Tandem Mn–I Exchange and Homocoupling Processes Mediated by a Synergistically Operative Lithium Manganate

Article abstract of DOI:10.1002/anie.202013153

Pairing lithium and manganese(II) to form lithium manganate [Li₂Mn(CH₂SiMe₃)₄] enables the efficient direct Mn–I exchange of aryliodides, affording transient (aryl)lithium manganate intermediates which in turn undergo spontaneous C?C homocoupling at room temperature to furnish symmetrical (bis)aryls in good yields under mild reaction conditions. The combination of EPR with X-ray crystallographic studies has revealed the mixed Li/Mn constitution of the organometallic intermediates involved in these reactions, including the homocoupling step which had previously been thought to occur via a single-metal Mn aryl species. These studies show Li and Mn working together in a synergistic manner to facilitate both the Mn–I exchange and the C?C bond-forming steps. Both steps are carefully synchronized, with the concomitant generation of the alkyliodide ICH₂SiMe₃ during the Mn–I exchange being essential to the aryl homocoupling process, wherein it serves as an in situ generated oxidant.

Full text of DOI:10.1002/anie.202013153

A Journal of the Gesellschaft Deutscher Chemiker
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Accepted Article
Title: Tandem Mn-I exchange and homocoupling processes mediated
by a synergistically operative lithium manganate
Authors: Eva Hevia, Marina Uzelac, Pasquale Mastropierro, Marco
De Tullio, Ivana Borilovic, Marius Tarres, Alan Kennedy, and
Guillem Aromi
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Tandem Mn-I exchange and homocoupling processes mediated
by a synergistically operative lithium manganate
Marina Uzelac,*[a] Pasquale Mastropierro,[b] Marco de Tullio,[c] Ivana Borilovic,[d,e] Marius Tarres,[c] Alan
R. Kennedy,[c] Guillem Aromí[d,f] and Eva Hevia*[b,c]
Dedicated to the memory of Gerard Cahiez.
[a]
[b]
Dr M. Uzelac
EastCHEM School of Chemistry, University of Edinburgh,
Edinburgh EH9 3FJ, United Kingdom
Dr M. de Tullio, Dr M. Tarres, Dr A. R. Kennedy,
WestCHEM, Department of Pure and Applied Chemistry
University of Strathclyde
295 Cathedral Street, G1 1XL, Glasgow, UK
P. Mastropierro, Prof. E. Hevia
Department für Chemie und Biochemie, Universität Bern
CH3012, Bern, Switzerland
E-mail; eva.hevia@dcb.unibe.ch
Dr I. Borilovic, Prof G. Aromí
Departament de Química Inorgànica
Universitat de Barcelona
Diagonal 645, 08028 Barcelona, Spain
Dr I. Borilovic
[c]
[d]
[e]
[f]
Department of Chemistry
University of Manchester and Photon Science Institute,
Oxford Road, Manchester, M13 9PL, UK
Prof G. Aromí
Institute of Nanoscience and Nanotechnology
of the University of Barcelona (IN2UB)
Supporting information for this article is given via a link at the end of the document
Abstract: Pairing lithium and manganese(II) to form lithium
manganate [Li2Mn(CH2SiMe3)4] (2b) enables the efficient direct Mn-I
exchange of aryliodides, affording transient (aryl)lithium manganate
intermediates which in turn undergo spontaneous C-C homocoupling
at room temperature to furnish a range of symmetrical (bis)aryls in
good yields under mild reaction conditions. Combining EPR with X-
ray crystallographic studies light has been shone on the mixed Li/Mn
constitution of the organometallic intermediates involved in these
reactions, including the homocoupling step which had previously been
thought to occur via single-metal Mn aryl species. These studies have
illuminated how Li and Mn work together in a synergistic manner to
facilitate both the Mn-I exchange and the C-C bond forming steps.
Both steps are carefully synchronised, with the alkyliodide ICH2SiMe3
concomitantly generated during the Mn-I exchange, being essential to
enable the aryl homocoupling process by acting as an in-situ
generated oxidant.
