Iodoferrocene as a partner inN-arylation of amides

Article abstract of DOI:10.1039/d0nj03470c

In this study, we developed a convenient methodology for theN-arylation of various acetamides, benzamides and related compounds by iodoferrocene. Optimization of the reaction was first performed from acetamide on the basis of the achievements in the benzene series. Next, the identified conditions (use of copper(i) iodide,N,N′-dimethylethylenediamine, tripotassium phosphate in dioxane at 90 °C for 14 h) were applied to different aliphatic/aromatic primary and cyclic/acyclic secondary amides in order to determine the scope of the reaction, thus easily generating a small library of ferrocene amides.

Full text of DOI:10.1039/d0nj03470c

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DOI: 10.1039/D0NJ03470C
Iodoferrocene as partner in N-arylation of amides
Lingaswamy Kadari,a,b William Erb,*a Thierry Roisnel,a Palakodety Radha Krishna *b and Florence
Mongin a
Received 00th January 20xx,
Accepted 00th January 20xx
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In this study, we developed a convenient methodology for the N-arylation of various acetamides, benzamides and related
compounds by iodoferrocene. Optimization of the reaction was first performed from acetamide on the basis of the
achievements in the benzene series. Next, the identified conditions (use of copper(I) iodide, N,N’-
dimethylethylenediamine, tripotassium phosphate in dioxane at 110 °C for 14 h) were applied to different
aliphatic/aromatic primary and cyclic/acyclic secondary amides in order to determine the scope of the reaction, thus easily
generating a small library of ferrocene amides.
DOI: 10.1039/x0xx00000x
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can favourably replace the ligand in such reactions while the
dimsyl anion generated in situ can play a role as base or
ligand.16 The involvement of copper(I) species in the catalytic
Introduction
The Goldberg condensation, which is the copper-catalysed N-
arylation of amides using aromatic halides, has been the topic of
numerous studies since its discovery in the early 1900’s.1 The
original protocol requiring harsh reaction conditions (stoichiometric
amounts of copper salts, high temperatures and long reaction
times), smoother variants have been developed,2-4 either involving
cycle was confirmed, with copper(I) iodide or triflate being the
best sources. Regarding the iodo partner, an electron-
withdrawing group at the para position of iodobenzene seems
to favour the reaction (e.g. full conversion for the reaction
between 1-iodo-4-nitrobenzene and 2-pyrrolidinone at only 90
°C), when compared with an electron-donating group (e.g. 89%
conversion for the same reaction with 4-iodotoluene). While it
is established that electron-deficient aryl iodides are more
easily activated, the effect of the nature of the amido group on
the course of the reaction is more difficult to detect.12
Different amides, including secondary ones that are less
reactive than the primary ones, were evaluated in 24 h
reaction with iodobenzene using copper(I) iodide (0.1 equiv)
and tripotassium phosphate (2 equiv).16 According to the
authors, amide deprotonation is not rate limiting; instead,
stabilization of a putative aryl-Cu(III)-amido would be more
relevant in the mechanism.17-21 This is in agreement with
findings of Hartwig and his group who discarded pathways
involving electron transfer to afford a radical anion and
subsequent halide dissociation in favour of arylcopper(III)
intermediates.15
Due to specificities such as three-dimensional structure
and redox behaviour, ferrocenes cannot be considered as
classical aromatic compounds in numerous reactions. While N-
arylation of amides has been largely developed with various
aromatic and heteroaromatic halides, the corresponding
reaction between amides and halogenated derivatives of
electron-rich ferrocene has been scarcely explored. Indeed,
whereas iodoferrocene reacts with imides in the presence of
copper(I) oxide (for example with phthalimide at the reflux
temperature of pyridine,22 or with L-proline hydantoin in
DMSO at 120 °C23), its reaction with amides is much less
documented.
6
palladium-catalysed processes5, or by identification of suitable
chelating ligands for copper catalysis.7-9
The group of Buchwald contributed to the development of an
efficient and general system based on copper catalysis for the N-
arylation (or -heteroarylation) of amides using iodides.10 It consists
in a combination of an air stable copper(I) salt (copper(I) iodide
giving the best results) and an aliphatic 1,2-diamine (such as N,N’-
dimethylethylenediamine
and
racemic
trans-1,2-
cyclohexanediamine) in the presence of a base (either of low
solubility in the solvent used11 such as tripotassium phosphate and
potassium carbonate, or delivered gradually if soluble such as
potassium hexamethyldisilazide).12 Studies dedicated to the
mechanism showed that the rate determining step is the reaction
between the aryl iodide and a 1,2-diamine ligated copper(I)
amidate,13, 14 and that the N-arylation does not take place with bis-
amido copper(I) species.15 As a consequence, both the 1,2-diamine
and the amide involved can modulate the overall reactivity of the
active species and thus impact the reaction outcome. Concerning
this first step, two pathways are generally proposed. One involves a
rate determining single electron transfer from the amidate
copper(I) to the aryl iodide; the product is next formed by halide
transfer to copper(II), radical recombination giving a copper(III)
species, and reductive elimination. The other starts with the rate
determining formation of an η2 complex between the copper(I)
amidate and the aryl iodide before oxidative addition to a
copper(III) species and reductive elimination.13
In 2014, the group of Ribas showed that, owing to its
coordinating ability, dimethylsulfoxide (DMSO) used as solvent
A very first example was reported in 1983 by Herberhold
and co-workers who prepared triferrocenylamine from
acetamide by successive sequences of deprotonation using
sodium amide and coupling with bromoferrocene in the
presence of copper(I) bromide and pyridine in toluene at
reflux.24 By employing similar reaction conditions, the group of
Bildstein mono-N-arylated N,N’-diacetyl-1,2-phenylenediamine
with bromoferrocene (62% yield); however all attempts of
a.Univ Rennes, CNRS, ISCR (Institut des Sciences Chimiques de Rennes)-UMR 6226,
F-35000 Rennes, France. E-mail: william.erb@univ-rennes1.fr.
b.Organic Synthesis and Process Chemistry Division, CSIR-Indian Institute of
Chemical Technology, Hyderabad, 500007, India. E-mail: prkgenius@iict.res.in
† Electronic Supplementary Information (ESI) available: Copies of 1H, 13C, DEPT,
COSY, HSQC, HMBC and NOESY of most of the compounds; ORTEP diagrams.
CCDC 2014635-2014652. For ESI and crystallographic data in CIF or other
electronic format, see DOI: 10.1039/x0xx00000x
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N,N’-diarylation failed, a result attributed to steric hindrance.25
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In 2008, the group of Buchwald reported a waVteiewr-mArteicldeiOantleinde
DOI: 10.1039/D0NJ03470C
To the best of our knowledge, N-arylation of amides using catalyst activation protocol which allows the amidation of aryl
iodoferrocene has only been addressed by Bolm and co- chlorides in very good yields.30, 31 However, no reaction took
workers in 2007 with the successful reactions of iodoferrocene place (only traces of deiodination) when the three
with both acetamide and benzamide in the presence of halogenoferrocenes were treated by palladium(II) acetate
copper(I) iodide and potassium tert-butoxide in DMSO at 90 (Pd(OAc)2; 2 mol%), 2-(dicyclohexylphosphino)-3,6-dimethoxy-
°C.26
2′,4′,6′-triisopropyl-1,1′-biphenyl (BrettPhos; 4 mol%), water (4
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In the continuation of our studies dedicated to the mol%) and tripotassium phosphate (1.4 equiv) in tert-butanol
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synthesis of ferrocene amides and the evaluation of their at 110 °C for 14 h by following this protocol.
Inspired by both the use of bulky electron-rich phosphines
protocol for copper-catalysed C-N coupling between amides in cross-coupling32 and the use of electron-rich phosphines for
properties,27 we here report our efforts to identify an efficient
and iodoferrocene.
ferroceneamine arylation,33 we next attempted the same
coupling by employing Pd(OAc)2 (3 mol%), di(1-
adamantyl)butylphosphine (cataCXium® A; 6 mol%) and silver
carbonate (2 equiv) in dioxane at 110 °C for 14 h. However,
Results and discussion
none of the halogenoferrocenes was converted into 2-Me
,
In the frame of studies dedicated to the synthesis of
antiproliferative agents associated with ROS generation,
