C-C Bond Elimination from High-Valent Mn Aryl Complexes

Article abstract of DOI:10.1021/acs.organomet.1c00047

Manganese complexes have been considered as a cheap and readily available alternative to commonly used precious metal catalysts in C-C bond coupling reactions. Although high-valent Mn aryl intermediates have been proposed in such reactions, a mechanistic understanding of possible organometallic intermediates in Mn-mediated C-C coupling is still lacking due to their high reactivity. We report the synthesis of stable, isolable Mn(III) aryl complexes obtained by oxidative addition of aryl bromide or aryl chloride. These complexes react with a range of organometallic alkylating or arylating reagents (alkyl and aryl Grignard reagents, MeLi, ZnMe₂) to undergo C(sp²)-C(sp³) or C(sp²)-C(sp²) bond coupling, and a preliminary catalytic system could be demonstrated. The reagent scope and yield of the C(sp²)-C(sp³) coupled product can further be increased by addition of TEMPO as an oxidant, generating alkyl radicals.

Full text of DOI:10.1021/acs.organomet.1c00047

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C−C Bond Elimination from High-Valent Mn Aryl Complexes
Yu-Tao He, Ayumu Karimata, Olga Gladkovskaya, Eugene Khaskin, Robert R. Fayzullin, Abir Sarbajna,
and Julia R. Khusnutdinova*
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ABSTRACT: Manganese complexes have been considered as a
cheap and readily available alternative to commonly used precious
metal catalysts in C−C bond coupling reactions. Although high-
valent Mn aryl intermediates have been proposed in such reactions,
a mechanistic understanding of possible organometallic inter-
mediates in Mn-mediated C−C coupling is still lacking due to their
high reactivity. We report the synthesis of stable, isolable Mn(III)
aryl complexes obtained by oxidative addition of aryl bromide or aryl chloride. These complexes react with a range of organometallic
alkylating or arylating reagents (alkyl and aryl Grignard reagents, MeLi, ZnMe2) to undergo C(sp2)−C(sp3) or C(sp2)−C(sp2) bond
coupling, and a preliminary catalytic system could be demonstrated. The reagent scope and yield of the C(sp2)−C(sp3) coupled
product can further be increased by addition of TEMPO as an oxidant, generating alkyl radicals.
has also been proposed by Falck and co-workers as one of the
steps in Mn- or Mn/Cu(OTf)2-co-catalyzed Stille cross-
coupling.24 In more recent examples of homo- and cross-
coupling of Grignard reagents in the presence of oxygen as an
oxidant, C−C reductive elimination from MnIV bis-organyl
species has been proposed based on experimental and
theoretical studies. Another important class of reactions in
which intermediacy of either MnIII or MnIV has been
implicated is the directed C−H bond functionalization that
leads to C−C bond formation. Nakamura and Ilies reported
Mn-catalyzed alkylation of C(sp2)−H bonds using MeMgBr, in
which a (cyclometalated aryl)(alkyl)MnIII intermediate was
proposed to undergo C−C bond reductive elimination.27
Ackerman and co-workers proposed that a C−C bond
formations step occurs from a cyclometalated aryl MnIII
intermediate in Mn-catalyzed C−H bond arylation or
alkylation.28,29 Interestingly, Ar-Ar elimination from MnIV has
been proposed by Uzelac et al. in Mn-catalyzed homocoupling,
and MnIII species were isolated from the reaction mixtures
containing MnII aryl complexes under O2.30 However, to the
best of our knowledge, direct observation of the C−C bond
coupling step from isolated MnIII or MnIV aryl complexes has
not been reported, although the intermediacy of MnIV diaryl
complexes in C−C bond coupling has been demonstrated by
Taillefer and co-workers by electrospray ionization mass
spectrometry.31
INTRODUCTION
■
Transition-metal-catalyzed C−C bond coupling is one of the
most powerful and appealing methods for the construction of
C−C bonds in synthetic chemistry.1,2 For many decades,
precious metals, in particular palladium complexes, have been
predominant as highly efficient homogeneous catalysts in this
transformation.3 The commonly proposed mechanism of
palladium-catalyzed cross-coupling typically involves two-
electron oxidative addition, transmetalation, and reductive
elimination as crucial steps in the catalytic cycle.4
The replacement of precious metals with abundant, cheap,
and less toxic first-row transition metals has recently become a
perennial goal of increasing urgency in applied synthetic
chemistry.5−12 Despite this, Mn-catalyzed cross-coupling of
organic halides with organometallic reagents remains relatively
underdeveloped. There are notable examples of Mn-catalyzed
cross-coupling and homocoupling reactions reported by
Cahiez,13−20 Madsen,21,22 Rueping,23 Falck,24 and others.25
However, a mechanistic understanding of Mn-catalyzed C−C
bond formation reactions is complicated by the paramagnetism
of the vast majority of Mn complexes and intermediates due to
the large variety of available oxidation states to this metal, and
the frequently encountered low stability of organomanganese
compounds that leads to a larger number of paramagnetic
decomposition products.12 In particular, the C−C bond
elimination from Mn has sometimes been proposed to occur
via either MnIII or MnIV organometallic intermediates. For
example, in the homocoupling of alkenyl lithium derivatives
reported by Cahiez, Normant et al., the C−C elimination step
was proposed to occur via an initial formation of a MnIV
species, followed by bond homolysis and reductive elimination
from MnIII organometallic intermediates.26 Intermediacy of
high-valent Mn species in C(sp3)−C(sp2) bond elimination
Special Issue: Organometallic Solutions to Challenges
in Cross-Coupling
Received: January 26, 2021
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Scheme 2. Synthesis of (tBuN3C)MnIII(X)(Y) Complexes
Recently, we reported the isolation and characterization of
(aryl)MnIII complexes stabilized by chelation to the macro-
cyclic pyridinophane tBuN3C− ligand (Scheme 1).32 These
Scheme 1. Oxidative Addition and Reductive Elimination of
Ar-X Using (tBuN3C)Mn Aryl Complexes
complexes enabled us to study direct Ar−Br oxidative addition
to a MnI complex in the presence of light, to give stable and
fully characterized (tBuN3C)MnIII monoaryl complexes. We
also observed the subsequent oxidatively induced two-electron
nonradical reductive elimination. Notably, Ar−X (X = Br, I,
CN) bond elimination did not occur directly from MnIII
complexes, presumably due to the lack of a driving force to
prevent the reverse Ar−X bond oxidative addition and high
stability. Thus, these stable aryl MnIII complexes served as
convenient model compounds to study C−heteroatom bond
oxidative addition and demonstrated the necessity of one-
electron oxidation to induce aryl−X bond elimination.
In this work, we decided to study the possibility of C−C
bond coupling from stable isolated MnIII aryl complexes in the
absence and presence of oxidants. Notably, unlike in the case
of Ar-X elimination which did not occur from MnIII, we
observed C−C bond formation even from MnIII aryl complexes
in the presence of methylating or arylating reagents even in the
absence of oxidants, albeit with moderate or low efficiency and
limited by the alkylating reagent scope. Interestingly, we found
that addition of TEMPO or other one-electron oxidants to the
aryl MnIII complex in the presence of alkylating agents
promotes more selective and efficient aryl−C(sp3) bond
elimination, presumably via an alternative pathway involving
high-valent MnIV intermediates. This study confirms that
(aryl)MnIII complexes can be considered as possible
intermediates in C−C bond coupling. However, there is an
alternative pathway for Ar−C(sp3) bond coupling that is
strongly affected by the presence of oxidative additives.
previous study.32 Therefore, we decided to test whether the
formation of 1 can be achieved under thermal conditions in the
absence of UV light. Indeed, heating a mixture of tBuN3CBr
and MnBr(CO)5 in refluxing dichloroethane or toluene
solution at 110 °C for 16 h also produced 1, albeit in lower
isolated yields, 32% and 16%, respectively.
We further examined the reactivity of aryl chloride derivative
and reacted a chloro-substituted pyridinophane ligand
tBuN3CCl with MnCl(CO)5 in THF under UV light
irradiation, as photochemical conditions gave the optimal
yield of the desired product in the case of aryl bromide. Aryl
chloride tBuN3CCl was synthesized by the reaction of 2-chloro-
1,3-bis(bromomethyl)benzene with 2,6-bis(tert-butylamino-
methyl)pyridine in THF. The expected dichloro complex 2,
was obtained in 22% isolated yield after complexation with the
Mn precursor under standard conditions and recrystallization
(Scheme 2). This indicates that, although aryl chloride
undergoes oxidative addition, it is significantly less reactive
compared to the bromide analogue. The structure of the
dichloride complex 2 was confirmed by single-crystal X-ray
diffraction (Figure 1a). The octahedral complex 2 is
characterized by the positional C1/N1 disordering in the
crystal.
