph NH complicates a detailed
2
experimental kinetic analysis of this stoichiometric reaction,
we can estimate the half-life for formation of Ph NH and 2 at
2
4
0 min (120 ꢀC).
Supporting Information Available: Details of experiments and
calculations. This material is available free of charge via the
Internet at http://pubs.acs.org.
(31) Jones, G. O.; Liu, P.; Houk, K. N.; Buchwald, S. L. J. Am. Chem.
Soc. 2010, 132, 6205–6213.