Csámpai and co-workers recently studied the coupling
between 6-ferrocenyl-3-pyridazinone and iodoferrocene.28 By
dehalogenation being the only change observed in the case of
iodoferrocene. By replacing silver carbonate by silver acetate,
the same observations were made. Interestingly, from the
different halogenoferrocenes, the use of thallium carbonate as
base led to traces of an unknown product incorporating
ferrocene and phosphine as shown by NMR. To get insight into
the nature of this compound, we reacted iodoferrocene with
stoichiometric amounts of Pd(OAc)2 and cataCXium® in the
presence of thallium carbonate (2 equiv) but without
acetamide. This led to the isolation of the same compound,
tentatively assigned as a stable palladium complex (see ESI).
We next decided to combine palladium(II) trifluoroacetate
(Pd(tfa)2; 8 mol%), used for the amination of electron-rich
heteroaromatic halides34 or the amidation of aromatic
chlorides,35 with Xantphos (8 mol%) and cesium carbonate (1.4
equiv) in toluene at 110 °C. However, 2-Me was never
using copper(I)
iodide,
N,N’-dimethylethylenediamine
(DMEDA) and tripotassium phosphate in dimethylformamide
at 110 °C, which proved to be the best reaction conditions, a
moderate 33% yield of a mixture of O- (major) and N- (minor)
arylation products was observed and attributed to the steric
bulk associated with iodoferrocene. The use of palladium
complexes such as (Ph3P)2PdCl2 or (dppf)PdCl2 (dppf = 1,1’-
bis(diphenylphosphino)ferrocene) gave similar results, when
used in the presence of potassium carbonate. At the very
beginning of our study, we tried to identify in a quite similar
approach which of the transition metals, palladium or copper,
would be more appropriate for this purpose. In order to find
an efficient method to couple amides with iodoferrocene (1),
we started from acetamide and evaluated different protocols
optimized in the benzene series (Scheme 1).
detected after 14
h
reaction from the different
halogenoferrocenes. Finally, Pd(tfa)2 (5 mol%) and cataCXium®
A (10 mol%) were employed with potassium tert-butoxide as
base at the reflux of toluene, but the different
halogenoferrocenes were fully recovered.
These disappointing results observed with palladium
catalysts led us to turn to copper-based systems from which
the use of stoichiometric amounts becomes possible. As
above, in order to find an efficient method to couple amides
with iodoferrocene, we started from acetamide and evaluated
different protocols employed in the benzene series (Table 1).
First, we selected a system developed by Buchwald and co-
workers for the coupling between amides and iodobenzenes
involving copper(I) iodide, DMEDA and tripotassium phosphate
Scheme 1
Optimization plan.
Initially, we tested conditions reported by Yin and
Buchwald to couple iodo- and bromobenzenes with a large
range of amides in the presence of palladium catalysts.29 Thus,
iodoferrocene (
of dipalladium(0) tris(dibenzylideneacetone) (Pd2(dba)3;
mol%), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene
1) was reacted with acetamide in the presence
in dioxane.12 The reaction between iodoferrocene (
1) and
2
acetamide was first attempted in the presence of
stoichiometric copper(I) iodide, DMEDA and tripotassium
phosphate in dioxane at 110 °C; under these conditions, the
monoarylated 2-Me was isolated in 83% yield (entry 1).
Because the rest was ferrocene, the same reaction was carried
out at 90 °C (entry 2). In this case, 2-Me was produced in a
(Xantphos; 6 mol%) and cesium carbonate (1.4 equiv) in
dioxane at 100 °C for 14 h. However, under these conditions,
the expected product 2-Me was not detected and
recovered. The reaction was similarly attempted from bromo-
and chloroferrocene, also without success. In order to favour
the precipitation of the iodide, cesium carbonate was also
replaced by silver acetate or thallium carbonate, but without
variation.
1 was
similar 82% yield, the rest being a mixture of ferrocene and 1.
However, our attempts to reduce the amount of copper(I)
iodide failed (entry 3), as already noticed previously in the
ferrocene series.26, 28
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Journal Name
Xu and Wolf employed catalytic copper(I) oxide and cesium
ARTICLE
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Table 1 Optimization of the N-arylation of acetamide with iodoferrocene (1).
View Article Online
DOI: 10.1039/D0NJ03470C
carbonate to couple primary amides with iodobenzenes in N-
methylpyrrolidinone (NMP) at 90 °C.36 In our case, by replacing
dioxane with NMP, the yield dropped to 46% (entry 4). We
thus kept dioxane as solvent and attempted to replace
tripotassium phosphate with cesium carbonate; the reaction
worked at both 110 and 90 °C (entries 5 and 6), but the yields
appeared to be slightly lower than before due to competitive
deiodination (with ferrocene found in 16-17% estimated yield).
Cesium fluoride has been proposed by Phillips and co-
workers as an efficient alternative to bases to N-arylate
propanamide by 1-chloro-4-iodobenzene in the presence of
copper(I) iodide, DMEDA and cesium fluoride in
tetrahydrofuran at room temperature.37 However, in our case,
this led to the desired product 2-Me in a lower 54% yield
(entry 7), partly due to competitive deiodination (with
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Entry Ligand
Base/Other Solvent, Temp.
Yield (%)a
Dioxane, 110 °C 83b
1
DMEDA
DMEDA
DMEDA
DMEDA
DMEDA
DMEDA
DMEDA
K3PO4
K3PO4
K3PO4
K3PO4
Cs2CO3
Cs2CO3
CsF
2
3e
Dioxane, 90 °C
Dioxane, 90 °C
NMP, 110 °C
Dioxane, 110 °C 74b
Dioxane, 90 °C
78b
Dioxane, 110 °C 54c
82c (64)d
56f,c (58)g,c
46f
4
5
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7
ferrocene obtained in about 17% yield) and recovery of
(about 5%).
1
h
8
1,10-phenanthroline KF on Al2O3 Toluene, 110 °C 17f
9
1,10-phenanthroline K3PO4
Dioxane, 110 °C 10f
Dioxane, 110 °C 21c
In the same vein, Hosseinzadeh, Tajbakhsh and co-workers
quantitatively formed the expected coupled product by
reaction between benzamide and iodobenzene in the presence
of copper(I) iodide, 1,10-phenanthroline and potassium
fluoride on alumina in toluene at reflux for 1.5 h.38 However,
when adapted, these conditions were hardly transposed to the
reaction between acetamide and iodoferrocene, with the
expected product 2-Me only formed in a 17% yield with the
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12i
glycine
-
K3PO4
K3PO4
K3PO4
Dioxane, 90 °C
Dioxane, 90 °C
0f
70j
DMEDA
a
After purification (see experimental part). In all these reactions, 1,1’-
b
c
biferrocene was formed in <2% yield. The rest was mainly ferrocene. The rest
was mainly recovered
and ferrocene. d Performed on a 5 mmol scale instead of
1
e
1 mmol for the other reactions. By using 0.5 equiv of CuI and 0.5 equiv of
f
g
h
DMEDA. The rest was mainly recovered
1.
With 48 h reaction time. Only 1
i
equiv was used. From bromoferrocene; the rest was starting bromoferrocene
and ferrocene. j The rest was mainly bromoferrocene and ferrocene.
recovery of about 72% of
also tested as ligand, but the reactivity of
under these conditions (69% of recovered) and 2-Me was
1
(entry 8). 1,10-Phenanthroline was
1
proved to be low
1
With these optimized conditions in hand, we next turned
our attention to the use of different amides to perform the N-
arylation of iodoferrocene (1), and we first considered the
only isolated in a low 10% yield (entry 9).
Glycine was also identified by Liu, Guo and co-workers as a
potent ligand to N-arylate various amides with iodobenzenes.
For example, the reaction between acetamide and
iodobenzene gave the expected derivative in 95% yield in the
presence of copper(I) iodide (5 mol %), glycine (0.2 equiv) and
tripotassium phosphate (2.5 equiv) in dioxane at 100 °C for 24
reactivity of substituted acetamides (Table 2). When the
methyl group of acetamide was replaced by cyclopropyl and
more sterically hindered tert-butyl groups, the yield of the
reaction respectively dropped to 57% (product 2-cPr, entry 2)
and 50% (product 2-tBu, entry 3). These results are in
accordance with previous studies invoking steric hindrance of
the amide as partly responsible for the narrow scope of
copper-catalysed N-arylation of amides.41
Replacing acetamide by less hindered formamide led to the
coupled product 2-H in a modest 26% yield, partly due to the
formation of the N,N-diarylated derivative (entry 4). While
successful reactions have been documented in the benzene
series,42 there is to the best of our knowledge no
corresponding reactions reported in the ferrocene series.
However, examples in which N-substituted formamides are
coupled with iodoferrocenes are reported under similar
conditions,43 explaining why single N-arylation is difficult in
this case.
h.39 However, when transposed to iodoferrocene (
1), a
moderate 21% yield was recorded for 2-Me (entry 10).