RESULTS AND DISCUSSION
■
Synthesis of (Aryl)MnIII Complexes. We have previously
reported the synthesis of complex 1 via oxidative addition of an
aryl bromide tBuN3CBr to MnBr(CO)5 at room temperature
(RT) under mercury lamp irradiation in 1,2-dichloroethane
(DCE) as a solvent (Scheme 1).32 Screening of solvents
showed that comparable yields can be obtained when the
reaction is performed in THF to afford 1 in 51% isolated yield
(Scheme 2). We hypothesized that the role of UV light was to
remove CO ligands from the Mn center, and that the oxidative
addition occurs by a nonradical pathway as confirmed by the
In a similar way, we attempted the synthesis of mixed chloro
bromo complexes by the oxidative addition of tBuN3CBr to
MnCl(CO)5 and the oxidative addition of tBuN3CCl to
B
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formation must be preceded by oxidation with a strong one-
electron oxidant.32 As C−C bond elimination is a different
type of reaction, where the metal center in the intermediate has
stronger σ-donor ligands, we set out to investigate whether
MnIII complexes are capable of C−C bond elimination directly,
in the absence of any oxidants. We hypothesized that the
reaction of complex 1 with common organometallic reagents
might lead to the initial transmetalation to form MnIII aryl alkyl
or diaryl complexes, followed by the C−C reductive
elimination (Scheme 3).
Scheme 3. Proposed C−C Elimination from (tBuN3C)MnIII
Complexes
Figure 1. ORTEP of complexes 2 (a) and 3 (b) at 70% probability
level according to single-crystal X-ray diffraction data. Hydrogen
atoms and minor disorder components are omitted for clarity.
Selected interatomic distances [Å]: Mn1−Cl1 2.3087(8), Mn1−Cl2
2.3266(8), Mn1−C1 2.02(3), Mn1−N1 2.07(2), Mn1−N2 2.442(3),
Mn1−N3 2.449(2) for 2; Mn1−Br1 2.4576(14), Mn1−Cl2 2.321(2),
Mn1−C1 1.98(3), Mn1−N1 2.10(2), Mn1−N2 2.442(3), Mn1−N3
2.465(2) for 3.
MnBr(CO)5. As expected, oxidative addition of aryl bromide
afforded the product 3 in a good yield of 74%, while the
reaction with aryl chloride afforded the analogous mixed
chloro bromo complex 3 in a much lower yield of 23%. The X-
ray structure of the complex obtained by the first method is
shown in Figure 1b. The complex appeared to be almost
equally disordered with respect to Cl/Br and C1/N1 sites in
the crystal studied. Molecule 3 shows distorted octahedral
geometry at the Mn center with elongated Mn−Namine
distances (2.442(3)−2.465(2) Å) as compared to Mn−Npyridine
distances (2.10(2) Å). The Mn−Cipso bond distances in
complexes 2 (2.02(3) Å) and 3 (1.98(3) Å) are comparable to
that previously reported for complex 1 (2.027(14) Å). The
analogous structure was established for complex 3 obtained by
the oxidative addition of tBuN3CCl to MnBr(CO)5, and its X-
ray structure is shown in Figure S60 (see the Supporting
Information (SI)). Besides single-crystal X-ray diffraction,
complexes 2 and 3 were characterized by UV−vis, IR
spectroscopy, high-resolution mass spectrometry (HRMS),
and elemental analysis. Complex 3 shows two peaks at
440.1641 and 484.1138 (z = 1) assigned to [M − Br]+ and [M
− Cl]+, respectively, displaying the expected isotopic patterns.
Similarly, two peaks at 440.1637 and 484.1119 were also
observed in complex 3 obtained by the inverted halogen
precursor method.
We reacted complex 1 with 3 equiv of MeMgBr in THF
solution in the absence of any additives at room temperature
(RT). Attempts to isolate or spectroscopically detect trans-
metalation intermediates either at RT or low temperature were
not successful, and the reaction proceeded immediately to
undergo C−C bond coupling and give the expected C−C
coupling product, tBuN3CMe, which was obtained after
quenching the excess MeMgBr with aqueous ammonium
chloride and basic workup to remove Mn residues (58% crude
NMR yield, Table 1). The C−C coupling product was further
isolated and characterized by NMR and HRMS. The low yield
of the desired C−C coupling product is likely due to the
formation of the protonated ligand tBuN3CH as a side-product,
obtained in 28% NMR yield after workup of the reaction
mixture. Reaction selectivity was decreased when only 1 equiv
of MeMgBr was used, giving tBuN3CMe and tBuN3CH in 48%
and 46% yields, respectively (entry 2).
Under analogous conditions, with 3 equiv of MeMgBr,
dichloro complex 2 gave a 56% yield of tBuN3CMe and a 39%
yield of tBuN3CH (entry 3).
The effective magnetic moment of new complexes 2 and 3 in
solution measured by the Evans method in CD2Cl2 solution
was determined as 4.71 and 4.78 μB, consistent with the
presence of a high-spin d4 MnIII center (S = 2), similar to
previously reported complex 1. The magnetic susceptibility
measurements in the solid state for 2 and 3 also have χMT
values of 3.1−3.2 T·cm3·mol−1 and 2.9−3.1 T·cm3·mol−1,
respectively, in the temperature range from 10 to 300 K,
corresponding to a high-spin d4 center (μeff of 5.0−5.1 and
4.8−4.9 μB, respectively).
The formation of tBuN3CH likely results from quenching
starting material, aryl complex 1, with aqueous ammonia
solution used to remove an excess of methylating reagent.
Thus, if a typical workup procedure involving treatment with
aqueous NH4Cl solution and extraction is applied to complex
1 in the absence of methylating agents, formation of tBuN3CH
is also detected. Although the alternative route to the
formation of tBuN3CH could involve formation of aryl radical,
the reaction with MeMgBr under typical conditions (RT, 16 h)
in THF-d8 showed that the tBuN3CH byproduct is formed
exclusively and no deuterated product tBuN3CD was detected
by GC-MS, ESI-MS, or NMR.
C−C Elimination from MnIII Complexes without
Oxidants. Our previous study of Ar−X (X = Br, I, or CN)
reductive elimination from MnIII showed that Ar−X bond
C
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−80 °C, followed by slow warming up to RT. Under these
conditions, a higher yield of methylation product was obtained,
while formation of tBuN3CH was significantly suppressed,
leading to more selective reaction (entry 5).
Table 1. C−C Coupling from Complexes 1, 2, and 3 in the
Presence of Organomagnesium, Zinc, and Lithium Reagents
a
without Oxidants
We have also tested the reactivity with other methylating
reagents, ZnMe2 and MeLi. In these cases, lower yields of the
C−C coupling product tBuN3CMe were obtained under
analogous conditions. In the case of MeLi, low temperature
also had a beneficial effect, leading to higher yield of
tBuN3CMe and suppressed formation of tBuN3CH as compared
to the analogous reaction at RT (entries 8 and 9), whereas no
significant effect of temperature was observed for ZnMe2
(entries 6 and 7), probably due to its lower reactivity
compared to MeLi and MeMgBr. Notably, in the presence
i
of PrMgBr and (allyl)MgBr, no desired C−C bond coupling
product was obtained, with the major product after workup
being tBuN3CH (Table 1).
We have further tested the possibility of aryl−aryl coupling
and reacted complex 1 with 3 equiv of PhMgBr in THF at RT.
This resulted in the formation of 67% of phenylated product,
tBuN3CPh, after 16 h. The reaction with less nucleophilic
pentafluorophenyl Grignard reagent, C6F5MgBr, gave no
product at RT. However, when complex 1 was heated in the
presence of 6 equiv of C6F5MgBr in benzene at 80 °C, the
pentafluorophenyl derivative, tBuN3CC6F5, was obtained in
49% yield.
These results show that, unlike Ar-X reductive elimination,
aryl−C(sp3) and aryl−C(sp2) bond elimination in (tBuN3C)-
MnIII complexes does not necessarily require an oxidant and
likely proceeds directly via the MnIII oxidation state, although
the proposed methyl-aryl or bis(aryl) intermediates could not
be isolated or observed, presumably due to fast C−C coupling
following transmetalation (Scheme 3). We attempted a
different approach to obtain such intermediates using MeMn-
(CO)5 as a precursor and reacted it with tBuN3CBr under UV
irradiation (Scheme 4). If the reactivity of MeMn(CO)5 is
Scheme 4. Reaction of MeMn(CO)5 with tBuN3CBr
similar to that of MnBr(CO)5, we could expect formation of
the Ar−Br oxidative addition product where a methyl group is
present instead of one bromo ligand. As anticipated, when
MeMn(CO)5 was reacted in the presence of 1 equiv of
tBuN3CBr under UV light irradiation in THF or toluene
solution, the reaction proceeded to form the C−C coupled
product, tBuN3CMe, in 7−13% yield. No intermediates could
be isolated, suggesting that, once the expected aryl methyl
complex is formed, it immediately undergoes C−C elimi-
nation.
a
Reaction was performed in THF for 16 h at RT in the presence of 3
b
equiv of alkylating or arylating reagent. Yields were determined after
quenching excess reagent by NMR integration against 1,3,5-
trimethoxybenzene as an internal standard. 1 equiv of MeMgBr
was added at RT. Methylating reagent was added at −80 °C, and
then the reaction mixture was slowly warmed up to RT. Not
detected. Heated at 80 °C in benzene solution for 40 h in the
presence of 6 equiv of C6F5MgBr.
c
d
e
f
The low yield of the coupling product could be due to only
one Me group being present in the oxidative addition product,
while the reaction of 1 with excess MeMgBr could lead to
replacement of both bromo ligands with the Me groups.
