A catalytic application of Co/Zr heterobimetallic complexes: Kumada coupling of unactivated alkyl halides with alkyl grignard reagents

Article abstract of DOI:10.1002/ejic.201100109

Tris(phosphanylamide) early/late heterobimetallic Zr/Co complexes, ClZr(R′NPR₂)₃CoI [R′ = iPr, R = Ph (1), R′ = 2,4,6-trimethylphenyl, R = iPr (2), R′ = R = iPr (3)], have been utilized as catalysts for the cross-coupling of alkyl halides with n-octylmagnesium bromide. While yields are consistently higher for alkyl bromide substrates, it is found that these unusual heterobimetallic complexes are also active towards more challenging alkyl chloride substrates. This is particularly interesting in light of the fact that monometallic cobalt complexes are inert towards these substrates, suggesting that Zr also plays a role in catalysis. Radical trapping studies suggest that a one-electron transfer radical oxidative addition pathway is operative.

Full text of DOI:10.1002/ejic.201100109

SHORT COMMUNICATION
DOI: 10.1002/ejic.201100109
A Catalytic Application of Co/Zr Heterobimetallic Complexes: Kumada
Coupling of Unactivated Alkyl Halides with Alkyl Grignard Reagents
[a]
[a]
[a]
Wen Zhou, Jonathan Wesley Napoline, and Christine M. Thomas*
Keywords: Heterometallic complexes / Cobalt / Radical reactions / Metal-metal interactions / Cross-coupling
Tris(phosphanylamide) early/late heterobimetallic Zr/Co
complexes, ClZr(RЈNPR CoI [RЈ = iPr, R = Ph (1), RЈ = 2,4,6-
more challenging alkyl chloride substrates. This is particu-
larly interesting in light of the fact that monometallic cobalt
complexes are inert towards these substrates, suggesting
that Zr also plays a role in catalysis. Radical trapping studies
suggest that a one-electron transfer radical oxidative ad-
dition pathway is operative.
2 3
)
trimethylphenyl, R = iPr (2), RЈ = R = iPr (3)], have been uti-
lized as catalysts for the cross-coupling of alkyl halides with
n-octylmagnesium bromide. While yields are consistently
higher for alkyl bromide substrates, it is found that these un-
usual heterobimetallic complexes are also active towards
Introduction
We previously reported the synthesis and characteriza-
tion of a family of Zr/Co heterobimetallic complexes linked
Cross-coupling reactions to form carbon–carbon bonds by three phosphanylamide ligands, ClZr(RЈNPR ) CoI (1:
2
3
have become one of the most common catalytic processes RЈ = iPr, R = Ph; 2: RЈ = 2,4,6-trimethylphenyl, R = iPr;
[
1]
[18]
in organic synthesis. Many such reactions have found 3: RЈ = R = iPr), as shown in Scheme 1.
It was found
large scale applications,[
2–4]
and transition metal-catalyzed that the dative CoǞZr interactions in these complexes facil-
cross couplings have also been used for key steps in the itated two electron reduction at potentials ca. 1 V more pos-
total synthesis of a number of natural products.[ While the itive than observed for an analogous monometallic cobalt
5]
[
18]
palladium catalyzed cross-coupling reactions of aryl and vi- complex, ICo(Ph PNHiPr)3 (4).
Upon chemical re-
2
nyl halides have become ubiquitous methods, this chemistry duction, highly reduced Zr/Co species, such as (THF)Zr-
has only recently been extended to alkyl halides and trans- (MesNPiPr ) Co-N (5), featuring metal-metal multiple
2
3
2
formations of this type are far from becoming widely appli- bonds and weakly coordinating apical ligands are gener-
[
6]
[19]
cable. Recently, researchers have begun focusing on first ated. These species are highly reactive towards oxidative
row transition metal catalysts to access cross-coupling reac- addition of small molecule substrates, including alkyl ha-
tions with alkyl halide substrates.[
7–12]
The resistance of first lides such as methyl iodide, cyclohexyl chloride, and 2-iodo-
2
row transition metal complexes to β-hydride elimination, propane to generate species such as (η -MesNPiPr )Zr-
combined with their availability and low cost, renders these (MesNPiPr ) (μ-CH )CoI (6) and {η -PiPr N[C (CH ) H -
complexes sustainable targets for cross-coupling applica- (CH )]}Zr(MesNPiPr ) CoI (7).