All these results led us to maintain copper(I) iodide,
DMEDA (1 equiv each) and tripotassium phosphate (2 equiv) in
dioxane at 90 °C for 14 h as the best reaction conditions to
pursue the study with other amides. The usefulness of DMEDA
was evidenced (entry 11), and the conditions were successfully
tested with bromoferrocene, allowing 2-Me to be obtained in
a promising 70% yield (entry 12). Unsurprisingly due to
precedents in the literature,40 applying the optimized
conditions to 1,1’-diiodoferrocene or 1,1’-dibromoferrocene
did not afford the ferrocene diamide but only product 2-Me
(formed in about 40 or 20% yield, respectively). Finally, all
along these experiments, and even when employing only 0.55
equivalent of acetamide, bis-coupling of the amide was never
observed, suggesting a much more difficult reaction from the
secondary amides than from the primary ones.
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rationalized that, upon reacting DiOoId: o10fe.1r0r3o9c/De0nNeJ034w7i0tCh
trifluoroacetamide, a more stable amidate complex might be
formed when using the CuI/DMEDA combination compared to
the CuI/DMSO combination. Thus, it appears that the method
developed by Bolm is more suitable for an acetamide bearing
strong electron-withdrawing groups. It might avoid the
formation of bare ferrocene which is an important side
reaction that takes place in this case by using our protocol.
Finally, we attempted to N-arylate cyanoacetamide and tert-
butyl carbamate (not shown), but without success due to the
formation of an unidentified product under our conditions.
The activated methylene group of the former and
unfavourable electronic or steric factors for the later could be
advanced to rationalize these results.
We next studied the reactivity of benzamides and related
compounds (Table 3). Ribas and co-workers showed that,
under the coupling conditions they proposed (0.1 equiv of
copper(I) iodide and 2 equiv of tripotassium phosphate in
DMSO), benzamide (almost complete conversion at 90 °C) is
more reactive towards iodobenzene than acetamide (complete
conversion at 130 °C).16 With the method here optimized for
iodoferrocene, the yield obtained for benzamide (70%,
product 2-Ph, entry 1) proved to be slightly lower than for
acetamide (82%, product 2-Me, Table 2, entry 1), as previously
noticed by Bolm and co-workers (70% yield in the case of
acetamide and 57% from benzamide).26
In the course of their study on the reactivity of secondary
benzamides with methyl 2-iodobenzoate, Wu, Shang and co-
workers showed a substituent onto the benzamide ring has an
existing (4-nitro < H) but moderate impact on the course of the
reaction, even when located next to the amide function.41
Here, in the presence of an electron-donating group on the
primary benzamide (a 4-methoxy), no significant yield change
was noticed (77%, product 2-4OMe, entry 2). While the
presence of an electron-withdrawing 4-nitro group seems to
reduce the yield (56%, product 2-4NO2, entry 3), good results
were observed with 3-methoxy (80%, product 2-3OMe, entry
4) and 3-chloro (85%, product 2-3Cl, entry 5) although they all
should exhibit the same electron-withdrawing effect. This
difference might result from the lower solubility of the product
formed from 4-nitrobenzamide.
Unlike 4-fluorobenzamide which allowed 2-4F to be formed
in a good yield (79%, entry 6), 4- and 2-bromobenzamide failed
in providing the expected derivatives (entries 7 and 8). While
steric hindrance can be proposed to explain the low reactivity
of 2-bromobenzamide, it can hardly be advanced in the case of
the 4-bromo isomer. Since bromo-substituted benzamides are
known to react with methyl 2-iodobenzoate,41 the lower
reactivity of iodoferrocene associated with the high propensity
of bromobenzamides to undergo side reactions under the
conditions used could be responsible for this result. We
evaluated the catalytic system used by Bolm and co-workers26
for this coupling, but this failed to provide the expected
derivative (entry 8). It confirmed that 2-bromobenzamide
(which is an activated aromatic halide) can react under these
4
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Table 2 Reaction between iodoferrocene (1) and aliphatic primary amides.
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Entry
1
Amide (Substituent X) Product, Yield (%)a
2-Me, 82b
2
3
4
5
2-cPr, 57 (13; 14)b
2-tBu, 50b
2-H, 26c (33; 1)b
2-CH2NEt2, 33 (7; 11)b
6
7
X = Cl
X = F
0
2-CF3, 10d, 56e
a
b
After purification (see experimental part). The rest was mainly recovered 1 and
c
ferrocene; for some reactions, the respective yields are given in brackets. N,N-
d
Diferrocenylformamide was also isolated in 11% yield. Bare ferrocene was mainly
formed. e By using CuI (1 equiv) and tBuOK (2 equiv) in DMSO at 90 °C for 14 h.
Because of the similarity of N-ferrocenylated
diethylaminoacetamide with anaesthetic molecules,44 we
attempted the corresponding amidation using iodoferrocene.
Under our conditions, the expected product 2-CH2NEt2 was
isolated in 33% yield (entry 5). In contrast with
trichloroacetamide which did not react at all (entry 6),
trifluoroacetamide was converted into 2-CF3 in a low 10% yield
(entry 7). However, inspired by the N-arylation of acetamide
by iodoferrocene reported by Bolm and co-workers,26 we also
treated a mixture of trifluoroacetamide and iodoferrocene by
copper(I) iodide and potassium tert-butoxide in DMSO at 90
°C, and observed the formation of 2-CF3 in 56% yield (entry 7).
By N-arylating the two copper(I)-amido complexes
[(dppf)CuN(C6H4-4-OMe)C(=O)Me] and [(dppf)CuN(C6H4-4-
OMe)C(=O)CF3] with iodobenzene in dimethylformamide, Liu,
Feng and co-workers noticed a slightly better yield for the
latter, result explained by a more stabilized copper(I)-amido
complex due to F∙∙∙Cu interaction.45 It can be tentatively
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conditions as bromoferrocene was also identified at the end of
this reaction.
When more sterically hindered 2-methylbenzamide was
View Article Online
Table 3 Reaction between iodoferrocene (1) and aromatic primary amides.
DOI: 10.1039/D0NJ03470C
employed, a lower but still acceptable 63% yield was recorded
under the same reaction conditions (product 2-2Me, entry 9).
However, in the case of 2-naphthylamide, the reason for the
low 22% yield observed is no more steric hindrance, but rather
the low solubility of 2-Naph making its purification less
obvious (entry 10). While using electron-rich/-donating
ferrocenyl and 2-thienyl easily led to the coupled products 2-Fc
and 2-2Th (respective yields of 78 and 93%, entries 11 and 12),
using isonicotinamide which possesses an electron-poor/-
withdrawing 4-pyridyl ring delivered 2-4Py in a moderate 49%
yield (entry 13).
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Entry Ar/R (Substituent G)
Product, Yield (%)a
1
2
3
G = H
2-Ph, 70b, 79b,c
2-4OMe, 77 (1; 19)b
2-4NO2, 56 (2; 10)b
G = OMe
G = NO2
4
5
2-3OMe, 80d (<5; <5)b
2-3Cl, 85 (0; 11)b,
65e (0; 6)b
It is worth mentioning that a satisfying yield was also
noticed with the phenyl group separated from the primary
G = OMe
G = Cl
amide function through a double bond (76%, product 2-Acry
,
entry 14), but not through a triple bond (entry 15). These
results were predictable since primary acrylamides have
already been employed as coupling partners in copper-
catalysed N-arylation under similar conditions46 but primary
propiolamides have, to the best of our knowledge, never being
used in such reactions.
We next turned our attention to the N-arylation of
secondary amides (Table 4) which is known to be highly
substrate-dependent.47 In a study dedicated to the discovery
of a suitable ligand to couple secondary benzamides with
methyl 2-iodobenzoate, Wu, Shang and co-workers identified
steric hindrance and poor nucleophilicity as responsible for the
very few examples reported in the literature.41 In the reaction
using copper(I) iodide and tripotassium phosphate (2 equiv) in
DMSO for 24 h, acyclic secondary amides are reported as able
to react with iodobenzene at 130 °C for 24 h in the following
6
7
G = F
2-4F, 79 (2; 12)b
traces (66; 5)b
G = Br
8
9
G = Br
traces (64; 10)b,f
2-2Me, 63 (<5; <5)b
G = Me
10
11
2-Naph, 22g
2-Fc, 78g
order: N-methylacetamide (84% conversion)
>
N-
ethylacetamide (67% conversion) > N-phenylbenzamide (15%
conversion); in contrast, cyclic 2-pyrrolidinone can be 12
completely converted at only 110 °C.16
2-2Th, 93 (0; 5)b
2-4Py, 49 (1; 17)b
2-Acry, 76 (6; 16)b
0 (26; 15)b
In the present study, we submitted
a mixture of
iodoferrocene and 2-pyrrolidinone to our optimized
conditions, and isolated the expected product 2-Pyrr in a high
89% yield (entry 1). It is no accident that 2-pyrrolidinone has
been employed in different studies dedicated to the
mechanism of copper-catalysed N-arylations; indeed, lactams