However, formation of a small amount of (tBuN3C)MnIIIMe2
in this reaction cannot be excluded if Me group exchange
Although the standard reaction time of 16 h was used in all
experiments to ensure completion, the reaction in the case of
MeMgBr occurs within several minutes at RT. Therefore, we
also attempted methylation by slow addition of MeMgBr at
D
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between two monomethyl intermediates is involved, similar to
the Schlenk equilibrium33 present in solutions of Grignard
reagents. Alternatively, the low yield in the case of the
MeMn(CO)5 reaction could be due to the amount of the
isomer in which Ar and Me groups are present in mutual cis-
positions.32
Scheme 6. Control Experiment in the Absence of Mn
Complexes
Unfortunately, the MnI product of C−C bond coupling
could not be isolated due to the absence of stabilizing ligands
and basic workup of the reaction mixture leading to
precipitation of all Mn residues or their removal to the
aqueous phase.
5, bottom). The ESI-MS analysis of the reaction mixture
confirmed the presence of the characteristic peak with m/z
486.1114 corresponding to the [M − Br]+ fragment of
complex 1, along with peaks of tBuN3CMe, tBuN3CBr, and
tBuN3CH (see the SI). This experiment also shows that the
reaction of MnIBr(CO)5 with tBuN3CBr occurs prior to C-C
elimination. When MnIBr(CO)5 was reacted with MeMgBr in
the absence of tBuN3CBr, no MeMnI(CO)5 was observed.
C−C Elimination in the Presence of Oxidants. To
further test the mechanism of C−C coupling from complex 1
in the reaction with MeMgBr, we attempted to perform the
reaction in the presence of TEMPO as a radical trap.
Surprisingly, when C−C coupling from 1 using MeMgBr (3
equiv) as a methylating reagent was performed in the presence
of 1.1 equiv of TEMPO, we observed almost clean formation
of the C−C coupling product in 92% yield, while no
protonation product, tBuN3CH, was detected under these
conditions (Table 2). Notably, the yield was high even in the
Overall, these experiments indicate that C−C coupling
proceeds upon the reaction of common organometallic
reagents with isolated MnIII complexes in the absence of
oxidative additives or chlorinated solvents that could act as
oxidants, suggesting that the C−C coupling step likely occurs
at the MnIII aryl center, although the selectivity of this reaction
remains limited.
To demonstrate that the proposed sequence of oxidative
addition/transmetalation/C−C elimination steps may give rise
to a catalytic turnover, we performed a catalytic experiment
using a mixture of only 10 mol % of MnBr(CO)5, tBuN3CBr,
and 3 equiv of Grignard reagent in THF solution (Scheme 5,
Scheme 5. Mn-Catalyzed tBuN3CBr Methylation with
MeMgBr
Table 2. C−C Coupling from Complex 1 in the Presence of
a
TEMPO
equiv of
MeMgBr
equiv of
TEMPO
tBuN3CMe,
b
tBuN3CH,
b
entry
% yield
% yield
1
2
3
4
5
6
7
3.0
3.0
3.0
3.0
3.0
2.0
1.0
none
0.1
1.1
2.0
3.0
2.0
1.0
58
72
92
93
97
90
59
28
15
n.d.
n.d.
n.d.
n.d.
13
c
top). Interestingly, we observed catalytic turnover (TON 8.5)
under these conditions, leading to the formation of tBuN3CMe
in 85% yield after 20 h. This result confirms that (tBuN3C)Mn
complexes not only are suitable model compounds to study
Ar−X and Ar−C bond formation but also mimic Mn-catalyzed
Ar−C bond coupling. Notably, ICP-MS analysis of the catalyst
showed that no platinum group metals were present in the
sample at the detectable level (see the SI).
The control experiment showed that no reaction occurs in
the absence of Mn complexes when tBuN3CBr is treated with
an excess of MeMgBr, ZnMe2, or MeLi in THF under
analogous conditions (Scheme 6), confirming that manganese
complexes are indeed required to mediate the cross-coupling
reaction. To further confirm that the C−C coupling is
mediated by the formation of MnIII aryl species, we performed
the reaction in the presence of equivalent amounts of
MnIBr(CO)5, tBuN3CBr, and 3 equiv of MeMgBr (Scheme
a
Reaction was performed in THF for 16 h at RT in the presence of
indicated amounts of MeMgBr and TEMPO. Yields were
determined after quenching excess reagent by NMR integration
against 1,3,5-trimethoxybenzene as an internal standard. Not
b
c
detected.
presence of 1.1 equiv of TEMPO and only slightly increased
when the amount of TEMPO was changed to 2 and 3 equiv,
showing that even 1.1 equiv was sufficient to promote selective
C−C bond formation (Table 2). A more selective C−C
coupling was also observed in the reaction where only 1 equiv
of MeMgBr and 1 equiv of TEMPO were used, giving 59% of
tBuN3CMe and 13% of protonated product tBuN3CH, as
E
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compared to the reaction with 1 equiv of MeMgBr in the
absence of TEMPO, which gave only 43% of tBuN3CMe (vide
supra).
Encouraged by these results, we also examined if the scope
of alkylating reagents could be improved using these
conditions (Table 3). Interestingly, in the presence of 2
When MeMgBr was allowed to react with 1 equiv of TEMPO
in the absence of complex 1, we observed the formation of Me-
TEMPO in 52% yield, which indicates that the Me radical is
formed under these conditions trapped by TEMPO. This
observation is consistent with the reported detailed studies of
the reactivity of TEMPO with alkyl organometallic com-
pounds.34−37 TEMPO is known to react with alkyl organo-
metallic species first via a one-electron oxidation to produce an
alkyl radical, which is then trapped by another equivalent of
TEMPO (Scheme 7) to produce a Me-TEMPO adduct.
Table 3. C−C Coupling from Complexes 1, 2, and 3 with
Other Alkylating and Arylating Reagents in the Presence of
a
TEMPO as an Oxidant
Scheme 7. Reactivity of TEMPO with Grignard Reagents in
the Absence of Mn Complexes (This Work)
Independently prepared Me-TEMPO did not react with
complex 1 under typical reaction conditions. Interestingly,
aryl Grignard reagents react by a different pathway which does
involve the formation of high energy free aryl radicals.34
Indeed, the reaction of PhMgBr with 1 equiv of TEMPO did
not produce Ph-TEMPO, but led to homocoupling to give
biphenyl, as is consistent with literature precedents (Scheme
8).
Scheme 8. Literature-Reported Reactivity of TEMPO with
Alkylmetal Reagents
a
b
Reaction was performed in THF for 16 h at RT. Yields were
determined after quenching excess reagent by NMR integration
against 1,3,5-trimethoxybenzene as an internal standard.
equiv of TEMPO, the C−C coupling product was also
i
obtained using PrMgBr and (allyl)MgBr as coupling reagents
in 47% and 72% yields, respectively. High yield of methylation
product was also observed using ZnMe2 (95%). The reaction
with MeLi in the presence of TEMPO produced tBuN3CMe in
a moderate 40% yield, as compared to only 22% obtained in
the absence of additives. High yields of tBuN3CMe were also
obtained using the similar dichloro and chloro bromo
complexes 2 and 3 as coupling partners.
Incongruently, the presence of TEMPO did not play a
significant role in the promotion of PhMgBr reaction, and
tBuN3CPh was obtained in almost the same yield with and
without TEMPO.
On the basis of these observations, we propose that the
increased yield of C−C coupling product from complex 1 in
the presence of TEMPO could involve a different pathway via
the formation of an alkyl radical, which could then either react
with a MnIII center to give a (tBuN3C)MnIV(Me)X2 (X =
halogen or Me) intermediate (Path 1a, Scheme 9) or directly
attack a Mn-bound aryl ligand without changes in Mn
oxidation state (Path 1b, Scheme 9). The absence of the
boosting TEMPO effect in the reaction with aryl Grignard
reagents could be due to the absence of free radicals that would
To clarify the role of TEMPO, we first tested the reactivity
of complex 1 with 2 equiv of TEMPO; however, no reaction
was observed, and the starting material remained unchanged.
F
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Scheme 9. Proposed Mechanism of C−C Coupling in the
Presence of TEMPO or Other Oxidants
Table 4. C−C Coupling from Complex 1 in the Presence of
a
MeMgBr and One-Electron Oxidants
a
Reaction was performed in THF for 16 h at RT in the presence of 3
b
equiv of MeMgBr and 2 equiv of oxidant. Yields were determined
react with a MnIII complex, further suggesting that the
formation of alkyl radicals may be a prerequisite for the
observed more efficient C(sp2)−C(sp3) coupling reactivity.