Ce with Li, can also promote low polarity metal-halogen exchange
to access M-aryl intermediates that can in turn be employed in C-
C bond forming processes, usually with the aid of transition metal
catalysis.[2] While Mn(II) organometallic compounds have shown
considerable promise in organic synthesis, with seminal
contributions from Cahiez and Normant on their applications in
acylation, addition and other C-C bond forming processes,[3] their
ability to promote Mn-halogen exchange with aromatic halides
has not yet been established. This is somehow surprising
considering the comparable electronegativities and sizes of Mg
and Mn(II) as well as the reactivity patterns mentioned above for
which these high spin Mn(II) reagents have been previously
described as soft Grignard reagents.[4] Earlier work by Oshima[5]
and Hosomi[6] has shown that lithium manganates can undergo
metal-halogen exchange with allylbromides and other activated
substrates such as gem-dibromocyclopropanes although the
constitutions of the organometallic intermediates and the
exchange reagent have remained concealed.
In parallel to these studies, early seminal work by Cahiez has
shown that mixed salts such as MnCl2.2LiCl can catalyse the
homocoupling of aryl Grignard reagents using atmospheric
oxygen,[4],[7] providing a sustainable route to synthetically relevant
symmetrical bis(aryl) molecules.[8] More recent work by Tailler has
also proposed that in situ generated ArLi species can undergo
homocoupling in the presence of catalytic amounts of MnCl2.[9]
Supported by computational studies,[9],[10] these reactions have
been proposed to occur via formation of putative MnAr2
intermediate species which in turn can undergo oxidative
homocoupling in the presence of oxygen. However, limited
Introduction
Metal-halogen exchange constitutes one of the most powerful
and widely used methods for regioselective functionalization of
aromatic halides. Represented usually as an equilibrium, these
kinetic processes are driven by the formation of the more
stabilised aryl organometallic intermediates.[1] For decades this
methodology has been essentially the exclusive domain of the
classical highly polar organometallic reagents organolithium RLi
or Grignard reagents RMgX. However more recent reports have
shown that pairing a lower polarity metal M such as Zn, La, Sm or
1
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tangible experimental evidence is available on the actual
formation of these compounds which are hypothesised to form by
salt-metathesis in the presence of a large excess of the polar
organometallic aryl reagent.
to 20 °C (entry 1). Building on previous work in s-block
organometallic chemistry which has shown that ate activation can
enable effective Mg- and Zn-halogen exchange reactions,[15] we
next reacted equimolar amounts of 1a with triorganomanganate
LiMnR3 (2a) (prepared in situ by reaction of 3 equivalents of LiR
and MnCl2) leading to a 53% conversion after 15 min at -20 °C
(entry 3). This conversion could then be enhanced almost
quantitatively when using in-situ prepared lithium-rich manganate
Li2MnR4 (2b) (95%, entry 4) even at -78 °C. Furthermore, the
exchange also works using substoichiometric amounts of 2b
showing conversions of 86 and 94% when 0.25 and 0.33
equivalents of 2b were employed respectively, supporting the
view that the four alkyl groups present in 2b engage in the
exchange, making the process atom economical (entries 5 and 6).
It is significant that under the conditions studied these
conversions were higher than using LiR on its own (entry 2) or
using the magnesium analog of 2b, Li2MgR4 (entry 7) revealing
that under these reaction conditions Mn-I exchange occurs more
efficiently than Li-I or Mg-I exchange.
Since 2b is prepared in situ by salt metathesis with MnCl2, we
next pondered if this approach could also work using 4
equivalents of the Grignard reagent RMgCl as a precursor.
Surprisingly, no exchange was observed at lower temperatures
(from -78 to -20 °C) while allowing the reaction mixture to stir at
room temperature for 5 h showed a modest 18% conversion
(entry 8). The latter can then be boosted to 83% when adding 2
equivalents of LiCl, hinting at a crucial role for Li to facilitate this
transformation (entry 9). Further evidence was found when
assessing the influence of Lewis donors as additives when
combined with 2b. While bidentate TMEDA (N,N,N′,N′-
tetramethylethylenediamine) showed no observable effect, 12-
crown-4 which has the ability to coordinate and sequester the
lithium cations, completely shuts down the exchange process,
suggesting that the cooperation and/or close proximity between
Li and Mn may also be a key factor (entries 10 and 11).