of smaller or larger size such as 2-azetidinone (product 2-Azet),
2-piperidinone (product 2-Pipe) and hexahydro-2-azepinone
(product 2-Azep) also gave the expected products, but with
less success (entries 2-4). It is worth noting that these
conditions are not suitable for the coupling of both isatin and
phthalimide with iodoferrocene (not shown).
13
14
15
a
b
After purification (see experimental part). The rest was mainly recovered 1 and
ferrocene; for some reactions, the respective yields are given in brackets. c Performed
d
on a 6 mmol scale instead of 1 mmol for the other reactions
.
Performed on a 2
e
f
mmol scale. Performed on a 5 mmol scale. By using CuI (1 equiv) and tBuOK (2
equiv) in DMSO at 90 °C for 14h, recovered (24%), ferrocene (13.5%) and
bromoferrocene (8%) were obtained. g 1 and ferrocene were not recovered.
1
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present, post-functionalization was studiedViewaArntidcle Onwlinee
successfully performed a palladium-catalysed Suzuki coupling
with 2,5-dimethoxyphenylboronic acid to access 2-PF1 and a
Buchwald-Hartwig amination with morpholine to furnish 2-PF2
(Scheme 2).
Table 4 Reaction between iodoferrocene (1) and cyclic secondary amides.
DOI: 10.1039/D0NJ03470C
8
9
Table 5 Reaction between iodoferrocene (1) and acyclic secondary amides.
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Entry
1
Amide
Product, Yield (%)a
2-Pyrr, 89b
2-Azet, 66b
2-Pipe, 46b
Entry Amide
1
Product, Yield (%)a
2
3
2-AcFc, 8b
2
3
2-3OMeMe, 9c (24; 39)b
4
2-Azep, 32b
a
b
After purification (see experimental part). The rest was mainly recovered 1 and
2-3ClMe, 12c (22; 35)b
ferrocene.
We next turned our attention to more challenging acyclic
secondary amides (Table 5). In the course of their study
dedicated to the N-arylation of N-aryl benzamides, Wu, Shang
and co-workers showed that the outcome of the reaction
depends both on the aryl group itself (less hindered phenyl >
1-naphthyl) and on the substituent present on this aryl group
(e.g. no reaction in the presence of a 4-nitro group) or even on
the position of this substituent (higher yields when it is remote
from the carboxamide function, e.g. 4-chloro > 2-chloro).41 We
tested our conditions for the reaction between iodoferrocene
and an acetamide bearing a hindered ferrocenyl group onto
nitrogen; by this way, 2-AcFc was isolated in 8% yield from 2-
Me (entry 1), a yield much more lower than from acetamide
(82%). Similarly, when compared with the reactions from 3-
methoxy- and 3-chlorobenzamide (80 and 85% yield,
respectively), the N-arylation of the corresponding N-methyl
benzamides proceeded in much more lower yields of 9%
a
b
After purification (see experimental part). The rest was mainly recovered 1 and
c
ferrocene; for some reactions, the corresponding yields are given in brackets. By
performing the reaction on a 5 mmol scale.
(product 2-3OMeMe, entry 2) and 12% (product 2-3ClMe
,
entry 3). In such challenging reactions, ferrocene was
competitively produced to a significant extent due to the low
reactivity of these secondary amides.
As
a consequence, the preferred route towards N-
ferrocenyl-N-alkyl acetamides seems to be the N-alkylation of
N-ferrocenyl benzamides rather than the N-ferrocenylation of
N-methyl benzamides. We confirmed this assumption by N-
methylating or -benzylating the N-ferrocenyl benzamides 2-Ph
2-3OMe and 2-3ClPh, thus affording the ferrocenyl-based
tertiary amides 2-PhMe 2-3OMeMe and 2-3ClBn in 70-76%
Scheme 2Alternative way to N-alkyl-N-ferrocenylbenzamides; Post-functionalization
and ORTEP diagram (30% probability) of N-benzyl-N-ferrocenylbenzamide (2-3ClBn).
,
Most of the ferrocenecarboxamides derivatives obtained
through this study were crystalline solids and their structures
at the solid state were studied by X-ray diffraction (see ESI).
While 2-Me and 2-CF3 feature H-bonds strings as observed
,
overall yields from the required iodoferrocene and primary
carboxamides. Finally, by taking advantage of the chloro group
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with all the secondary carboxamides, differences between the methoxybenzamide and N-methyl-3-chlorobenzamide were
View Article Online
two compounds are present. Indeed, two molecules were prepared by reacting 3-methoxybenzDoOylI: 1c0h.1l0o3r9i/dDe0NaJ0n3d4703C-
found in the asymmetric unit of 2-Me while only one for 2-CF3
.
chlorobenzoyl chloride, respectively, with methylamine.53
Furthermore, while the packing structure of 2-Me revealed 3
Crystallography. The X-ray diffraction data were collected
strings of H-bonds, two being parallel and almost for the compounds 2-Me
perpendicular to the third one, only two parallel H-bond 4NO2 2-3Cl 2-4F 2-4Py
strings are noticed for 2-CF3. Finally, in a same string, the AcFc 2-3OMeMe 2-3ClMe
,
,
2-cPr
2-Pyrr
,
2-CH2NEt2
,
2-Ph
,
,
2-4OMe
2-Azep,
,
2-
2-
,
,
,
,
,
2-Azet
,
2-Pipe
,
,
2-CF3, 2-PhMe and 2-3ClBn at
methyl groups of 2-Me are arranged in pairs pointing in 150(2) K on a D8 VENTURE Bruker AXS diffractometer
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opposite direction while the trifluoromethyls point in the same equipped with a (CMOS) PHOTON 100 detector by using Mo-
direction in 2-CF3. Otherwise, the structures of 2-Me and 2-CF3
K radiation ( = 0.71073 Å; multilayer monochromator). The
are very similar: they both share staggered conformation (C1- structure was solved by dual-space algorithm using the SHELXT
Cg∙∙∙Cg-C1’, Cg being the centroid of the respective Cp ring, program,54 and then refined with full-matrix least-square
22.0 ° and 13.6 ° for 2-Me while 14.1 ° for 2-CF3) and have methods based on F2 (SHELXL program).55 All non-hydrogen
close Cp-carboxamide torsion angles (22.1 ° and 19.8 ° for 2- atoms were refined with anisotropic atomic displacement
Me, 26.4 ° for 2-CF3).
parameters. Except hydrogen atoms linked to nitrogen atoms
(in the case of 2-Ph 2-4NO2 2-4F 2-4Py 2-CH2NEt2 2-cPr 2-
CF3 2-3Cl 2-4OMe) and 2-Me) that were introduced in the
,
,
,
,
,
,
,
,
structural models through Fourier difference maps analysis, H
atoms were finally included in their calculated positions and
treated as riding on their parent atom with constrained
thermal parameters. The molecular diagrams were generated
by ORTEP-3 (version 2.02).56
General procedure 1. Iodoferrocene (1; unless otherwise
specified in the product description, 1.0 mmol), CuI (0.19 g, 1.0
mmol), K3PO4 (0.42 g, 2.0 mmol), DMEDA (0.11 mL, 1.0 mmol)
and the amide (1.1 mmol) were introduced in a degassed
Schlenk tube and dissolved in dioxane (2 mL). The reaction
mixture was stirred under argon and heated at 90 °C for 14 h.
It was then allowed to cool to room temperature before
addition of water (10 mL). After extraction with AcOEt (3 x 20
mL), drying over MgSO4 and evaporation of the solvent under
reduced pressure, the coupling product was purified by
chromatography over silica gel (the eluent is given in the
product description).
Figure 1 Packing of 2-Me and 2-CF3 observed at the solid state highlighting the
hydrogen bonds observed as red dotted lines (thermal ellipsoids shown at the 30%
probability level).
N-Ferrocenylacetamide
general procedure 1 starting from acetamide (65 mg) gave 2-
(2-Me; mixture of rotamers). The
Experimental
All the reactions were performed under an argon atmosphere Me (eluent: hexane-AcOEt 60:40) in 82% yield (0.20 g) as an
in dried Schlenk tubes. Column chromatography separations orange solid: mp 178-180 °C (lit.57 158-167 °C); IR (ATR) 747,
were achieved on silica gel (40-63 μm). Melting points were 800, 998, 1103, 1285, 1371, 1386, 1478, 1568, 1650, 3088,
1
measured on a Kofler apparatus. IR spectra were taken on a 3257 cm-1; H NMR ((CD3)2CO)
 1.94 (s, 3H, Me), 3.91 (t, 2H, J
Perkin-Elmer Spectrum 100 spectrometer. H and 13C Nuclear = 1.9 Hz, H3 and H4), 4.09 (s, 5H, Cp), 4.60 (t, 2H, J = 1.9 Hz, H2
Magnetic Resonance (NMR) spectra were recorded either on a and H5), 8.46 (br s, 1H, NH); 1H NMR (CDCl3, only main rotamer
Bruker Avance III spectrometer at 300 MHz and 75 MHz described) 2.06 (s, 3H, Me), 3.98 (s, 2H, H3 and H4), 4.15 (s,
respectively, or a or Bruker Avance III spectrometer at 400 5H, Cp), 4.57 (s, 2H, H2 and H5), 7.05 (br s, 1H, NH); 13C NMR
1
MHz and 100 MHz respectively, or even on a Bruker Avance III (CDCl3)
 24.1 (CH3), 61.8 (2CH, C2 and C5), 64.7 (2CH, C3 and
HD spectrometer at 500 MHz and 126 MHz respectively. 1H C4), 69.2 (5CH, Cp), 96.5 (C, C1, C-N), 168.6 (C, C=O); MS (EI, 70
chemical shifts (δ) are given in ppm relative to the solvent eV): 243 [M]. These data are similar to those reported
residual peak and 13C chemical shifts are relative to the central previously.57 Crystal data for 2-Me. C12H13FeNO, M = 243.08,
peak of the solvent signal.48 Unless otherwise stated, all monoclinic, P 21, a = 5.9103(2), b = 7.4810(2), c = 23.4895(8) Å,
reagents are commercially available and used as received.

