Iron-Catalyzed Cross-Coupling of Bis-(aryl)manganese Nucleophiles with Alkenyl Halides: Optimization and mechanistic investigations

Article abstract of DOI:10.3390/molecules25030723

Various substituted bis-(aryl)manganese species were prepared from aryl bromides by one-pot insertion of magnesium turnings in the presence of LiCl and in situ trans-metalation with MnCl₂ in THF at ?5 ^?C within 2 h. These bis-(aryl)manganese reagents undergo smooth iron-catalyzed cross-couplings using 10 mol% Fe(acac)₃ with various functionalized alkenyl iodides and bromides in 1 h at 25 ^?C. The aryl-alkenyl cross-coupling reaction mechanism was thoroughly investigated through paramagnetic ¹H-NMR, which identified the key role of tris-coordinated ate-iron(II) species in the catalytic process.

Full text of DOI:10.3390/molecules25030723

molecules
Article
Iron-Catalyzed Cross-Coupling of Bis-(aryl)manganese
Nucleophiles with Alkenyl Halides: Optimization and
Mechanistic Investigations
Lidie Rousseau 1,2, Alexandre Desaintjean 3, Paul Knochel 3 and Guillaume Lefèvre 1,
*
1
Chimie ParisTech, PSL University, CNRS, Institute of Chemistry for Life and Health Sciences (i-CLeHS
FRE2027), CSB2D, 75005 Paris, France; lidie.rousseau@cea.fr
NIMBE, CEA, CNRS, Univ. Paris-Saclay, 91191 Gif-sur-Yvette, France
Department of Chemistry, Ludwig-Maximilians-Universitat München, Butenandstr. 5-13, Haus F,
81377 Munich, Germany; Alexandre.Desaintjean@cup.uni-muenchen.de (A.D.);
Paul.Knochel@cup.uni-muenchen.de (P.K.)
2
3
*
Correspondence: guillaume.lefevre@chimieparistech.psl.eu; Tel.: +33-1-85-78-41-70
ꢀꢁꢂꢀꢃꢄꢅꢆꢇ
ꢀꢁꢂꢃꢄꢅꢆ
Received: 15 January 2020; Accepted: 6 February 2020; Published: 7 February 2020
Abstract: Various substituted bis-(aryl)manganese species were prepared from aryl bromides by
one-pot insertion of magnesium turnings in the presence of LiCl and in situ trans-metalation with
MnCl2 in THF at
5 ◦C within 2 h. These bis-(aryl)manganese reagents undergo smooth iron-catalyzed
−
cross-couplings using 10 mol% Fe(acac)3 with various functionalized alkenyl iodides and bromides
in 1 h at 25 ◦C. The aryl-alkenyl cross-coupling reaction mechanism was thoroughly investigated
through paramagnetic 1H-NMR, which identified the key role of tris-coordinated ate-iron(II) species
in the catalytic process.
Keywords: iron catalysis; cross-coupling; bis-(aryl)manganese; alkenyl halides; ate iron(II) complex
1. Introduction
Transition-metal catalyzed cross-couplings are widely used in the development and production
of pharmaceutical compounds [
nickel-catalyzed cross-couplings [
coupling partners. Yet, these metals have drawbacks such as toxicity [
of palladium [ ]. That is one of the reasons why copper [ ], iron [10
developed as alternative metal-catalysts.
Organomanganese species pioneered by Cahiez [15] often considerably reduce the amount of side
reactions such as homo-coupling [16 17] and have proven to be excellent nucleophiles in various types
of reactions [18 24] including cross-couplings [25 26]. Organomanganese species then constitute an
1
2–5
]. The most versatile of them are palladium-catalyzed and
] as they tolerate a great variety of functionalities on both
] and high prices in the case
13], or cobalt [14] have been
6,7
–
8
9
,
–
,
interesting alternative to usual cross-coupling partners such as organomagnesium [27], organozinc [28],
and organo-boronic esters, which may have genotoxic properties [29,30].
Recently, we have developed a two-step preparation of functionalized bis-(aryl)manganese
reagents by oxidative insertion of magnesium into the C-Br bond of aryl bromides, which is followed
by a trans-metalation with MnCl2
of those functionalized bis-(aryl)manganese reagents (Ar2Mn
Scheme 1) starting from aryl bromides, which are followed by an iron-catalyzed cross-coupling of 1
with alkenyl iodides and bromides, and provide a range of polyfunctionalized alkenes (4, Scheme 1).