The fast reactions of Me or other alkyl radicals with
transition metals, leading to their formal one-electron
oxidation and M−C bond formation, have been studied
extensively for some first-row transition metals,38,39 and a
similar mechanism was proposed for C(sp3)−C(sp3) bond
elimination from a monomethyl PdIII complex via oxidation to
PdIV by a Me radical.40 Although the MnIII complex 1 is six-
coordinate, with a κ4-bound tBuN3C− ligand, a vacant
coordination site in Path 1b could form via dissociation of a
bulky tBu-substituted amine group. The hemilability of tBu-
amine groups in structurally similar tBuN4-pyridinophane
ligands has been studied extensively, showing facile inter-
conversion between the κ4-bound and κ3-bound ligand
coordination modes.41−43
Interestingly, higher yields of C−C coupling product were
also observed in the presence of some other one-electron
oxidants including CuII(OTf)2, ferrocenium hexafluorophos-
phate, and thianthrenyl hexachloroantimontate, whereas the
yield remained unchanged or decreased in the presence of
silver tetrafluoroborate and tris(4-bromophenyl)aminium
hexachloroantimonate (Magic Blue), respectively, compared
to the reaction in the absence of any additives (Table 4). The
increased yield of tBuN3CMe coupling product in the presence
of other one-electron oxidants could similarly be explained by
the generation of a Me radical. However, we cannot exclude an
alternative mechanism (Path 2, Scheme 9) via initial
transmetalation, followed by oxidation to a MnIV species and
oxidatively induced reductive elimination similar to the
mechanism proposed by us for Ar-X (X = Br, I, CN)
elimination in the presence of strong oxidants (Scheme 1).
after quenching excess reagent by NMR integration against 1,3,5-
trimethoxybenzene as an internal standard. Not detected.
c
several examples of Mn-catalyzed C−C bond coupling
reactions. In this work, we demonstrate that MnIII aryl species
are indeed viable intermediates in C−C bond elimination and
they undergo C−C bond coupling with a range of alkylating
and arylating organometallic reagents under mild conditions.
Although the couplings occur in the absence of any oxidants,
the presence of oxidative additives, in particular TEMPO,
significantly improves the reaction selectivity and the scope of
alkylating agents, presumably via oxidation to MnIV and/or
alkyl radical formation. Our results suggest that two pathways,
via either a MnIII or a MnIV center, may be operative in C−C
coupling bond elimination reactions. While we were able to
develop an initial catalytic protocol via the former pathway, the
latter leads to greater yield and selectivity despite requiring a
sacrificial oxidant. We are currently focusing on trying to
develop a more practical catalytic system via both the MnIII
and MnIV oxidation states for a greater variety of substrates.
EXPERIMENTAL SECTION
■
All manipulations, unless stated otherwise, were performed using
Schlenk or glovebox techniques under a dry argon atmosphere.
Anhydrous solvents were dispensed from an MBRAUN solvent
purification system and degassed before use. Anhydrous deuterated
solvents were purchased from Eurisotop and stored over 4 Å
molecular sieves. All chemicals unless noted otherwise were purchased
from major commercial suppliers (TCI, Sigma-Aldrich, and
NacalaiTesque) and used without purification. tBuN3CBr was
synthesized as described previously.32,44 2-Chloro-1,3-bis-
(bromomethyl)benzene was synthesized according to the literature
procedure.45 2,6-Bis(tert-butylaminomethyl)pyridine was synthesized
according to the modified literature method.46 MnCl(CO)5 and
47
48
MeMn(CO)5 were obtained according to literature procedures.
SUMMARY AND CONCLUSION
■
Instrumentation. NMR spectra were measured on JEOL
ECZ600R 600 MHz, JEOL ECZ400S 400 MHz, Bruker Avance II
400 MHz, and Bruker Avance III Neo 500 MHz (CryoProbe)
spectrometers. ESI-MS measurements were performed on a Thermo
Scientific ETD apparatus. Elemental analyses were performed using
an Exeter Analytical CE440 instrument. FT-IR spectra were measured
Mn-mediated C−C bond coupling reactions attract attention
as an inexpensive alternative to the use of precious metal in C−
C cross-coupling reactions. The intermediacy of MnIII or MnIV
species in C−C bond coupling has been a subject of debate,
and such complexes have been proposed as intermediates in
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using an Agilent Cary 630 with an ATR module in an argon-filled
glovebox. The following abbreviations are used for describing FT-IR
spectra: s (strong), m (medium), w (weak), br (broad). UV−vis
absorbance spectra were collected using an Agilent Cary 60
instrument. The magnetic properties were measured using a 9T
physical properties measurement system PPMS Dynacool from
Quantum Design, equipped with the vibrating sample magnetometer
(VSM) option, in a 2−300 K temperature range under a magnetic
field of 10 000 Oe. For these measurements, samples were ground
into powder and placed in plastic capsules. The Evans method
measurements were performed in the coaxial NMR tube at 298 K;
diamagnetic correction was applied.49
X-ray Structure Determination Details. The X-ray diffraction
data were collected on a Rigaku XtaLab PRO instrument in an ω-scan
mode with a PILATUS3 R 200 K hybrid pixel array detector and
MicroMax-003 microfocus X-ray tubes using Cu Kα (1.54184 Å) or
Mo Kα (0.71073 Å) radiation at low temperature. Images were
indexed and integrated using the CrysAlisPro (version 1.171.41.93a)
data reduction package. Data were corrected for systematic errors and
absorption using the ABSPACK module: Numerical absorption
correction based on Gaussian integration over a multifaceted crystal
model and empirical absorption correction based on spherical
harmonics according to the point group symmetry using equivalent
reflections. The GRAL module was used for the analysis of systematic
absences and space-group determination. All structures were solved
by the direct methods using SHELXT-2018/250 and refined by the
full-matrix least-squares on F2 using SHELXL-2018/3.51 Non-
hydrogen atoms were refined anisotropically. The hydrogen atoms
were inserted at the calculated positions and refined as riding atoms.
The positions of the hydrogen atoms of methyl groups were found
using rotating group refinement with idealized tetrahedral angles. The
disorder was resolved using free variables and reasonable restraints on
geometry and anisotropic displacement parameters. The crystal
structures of 3 obtained by different methods were refined as two-
component inversion twins.
were unique, Rint = 0.0746, Rσ = 0.0526; completeness to θmax 97.6%.
The refinement of 296 parameters with 113 restraints converged to R1
= 0.0626 and wR2 = 0.1667 for 4193 reflections with I > 2σ(I) and R1
= 0.0643 and wR2 = 0.1679 for all data with S = 1.075 and residual
electron density, ρmax/min = 1.191 and −0.862 e Å−3. The crystals were
grown by diethyl ether vapor diffusion to a dichloromethane solution.
Synthesis of tBuN3CCl. Synthesis of 2,6-Bis(tert-butylaminome-
thyl)pyridine. A 500 mL round-bottom flask equipped with a
magnetic stirring bar and a reflux condenser was charged with
chloroform (100 mL); tert-butylamine (100 mL, 950 mmol, 50 equiv)
was added to stirred chloroform slowly, in several portions. A solution
of 2,6-bis(bromomethyl)pyridine (5 g, 19 mmol, 1 equiv) in CHCl3
(150 mL) was slowly added to the stirred solution (Caution!
exothermic) at room temperature. The resulting solution was heated at
50 °C for 5 h under a N2 atmosphere. The sample of the reaction
mixture after heating for 5 h was evaporated to dryness and
redissolved in CDCl3 to check the completeness of the reaction;
according to 1H NMR, no starting material was present after 5 h and
the diamine was the only pyridine-containing product present in
solution. The reaction mixture was cooled down to RT; the
chloroform solution was washed with saturated aqueous NaHCO3
solution (2 × 150 mL) and water (150 mL). The organic layer was
separated and dried over MgSO4. The solvents were removed by
rotary evaporation at RT to give a colorless or pale yellow oil, which
was further dried under high vacuum for 1 h at RT and stored under
1
N2 at −20 °C. Yield 4.58 g, 97%. H NMR (CDCl3, 300 MHz), δ
(ppm): 7.56 (t, J = 7.5 Hz, 1H, Py CHpara), 7.17 (d, J = 7.5 Hz, 2H,
Py CHmeta) 3.86 (s, 4H, CH2), 1.67 (br s, 2H, NH), 1.19 (s, 18H,
tBu).
Synthesis of tBuN3CCl. A round-bottom flask was charged with 50
mL of toluene, 30 mL of 10 wt % Na2CO3 solution, and 2,6-bis(tert-
butylaminomethyl)pyridine (1.10 g, 4.4 mmol, 1 equiv). The flask was
supplemented with a two-neck extension; one neck was connected to
a reflux condenser, and the other one with an addition funnel. The
reaction mixture was heated up to 80 °C under a nitrogen
atmosphere. A solution of 2-chloro-1,3-bis(bromomethyl)benzene
(1.18 g, 4.0 mmol, 0.9 equiv) in 50 mL of toluene was added dropwise
through the addition funnel to the reaction mixture over 3 h. After
complete addition, the reaction mixture was heated with stirring at 90
°C for 36 h and then cooled down. The aqueous layer was discarded,
and the pale yellow toluene layer was washed three times with
saturated Na2CO3 aqueous solution and dried over anhydrous
Na2SO4. The solvent was removed, and the solid residue was washed
with a minimal amount of ethanol and filtered off. The solid product
was recrystallized from warm Et2O solution and cooled down in a
freezer overnight to give a pure white crystalline product, which was
filtered off and dried under vacuum. Yield 450 mg (1.17 mmol, 29%).