= 92.4820(10) °, V = 1037.61(6) Å3, Z = 4, d = 1.556 g cm-3, μ =
Dioxane was continuously refluxed and freshly distilled from 1.422 mm-1. A final refinement on F2 with 4398 unique
sodium-benzophenone under argon and transferred by using a intensities and 247 parameters converged at ωR(F2) = 0.0891
49
syringe.
Iodoferrocene,27,
bromoferrocene,50 (R(F) = 0.0351) for 4272 observed reflections with I > 2σ(I).
chloroferrocene,50 KF on Al2O3 ferrocenecarboxamide52 and CCDC 2014635.
(diethylamino)acetamide44 were prepared as described
N-(Ferrocenyl)cyclopropanecarboxamide
previously. 3-[5-(1,3-Benzodioxolyl)]-2-propenamide was general procedure 1 starting from cyclopropanecarboxamide
prepared by adapting a protocol described.52 N-Methyl-3- (94 mg) gave 2-cPr (eluent: petroleum ether-AcOEt 70:30; Rf =
51
(2-cPr). The
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0.37) in 57% yield (0.15 g) as an orange solid: mp 174-176 °C; (0.10 g) as an orange solid: mp 103-105 °C; IR (ATR) 723, 818,
IR (ATR) 726, 760, 807, 859, 882, 932, 960, 999, 1022, 1038, 930, 1000, 1034, 1068, 1104, 1163, 1199, 1232, 1262, 1288,
View Article Online
DOI: 10.1039/D0NJ03470C
1104, 1202, 1215, 1262, 1382, 1404, 1441, 1475, 1542, 1644, 1365, 1388, 1451, 1471, 1537, 1659, 2804, 2934, 2971, 3110,
1
3083, 3249 cm-1; 1H NMR (CDCl3)