These bis-(aryl)manganese reagents are generally stable at RT (25 ◦C) for several hours, which makes
them suitable reagents for mild cross-coupling reactions [32].
·
2LiCl [31]. Herein, we wish to report an effective one-pot preparation
•
2MgX2 4LiCl, denoted as Ar2Mn (1),
•
Molecules 2020, 25, 723; doi:10.3390/molecules25030723
www.mdpi.com/journal/molecules

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Scheme 1. One-pot preparation of bis-(aryl)manganese reagents by in situ trans-metalation followed
by iron-catalyzed cross-couplings with alkenyl iodides and bromides.
2. Results
In preliminary experiments, the bis-(aryl)manganese reagent 1a was conveniently prepared by
treating 4-bromoanisole (2a, 1.0 equiv.) in THF at
5 ◦C with magnesium turnings and LiCl (2.4 equiv.)
−
in the presence of MnCl2 (0.6 equiv.) within 1 h. Titration [31] with iodine led to a yield for 1a of 87%.
Cross-coupling methodologies involving those bis-(aryl)manganese species were then investigated
(see Supporting Information file for details).
In the absence of any iron catalyst, the cross-coupling of 1a with (Z)-ethyl 3-iodoacrylate (3a; 25 ◦C,
1 h) produced a Z/E = 50:50 mixture of the desired cross-coupling product 4a in 60% yield (Table 1,
entry 1). Although the cross-coupling performed with FeBr2 gave a moderate yield of 42%, the use
of FeCl3, FeBr3, or FeCl2 afforded the E isomer of 4a in 54–64% yield (entries 2–5). Using Fe(acac)2
proved to be more effective since the yield increased to 67% (entry 6). Our best result was obtained
with Fe(acac)3 (>99% purity) as a catalyst, producing the E isomer of 4a in a 79% yield (entry 7).
Table 1. Catalyst screening of the reaction between the bis-(aryl)manganese reagent 1a and (Z)-ethyl
3-iodoacrylate (3a).
Entry
Catalyst (10 mol%)
Yield (%) a
60 b
42
54
57
64
67
79
1
2
3
4
5
6
7
none
FeBr2
FeCl3
FeBr3
FeCl2
Fe(acac)2
Fe(acac)3 (>99% purity)
a
b
Yield of analytically pure product. A Z/E = 50:50 mixture of 4a was obtained.
Furthermore, the cross-coupling of 1a with (2-bromovinyl)trimethylsilane (3b; Z/E = 10:90) gave
the olefin 4b in 98% yield with complete E-selectivity (Z/E = 1:99) whereas the yield without iron salt
was 24% (Z/E = 20:80, Table 2, entry 1). When the electron-rich bis-(3,4-dimethoxyphenyl)manganese
(1b) was mixed with 3a, the E-acrylate 4c was generated in 69% yield and a Z/E = 69:31 mixture
of products was obtained in 58% yield without an iron catalyst (entry 2). The tri-substituted
bis-(3,4,5-trimethoxyphenyl)manganese (1c) underwent smooth cross-coupling with 3b to afford the
E-alkene 4d in 80% (8% were obtained without a catalyst, entry 3). Additionally, 1c reacted with

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3a and 2-bromostyrene (3c; Z/E = 18:82) to give the acrylate 4e and 4f (Z/E = 1:99) in 57% and 82%
yield whereas 66% (Z/E = 72:28) and 80% (Z/E = 53:47) were, respectively, obtained without a catalyst
(entries 4–5). In the last experiment, 1c reacted with (E)-1-iodooctene (3d) to provide the alkene 4g
in 87% yield (Z/E = 9:91) when 77% yield (Z/E = 4:96) was obtained without a catalyst (entry 6).
Furthermore, bis-(4-(trifluoromethoxy)phenyl)manganese (1d) reacted with 3a to provide the acrylate
4h (Z/E = 1:99) in 77% yield (entry 7). The reaction without Fe(acac)3 gave a similar yield but a mix
of the two isomers (74%, Z/E = 81:19, entry 7). The silicon-containing bis-(aryl)manganese reagent
1e could also react with 3a, which produces 4i (Z/E = 1:99) in 64% yield (51%, Z/E = 57:43 were
obtained without Fe(acac)3, entry 8). Some good yields could be achieved in the absence of the iron
catalyst (entries 2, 4–8), which could be attributed to the catalytic activity of the manganese(II) itself.