Allowing the reaction of 1a with 0.33 equivalents of 2b to
reach room temperature and to stir for a further 5h formed
bis(aryl) 4,4’-dimethoxybiphenyl (3a) in an 87% isolated yield,
indicating that as the temperature is raised, in addition to the Mn-
I exchange taking place, a C-C bond forming homocoupling
process occurs (Scheme 1). This approach can be also extended
to a range of substituted aromatic iodides, bearing electron-
donating or electron-withdrawing groups, affording the relevant
symmetric bis(aryls) 3a-3o in good to excellent yields (33-87%
yields, Scheme 1). Steric effects seem to play a detrimental role
as indicated by the contrasting yields obtained when using
different iodotoluene substrates. Thus, 3c with the methyl group
located at the C4 position is furnished in a 74% yield, whereas a
modest 33% is obtained for 3m when starting with 2-iodotoluene.
The same trend is observed for the homocoupled anisole
derivatives 3a, 3j, and 3l (87, 68, and 60% yield respectively);
whereas no reaction is observed at all when 2-iodomesitylene
was employed. This method is also compatible with electron
withdrawing groups such as CF3 or F furnishing bis(aryls) 3e, 3f
and 3i in 73, 68, and 69% yields respectively, although in the case
of 3g containing a CO2Et substituent a significantly lower yield
was observed (30%). Interestingly, 2b also reacts with 3-
iodopyridine (1o) affording homocoupled product 3o (63%), along
with 3- monosilylpyridine 3o’. The latter is a minor product (20%)
resulting from the coupling between the C(sp2) of the substrate
Merging these two fundamental types of transformations
reactions, here we describe the first examples of direct Mn-
halogen exchange reactions of aryliodides based on aryl
manganate species that in turn can undergo oxidative
homocoupling to access synthetically valuable symmetrical
bis(aryl) compounds in good yields. In addition, structural and
spectroscopic studies on the organometallic intermediates
involved in this tandem protocol uncover some of the hitherto
unknown constitution of the intermediates involved in these
reactions.
Results and Discussion
Assessing Mn-I exchange of iodoarenes. Considering that
an important limitation to the stability of alkylmanganese
compounds is their tendency to undergo β-hydride elimination,[11]
we started our studies probing the reactivity of 4-iodoanisole (1a)
with MnR2 (R= CH2SiMe3).[12] Containing bulky monosilyl
substituents with no protons in the β-position, this bis(alkyl) Mn(II)
species has previously been used as a precursor to access
sodium and potassium alkali-metal manganates and has shown
remarkable thermal stability.[13] Our reactions were initially carried
out at -78 °C in THF (Table 1).[14]
Table 1. Optimization of the reaction conditions for the I/Mn exchange using
manganese reagents containing CH2SiMe3 ligands
I
[M]
n MRx
-78oC, THF, 15 min
MeO
MeO
1a
Entry
n
1
1
1
1
MRx
Yield[a]
1
2
Mn(CH2SiMe3)2
0[b]
LiCH2SiMe3
62(71)[c]
56[d]
95
3
LiMn(CH2SiMe3)3 (2a)
Li2Mn(CH2SiMe3)4 (2b)
Li2Mn(CH2SiMe3)4 (2b)
Li2Mn(CH2SiMe3)4 (2b)
Li2Mg(CH2SiMe3)4
4
5
0.25
86
6
0.33
0.33
0.33
0.33
0.33
0.33
94
7
82
8
4 eq Me3SiCH2MgCl + MnCl2
4 eq Me3SiCH2MgCl + MnCl2.2LiCl
Li2Mn(CH2SiMe3)4 (2b)+ 2eq TMEDA
Li2Mn(CH2SiMe3)4 (2b) + 4 eq 12-c-4
0[d](18)[e]
0[d](83)[e]
93
9
10
11
0
[a] Yields have been determined by GC analysis of reaction aliquots after an
aqueous quench using hexamethylbenzene as internal standard. Formation
only of anisole and unreacted 1a were observed. [b] 20oC. [c] Reaction
carried out using 1.32 eq of RLi. [d] -20oC. [e] When the reaction was allowed
to stir at room temperature for 5h, only homocoupled product 4,4'-dimethoxy-
1,1'-biphenyl (3a) was detected along with starting material 1a
Under these conditions homometallic MnR2 failed to promote
Mn-I exchange of 1a even when the temperature was increased
2
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10.1002/anie.202013153
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and the C(sp3) center of a CH2SiMe3 group (see Supporting
Information for details).