1H NMR (500 MHz, CDCl3) δ 7.13 (t, J = 7.6 Hz, 1H), 6.82 (d, J =
7.4 Hz, 2H), 6.75 (d, J = 7.6 Hz, 2H), 6.59 (t, J = 7.4 Hz, 1H), 4.15
(dd, J = 16.7, 13.3 Hz, 4H), 3.96 (d, J = 12.9 Hz, 2H), 3.52 (d, J =
13.4 Hz, 2H), 1.32 (s, 18H). 13C NMR (126 MHz, CDCl3) δ 159.86,
137.26, 136.84, 135.00, 131.13, 124.99, 121.38, 56.77, 55.79, 51.38,
27.71. HRMS (ESI) (m/z): calculated for C23H32ClN3 [M + H]+
386.2358; found 386.2335.
Crystallographic Data for 2. C23H32Cl2MnN3, brown prism
(0.111 × 0.061 × 0.046 mm3), formula weight 476.35; orthorhombic,
Pbca (No. 61), a = 14.38378(7) Å, b = 11.29423(6) Å, c =
27.85495(19) Å, V = 4525.14(5) Å3, Z = 8, Z′ = 1, T = 95(2) K, dcalc
= 1.398 g cm−3, μ(Cu Kα) = 7.016 mm−1, F(000) = 2000; Tmax/min
=
1.000/0.636; 44 277 reflections were collected (4.419° ≤ θ ≤
78.086°, index ranges: −18 ≤ h ≤ 18, −14 ≤ k ≤ 13, −27 ≤ l ≤ 34),
4819 of which were unique, Rint = 0.0277, Rσ = 0.0158; completeness
to θmax 99.4%. The refinement of 275 parameters with 84 restraints
converged to R1 = 0.0466 and wR2 = 0.1086 for 4789 reflections with
I > 2σ(I) and R1 = 0.0468 and wR2 = 0.1087 for all data with S =
1.159 and residual electron density, ρmax/min = 0.544 and −0.394 e
Å−3. The crystals were grown by diethyl ether vapor diffusion to a
dichloromethane solution.
Crystallographic Data for 3. C23H32Br0.88Cl1.12MnN3, red prism
(0.194 × 0.170 × 0.094 mm3), formula weight 515.62; orthorhombic,
Pca21 (No. 29), a = 14.6467(3) Å, b = 13.8349(3) Å, c = 11.2247(3)
Å, V = 2274.53(9) Å3, Z = 4, Z′ = 1, T = 95(2) K, dcalc = 1.506 g cm−3,
μ(Mo Kα) = 2.278 mm−1, F(000) = 1064; Tmax/min = 1.000/0.629;
26 895 reflections were collected (2.719° ≤ θ ≤ 32.230°, index
ranges: −19 ≤ h ≤ 21, −19 ≤ k ≤ 20, −15 ≤ l ≤ 16), 7151 of which
were unique, Rint = 0.0339, Rσ = 0.0344; completeness to θmax 93.3%.
The refinement of 296 parameters with 113 restraints converged to R1
= 0.0321 and wR2 = 0.0737 for 6532 reflections with I > 2σ(I) and R1
= 0.0366 and wR2 = 0.0747 for all data with S = 1.055 and residual
electron density, ρmax/min = 0.423 and −0.415 e Å−3. The crystals were
grown by diethyl ether vapor diffusion to a dichloromethane solution.
Crystallographic Data for 3 Obtained by the Oxidative Addition
of tBuN3CCl to MnBr(CO)5. C23H32Br0.84Cl1.16MnN3, red prism (0.223
× 0.126 × 0.103 mm3), formula weight 513.86; orthorhombic, Pca21
(No. 29), a = 14.6407(4) Å, b = 13.8107(4) Å, c = 11.2124(4) Å, V =
2267.12(12) Å3, Z = 4, Z′ = 1, T = 95(2) K, dcalc = 1.505 g cm−3,
μ(Cu Kα) = 7.830 mm−1, F(000) = 1061; Tmax/min = 1.000/0.368;
14 985 reflections were collected (3.200° ≤ θ ≤ 77.818°, index
ranges: −18 ≤ h ≤ 18, −15 ≤ k ≤ 17, −13 ≤ l ≤ 13), 4393 of which
Synthesis of (tBuN3C)MnIIICl2 (2). 38.5 mg of tBuN3CCl (0.1
mmol) and 23 mg of MnCl(CO)5 (0.1 mmol) were combined in a
flame-dried Schlenk flask inside a glovebox, and 2 mL of THF was
added to give a yellow suspension. The flask was taken outside the
glovebox and stirred in a water bath in front of a mercury lamp. The
reaction vessel was subjected to vacuum for 1 s every hour, then
stirred under static vacuum, and after 3 h, the reaction was then
stirred under a static vacuum overnight. After 13 h, the solution color
changed to wine-red and the entire solvent was evaporated under
reduced pressure. The solid obtained was redissolved in a minimal
amount of dichloromethane and filtered through Celite. The filtrate
was evaporated under reduced pressure to yield a red solid which was
washed three times with copious amounts of ether (ca. 3 mL) and
then dried under vacuum. Deep red crystals were grown by vapor
diffusion of ether into a dichloromethane solution of the complex
(about 2 mL of DCM); yield of isolated product (tBuN3C)MnIIICl2
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(2) 10.4 mg, 22% yield. Evans method (CD2Cl2, 298 K): μeff = 4.71
μB. ESI-HRMS of C23H32Cl2N3Mn in MeOH (m/z): calculated for
[C23H32ClN3Mn]+, ([M − Cl]+) 440.1660; found 440.1632 (z = 1).
Anal. Calcd. for MnC23H32Cl2N3: C, 57.99; H, 6.77; N, 8.82. Found:
C, 57.74; H, 6.65; N, 8.73. UV−vis, λ, nm (ε, M−1 cm−1), CH2Cl2:
534 (328), 301 (3412), 235 (8934). FT-IR (ATR, solid, cm−1): ν
2966 (w), 2893 (w), 1601 (w), 1576 (w),1428 (w), 1376 (s), 1189
(s), 909 (w), 849 (w), 772 (s).
Trimethoxybenzene (0.05 mmol, 1.0 equiv) was then added to this
mixture as an internal standard, and NMR yields of the products were
determined in C6D6 (see the SI). Then the above crude product was
purified by flash column chromatography on a silica gel (CH2Cl2/
MeOH = 20/1−15/1) give the desired product.
For low temperature experiments, the solution of 1 (0.05 mmol) in
THF (8 mL) was placed in a Schlenk tube, cooled down to −80 °C
using a methanol-dry ice cooling bath. The solution of MeMgBr (3.0
M in diethyl ether) (0.05 mL, 0.150 mmol, 3 equiv) was added slowly
to the reaction mixture under argon gas flow. The reaction mixture
was warmed up to RT slowly over the course of 4 h, then stirred at
RT for another 16 h. The workup procedure was carried out as
described above. The same procedure was followed for the reactions
with MeLi and ZnMe2.
General Procedure for C−C Coupling with Oxidant. 0.05
mmol of a manganese complex (1, 2, or 3) was dissolved in 2 mL of
THF. Then, 15.6 mg of TEMPO (2 equiv) and 3.0 equiv of an
organometal reagent were added and stirred at room temperature in a
glovebox for 16 h. The vial was then taken out of the glovebox and
quenched by addition of a saturated aqueous solution of ammonium
chloride (0.2 mL); then a 2 mL saturated solution of K2CO3 was
added to it and vigorously stirred for 30 min. The mixture was
extracted with ethyl acetate (3 × 10 mL). The combined organic
extracts were washed with saturated brine (15 mL) and dried over
Na2SO4. The solvent was removed by rotary evaporation. 1,3,5-
Trimethoxybenzene (0.05 mmol, 1.0 equiv) was then added to this
mixture as an internal standard, and NMR yields of the products were
determined in C6D6 (see the SI). Then the above crude product was
purified by flash column chromatography on a silica gel (CH2Cl2/
MeOH = 20/1−15/1) to give the desired product.
Isolation and Characterization of C−C Coupling Products.
tBuN3CMe. Following the general procedure for C−C coupling with
oxidant, the crude product of the reaction was collected and purified
by flash column chromatography on silica gel (CH2Cl2/MeOH, 20:1)
to provide tBuN3CMe as a white solid in 93% isolated yield. The
desired product was confirmed by ESI-(HR)MS and NMR. 1H NMR
(500 MHz, C6D6) δ 6.98−6.95 (m, 3H), 6.84 (t, J = 7.4 Hz, 1H),
6.61 (d, J = 7.6 Hz, 2H), 4.14 (d, J = 12.0 Hz, 2H), 3.73 (d, J = 13.2
Hz, 2H), 3.65 (d, J = 11.8 Hz, 2H), 3.59 (d, J = 14.3 Hz, 2H), 2.84 (s,
3H), 1.15 (s, 18H). 13C NMR (126 MHz, C6D6) δ 161.15, 138.55,
135.08, 130.98, 128.68, 124.74, 120.32, 56.10, 53.73, 27.73, 18.17.