2
2
2
2
3
2
6
3 2
2
[
20]
Since alkyl halide acti-
2
2 2
tions. Researchers have recently demonstrated that, with the vation is an important step in carbon-carbon bond-forming
appropriate reaction conditions, cobalt complexes can be reactions, we have chosen to examine the catalytic perform-
utilized as catalysts for the formation of C–C bonds from ance of Zr/Co early/late heterobimetallic complexes in the
organic halides and Grignard reagents – a reaction known cross-coupling reactions of alkyl halides with alkyl Grig-
as Kumada–Corriu–Tamao, or simply Kumada cou- nard reagents (Kumada coupling). Herein we discuss the
[
13–17]
pling.
While cobalt catalysts, including those as simple remarkable catalytic activity of these Zr/Co complexes com-
as CoCl + LiI + TMEDA, that function adequately for pared to monometallic Co species, including activity
2
the coupling of alkyl bromides or iodides with Grignard towards alkyl chlorides.
reagents have been reported, the widespread utility of this
reaction has not been extended to more readily available
alkyl chlorides.
Results and Discussion
Heterobimetallic complexes 1–3 were screened as cata-
lysts for the Kumada coupling of alkyl halides with n-octyl-
magnesium bromide. Optimization of reaction conditions
see Supporting Information) suggested that catalytic per-
[
a] Department of Chemistry, Brandeis University,
4
15 South Street, Waltham, MA 02451, USA
Fax: +1-781-736-2516
E-mail: thomasc@brandeis.edu
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejic.201100109.
(
formance was better in THF than in Et O and the optimal
2
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W. Zhou, J. W. Napoline, C. M. Thomas
SHORT COMMUNICATION
Scheme 1. Heterobimetallic Zr/Co complexes 1–3 and 5–7 (Mes = 2,4,6-trimethylphenyl).
catalyst loading was 5 mol-%. Reactions were carried out at radical. A series of competition experiments were carried
room temperature, as low temperature conditions did not out to assess relative reaction rates. In coupling reactions
serve to improve yields. It is important to note that the ad- of 1:1 mixtures of alkyl iodide and alkyl bromide with sub-
dition of 30 mol-% TMEDA was necessary to obtain high stoichiometric quantities of nOctMgBr, iodide derived cou-
yields of coupled product and we suspect this is an effect pling products were formed preferentially in a ratio of 25:1,
of TMEDA chelation to the Grignard reagent, particularly while in a competition experiment of R–Br vs. R–Cl,
since neither 2 nor 5 reacted with TMEDA in control ex- bromide-derived products were formed exclusively. In ad-
periments. Kumada coupling processes catalyzed by first dition, competition experiments between cyclohexyl, sec-
row transition metal salts have also been found to require ondary, and primary alkyl halides showed product ratios of
excess TMEDA, however in these cases TMEDA is likely 1.25:1.15:1 and 1.20:1.00:1 with R–Br and R–Cl substrates,
coordinating to the transition metal salt.[
17,21,22]
Both pri- respectively.
Notably, the monometallic Co analogue of 1, ICo-
mary and secondary alkyl halide substrates, including iod-
ides, bromides, and chlorides were investigated. Yields of (Ph PNHiPr)3 (4), showed diminished catalytic activity
2
coupled product were obtained using GC–MS and the re- towards the Kumada coupling of 1-bromopentane with
sults for precatalysts 1–3 are shown in Table 1. No cross- nOctMgBr and comparable activity towards 2-bromopen-
coupling products were observed in the absence of Zr/Co tane (Table 2, entries 1–2). Interestingly, complex 4 was
precatalyst. Notably, the Ph P-substituted precatalyst 1 completely unreactive towards 1-chlorobutane and chloro-
2
I
showed significantly diminished activity from that of pre- cyclohexane (entries 3–4). Other monometallic Co tris-
catalysts 2 and 3. This is likely a result of both the less (phosphane) complexes including ICo(PPh3)3 and ICo-
electron-rich nature of 1 as well as the difference in the na- (PMe3)3 were equally ineffective (see Supporting Infor-
ture and reactivity of the two-electron reduction products mation). In addition, no coupling products between
[
20]
of 2 and 3.