For example, manganese salts proved to efficiently catalyze several couplings of organomagnesium
reagents with alkenyl electrophiles in the past [32]. The bis-benzo[d][1,3]dioxol-5-ylmanganese (1f)
also reacted with 3a and 3b to yield the E-alkenes 4j and 4k in 78–84% yield (entries 9–10). The bulkier
bis-mesitylmanganese 1g reacted with 3b to afford 4l with a small 20% yield (91% after 18 h, entry 11).
This method also proved to tolerate nitriles, since 4-(2-bromovinyl)benzonitrile 3e (Z/E = 98:2) could
be used as a coupling partner with 1d and 1e in good yields (entries 12–13). Moreover, the coupling
generally proceeds with an excellent E-selectivity when iodoalkenes are used. Total isomerization
is observed for Z-starting iodoalkenes (entries 2, 4, 7, 8, 10). A similar tendency is observed for
bromoalkenes, with the exception of 4-(2-bromovinyl)benzonitrile 3e (Z/E = 98:2), which, intriguingly,
did not lead to isomerization of the starting Z bond when coupled with nucleophile 1d, entry 12, or to
a slight isomerization when coupled with 1e, entry 13. In all cases, efficient transference of both aryl
groups from the starting bis-(aryl)manganese species has been observed.
Table 2. Iron-catalyzed couplings of bis-(aryl)manganese (1a–g) a with alkenyl electrophiles (3a–e).
Yield (%) b
Yield (%) b
Entry
Ar2Mn Electrophile
Entry Ar2Mn
Electrophile
1
1a
8
9
1e
1f
1f
3b: Z/E = 10:90
4b: 98, Z/E = 1:99
(24, Z/E = 20:80) c
3a
4i: 64, Z/E = 1:99
(51, Z/E = 57:43) c
2
3
1b
4j: 78,
Z/E = 1:99
3b: Z/E = 10:90
4c: 69, Z/E = 1:99
(58, Z/E = 69:31) c
3a
(39, Z/E = 20:80) c
1c
10
3b: Z/E = 10:90
4k: 84, Z/E = 1:99
(48, Z/E = 99:1) c
3a
4d: 80, Z/E = 1:99
(8, Z/E = 1:99) c
4
1c
11
1g
d
4l:
3b: Z/E = 10:90
3a
4e: 57, Z/E = 1:99
(66, Z/E = 72:28) c
20, Z/E = 21:79
91, Z/E = 5:95 e
(traces, Z/E = 50:50) c

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Table 2. Cont.
Yield (%) b
Yield (%) b
Entry
Ar2Mn Electrophile
Entry Ar2Mn
Electrophile
5
1c
12
13
1d
1e
3c: Z/E = 18:82
4f: 82, Z/E = 1:99
(80, Z/E = 53:47) c
4m: 74, Z/E = 98:2
(19, Z/E = 73:27) c
3e: Z/E = 98:2
6
7
1c
3d
3a
4g: 87, Z/E = 9:91
(77, Z/E = 4:96) c
4n: 66, Z/E = 70:30
(41, Z/E = 72:28)c
3e: Z/E = 98:2
1d
4h: 77, Z/E = 1:99
(74, Z/E = 81:19) c
a
b
c
For clarity reasons, the magnesium salt has been omitted. Yield of analytically pure product. In parentheses,
yield and Z/E ratio obtained without catalysis. Yields determined by GC and 1H-NMR. e After 18 h.
d
3. Discussion
In order to rationalize some of the mechanistic features of the transformations reported in the
first section, we focused our efforts on the coupling system involving various bis-(aryl)manganese
nucleophiles (bis-mesitylmanganese and bis-phenylmanganese) with (2-bromovinyl)-trimethylsilane
(3b). This choice has been motivated by the low cross-coupling yields obtained with this electrophile
in the absence of the iron catalyst, which ascertains the requirement of an Fe-based catalysis for this
coupling (see Table 2, entries 1, 3, 9 and 11).
The bis-(mesityl)manganese reagent was prepared by adding MesMgBr (2.0 equiv.) into a solution
◦
of MnCl2
•
LiCl (1.0 equiv.) in THF at
−
5 C within 1 h. 1H-NMR showed no free MesMgBr left.
The spectra presented high signal-to-noise ratios and broad signals, due to the high paramagnetism
of manganese(II) species, which could not be attributed to a specific molecule (Figure 1a) [33].