ESI-(HR)MS of the product from methanol solution (m/z):
calculated for M*H+, C24H35N3, 366.2904; found 366.2884.
Synthesis of (tBuN3C)MnIIIBrCl (3) by Oxidative Addition of
tBuN3CBr. 42.9 mg of tBuN3CBr (0.1 mmol) and 23 mg of
MnCl(CO)5 (0.1 mmol) were combined in a flame-dried Schlenk
flask inside a glovebox, and 2 mL of THF was added to give a yellow
suspension. The flask was taken outside the glovebox and stirred in a
water bath in front of a mercury lamp. The reaction vessel was
subjected to vacuum for 1 s every hour, then stirred under static
vacuum, and after 3 h, the reaction was then stirred under a static
vacuum overnight. After 13 h, the solution appeared wine-red and the
entire solvent was evaporated under reduced pressure. The solid
obtained was redissolved in a minimal amount of dichloromethane
and filtered through Celite. The filtrate was evaporated under reduced
pressure to yield a red solid which was washed three times with
copious amounts of ether (ca. 3 mL) and then dried under vacuum.
Deep red crystals were grown by vapor diffusion of ether into a
dichloromethane solution of the complex (about 2 mL of DCM);
yield of isolated product (tBuN3C)MnIIIBrCl (3) 38.2 mg, 74% yield.
HRMS (ESI) in MeOH for C23H32BrClN3Mn (m/z): calculated for
[C23H32ClN3Mn]+ ([M − Br]+) 440.1660; found 440.1641 (z = 1)
and calculated for [C23H32BrN3Mn]+ ([M − Cl]+): 484.1155; found:
484.1138 (z = 1), both peaks showing expected isotopic patterns.
Evans method (CD2Cl2, 298 K): μeff = 4.78 μB. Anal. Calcd. for
Mn1C23H32BrClN3: C, 53.04; H, 6.19; N, 8.07. Found: C, 53.45; H,
6.05; N, 8.07. UV−vis, λ, nm (ε, M−1 cm−1), CH2Cl2: 539 (854), 304
(6637), 260 (10817). FT-IR (ATR, solid, cm−1): ν 2968 (w), 2898
(w), 1601 (w), 1462 (w), 1429 (w), 1376 (s), 1188 (s), 910 (w), 849
(w), 770 (s).
Synthesis of (tBuN3C)MnIIIBrCl (3) by Oxidative Addition of
tBuN3CCl. 19.3 mg of tBuN3CCl (0.05 mmol) and 13.7 mg of
MnBr(CO)5 (0.05 mmol) were combined in a flame-dried Schlenk
flask inside a glovebox, and 2 mL of THF was added to give a yellow
suspension. The flask was taken outside the glovebox and stirred in a
water bath in front of a mercury lamp. The reaction vessel was
subjected to vacuum for 1 s every hour, then stirred under static
vacuum, and after 3 h, the reaction was then stirred under a static
vacuum overnight. After 13 h, the solution turned wine-red and the
entire solvent was evaporated under reduced pressure. The solid
obtained was redissolved in a minimal amount of dichloromethane
and filtered through Celite. The filtrate obtained was evaporated
under reduced pressure to yield a red solid which was washed three
times with copious amounts of ether (ca. 3 mL) and then dried under
vacuum. Deep red crystals were grown by vapor diffusion of ether into
a dichloromethane solution of the complex (about 2 mL of DCM);
yield of isolated product (tBuN3C)MnIIIBrCl (3) 6.0 mg, 23% yield.
HRMS (ESI) in MeOH for C23H32BrClN3Mn (m/z): calculated for
[C23H32ClN3Mn]+ ([M − Br]+) 440.1660; found: 440.1637 (z = 1)
and calculated for [C23H32BrN3Mn]+ ([M − Cl]+): 484.1155; found:
484.1119 (z = 1), both peaks showing expected isotopic patterns.
General Procedure for C−C Coupling without Oxidant. 0.05
mmol of a manganese complex (1, 2, or 3) was dissolved in 2 mL of
THF. Then, 3.0 equiv of an organometal reagent were added and the
reaction mixture was stirred at RT in a glovebox for 16 h. The vial was
then taken out of the glovebox and quenched by addition of a
saturated aqueous solution of ammonium chloride (0.2 mL); then a 2
mL saturated solution of K2CO3 was added to it and vigorously stirred
for 30 min. Workup using basic aqueous solutions was needed to
remove all unreacted Mn residues after reaction and avoid the
presence of unreacted paramagnetic species in solution that can
potentially lead to broadening of NMR spectra. The mixture was
extracted with ethyl acetate (3 × 10 mL). The combined organic
extracts were washed with saturated brine (15 mL) and dried over
Na2SO4. The solvent was removed by rotary evaporation. 1,3,5-
tBuN3CiPr. 28.3 mg (0.05 mmol) of (tBuN3C)MnIIIBr2 (1) was
dissolved in 2 mL of THF. Then, 15.6 mg of TEMPO (2 equiv) and
75 μL of isopropylmagnesium chloride (2.0 M in THF, 3 equiv) were
added to the mixture and stirred at room temperature in a glovebox
for 16 h. The mixture was quenched by addition of a saturated
aqueous solution of ammonium chloride (0.2 mL); then a 2 mL
saturated solution of K2CO3 was added to it and vigorously stirred for
30 min. The mixture was extracted with ethyl acetate (3 × 10 mL).
The combined organic extracts were washed with saturated brine (15
mL) and dried over Na2SO4. The ethyl acetate was completely
evaporated by a rotavapor, and the solid left was isolated by a short
flash column chromatography on silica gel with DCM/MeOH (15/1)
1
to provide tBuN3CiPr (9.2 mg, 47%). H NMR (500 MHz, C6D6) δ
7.00−6.97 (m, 3H), 6.66−6.63 (m, 3H), 4.13−4.09 (m, 2H), 3.92−
3.88 (m, 4H), 3.77−3.71 (m, 2H), 3.59−3.55 (m, 1H), 1.83 (s, 6H),
1.19 (s, 18H). 13C NMR (126 MHz, C6D6) δ 160.99, 138.61, 134.65,
131.85, 125.12, 120.54, 57.72, 56.01, 31.26, 28.00, 24.55, 23.39. ESI-
(HR)MS of the product from methanol solution (m/z): calculated for
[M + H]+, C26H39N3, 394.3217; found m/z 394.3215.
tBuN3CC3H5. 28.3 mg (0.05 mmol) of (tBuN3C)MnIIIBr2 (1) was
dissolved in 2 mL of THF. Then, 15.6 mg of TEMPO (2 equiv) and
150 μL of allylmagnesium bromide (1 M in diethyl ether, 3 equiv)
were added to the mixture and stirred at room temperature for 16 h.
The vial was then taken out of the glovebox and quenched by addition
of a saturated aqueous solution of ammonium chloride (0.2 mL); then
a 2 mL saturated solution of K2CO3 was added to it and vigorously
stirred for 30 min. The mixture was extracted with EtOAc (3 × 10
I
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mL). The combined organic extracts were washed with brine (15 mL)
and dried over Na2SO4. The solvent was removed by rotary
evaporation, and a 72% yield of product tBuN3CC3H5 was obtained
and confirmed by the NMR spectrum. This product was not stable
and decomposed after isolation from column chromatography, but it
Accession Codes
CCDC 2056056, 2056057, and 2056899 contain the
supplementary crystallographic data for this paper. These
data can be obtained free of charge via www.ccdc.cam.ac.uk/
data_request/cif, or by emailing data_request@ccdc.cam.ac.
uk, or by contacting The Cambridge Crystallographic Data
Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44
1223 336033.
1
was stable in solution for a few days. H NMR (400 MHz, C6D6) δ
7.01−6.97 (m, 3H), 6.92−6.88 (m, 1H), 6.60 (d, J = 7.6 Hz, 2H),
6.20−6.11 (m, 1H), 5.06−5.05 (m, 2H), 4.58 (d, J = 5.5 Hz, 2H),
4.22 (d, J = 12.0 Hz, 2H), 3.71 (d, J = 14.5 Hz, 2H), 3.63−3.59 (m,
4H), 1.14 (s, 18H). 13C NMR (101 MHz, C6D6) δ 161.15, 140.06,
138.32, 135.18, 131.80, 125.42, 120.34, 114.28, 56.09, 55.70, 53.66,
33.98, 27.65. ESI-(HR)MS of the product from methanol solution
(m/z): calculated for [M + H]+, C26H37N3, m/z 392.3060; found
392.3058.