X-ray crystallographic studies confirmed the bimetallic
constitution of 2b.2TMEDA, exhibiting the same classical “Weiss
motif”
previously
reported
for
its
Mg
analogue
[(TMEDA)2Li2MgR4].[16] It comprises a C4-coordinated Mn atom
flanked by two TMEDA-solvated Li cations, displaying a nearly
linear Li⋯Mn⋯Li arrangement [176.082(2)°]. Each alkyl group in
the structure bridges Mn with a Li centre with an average Mn-C
distance of 2.275 Å (Figure 1i).
These structural features are typical of high-spin Mn(II)
centre and this magnetic state was confirmed by SQUID
magnetometry and EPR spectroscopy (Fig S1-S3 in Supporting
Information). 2b.2TMEDA is also isostructural with a series of
lithium manganates reported by Girolami[17] containing Me, Et or
t
CH2CH2 Bu alkyl groups although as far as we can ascertain the
reactivity of these compounds has barely been studied.
Contrastingly, showing the complexity of some metathetical
approaches, when 4 equivalents of RMgCl are reacted with MnCl2
in THF, heteroleptic mixed-metal [(THF)4MgCl2MnR2] (4) was
obtained as a crystalline solid along with variable amounts of the
adduct [(THF)2MgCl2] (Figure 1ii). Established by X-ray
crystallography, the molecular structure of 4 (Figure 1ii) displays
Mn and Mg connected by two Cl bridges with Mn completing its
distorted tetrahedral geometry with two terminal monosilyl groups;
whereas Mg is solvated by four molecules of THF giving rise to a
distorted octahedral environment. Thus, compound 4 can be
envisaged as a co-complex between MgCl2 and MnR2.[18] The
contrasting constitutions of 2b.2TMEDA and 4 when both are
prepared by reacting 4 equivalents of either RLi or RMgCl with
MnCl2 can help explain their different reactivity towards Mn-I
exchange (Table 1, entries 8 and 10), since 2b.2TMEDA in having
a Mn centre attached to four alkyl groups can be expected to be
significantly more reactive than 4 which possesses two such
anions. Consistent with this, previous work in s-block bimetallic
chemistry has shown the excellent ability of lithium tri- and tetra-
alkyl magnesiates and zincates to promote direct metal-halogen
exchange.[15]
Scheme 1. Reaction of various iodoarenes with Li2MnR4 (2b) prepared in situ
by addition of LiR to MnCl2 in a 4:1 ratio in THF (R= CH2SiMe3). Isolated yields
are given for 3a-3o, see Supporting Information for details.
Prompted by these intriguing observations we next set out
to identify the constitution of bimetallic intermediates formed in
these mixtures. Lithium manganate 2b.2TMEDA could be isolated
as a crystalline solid in two different ways: co-complexation of 2
equivalents of LiR and TMEDA with MnR2 in hexane or by salt
metathesis using a 4:1 mixture of LiR and MnCl2 in THF in the
presence of 2 equivalents of TMEDA (Figure 1i). It should be
noted that while the synthesis and EPR characterisation of 2b has
been reported by Wilkinson in a seminal paper from 1976,[12a] its
structure in the solid state has remained concealed.
Manganate-mediated aryl-aryl oxidative homocouplings.