High-spin organomanganese compounds are often reported to be NMR silent [34] or without NMR
characterization at all [35–37]. Yet, after addition of a catalytic load of FeCl2 (0.10 equiv.) to the Mes2Mn
solution, the ate complex [Mes3FeII]− was detected by 1H-NMR from the three signals at 127 ppm (s,
6H, meta-H of the Mes group), 110 ppm (s, 9H, para-CH3), and 26 ppm (bs, 18 H, ortho-CH3), as shown
in Figure 1b. These signals attest to a strong paramagnetism, due to the high-spin (S = 2) configuration
of this complex [38]. This proves a fast trans-metalation of the aryl groups from the manganese toward
the iron(II) center. A similar result was obtained while adding an excess of the Mes2Mn solution
onto Fe(acac)3 (0.10 equiv.) as an iron(III) precursor. [Mes3FeII]− was detected by 1H-NMR, showing
that, when an iron(III) precursor is used, a first 1-electron reduction of the latter by the nucleophile
can take place, affording an iron(II) species. This is in agreement with recent reports by Neidig [39
]
and by some of us [40] regarding the reduction of iron(III) salts by Grignard reagents as MeMgBr
and PhMgBr. Accordingly, all the mechanistic studies discussed thereafter were performed using an
iron(II) precursor.
Upon addition of the electrophile 3b ((2-bromovinyl)trimethylsilane) to a mixture of FeCl2 and
Mes2Mn at 25 ◦C, the signals corresponding to [Mes3FeII]− were observed to slowly decrease, affording
[Mes2BrFeII]−, characterized by new signals at 128 ppm (s, 4H, meta-H of the Mes group), 104 ppm
(s, 6H, para-CH3), and 29 ppm (bs, 12 H, ortho-CH3) (see Figure 1c) (this tricoordinate ate species also
presents a high-spin S = 2 configuration) [38]. The same reaction was run at 25 ◦C for 1 h, then quenched,
and analyzed by GC-MS, which proved formation of the desired cross-coupling product with a low
conversion (ca. 20%). This is in fair agreement with the result given in Table 2, entry 11 (due to the high

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paramagnetism of the NMR-analyzed solution and due to the presence of non-deuterated solvents
(THF solutions of organometallics), NMR monitoring of the coupling product formation could not be
efficiently performed).
Figure 1. 1H-NMR spectra (recorded at 25 ◦C in d8-THF) of a 0.08 M solution of (
a) Mes2Mn, (b) Mes2Mn
+ 0.10 equiv. FeCl2, (c) Mes2Mn + 0.10 equiv. FeCl2 + 1.0 equiv. 3b, (d) FeCl2 + 3.0 equiv. MesMgBr +
10 equiv. 3b.
The same observations were made while performing the coupling of 3b with MesMgBr as a
sole nucleophilic partner in a Kumada-type reaction using FeCl2, as [Mes3FeII]− and [Mes2BrFeII]−
were also detected under these cross-coupling conditions (Figure 1d, in the absence of manganese,
the signals of [Mes2BrFeII]− shifted to 131, 106, and 30 ppm). These series of experiments, therefore,
confirm that both [Ar3FeII]− and [Ar2BrFeII]− ate complexes are part of a coupling catalytic cycle and
[Ar3FeII]− can be involved in the activation step of the electrophile. The following catalytic cycle
(Scheme 2) can be suggested, which echoes recent reports by Neidig on the Fe-catalyzed alkyl-alkenyl
coupling reactions [39], and by ourselves on the benzyl-alkenyl coupling [26].
[Ar3FeII]–
ArMnBr
Ar2Mn
Br
Ar
TMS
TMS
Cross-coupling
[Ar2BrFeII]–
Scheme 2. Proposed catalytic cycle for the aryl-alkenyl cross-coupling between Ar2Mn and an alkenyl
bromide under Fe-catalytic conditions.
Thanks to the steric hindrance in the ortho positions, the ate [Mes3FeII]− species remains stable for
hours at 25 ◦C [38
,41]. Thus, the use of a mesityl nucleophile in the mechanistic experiments discussed
earlier prevents any degradation of the FeII catalyst toward lower oxidation states. In order to delineate
the influence of the formation of lower oxidation states on the system, additional investigations were,
therefore, carried out using PhMgBr as a less hindered nucleophile [42].