AUTHOR INFORMATION
Corresponding Author
■
Julia R. Khusnutdinova − Coordination Chemistry and
Catalysis Unit, Okinawa Institute of Science and Technology
Graduate University, Onna-son, Okinawa 904-0495, Japan;
orcid.org/0000-0002-5911-4382; Email: juliak@oist.jp
tBuN3CPh. 28.3 mg (0.05 mmol) of (tBuN3C)MnIIIBr2 (1) was
dissolved in 2 mL of tetrahydrofuran. Then, 15.6 mg of TEMPO (2
equiv) and 50 μL of phenylmagnesium bromide (3 M in diethyl ether,
3 equiv) were added and stirred at room temperature in a glovebox
for 16 h. The vial was then taken out of the glovebox and quenched
by addition of a saturated aqueous solution of ammonium chloride
(0.2 mL); then a 2 mL saturated solution of K2CO3 was added to it
and vigorously stirred for 30 min. The mixture was extracted with
ethyl acetate (3 × 10 mL). The combined organic extracts were
washed with saturated brine (15 mL) and dried over Na2SO4. The
solvent was removed by rotary evaporation, and a 71% yield was
shown from crude NMR using 1,3,5-trimethoxybenzene as an internal
standard. The crude product was purified by flash column
chromatography on silica gel (DCM/MeOH, 20:1) to provide
Authors
Yu-Tao He − Coordination Chemistry and Catalysis Unit,
Okinawa Institute of Science and Technology Graduate
University, Onna-son, Okinawa 904-0495, Japan
Ayumu Karimata − Coordination Chemistry and Catalysis
Unit, Okinawa Institute of Science and Technology Graduate
University, Onna-son, Okinawa 904-0495, Japan
Olga Gladkovskaya − Coordination Chemistry and Catalysis
Unit, Okinawa Institute of Science and Technology Graduate
University, Onna-son, Okinawa 904-0495, Japan
Eugene Khaskin − Coordination Chemistry and Catalysis
Unit, Okinawa Institute of Science and Technology Graduate
University, Onna-son, Okinawa 904-0495, Japan;
orcid.org/0000-0003-1790-704X
Robert R. Fayzullin − Arbuzov Institute of Organic and
Physical Chemistry, FRC Kazan Scientific Center, Russian
Academy of Sciences, Kazan 420088, Russian Federation;
orcid.org/0000-0002-3740-9833
Abir Sarbajna − Coordination Chemistry and Catalysis Unit,
Okinawa Institute of Science and Technology Graduate
University, Onna-son, Okinawa 904-0495, Japan;
orcid.org/0000-0003-2478-5044
1
tBuN3CC6H5 (12.8 mg, 60%) as a white solid. H NMR (500 MHz,
C6D6) δ 9.81 (d, J = 7.1 Hz, 1H), 7.57 (t, J = 7.5 Hz, 1H), 7.25−7.22
(m, 2H), 7.01−6.96 (m, 4H), 6.81 (t, J = 7.5 Hz, 1H), 6.66 (s, 2H),
3.85 (s, 4H), 3.76 (s, 4H), 1.00 (s, 18H). 13C NMR (126 MHz,
C6D6) δ 161.54, 142.04, 137.93, 134.84, 132.04, 130.97, 128.89,
127.57, 127.22, 126.64, 120.30, 56.75, 55.92, 53.29, 27.72. ESI-
(HR)MS of the product from methanol solution (m/z): calculated for
[M + H]+, C29H38N3, m/z 428.3060; found 428.3049.
tBuN3CC6F5. 28.3 mg (0.05 mmol) of (tBuN3C)MnIIIBr2 (1) was
weighed out in a scintillation vial inside a glovebox, and 2 mL of
benzene was added and stirred for 20 min at RT. To the red solution
was added 600 μL (0.3 mmol) of pentafluorophenylmagnesium
bromide solution (0.5 M in diethyl ether, 6 equiv) in one portion, and
the mixture was allowed to stir for 40 h at 80 °C over which time
period the color of the solution gradually changed to brown and the
reaction was stopped. The vial was then taken out of the glovebox,
and then 2 mL of a saturated aqueous solution of K2CO3 was added
to it and vigorously stirred for 30 min. The aqueous solution was
extracted with ethyl acetate, filtered, and then dried over anhydrous
Na2SO4. The ethyl acetate was completely evaporated by a rotavapor,
and the solid left was isolated by a short flash column chromatography
on silica gel with hexane/ethyl acetate (2/1−1.5/1) to provide
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.organomet.1c00047
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
1
tBuN3CC6F5 (12.6 mg, 49%). H NMR (400 MHz, C6D6) δ 7.10−
This work was supported by JSPS Kakenhi Grant 20K15305.
We thank the Instrumental Analysis Section (Dr. Michael Roy
and Dr. Yoshiteru Iinuma) and Engineering Support Section
(Dr. Hyung Been Kang) for technical support. The authors
acknowledge the Okinawa Institute of Science and Technology
Graduate University for start-up funding.
7.04 (m, 3H, ArH), 6.95 (t, J = 7.6 Hz, 1H, ArH), 6.49 (d, J = 7.6 Hz,
2H, ArH), 3.70−3.65 (m, 2H, CH2), 3.54−3.46 (m, 4H, CH2), 3.27−
3.21 (m, 2H, CH2), 0.85 (s, 18H). 13C NMR (126 MHz, C6D6) δ
161.06, 146.14, 141.11, 135.29, 131.90, 128.68, 119.95, 56.21, 54.70,
53.52, 27.09. 19F NMR (376 MHz, C6D6) δ −106.51, −117.34,
−138.00 (dt, J = 25.4, 6.1 Hz), −158.34, −164.83 (d, J = 111.4 Hz).
19F NMR (376 MHz, C6D6) δ −106.5, −117.3, −138.0 (dt, J = 25.4,
6.1 Hz), −158.3, −164.8 (d, J = 111.4 Hz). ESI-(HR)MS of the
product from methanol solution (m/z): calculated for [M + H]+,
C29H33F5N3, m/z 518.2589; found 518.2601.
REFERENCES
■
(1) Beller, M.; Varela-Fernandez, A.; Vries, J. G.; Man Wong, S.;
Ming So, C.; Kwong, F. Y. Cross Coupling Reactions. Appl.
Homogeneous Catal. Organomet. Compd. (3rd Ed.) 2017, 2, 411−464.
(2) de Meijere, A.; Diederich, F. Metal-Catalyzed Cross-Coupling
Reactions; Wiley-VCH, 2004.
ASSOCIATED CONTENT
■
(3) Negishi, E.; de Meijere, A. Handbook of Organopalladium
Chemistry for Organic Synthesis; Wiley, 2003.
(4) Johansson Seechurn, C. C. C.; Kitching, M. O.; Colacot, T. J.;
Snieckus, V. Palladium-Catalyzed Cross-Coupling: A Historical
Contextual Perspective to the 2010 Nobel Prize. Angew. Chem., Int.
Ed. 2012, 51, 5062−5085.
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.organomet.1c00047.
Experimental details and characterization data (PDF)
J
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Article
(5) Carney, J. R.; Dillon, B. R.; Thomas, S. P. Recent Advances of
Manganese Catalysis for Organic Synthesis. Eur. J. Org. Chem. 2016,
2016, 3912−3929.
(27) Sato, T.; Yoshida, T.; Al Mamari, H. H.; Ilies, L.; Nakamura, E.
Manganese-Catalyzed Directed Methylation of C(sp2)-H Bonds at 25
°C with High Catalytic Turnover. Org. Lett. 2017, 19, 5458−5461.
(28) Zhu, C.; Oliveira, J. C. A.; Shen, Z.; Huang, H.; Ackermann, L.
Manganese(II/III/I)-Catalyzed C−H Arylations in Continuous Flow.
ACS Catal. 2018, 8, 4402−4407.
(6) Bauer, I.; Knölker, H.-J. Iron Catalysis in Organic Synthesis.
Chem. Rev. 2015, 115, 3170−3387.
(7) Bolm, C.; Legros, J.; Le Paih, J.; Zani, L. Iron-Catalyzed
Reactions in Organic Synthesis. Chem. Rev. 2004, 104, 6217−6254.
(8) Liu, W.; Ackermann, L. Manganese-Catalyzed C−H Activation.
ACS Catal. 2016, 6, 3743−3752.
(9) Hu, Y.; Zhou, B.; Wang, C. Inert C−H Bond Transformations
Enabled by Organometallic Manganese Catalysis. Acc. Chem. Res.
2018, 51, 816−827.
(10) Liu, W.; Groves, J. T. Manganese Catalyzed C−H
Halogenation. Acc. Chem. Res. 2015, 48, 1727−1735.
(11) Bedford, R. B. How Low Does Iron Go? Chasing the Active
Species in Fe-Catalyzed Cross-Coupling Reactions. Acc. Chem. Res.
2015, 48, 1485−1493.
(12) Valyaev, D. A.; Lavigne, G.; Lugan, N. Manganese organo-
metallic compounds in homogeneous catalysis: Past, present, and
prospects. Coord. Chem. Rev. 2016, 308, 191−235.
(13) Bottoni, A.; Cahiez, G.; Calvaresi, M.; Moyeux, A.; Giacinto, P.;
Miscione, G. P. A mechanistic insights into manganese-catalyzed
oxidative homocoupling reactions of Grignard reagents: A computa-
tional DFT investigation. J. Organomet. Chem. 2016, 814, 25−34.
(14) Cahiez, G.; Duplais, C.; Buendia, J. Manganese-Catalyzed
Oxidative Cross-Coupling of Grignard Reagents with Oxygen as an
Oxidant. Angew. Chem., Int. Ed. 2009, 48, 6731−6734.