0.78-0.82 (m, 2H, CH2), 3284 cm-1; H NMR ((CD3)2SO)

1.03 (t, 6H, J = 7.1 Hz, 2Me),
1.02-1.06 (m, 2H, CH2), 1.36-1.41 (m, 1H, CH-CH2), 4.00 (s, 2H, 2.57 (q, 4H, J = 7.1 Hz, 2CH2-Me), 3.01 (s, 2H, CH2-C=O), 3.95 (s,
H3 and H4), 4.17 (s, 5H, Cp), 4.59 (s, 2H, H2 and H5), 6.79 (br s, 2H, H3 and H4), 4.09 (s, 5H, Cp), 4.70 (s, 2H, H2 and H5), 8.93
1H, NH); 13C NMR (CDCl3)
  12.0 (2CH3), 47.8 (2CH2,
7.8 (2CH2), 15.5 (CH-CH2), 61.5 (br s, 1H, NH); 13C NMR ((CD3)2SO)
(2CH, C2 and C5), 64.6 (2CH, C3 and C4), 69.4 (5CH, Cp), 95.2 2CH2-Me), 57.2 (CH2, CH2-C=O), 60.7 (2CH, C2 and C5), 63.8
(C, C1, C-N), 171.8 (C, C=O); MS (EI, 70 eV): 269 [M], 201 [M- (2CH, C3 and C4), 68.6 (5CH, Cp), 95.0 (C, C1, C-N), 169.3 (C,
C(O)cPr+H]. Crystal data for 2-cPr. C14H15FeNO, M = 269.12, C=O); MS (EI, 70 eV): 314 [M]. Crystal data for 2-CH2NEt2.
monoclinic, C 2/c, a = 29.192(3), b = 8.5607(8), c = 9.4060(9) Å, C16H22FeN2O, M = 314.20, monoclinic, P 21/c, a = 12.7745(16),
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
= 92.452(4) °, V = 2348.5(4) Å3, Z = 8, d = 1.522 g cm-3, μ = b = 11.0716(16), c = 10.5180(12) Å,
 = 94.122(4) °, V =
1.265 mm-1. A final refinement on F2 with 2689 unique 1483.8(3) Å3, Z = 4, d = 1.407 g cm-3, μ = 1.013 mm-1. A final
intensities and 157 parameters converged at ωR(F2) = 0.0746 refinement on F2 with 3384 unique intensities and 186
(R(F) = 0.0265) for 2445 observed reflections with I > 2σ(I). parameters converged at ωR(F2) = 0.1092 (R(F) = 0.0420) for
CCDC 2014636.
2856 observed reflections with I > 2σ(I). CCDC 2014637.
N-Ferrocenylbenzamide 2-Ph). The general procedure 1,
N-Ferrocenylpivalamide
(2-tBu). The general procedure 1
(
starting from pivalamide (0.11 g) gave 2-tBu (eluent: hexane- but performed on a 6.0 mmol scale, starting from benzamide
AcOEt 90:10) in 50% yield (0.14 g) as an orange solid: mp 250- (0.78 g, 6.6 mmol) gave 2-Ph (eluent: hexane-AcOEt 60:40) in
252 °C; IR (ATR) 807, 928, 1002, 1106, 1183, 1247, 1360, 1478, 79% yield (1.4 g) as an orange solid: mp 188-190 °C (lit.26 179-
1
1547, 1649, 2963, 3298 cm-1; H NMR ((CD3)2CO)

1.23 (s, 9H, 181 °C); IR (ATR) 692, 816, 1000, 1285, 1367, 1475, 1495, 1557,
tBu), 3.90 (t, 2H, J = 2.0 Hz, H3 and H4), 4.07 (s, 5H, Cp), 4.71 1643, 3307 cm-1; H NMR (CDCl3)
 4.15 (s, 2H, H3 and H4),
1
(t, 2H, J = 2.0 Hz, H2 and H5), 8.10 (br s, 1H, NH); 13C NMR 4.24 (s, 5H, Cp), 4.81 (s, 2H, H2 and H5), 7.14 (br s, 1H, NH),
((CD3)2CO) 27.8 (3CH3, CMe3), 39.8 (C, CMe3), 61.8 (2CH, C2 7.44-7.56 (m, 3H, H2’, H4’ and H6’), 7.80 (d, 2H, J = 7.7 Hz, H3’
and C5), 64.5 (2CH, C3 and C4), 69.6 (5CH, Cp), 97.5 (C, C1, C- and H5’); 13C NMR (CDCl3)
61.8 (2CH, C2 and C5), 65.0 (2CH,
N), 176.8 (C, C=O); MS (EI, 70 eV): 285 [M], 220 [M-Cp]. The 1H C3 and C4), 69.6 (5CH, Cp), 95.4 (C, C1, C-N), 127.0 (2CH, C3’
NMR data are similar to those reported previously.58
and C5’), 128.9 (2CH, C2’ and C6’), 131.8 (CH, C4’), 134.9 (C,
N-Ferrocenylformamide 2-H; 2.8:1 (cis/trans) mixture of C1’), 165.7 (C, C=O); MS (EI, 70 eV): 305 [M], 240 [M-Cp].