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First, [Ph3FeII]− was generated at
−
20 ◦C by stoichiometric trans-metalation between FeCl2 and
3.0 equiv. of PhMgBr, and characterized by its 1H-NMR signals at 116 and
−
41 ppm. As we recently
reported, [Ph3FeII]− is stable for more than 1 h at this temperature [40
,41]. Its fate upon addition of an
excess of the electrophile 3b (10 equiv.) was then monitored by paramagnetic 1H-NMR. [Ph3FeII]−
reacted rapidly, as attested by the decrease of its resonances (ca. 75% of the starting [Ph3FeII]− reacted
after 10 min). The reaction was quenched after 1 h, and the GC-MS confirmed formation of the
cross-coupling product, which confirms that [Ph3FeII]− was able to react with 3b in a cross-coupling
process, akin to [Mes3FeII]−. Moreover, several transient resonances in the
be detected in the course of the reaction (see Figure 2). These elusive resonances quickly disappeared,
and were not detected after 30 min at
20 ◦C. These signals echo the formation of ( 2-alkene)n-Fe0
−15/−
5 ppm area could also
−
η
intermediates, as recently reported by Deng, which exhibit similar resonances [43]. This suggests that
Fe0 species are formed in situ by 2-electron reductive elimination from [Ph3FeII]−, which is in agreement
with a recent report by some of us demonstrating that the evolution of [Ph3FeII]− led to the formation
of a distribution of Fe0 and FeI oxidation states (identified as ( 4-arene)2Fe0 and [( 6-arene)FeI(Ph)2]−,
η η
“arene” being an aromatic ligand present in the bulk medium (e.g., C6H6 or C6H5-C6H5 coming from
the oxidation of PhMgBr). Fe0 being preponderantly formed [40 41]). Those Fe0 intermediates would
then be trapped by alkene ligands present in the bulk medium, which leads to the observed resonances.
,
Figure 2. 1H-NMR spectrum (recorded at 20 ◦C in d8-THF) of a 0.08 M solution of [Ph3FeII]− followed
−
by addition of 3b (10 equiv.). Spectrum recorded 20 min after addition of 3b.
Then, the reactivity of the low valent Fe0 and FeI oxidation states in the reaction medium was
investigated. Following one of our recent procedures, reduction of FeII into a distribution of Fe0 and
FeI species was performed, by fast trans-metalation between FeCl2 and PhMgBr (2.0 equiv.) at room
temperature [40,
41]. After 10 min, 1.0 equiv. of MesMgBr was added. The 1H-NMR spectrum showed
no signal in the 100–150 ppm area, which attests to the absence of any Mes-FeII species, which shows
that all the starting FeII was reduced by PhMgBr (Figure 3a).
Figure 3. 1H-NMR spectra (recorded at 25 ◦C in d8-THF) of a 0.08 M solution of (
PhMgBr, + 1.0 equiv. MesMgBr after 10 min agitation at RT. ( ) Same tube, + 3.0 equiv. 3b, after 30 min.
a) FeCl2 + 2.0 equiv.
b
The addition of 3.0 equiv. of the electrophile 3b to the in situ generated solution of Fe0 and FeI
species led to a color change of the sample, which turned from dark brown to yellow. The 1H-NMR
spectrum showed that, after 30 min, ca. 20% of the iron contained in the solution was converted
into [Mes3FeII]− (Figure 3b). The presence of 3b, therefore, allows a re-oxidation of the reduced
Fe0 and/or FeI species to the FeII oxidation state, the latter being trapped by trans-metalation with

Molecules 2020, 25, 723
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MesMgBr to afford [Mes3FeII]−. The re-oxidation of low iron oxidation states by 3b to the FeII stage
was also confirmed by the observation of bis(trimethylsilyl)butadienes TMS-CH=CH-CH=CH-TMS
(TMS-(CH)4-TMS, E/E; Z/E; Z/Z) in GC-MS, after catalytic reactions involving 10 mol% of FeCl2,
PhMgBr, and 3b as coupling partners. Formation of TMS-(CH)4-TMS undoubtedly comes from
the sacrificial monoelectronic reduction of the electrophile that permits re-oxidation of the low Fe0
and/or FeI oxidation states. TMS-(CH)4-TMS, moreover, also appears as a suitable ligand for Fe0
oxidation state, and a (
field resonances in the in the
represents ca. 10% of the quantity of a detected coupling product, which shows that this off-cycle
sacrificial reduction pathway is not preponderant. By comparison, no traces of TMS-(CH)4-TMS were
detected when using mesityl nucleophiles (conditions of Figure 1), attesting that no sacrificial 1-electron
reduction of 3b by oxidation states lower than FeII formed in situ occurred.