nOctMgBr and alkyl bromides or chlorides were obtained
This catalytic system shows unusual activity towards with (triphos)CoI {triphos = 1,1,1-tris[(diphenylphos-
alkyl chlorides, although yields from reactions with alkyl phanyl)methyl]ethane}, indicating that the unusually high
iodide and bromide substrates are, in all cases, higher than yields observed for 1–3 are not simply a result of a chelate
the corresponding alkyl chlorides. While yields generally de- effect (see Supporting Information). Thus, the unusually ef-
crease in the order R–I, R–Br Ͼ R–Cl, these differences in ficient catalytic performance of catalysts 1–3 must rely, to
yields are relatively minor in some cases. For example, with some extent, on the metal···metal interactions within these
catalyst 3, only slight differences in yield are observed be- complexes.
tween 2-bromobutane and 2-chlorobutane (entries 1–2) and
between 2-iodobutane, 2-bromobutane, and 2-chlorobutane tions, the mechanism of monometallic cobalt catalysts for
entries 9–11). These modest differences in alkyl halide reac- Kumada coupling is generally believed to proceed via single
tivity imply a radical mechanism, rather than an oxidative electron transfer from the electron-rich cobalt complex to
In contrast to many Pd-catalyzed cross-coupling reac-
(
[
15–17,23]
addition mechanism. In addition, yields of coupling prod- the alkyl halide.
It is this radical mechanism that
ucts increase in the order cyclohexyl Ͼ primary Ͼ second- allows the activation of alkyl halides, whose oxidative ad-
ary, which could be attributed to a combination of radical dition is known to be sluggish. For heterobimetallic cata-
[
24]
stability and steric factors. It is also important to note that lysts 2 and 3,
the lowest yields are observed with aryl halide substrates trated for catalyst 2 in Scheme 2 based on results from stoi-
entries 13–14), consistent with the instability of the phenyl chiometric reactions as well as our observed trends in yield
we propose the radical mechanism illus-
(
2030
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Catalytic Application of Co/Zr Heterobimetallic Complexes
Table 1. Results of Kumada–Corriu–Tamao coupling using hetero-
bimetallic Zr/Co catalysts 1–3.
Table 2. Results of Kumada–Corriu–Tamao coupling using mono-
metallic cobalt catalysts 4.
[
a] Average of two values obtained via GC–MS analysis using tetra-
decane as an internal integration standard.
1
Co-N (based on H NMR and ν in IR spectrum, see
2
N2
[
19]
Supporting Information) with concomitant formation of
the homocoupling biphenyl product observed by GC–MS.
In addition, alkyl halide substrates do not react with the
dihalide precursors 1–3, suggesting that a Co /Co mecha-
nism is not operative.
I
III
Addition of alkyl halide across the highly polar metal-
metal multiple bond in intermediate 5 likely proceeds via
one electron-transfer to the alkyl halide. To confirm the for-
mation of alkyl radicals during the addition of alkyl halides
to 5, RX was added to 5 in the presence of the radical
trapping agent TEMPO (TEMPO = 2,2,6,6-tetramethyl-
[
25]
piperidine-1-oxyl). In the case of RX = benzyl chloride,
-iodopropane, EtI, and chlorocyclohexane, TEMPO-R
2
was observed by GC–MS. In a more catalytically relevant
reaction, a stoichiometric amount of TEMPO was added
to the reaction mixture of RX, 3 (5 mol-%) and TMEDA
(30 mol-%) and nOctMgBr was added slowly following the
typical catalysis procedure. In all cases, both cross-coupling
products and TEMPO-R were observed by GC–MS, with
the ratio of trapped radical to coupling product increasing
with alkyl radical stability (iPrϾCyϾnBu, see Supporting
Information). Organic radicals were not trapped by
TEMPO, however, in the absence of Grignard reagent to
accomplish the initial reduction of 3. Additional support
for a radical mechanism was obtained via stoichiometric
reaction of 6-chloro- and 6-bromo-1-hexene with reduced
complex 5. In the case of both substrates, the radical cycli-
zation product 1-methylcyclopentane was formed exclu-
sively. Under catalytic conditions (5 mol-% 3, 30 mol-%
[
a] Average of two values obtained via GC–MS analysis using tetra-
decane as an internal integration standard.