(15) Cahiez, G.; Duplais, C.; Buendia, J. Chemistry of
Organomanganese(II) Compounds. Chem. Rev. 2009, 109, 1434−
1476.
(16) Cahiez, G.; Gager, O.; Lecomte, F. Manganese-Catalyzed
Cross-Coupling Reaction between Aryl Grignard Reagents and
Alkenyl Halides. Org. Lett. 2008, 10, 5255−5256.
(17) Cahiez, G.; Moyeux, A.; Buendia, J.; Duplais, C. Manganese- or
Iron-Catalyzed Homocoupling of Grignard Reagents Using Atmos-
pheric Oxygen as an Oxidant. J. Am. Chem. Soc. 2007, 129, 13788−
13789.
(18) Cahiez, G.; Luart, D.; Lecomte, F. Unexpected Cross-Coupling
Reaction between o-Chloroaryl Ketones and Organomanganese
Reagents. Org. Lett. 2004, 6, 4395−4398.
(19) Cahiez, G.; Lepifre, F.; Ramiandrasoa, P. Manganese-catalyzed
substitution of activated aryl halides (X = Cl, Br, and F) and aryl
ethers by organomagnesium reagents. Synthesis 1999, 1999, 2138−
2144.
(20) Alami, M.; Ramiandrasoa, P.; Cahiez, G. Stereoselective
Manganese-Catalyzed Coupling Reaction of Conjugated Chloroe-
nynes and Chlorodienes with Grignard Reagents. Synlett 1998, 09,
325−327.
(21) Santilli, C.; Beigbaghlou, S. S.; Ahlburg, A.; Antonacci, G.;
Fristrup, P.; Norrby, P.-O.; Madsen, R. The Manganese-Catalyzed
Cross-Coupling Reaction and the Influence of Trace Metals. Eur. J.
Org. Chem. 2017, 2017, 5269−5274.
(22) Antonacci, G.; Ahlburg, A.; Fristrup, P.; Norrby, P.-O.; Madsen,
R. Manganese-Catalyzed Cross-Coupling of Aryl Halides and
Grignard Reagents by a Radical Mechanism. Eur. J. Org. Chem.
2017, 2017, 4758−4764.
(23) Rueping, M.; Ieawsuwan, W. A manganese-catalyzed cross-
coupling reaction. Synlett 2007, 2007, 247−250.
(29) Liu, W.; Cera, G.; Oliveira, J. C. A.; Shen, Z.; Ackermann, L.
MnCl2-Catalyzed C−H Alkylations with Alkyl Halides. Chem. - Eur. J.
2017, 23, 11524−11528.
(30) Uzelac, M.; Mastropierro, P.; de Tullio, M.; Borilovic, I.;
Tarrés, M.; Kennedy, A. R.; Aromí, G.; Hevia, E. Tandem Mn−I
Exchange and Homocoupling Processes Mediated by a Synergistically
Operative Lithium Manganate. Angew. Chem., Int. Ed. 2021, 60,
3247−3253.
(31) Liu, Y.; Berges, J.; Zaid, Y.; Chahdi, F. O.; Van Der Lee, A.;
Harakat, D.; Clot, E.; Jaroschik, F.; Taillefer, M. Aerobic and Ligand-
Free Manganese-Catalyzed Homocoupling of Arenes or Aryl Halides
via in Situ Formation of Aryllithiums. J. Org. Chem. 2019, 84, 4413−
4420.
(32) Sarbajna, A.; He, Y.-T.; Dinh, M. H.; Gladkovskaya, O.;
Rahaman, S. M. W.; Karimata, A.; Khaskin, E.; Lapointe, S.; Fayzullin,
R. R.; Khusnutdinova, J. R. Aryl−X Bond-Forming Reductive
Elimination from High-Valent Mn−Aryl Complexes. Organometallics
2019, 38, 4409−4419.
(33) Smith, M. B. March’s Advanced Organic Chemistry: Reactions,
Mechanisms, and Structure; Wiley, 2020.
̈
(34) Murarka, S.; Möbus, J.; Erker, G.; Muck-Lichtenfeld, C.;
Studer, A. TEMPO-mediated homocoupling of aryl Grignard
reagents: mechanistic studies. Org. Biomol. Chem. 2015, 13, 2762−
2767.
(35) Whitesides, G. M.; Newirth, T. L. Reaction of n-butyllithium
and 2,2,6,6-tetramethylpiperidine nitroxyl. J. Org. Chem. 1975, 40,
3448−3450.
(36) Nagashima, T.; Curran, D. P. Reactions of Tempo with
Alkylsamarium and Other Organometallic Reagents. Synlett 1996,
1996, 330−332.
́
(37) Budny-Godlewski, K.; Kubicki, D.; Justyniak, I.; Lewinski, J. A
New Look at the Reactivity of TEMPO toward Diethylzinc.
Organometallics 2014, 33, 5093−5096.
(38) Espenson, J. H. Chemistry of organochromium(III) complexes.
Acc. Chem. Res. 1992, 25, 222−227.
(39) Kochi, J. K. Electron-transfer mechanisms for organometallic
intermediates in catalytic reactions. Acc. Chem. Res. 1974, 7, 351−360.
(40) Khusnutdinova, J. R.; Rath, N. P.; Mirica, L. M. Stable
Mononuclear Organometallic Pd(III) Complexes and Their C−C
Bond Formation Reactivity. J. Am. Chem. Soc. 2010, 132, 7303−7305.
(41) Meneghetti, S. P.; Lutz, P. J.; Kress, J. Neutral and Cationic
Palladium(II) Complexes of a Diazapyridinophane. Structure,
Fluxionality, and Reactivity toward Ethylene. Organometallics 2001,
20, 5050−5055.
(42) Khusnutdinova, J. R.; Rath, N. P.; Mirica, L. M. The
Conformational Flexibility of the Tetradentate Ligand tBuN4 is
Essential for the Stabilization of (tBuN4)PdIII Complexes. Inorg.
Chem. 2014, 53, 13112−13129.
(43) Patil, P. H.; Filonenko, G. A.; Lapointe, S.; Fayzullin, R. R.;
Khusnutdinova, J. R. Interplay between the Conformational Flexibility
and Photoluminescent Properties of Mononuclear
Pyridinophanecopper(I) Complexes. Inorg. Chem. 2018, 57, 10009−
10027.
(24) Dakarapu, R.; Falck, J. R. Stereospecific Stille Cross-Couplings
Using Mn(II)Cl2. J. Org. Chem. 2018, 83, 1241−1251.
(25) Kang, S.-K.; Kim, J.-S.; Choi, S.-C. Copper- and Manganese-
Catalyzed Cross-Coupling of Organostannanes with Organic Iodides
in the Presence of Sodium Chloride. J. Org. Chem. 1997, 62, 4208−
4209.
(26) Cahiez, G.; Bernard, D.; Normant, J. F. Catalysis by
manganese(II). I. Coupling reactions of iodoalkenes to dienes
initiated by organolithium reagents in the presence of manganese(II).
J. Organomet. Chem. 1976, 113, 99−106.
(44) Zhou, W.; Schultz, J. W.; Rath, N. P.; Mirica, L. M. Aromatic
Methoxylation and Hydroxylation by Organometallic High-Valent
Nickel Complexes. J. Am. Chem. Soc. 2015, 137, 7604−7607.
̀
(45) Casitas, A.; Canta, M.; Sola, M.; Costas, M.; Ribas, X.
Nucleophilic Aryl Fluorination and Aryl Halide Exchange Mediated
by a CuI/CuIII Catalytic Cycle. J. Am. Chem. Soc. 2011, 133, 19386−
19392.
(46) Gemel, C.; Folting, K.; Caulton, K. G. New Approach to Ru(II)
Pincer Ligand Chemistry. Bis(tert-butylaminomethyl)pyridine Coor-
dinated to Ruthenium(II). Inorg. Chem. 2000, 39, 1593−1597.
K
https://doi.org/10.1021/acs.organomet.1c00047
Organometallics XXXX, XXX, XXX−XXX

Organometallics
pubs.acs.org/Organometallics
Article
(47) Motterlini, R. A.; Mann, B. E.; Scapens, D. A. WO 2008003953
A3, 2008.
(48) Kadassery, K. J.; Lacy, D. C. Pentacarbonylmethylmanganese-
(I) as a synthon for Mn(I) pincer catalysts. Dalton Trans. 2019, 48,
4467−4470.
(49) McQuarrie, D. A.; Cox, H.; Simon, J. D.; Choi, J. Physical
Chemistry: A Molecular Approach; University Science Books, 1997.
(50) Sheldrick, G. M. SHELXT - Integrated space-group and crystal-
structure determination. Acta Crystallogr., Sect. A: Found. Adv. 2015,
71, 3−8.
(51) Sheldrick, G. M. Crystal structure refinement with SHELXL.
Acta Crystallogr., Sect. C: Struct. Chem. 2015, 71, 3−8.
L
https://doi.org/10.1021/acs.organomet.1c00047
Organometallics XXXX, XXX, XXX−XXX