Germane to the formation of bis(aryls) 3a-3o, work on Mn(II)-
catalysed homocoupling of ArM (M= Li, MgX) has shown that
atmospheric oxygen is required in order to facilitate the Csp2-Csp2
bond forming process.[7],[9],[10] Since our experiments were carried
out under strict inert atmosphere conditions, it should then be the
alkyl iodide Me3SiCH2I concomitantly generated during the Mn-I
exchange process which acts as an oxidant of putative in situ
generated lithium aryl manganates Li2MnAr4 (I), facilitating the
homocoupling process (Figure 2i). Previous work by Zhou has
also shown that MnCl2 can catalyse homocoupling of Grignard
reagents using dichloroethane (DCE) as an external oxidant.[19]
Interestingly in our case, the C-C bond forming step seems to
occur very quickly as soon as the temperature raises from -78 °C
to RT, thus all attempts to trap and characterize intermediates I
led to the isolation of the relevant homocoupling product as well
as to variable amounts of LiI which in the presence of TMEDA
crystallises as [{(TMEDA)LiI}2].
Figure 1. Salt-metathesis reactions of MnCl2 with (i) 4 eq of LiCH2SiMe3 and 2
eq TMEDA and (ii) with 4 eq of ClMgCH2SiMe3 to give 2b.2TMEDA and 4
respectively. Molecular structure of 2b.2TMEDA and 4 with thermal ellipsoids
drawn at the 50% probability level, all hydrogen atoms omitted for clarity. In
2b.2TMEDA minor disorder components in TMEDA ligand and SiMe3 group
have been omitted. Symmetry operator: x-, y+1, -z+2. The unit cell of 4 contains
two crystallographically independent molecules with identical connectivity, only
one is shown here.
Aiming to advance the understanding of the homocoupling
process we next attempted to prepare Li2MnAr4 (I) via an indirect
route using a salt-metathesis approach in order to probe its
reactivity towards ICH2SiMe3. Reacting 4 equivalents of aryl
lithium Li(2-OMe-C6H4) with MnCl2 in diethyl ether produced pale
orange crystals of [Li2Mn(2-OMe-C6H4)4(OEt2)] (5) (Figure 2ii).[20]
3
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Exhibiting a contacted ion pair manganate structure in which
distorted tetrahedral Mn is bonded to four ortho-metallated
molecules of anisole by short (strong) bonds [average Mn-C
distance: 2.111 ꢀ]. Each lithium has a different coordination
environment. Li1 binds to the O donors of three OMe substituents
from the aryl fragments, whereas Li2 coordinates to the remaining
OMe group as well as to the ortho-C’s of two other aryls, adopting
a perpendicular disposition with respect to the aromatic rings. The
distinct bonding modes of the Li atoms must contribute towards
the marked nonlinearity of the Li···Mn···Li vector [91.09(15)°]
which contrasts with the nearly linear arrangement found in
2b.2TMEDA (Li···Mn···Li, 176.082(2)°, Figure 1i) and other
related lithium manganates.[17]
atmospheric oxygen is used as an oxidant, an in-situ prepared
solution of 5 was exposed to dry air for 15 min at -78 °C using a
drying tube charged with oven-dried CaCl2. This led to the
isolation of unusual bimetallic clusters [(THF)Li4Mn2Ar6(μ6-O)] (6)
and [(THF)4Li4Mn2Ar4Cl2(μ4-O)2] (7) (Figure 3) containing reduced
oxide anions which co-crystallised with variable amounts of
homocoupling product bis(aryl) 3l.
Though both 6 and 7 are dimers, Mn in 6 exhibits the +2 oxidation
state, while in 7 the oxidation state is +3. In 6 μ6-oxide is trapped
in the core of a dicationic {Li4Mn2Ar6}2+ cage where the metals are
connected by ambidentate 2-anisolyl anions that bind to Mn
exclusively via their C atoms and to Li by a combination of Li-O
and Li-C bonds (Figure 3, LHS). The central μ6-oxide exhibits a
distorted octahedral geometry with the two tetrahedrally
coordinated Mn atoms occupying the axial positions [mean Mn-O,
2.072 Å; Mn-O-Mn, 175.7(2)o]; whereas the equatorial positions
are filled by the four Li atoms [mean Li-O, 1.91 Å; sum of LiOLi
angles, 360.2o].
Figure 2. (i) Proposed ate-mediated reaction sequence for the formation of
symmetrical bis(aryls) 3a-3o from iodoarenes 1a-1o; (ii) indirect synthesis of 5
via salt-metathesis and formation of 3l; and (iii) molecular structure of 5 with
thermal ellipsoids drawn at the 50% probability level. All hydrogen atoms
omitted and all but contact atoms shown wireframe for clarity.