(
rotamers). The general procedure 1 starting from formamide These data are similar to those reported previously.26 Crystal
(44 μL) gave 2-H (eluent: petroleum ether-AcOEt 70:30; Rf = data for 2-Ph. C17H15FeNO, M = 305.15, orthorhombic, P c c n,
0.21) in 26% yield (60 mg) as an orange solid: mp 82-84 °C a = 10.2809(14), b = 26.782(4), c = 9.9687(13) Å, V = 2744.8(7)
(lit.59 86-87 °C); IR (ATR) 712, 817, 928, 1001, 1020, 1050, Å3, Z = 8, d = 1.477 g cm-3, μ = 1.092 mm-1. A final refinement
1104, 1167, 1207, 1267, 1388, 1410, 1510, 1654, 1683, 2889, on F2 with 3135 unique intensities and 185 parameters
1
3085, 3253 cm-1; H NMR ((CD3)2SO; the signals of the main converged at ωR(F2) = 0.0650 (R(F) = 0.0273) for 2814
rotamer are marked by an asterisk)
1.8 Hz, H3 and H4), 4.12* and 4.17 (s, 5H, Cp), 4.35 and 4.57*

3.97* and 4.02 (t, 2H, J = observed reflections with I > 2σ(I). CCDC 2014639.
N-Ferrocenyl-4-methoxybenzamide 2-4OMe). The general
(
(t, 2H, J = 1.8 Hz, H2 and H5), 8.08* (d, 1H, J = 1.6 Hz, CHO) and procedure 1 starting from 4-methoxybenzamide (0.17 g) gave
8.44 (d, 1H, J = 11.3 Hz, CHO), 9.28 (d, 1H, J = 11.3 Hz, NH) and 2-4OMe (eluent: petroleum ether-AcOEt 70:30; Rf = 0.45) in
9.49* (br s, 1H, NH); 13C NMR ((CD3)2SO)
 59.9 and 60.9* 77% yield (0.27 g) as an orange solid: mp 179-181 °C; IR (ATR)
(2CH, C2 and C5), 64.0* and 64.5 (2CH, C3 and C4), 68.8* and 669, 762, 813, 841, 892, 938, 1002, 1029, 1106, 1126, 1176,
69.0 (5CH, Cp), 93.7* and 95.4 (C, C1, C-N), 159.2* and 163.1 1209, 1255, 1285, 1310, 1348, 1365, 1388, 1411, 1465, 1475,
(C, C=O). N,N-Diferrocenylformamide was similarly isolated 1509, 1552, 1607, 1631, 2052, 2836, 2932, 2960, 3068, 3099,
1
(eluent: petroleum ether-AcOEt 70:30; Rf = 0.75) in 11% yield 3302 (br) cm-1; H NMR ((CD3)2SO)
 3.83 (s, 3H, OMe), 3.99 (t,
(45 mg) as an orange solid: mp 155-157 °C; IR (ATR) 808, 909, 2H, J = 1.9 Hz, H3 and H4), 4.11 (s, 5H, Cp), 4.79 (t, 2H, J = 1.7
964, 998, 1028, 1058, 1105, 1171, 1211, 1298, 1356, 1408, Hz, H2 and H5), 7.03 (d, 2H, J = 8.8 Hz, H3’ and H5’), 7.90 (d,
1
1460, 1674 (s), 2917, 3092 cm-1; H NMR ((CD3)2SO)

4.01 (s, 2H, J = 8.8 Hz, H2’ and H6’), 9.10 (s, 1H, NH); 13C NMR
2H, H3’ and H4’), 4.08 (s, 5H, Cp or Cp’), 4.30 (s, 5H, Cp or Cp’), ((CD3)2SO)
4.33 (s, 2H, H3 and H4), 4.47 (s, 2H, H2’ and H5’), 4.51 (s, 2H, C3 and C4), 68.8 (5CH, Cp), 96.1 (C, C1, C-N), 113.5 (2CH, C3’
H2 and H5), 9.24 (s, 1H, CHO); 13C NMR ((CD3)2SO)
61.9 (2CH, and C5’), 126.9 (C, C1’, C-C=O), 129.2 (2CH, C2’ and C6’), 161.6
 55.4 (CH3, OMe), 61.0 (2CH, C2 and C5), 63.8 (2CH,

C2’ and C5’), 64.2 (2CH, C3’ and C4’), 65.9 (2CH, C3 and C4), (C, C4’, C-OMe), 164.3 (C, C=O). Crystal data for 2-4OMe.
66.1 (2CH, C2 and C5), 68.9 (5CH, Cp or Cp’), 69.4 (5CH, Cp or C18H17FeNO2, M = 335.17, monoclinic, P 21/c, a = 14.3999(12),
Cp’), 98.5 (C, C1 or C1’, C-N), 98.6 (C, C1 or C1’, C-N), 164.1 (C, b = 10.4832(7), c = 10.1885(9) Å,
 = 98.290(3) °, V = 1522.0(2)
C=O).
2-(Diethylamino)-N-ferrocenylacetamide
Å3, Z = 4, d = 1.463 g cm-3, μ = 0.997 mm-1. A final refinement
(
2-CH2NEt2). The on F2 with 3581 unique intensities and 204 parameters
general procedure 1 starting from iodoferrocene (0.31 g) and converged at ωR(F2) = 0.1975 (R(F) = 0.0761) for 3003
using 2-(diethylamino)acetamide (0.14 g) gave 2-CH2NEt2 observed reflections with I > 2σ(I). CCDC 2014640.
(eluent: petroleum ether-AcOEt 70:30; Rf = 0.31) in 33% yield
8 | New J. Chem., 2020, 00, 1-3
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Page 9 of 15
New Journal of Chemistry
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Journal Name
N-Ferrocenyl-4-nitrobenzamide
ARTICLE
1
2
3
4
5
6
7
8
(
2-4NO2). The general 4F (eluent: petroleum ether-AcOEt 70:30; Rf = 0.80) in 79%
View Article Online
DOI: 10.1039/D0NJ03470C
procedure 1 starting from 4-nitrobenzamide (0.18 g) gave 2- yield (0.27 g) as an orange solid: mp 211-213 °C; IR (ATR) 671,
4NO2 (eluent: petroleum ether-AcOEt 70:30; Rf = 0.60) in 56% 723, 758, 807, 836, 857, 893, 931, 998, 1024, 1037, 1096,
yield (0.21 g) as a dark purple solid: mp 242-245 °C; IR (ATR) 1104, 1124, 1159, 1229, 1282, 1300, 1310, 1349, 1367, 1389,
710, 738, 802, 824, 851, 867, 895, 928, 1105, 1278, 1341, 1408, 1477, 1505, 1561, 1601, 1640, 3109, 3272 cm-1; H NMR
1
1365, 1387, 1494, 1519, 1552, 1600, 1645, 2924, 3317 cm-1; 1H ((CD3)2SO)

4.01 (t, 2H, J = 1.6 Hz, H3 and H4), 4.13 (s, 5H, Cp),
4.05 (t, 2H, J = 1.7 Hz, H3 and H4), 4.15 (s, 4.79 (t, 2H, J = 1.6 Hz, H2 and H5), 7.34 (t, 2H, J = 8.9 Hz, H3’
5H, Cp), 4.81 (t, 2H, J = 1.7 Hz, H2 and H5), 8.14 (d, 2H, J = 8.7 and H5’), 7.99 (dd, 2H, J = 8.7 and 5.6 Hz, H2’ and H6’), 9.74 (br
Hz, H2’ and H6’), 8.35 (d, 2H, J = 8.7 Hz, H3’ and H5’), 10.09 (br s, 1H, NH); 13C NMR ((CD3)2SO)
61.1 (2CH, C2 and C5), 63.9
s, 1H, NH); 13C NMR ((CD3)2SO)
61.4 (2CH, C2 and C5), 64.2 (2CH, C3 and C4), 68.8 (5CH, Cp), 95.7 (C, C1, C-N), 115.2 (d,
NMR ((CD3)2SO)