η
4-TMS-(CH)4-TMS)Fe0 complex might, thus, contribute to the group of high
15/ 5 ppm area (Figure 2). Quantity of detected TMS-(CH)4-TMS
−
−
Scheme 3 presents a summary of the competitive reactions that were observed in this work during
the Fe-catalyzed coupling of Ph2Mn with (2-bromovinyl)-trimethylsilane (3b), taking into account the
possibility of an off-cycle process involving in situ formed low iron oxidation states.
Scheme 3. Proposed catalytic cycle and side reactions for the aryl-alkenyl cross-coupling between
Ph2Mn and an alkenyl bromide under Fe-catalytic conditions.
Kinetic studies will further be pursued in order to determine the global kinetics of the aryl-alkenyl
cross-coupling reaction, and to examine the possibility for the low Fe0 and FeI oxidation states
involved in a cross-coupling catalytic cycle, in addition to the off-cycle sacrificial reduction of the
alkenyl electrophile evidenced herein. Such studies will also help analyze the mechanism of the
activation of the C-X bond of the alkenyl halide. Isomerization toward the sterically more stable
E coupling products may suggest the implication of an iron-based radical activation of the alkenyl
halide, as observed in the case of alkyl electrophiles [44], albeit formation of the Csp2-centered radical is
generally more energetically-demanding. Additionally, it cannot be excluded in an alternative scenario
that isomerization of the C=C bond occurs after the coupling step, akin to the observations made by
Jacobi von Wangelin for the iron-catalyzed isomerization of Z-olefins to their E analogues [45].
4. Materials and Methods
4.1. Materials and Instruments
All reactions, except otherwise noted, were carried out in flame-dried glassware equipped
with magnetic stirring under an argon atmosphere using standard Schlenk techniques. To transfer
solvents or reagents, syringes were used, which were purged three times with argon prior to use.
After purification by flash column chromatography, products were concentrated using a rotary

Molecules 2020, 25, 723
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evaporator and, subsequently, dried under high vacuum. Indicated yields are isolated yields of
compounds estimated to be >95% pure, as determined by 1H-NMR (25 ◦C) and capillary GC.
To examine the reaction progress of the performed reactions, GC-analysis of quenched hydrolyzed
and iodolyzed reaction aliquots relative to an internal standard was used. For this purpose, small
amounts of the reaction mixture were hydrolyzed using a saturated aqueous solution of NH4Cl,
subsequently extracted with EtOAc, dried over MgSO4 and gaschromatographically quantified.
To monitor the process of directed metalations and oxidative insertion reactions, small amounts of the
reaction mixture were iodolyzed. A small quantity of iodine was dissolved in freshly distilled THF
(0.50 mL), charged with the reaction mixture, and added to a solution of Na2S2O3. The mixture was
extracted with EtOAc, dried over MgSO4, and was then gas chromatographically measured.
To determine the concentration of the different synthesized metallic reagents, iodometric titration
was used. For this purpose, a known amount of iodine was charged with freshly distilled THF (1.00 mL)
to give a deep red solution. The metallic reagent was added dropwise at 2 ◦C to the iodine solution
until the red coloration went colorless. The concentration of the organometallic reagent could be
calculated via the consumed volume of the reaction mixture and the amount of used iodine.
Thin layer chromatography (TLC) was implemented on alumina plates coated with SiO2 (Merck 60,
F-254, Merck, Darmstadt, Germany). To visualize the spots of the different products, UV light was used.
Flash column chromatography was performed using SiO2 (0.04–0.06 mm, 230–400 mesh)
from Merck.
1H-NMR, 13C-NMR, 19F-NMR, and 2D-NMR spectra were recorded on VARIAN Mercury 200,
BRUKER ARX 300, VARIAN VXR 400 S, and BRUKER AMX 600 instruments (Bruker, Billerica,
MA, USA). Chemical shifts are reported as δ-values in ppm relative to tetramethylsilane. The following
abbreviations were used to characterize signal multiplicities: s (singlet), d (doublet), t (triplet),
q (quartet), m (multiplet), and bs (broad singlet).