Figure 3. Formation of oxygen insertion products 6 and 7 and their molecular
structures with thermal ellipsoids drawn at the 50% probability level. All
hydrogen atoms omitted and aromatic and THF rings shown wireframe for clarity.
Co-crystallised molecule of THF in both 6 and 7 and minor disorder components
in THF ligands in 7 have been omitted for clarity.
Interestingly, while 5 is stable at room temperature in solution
under inert atmosphere conditions, it rapidly proceeds to form
bis(aryl) 3l when reacted with ICH2SiMe3 or by being exposed to
air. The yields observed for 3l (70 and 68% respectively) are
comparable with those seen when 2b is reacted with 2-
iodoanisole (Scheme 1). Furthermore, the EPR spectrum of 5 in
THF at 80 K is identical to that observed for a mixture of 2b and 4
equivalents of 2-iodoanisole at 80 K (see Fig S13 in Supporting
Information), offering further credence to the view that 5 is an
intermediate in the homocoupling processes. Illustrating the
crucial role of Mn in order to facilitate the Csp2-Csp2 bond forming
process, the reaction of aryl lithium Li(2-OMe-C6H4) with
ICH2SiMe3 failed to form 3l, yielding instead the relevant 2-
monosilyl-substituted anisole in a modest 14% resulting from
electrophilic interception.
In previous MnCl2-catalysed homocoupling studies of ArLi and
ArMgX under air, it has been proposed that reactions take place
via a Mn(IV) bis(aryl)oxo complex where the O2 is η2-bonded to
Mn.[7],[9],[10] However, taking into account that the polar aryl
reagent ArM (M= Li, MgX) is present in a large excess in
comparison to the MnCl2 catalyst (10-20 mol%), we ponder
whether a more accurate scenario may involve lithium (or
magnesium) manganate intermediates. In an attempt to further
understand the fate of Mn during the homocoupling process when
In contrast, 7 incorporates LiCl in its constitution (present in the
reaction media as co-product of the synthesis of the Li2MnAr4
precursor) (Figure 3, RHS). It comprises two antiferromagnetically
coupled Mn(III) centres connected/bridged by two oxo and two
chloride anions. In addition, 4 anisolyl ligands coordinate through
their ortho C and the O of the OMe group to Mn and Li,
respectively (Fig S4 in Supporting Information). Each Li atom
present in the structure completes its coordination sphere by
bonding to a THF molecule. As far as we can ascertain 6 and 7
constitute the first structurally defined potential intermediates from
Mn(II) mediated homocoupling processes in the presence of air.
Providing the first insights into the possible fate of Mn during these
transformations, their bimetallic constitutions along with the
structure of 5 supports that, unlike previously proposed,[7],[9],[10]
manganate intermediates generated by salt-metathesis may
actually be more representative of the species active in literature
catalytic studies combining ArM (M= Li, MgX) and
substoichiometric amounts of MnCl2. Furthermore, even under
stoichiometric conditions, when treating two equivalents of
PhMgCl with MnCl2 in THF the mixed-metal complex
[(THF)4MgCl2MnPh2] (8) was isolated in 51% yield (Figure 4).
4
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Crystallographic characterisation of 8 revealed a structure almost
identical to that of 4 (vide supra), when replacing the CH2SiMe3
alkyls by Ph groups, showing that cocomplexation of (THF)4MgCl2
to MnR2 reagents is likely to be a general phenomenon.
Compound 8 can be interpreted as a dianionic manganate with a
tetrahedral Mn(II) centre formally bonded to four anionic ligands
(2Cl, 2Ph). Interestingly, exposure of mixed Mg/Mn complex 8 to
air or reaction with two equivalents of RI led to the formation of
biphenyl in 88 and 74% respectively (Figure 4, see Supporting
Information for details).
This proposal could also explain the formation of 3-
monosilylpyridine 3o’ as a side product when 2b is reacted with
3-iodopyridine, resulting from heterocoupling of the pyridyl
fragment with a monosilyl group. Interestingly if 2b is reacted with
2-iodobenzothiazole, only the relevant heterocoupling product is
obtained in a 64% yield (see SI for details) (Scheme 3i and 3ii).