as a function of substrate. Entry into the catalytic cycle is TMEDA), however, coupling of 6-bromo-1-hexene and 6-
achieved via addition of two equivalents of RMgBr to 2 chloro-1-hexene with nOctMgBr leads to acyclic C–C cou-
(or 3), followed by reductive elimination to generate a two- pling products in 88.5 and 48.5% yield, respectively. Only a
electron reduced species, 5, analogous to the Zr–Co multi- small percentage of cyclized products were formed, im-
ply-bonded species previously reported.[ In support of plying that the coupling reaction is significantly faster than
this step, addition of two equivalents of phenylmagnesium the cyclization of the 5-hexenylradical intermediate.
19]
bromide to 2 resulted in a red/brown product with spectro-
We previously reported the products of alkyl halide ad-
scopic features identical to that of (THF)Zr(MesNPiPr ) - dition to the reduced complex 5 and found that while MeI
2
3
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W. Zhou, J. W. Napoline, C. M. Thomas
SHORT COMMUNICATION
Scheme 2. Proposed mechanism for the coupling of alkyl halides and Grignard reagents by heterobimetallic Zr/Co complexes.
leads to bridging Zr-Me species 6 with one phosphane li- actions, particularly those involving challenging alkyl chlor-
gand dissociated from Co, intramolecular C–H activation ides substrates. These catalysts, which feature inexpensive
product 7 is isolated from reactions of 5 with RX substrates and naturally abundant metals, show activity for both pri-
[
20]
where R ϶ Me.
We suspect that this difference can be mary and secondary alkyl bromides at room temperature
attributed to both sterics and to the lesser stability of the and perform modestly better than comparable monometal-
methyl radical compared to other alkyl radicals. In support lic cobalt complexes. More importantly, the Zr/Co heterobi-
of this, in reactions between MeI and 5 in the presence of metallic complexes dramatically increase the yield of cou-
TEMPO, TEMPO-Me was not detected by GC–MS and pling products with chlorides at room temperature in com-
the MeI addition product 6 was formed in high yield.
parison to monometallic Co complexes, which in most cases
Once one-electron transfer from 5 to RX occurs to gener- are completely inactive towards these substrates. Thus, both
ate an alkyl radical, we propose that it recombines with the Co and Zr are essential for catalytic activity. Future studies
one-electron oxidized bimetallic Co/Zr species. Addition of will aim at further investigating the potential bimetallic
RЈMgBr to the resulting complex, followed by subsequent mechanism leading to this remarkable activity and examin-
reductive elimination of the cross-coupling product R-RЈ ing additional new catalytic applications of heterobimetallic
would regenerate the catalytically active species 5. While complexes.
obvious questions still remain regarding the connectivity of
Supporting Information (see footnote on the first page of this arti-
key intermediates in the catalytic cycle and the role of each
transition metal center, we have strong evidence for a radi-
cal mechanism which is highly dependent on the presence
of both Zr and Co. A mechanistic study is currently un-
derway to determine whether Zr’s role is to facilitate re-
ductive elimination by withdrawing electron density from
Co or if Zr is playing a more active substrate-binding role
in this catalytic mechanism.
cle): Experimental procedures and additional tables of data.
Acknowledgments
This material is based upon work supported by the United States
Department of Energy under Award Number DE-SC0004019 and
by startup funds provided by Brandeis University. We also thank
Prof. Thomas Pochapsky and Drew Tietz for access and assistance
with their GC–MS, which was purchased with an American Recov-
ery and Reinvestment Act (ARRA) supplement to their United
States Public Health Service (USPHS) grant R01-GM44191.
Conclusions
We have begun to examine the catalytic applications of
early/late heterobimetallic Zr/Co complexes and uncovered
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2
Received: February 1, 2011
Published Online: March 29, 2011
2
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