Mass spectroscopy: High resolution (HRMS) and low resolution (MS) spectra were recorded on a
FINNIGAN MAT 95Q instrument (now Thermo Fisher company, Waltham, MA, USA). Electron impact
ionization (EI) was conducted with an ionization energy of 70 eV. For coupled gas chromatography/mass
spectrometry, a HEWLETT-PACKARD HP 6890 /MSD 5973 GC/MS system was used. Molecular
fragments are reported starting at a relative intensity of 10%.
Infrared spectra (IR) were recorded from 4500 cm−1 to 650 cm−1 on a PERKIN ELMER
Spectrum BX59343 instrument (Perkin Elmer, Wellesley, MA, USA). For detection, a SMITHS
DETECTION DuraSamplIR IIDiamond ATR sensor (Smiths Detection, Hemel Hempstead, UK)
was used. Wavenumbers are reported in cm−1 starting at an absorption of 10%.
Melting points (m.p.) were determined on a BÜCHI B-540 melting point apparatus (BÜCHI
LabortechnikAG, Flawil, Switzerland) and are uncorrected. Compounds decomposing upon melting
are indicated by (decomp.).
Gas chromatography was executed with machines of type Agilent Technologies 7890A GC-Systems
with 6890 GC inlets, detectors (Agilent, Santa Clara, CA, USA), a GC oven, and a column of type HP 5
(Hewlett-Packard, 5% phenylmethylpolysiloxane; length: 10 m, diameter: 0.25 mm, film thickness:
0.2 µm).
Gas chromatography-Mass spectra were recorded on a networking system called Hewlett-Packard
6890/MSD 5973 GC/MS (Hewlett Packard, Palo Alto, CA, USA) with a column of type HP 5
(Hewlett-Packard, 5% phenylmethylpolysiloxane; length: 10m, diameter: 0.25 mm, film thickness:
0.2 µm).
4.2. Chemicals, Solvents, and Typical Procedures
All chemicals were purchased from commercial sources and were used without any further
purification unless otherwise noted.

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THF was continuously refluxed and freshly distilled from benzophenone ketyl under nitrogen.
The freshly distilled THF was stored over a molecular sieve (4 Å) under argon. Solvents for column
chromatography were distilled prior to use.
4.2.1. Typical Procedure for the One-Pot Preparation of Bis-(aryl)manganese Reagents 1a–g
A dry and argon-flushed Schlenk-tube, equipped with a magnetic stirring bar and a rubber
septum, was charged with LiCl (0.610 g, 14.4 mmol, 2.4 equiv.), heated to 450 ◦C under high vacuum,
and then cooled to room temperature. After being switched to argon, the same procedure was applied
after MnCl2 was added (453 mg, 3.60 mmol, 0.6 equiv.). After cooling to room temperature, magnesium
turnings were added (0.350 g, 14.4 mmol, 2.4 equiv.), which was followed by freshly distilled THF
(12 mL). After the reaction mixture was cooled to –g were then added
5 ◦C, the aryl bromides 2a
−
dropwise using 1 mL syringes (6.0 mmol, 1.0 equiv., addition time: 1 min) and the reaction mixture
was stirred until a complete conversion of the starting material was observed. The reaction progress
was monitored by GC-analysis of hydrolyzed and iodolyzed aliquots.
When the metalation was completed, the concentration of the bis-(aryl)manganese species was
determined by titration against iodine in freshly distilled THF. The black solutions of the aryl reagents
1a
into another pre-dried and argon-flushed Schlenk-tube, which was cooled to
against iodine in freshly distilled THF was performed, the reagent was ready to use for Cross-Couplings.
–
g
were then separated from the magnesium turnings using a syringe and, subsequently, transferred
−
5 ◦C. After a titration
4.2.2. Typical Procedure for the Cross-Coupling Reactions of Bis-(aryl)manganese Reagents 1a
–g with
Different Electrophiles 3a–e
A pre-dried and argon-flushed Schlenk-tube equipped with a magnetic stirring bar and a rubber
septum was charged with Fe(acac)3 (35 mg, 0.10 mmol, 10 mol%), the corresponding electrophile (3a
1.0 mmol, 1.0 equiv.), tetradecane as internal standard (50 L) and freshly distilled THF (1.0 mL) as
solvent. The reaction mixture was cooled to 0 ◦C and the bis-(aryl)manganese solution (1a
, 0.6 equiv.)