While SET-dehalogenation reactions induced by magnesium
manganates have been reported in the literature,[3],[5c][21] this
scenario seems to be unlikely here, as suggested by carrying the
reaction of 1a with 2b in the presence of radical scavengers such
as TEMPO or galvinoxyl which allowed the isolation of bis(aryl)
3a in yields comparable to those reported in Table 1 (Scheme 3iii).
N
i)
I
CH2SiMe3
0.33 Li2MnR4 (2b)
+
THF, -78oC to RT, 10h
N
1o
N
3o’
N
3o
63%
20%
ii)
N
S
N
S
0.33 Li2MnR4 (2b)
I
CH2SiMe3
THF, -78oC to RT, 10h
3p 64%
1p
Figure 4. Salt-metathesis reaction of MnCl2 with 2 eq of PhMgCl to give 8 and
homocoupling reactions to give biphenyl. Molecular structure of 8 with thermal
ellipsoids drawn at 50% probability level. All H atoms and minor disorder
component in one THF ligand are omitted for clarity.
iii)
OMe
I
0.33 Li2MnR4 (2b)
THF, -78oC to RT, 10h
MeO
TEMPO or
galvinoxyl
73-69%
3a
1a
MeO
Regarding previouly proposed mechanisms for the homocoupling
of aryls using an alkylhalide as an external oxidant, Zhou’s initial
reports for DCE-driven Mn-catalysed homocoupling of ArMgX
tentatively proposed the involvement of MnAr2 species
undergoing reductive elimination to furnish the relevant bis(aryl)
and a Mn(0) reactive intermediate that can react in turn with DCE
to regenerate MnCl2.[19] However, more recently Valyaev and
Scheme 3. Reactivity studies of 2b with (i) 3-iodopyridine (1o); and (ii) 2-
iodobenzothiazole (1p). (iii) Homocoupling of 1a in the presence of TEMPO.
Finally, in order to gain further understanding on this tandem Mn-
I exchange/C-C coupling process we monitored the reaction of 2b
and 2-iodoanisole (1l) by X-band cw EPR at 80 K. Initial spectra
of 2b in a frozen THF solution confirm the presence of an axially
anisotropic high-spin S=5/2 Mn(II) species (D=0.20 cm−1, E=0
cm−1), as seen previously for related tetra-alkyl Mn(II) compounds
reported by Girolami and Wilkinson (Fig 5a, S7).[12a, 17b]
Lugan have suggested an alternative mechanism via
a
Mn(II)/Mn(IV) redox manifold, with the initial formation of a
tris(aryl) magnesium manganate. The latter can react with DCE to
form an unstable Mn(IV) intermediate which subsequently could
undergo reductive elimination to give the homocoupling product
and MnAr2 that via co-complexation with the excess of ArMgCl
can regenerate the reactive manganate species.[3] A similar
mechanism could be envisaged for our stoichiometric studies with
the initial formation of [Li2MnAr4](I) followed by a sequence of
oxidative addition/reductive elimination steps (Scheme 2)
involving Mn(II)/Mn(IV) species with concomitant elimination of LiI,
along with Me3SiCH2CH2SiMe3 (whose formation could be
detected by GC-MS spectrometry).
Figure 5. EPR monitoring (X-band, f = 9.412 GHz) of the reaction of 2b with
four equivalents of 2-iodoanisole (1l) acquired in frozen THF solutions at 80 K
(Full line in the EPR spectra represents experimental data while simulated
spectra are shown using dashed line).
In situ addition of 2-iodoanisole to 2b at low temperature produces
the more rhombic Mn(II) species which can be identified
confidently as compound 5 by comparison of its EPR spectrum
with that of a frozen solution of isolated crystals of 5 in THF
(D=0.18 cm−1, E=0.042 cm−1, Fig 5b and Supporting Information).
Thus, the Mn(II) oxidation state is maintained during the Mn-I
Scheme 2. Proposed mechanism for oxidative homocoupling of Li2MnAr4(I)
driven by ICH2SiMe3 which is generated via Mn-I exchange of ArI (1a-1o) with
2b.