–e,
µ
–g
was added dropwise whereupon a color change to dark brown could be recognized. After the addition
was complete, the reaction mixture was stirred for a given time at room temperature and the completion
of the cross-coupling reaction was monitored by GC-analysis of hydrolyzed aliquots. Thereupon, a
saturated aqueous solution of NH4Cl was added and the aqueous layer was extracted with EtOAc
(
3 × 100 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated under
reduced pressure. Purification of the crude products by flash column chromatography afforded the
desired cross-coupling reaction products (4a–k, 4m, 4n).
4.3. Studies on the Catalytically Active Species and Catalytic Cycle
All the samples were prepared in a recirculating JACOMEX inert atmosphere (Ar) drybox and
◦
vacuum Schlenk lines. Glassware was dried overnight at 120 C before use. NMR spectra were
obtained using a Bruker DPX 400 MHz spectrometer (Bruker, Billerica, MA, USA). Chemical shifts
for 1H-NMR spectra were referenced to solvent impurities (herein, THF). NMR tubes were equipped
with a J. Young valves were used for all 1H-NMR experiments and catalytic tests. The GC-MS analysis
was performed using n-decane as an internal standard. The reaction media aliquots were quenched by
the addition of distilled water under air. The organic products were extracted using DCM, and injected
into the GC-MS. Mass spectra were recorded on a Hewlett-Packart HP 5973 mass spectrometer (Hewlett
Packard, Palo Alto, CA, USA) via a GC-MS coupling with a Hewlett-Packart HP 6890 chromatograph
(Hewlett Packard, Palo Alto, CA, USA) equipped with a capillary column HP-5MS (50 m
×
0.25 mm
×
0.25 m, Hewlett Packard, Palo Alto, CA, USA). Ionisation was due to an electronic impact (EI, 70 eV).
µ
5. Conclusions
In summary, various functionalized bis-(aryl)manganese species have been readily prepared in
one-pot conditions from the corresponding aryl bromides by inserting magnesium in the presence of

Molecules 2020, 25, 723
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LiCl and in situ trans-metalation with MnCl2 in THF at
−
5 ◦C within 2 h. These bis-(aryl)manganese
reagents have been allowed to undergo smooth iron-catalyzed cross-couplings using 10 mol% Fe(acac)3
and various functionalized alkenyl iodides and bromides at 25 ◦C for 1 h. Mechanistic investigations
carried out by 1H-NMR showed that ate-iron(II) species [Ar3FeII]− are formed by trans-metalation of
the bis-(aryl)manganese reagent with the iron catalyst, and that they can react with alkenyl bromides to
afford the expected cross-coupling product. Low-valent Fe0 and FeI oxidation states can also be formed
by the reduction of the ate-iron(II) catalyst under these conditions. This leads to the sacrificial reduction
of the alkenyl electrophile via an off-cycle pathway, which partly regenerates the FeII oxidation state,
where the latter is able to enter a new catalytic cycle.
Supplementary Materials: The following are available online. Additional synthesis and characterization (NMR,
IR, HRMS, m.p.) data are available online.
Author Contributions: Conceptualization, G.L. and P.K. Methodology, A.D. and L.R. Writing—original draft
preparation, G.L., L.R., and A.D. Writing—review and editing, G.L. and P.K. Supervision, G.L. and P.K. Project
administration, G.L. and P.K. Funding acquisition, G.L. and P.K. All authors have read and agreed to the published
version of the manuscript.
Funding: This work was supported by the CNRS, Chimie ParisTech (Paris), and LMU (Munich) in the framework
of the International Associated Laboratory IrMaCar.
Acknowledgments: We thank the DFG (SFB749) for financial support, and Albemarle (Germany) and BASF
(Ludwigshafen, Germany) for the generous gift of chemicals. G.L. also thanks the ANR research program (project
JCJC SIROCCO). Aurélien Adenot (CEA Saclay) is warmly thanked for his kind technical assistance.
Conflicts of Interest: The authors declare no conflict of interest.
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Sample Availability: Samples of all the compounds described in this article are available from the authors.
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2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access
article distributed under the terms and conditions of the Creative Commons Attribution
(CC BY) license (http://creativecommons.org/licenses/by/4.0/).