5
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10.1002/anie.202013153
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RESEARCH ARTICLE
exchange of all four alkyl groups. By allowing the in situ generated
solution of 5 to warm up at room temperature new drastic
modifications of EPR spectrum are detectable (Figs 5c, S12). This
includes a significantly decrease in intensity and the generation of
a complex pattern which can be attributed to the mixture of an
anisotropic mononuclear RMnI (D=0.47 cm−1, E=0.16 cm−1, Fig
S8) and a MnIx species (Fig S9-S10) and/or to heteroleptic Mn(II)
iodide and alkyl oligomers. In the latter case, dominant
antiferromagnetic interactions populate the S=0 ground state at
low temperatures which causes the decrease of intensity.[12b, 22] It
should also be noted that the same changes in the EPR spectra
are observed if 4 molar equivalents of RI are added at room
temperature to a solution of isolated crystals of 5.
These findings were additionally corroborated by studying the
reaction of 2b and 2b·2TMEDA with 3-iodopyridine (Figs S5-S6).
Here, the initial addition of substate at low temperature generates
one broad isotropic resonance (D=0.03 cm−1, E=0 cm−1) centered
at g=2.00 attributed to the formed Li2MnIIAr4 (I) species formed of
nearly Td symmetry which precludes any possibility of SET-
induced radical intermediates. Allowing the reaction mixture to
reach room temperature induces the homocoupling process
causing significant reduction of intensity of the EPR signals, giving
rise to a poorly resolved rhombic spectrum originating from the
previously identified alkyl and iodo Mn(II) compounds as final
products. Further support to this interpretation and to the
proposed mechanism was found when analyzing the mixture in
the end reaction products using mass spectrometry (MALDI-TOF
negative mode), which unveiled the presence of several LiI and
Mn(II) iodide species with {MnI3}− being predominant (Fig S14).
The absence of any formed alkyl Mn(II) oligomers among the
products is likely due to fragmentation and their sensitivity to air
and moisture, as reported previously by Godfrey and McAuliffe.
They indeed isolated [HNMe3][MnI3(NMe3)] from its parent diiodo
compound for which a dimeric structure is established in THF with
a series of amines.[23] In addition, detection of Mn(III) species in
the positive mode of MALDI-TOF hints the possibility of partial
oxidation of the resulting Mn(II) products to their Mn(III) analogues
at the expense of the reduction of the remaining RI species to the
coupled R-R product, as detected by GC-MS.
atmospheric oxygen, a type of reactivity previously noted in the
literature but for which the constitution of the organomanganese
intermediates involved had hitherto proved elusive.
(Full experimental details and copies of NMR, EPR spectra and SQUID
measurements are included in the Supporting Information.)
Acknowledgements
We thank Robert Mulvey (University of Strathclyde) and Martin
Albrecht (University of Bern) for their helpful comments on this
work and Wowa Stroek for his valuable assistance on the use of
EPR. We are also grateful to the University of Bern, ERC Stg-
MixMetApps_279590, the SNF (188573) and Spanish MINECO
(PGC2018-098630-B-I00) for the generous sponsorship of this
research. The X-ray crystal structure determination service unit of
the Department of Chemistry and Biochemistry of the University
of Bern is acknowledged for measuring, solving, refining and
summarizing the structure of compound 5. The Synergy
diffractometer was partially funded by the SNF within the R'Equip
programme (206021_177033).
Keywords: manganates • lithium • cooperative effects •
metallation • homocoupling
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6
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10.1002/anie.202013153
Angewandte Chemie International Edition
RESEARCH ARTICLE
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RESEARCH ARTICLE
Entry for the Table of Contents
Insert graphic for Table of Contents here.
Two steps at a time Exploiting chemical cooperativity between Li and Mn(II), a series of symmetrical bis(aryls) has been prepared
via a stepwise direct Mn-I exchange/oxidative C-C homocoupling protocol. Trapping and characterization of key reaction
intermediates demonstrates the involvement of lithium manganate species, in which Li and Mn work together to facilitate these
transformations.
Institute and/or researcher Twitter usernames: @DCBunibern @EvaHeviaGroup @marina_uzelac
8
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