9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60


(2CH, C3 and C4), 68.9 (5CH, Cp), 95.1 (C, C1, C-N), 123.5 (2CH, 2CH, J = 21.8 Hz, C3’ and C5’), 130.0 (d, 2CH, J = 9.1 Hz, C2’ and
C3’ and C5’), 128.9 (2CH, C2’ and C6’), 140.3 (C, C1’, C-C=O), C6’), 131.2 (d, C, J = 2.3 Hz, C1’, C-C=O), 163.8 (C, C=O), 163.9
149.0 (C, C4’, C-NO2), 163.1 (C, C=O). Crystal data for 2-4NO2. (d, C, J = 249 Hz, C4’, C-F); MS (EI, 70 eV): 323 [M], 258 [M-Cp].
C17H14FeN2O3, M = 350.15, orthorhombic, P b c n, a = Crystal data for 2-4F. C17H14FFeNO, M = 323.14, monoclinic, P
18.433(3), b = 10.1869(16), c = 15.329(3) Å, V = 2878.4(9) Å3, Z 21/c, a = 10.7882(11), b = 14.3983(13), c = 9.0245(9) Å,
 =
= 8, d = 1.616 g cm-3, μ = 1.065 mm-1. A final refinement on F2 102.111(4) °, V = 1370.6(2) Å3, Z = 4, d = 1.566 g cm-3, μ = 1.108
with 3282 unique intensities and 212 parameters converged at mm-1. A final refinement on F2 with 3149 unique intensities
ωR(F2) = 0.0899 (R(F) = 0.0353) for 2721 observed reflections and 193 parameters converged at ωR(F2) = 0.0631 (R(F) =
with I > 2σ(I). CCDC 2014641.
N-Ferrocenyl-3-methoxybenzamide
procedure 1, but on a 2 mmol scale, starting from 3-
0.0248) for 2895 observed reflections with I > 2σ(I). CCDC
2-3OMe). The general 2014643.
N-Ferrocenyl-2-methylbenzamide
(
(2-2Me). The general
methoxybenzamide (0.34 g) gave 2-3OMe (eluent: petroleum procedure 1 starting from 2-methylbenzamide (0.15 g) gave 2-
ether-AcOEt 90:10; Rf = 0.25) in 80% yield (0.56 g) as an 2Me (eluent: petroleum ether-AcOEt 70:30; Rf = 0.73) in 63%
orange solid: mp 160-161 °C; IR (ATR) 692, 713, 749, 806, 825, yield (0.21 g) as an orange solid: mp 186-188 °C; IR (ATR) 670,
866, 880, 899, 921, 932, 1002, 1036, 1076, 1108, 1184, 1228, 701, 726, 793, 815, 926, 1008, 1028, 1055, 1105, 1131, 1155,
1257, 1281, 1351, 1366, 1385, 1450, 1472, 1490, 1553, 1581, 1180, 1223, 1293, 1333, 1354, 1368, 1402, 1422, 1446, 1487,
1600, 1635, 2837, 2972, 3104, 3332 cm-1; H NMR (CDCl3)

1574, 1598, 1628, 2933, 3094 cm-1; H NMR (CDCl3)
 2.51 (s,
1
1
3.87 (s, 3H, OMe), 4.07 (t, 2H, J = 1.8 Hz, H3 and H4), 4.20 (s, 3H, Me), 4.05 (t, 2H, J = 1.8 Hz, H3 and H4), 4.21 (s, 5H, Cp),
5H, Cp), 4.74 (t, 2H, J = 1.8 Hz, H2 and H5), 7.07 (ddd, 1H, J = 4.71 (t, 2H, J = 1.8 Hz, H2 and H5), 6.86 (br s, 1H, NH), 7.21-
8.0, 2.6 and 1.3 Hz, Ar), 7.21 (br s, 1H, NH), 7.31 (dd, 1H, J = 7.7 7.24 (m, 1H, Ar), 7.26-7.27 (m, 1H, H3’), 7.33 (dd, 1H, J = 7.3
and 1.3 Hz, Ar), 7.34-7.41 (m, 2H, Ar); 13C NMR (CDCl3)
 
55.7 and 1.2 Hz, Ar), 7.39 (d, 1H, J = 7.6 Hz, H6’); 13C NMR (CDCl3)
(CH3, OMe), 61.8 (2CH, C2 and C5), 64.9 (2CH, C3 and C4), 69.4 20.0 (CH3), 61.7 (2CH, C2 and C5), 64.9 (2CH, C3 and C4), 69.4
(5CH, Cp), 94.9 (C, C1, C-N), 112.5 (CH, Ar), 118.0 (CH, Ar), (5CH, Cp), 94.8 (C, C1, C-N), 126.0 (CH, C4’ or C5’), 126.6 (CH,
118.6 (CH, Ar), 129.8 (CH, Ar), 136.4 (C, C1’, C-C=O), 160.2 (C, C6’), 130.2 (CH, C4’ or C5’), 131.3 (CH, C3’), 136.3 and 136.7 (C,
C3’, C-OMe), 165.4 (C, C=O).
C2’, C-Me and C, C1’, C-C=O), 168.1 (C, C=O).
N-Ferrocenyl-2-naphthalenecarboxamide (2-Naph). The
3-Chloro-N-ferrocenylbenzamide
(2-3Cl). The general
procedure 1 starting from 3-chlorobenzamide (0.17 g) gave 2- general procedure 1 starting from 2-naphthalenecarboxamide
3Cl (eluent: petroleum ether-AcOEt 90:10; Rf = 0.38) in 85% (0.19 g) gave 2-Naph (eluent: petroleum ether-AcOEt 70:30; Rf
yield (0.23 g) as an orange solid: mp 170-172 °C; IR (ATR) 671, = 0.60) in 22% yield (82 mg) as an orange solid: mp 208-210 °C;
699, 747, 777, 801, 815, 827, 881, 911, 936, 1003, 1017, 1035, IR (ATR) 682, 711, 761, 773, 811, 821, 863, 905, 937, 957,
1105, 1136, 1270, 1292, 1349, 1365, 1389, 1407, 1480, 1558, 1003, 1017, 1028, 1108, 1133, 1201, 1236, 1256, 1273, 1293,
1597, 1643, 3096, 3301 cm-1; 1H NMR (CDCl3)
and H4), 4.21 (s, 5H, Cp), 4.75 (s, 2H, H2 and H5), 7.29 (br s, cm-1; H NMR ((CD3)2SO)

4.09 (s, 2H, H3 1350, 1366, 1387, 1475, 1506, 1556, 1628, 1637, 3103, 3315
1
 4.04 (t, 2H, J = 1.8 Hz, H3 and H4),
1H, NH), 7.39 (t, 1H, J = 7.7 Hz, H5’), 7.49 (d, 1H, J = 7.7 Hz, 4.16 (s, 5H, Cp), 4.85 (t, 2H, J = 1.8 Hz, H2 and H5), 7.60-7.65
H4’), 7.67 (d, 1H, J = 7.6 Hz, H6’), 7.79 (s, 1H, H2’); 13C NMR (m, 2H, Ar), 7.99-8.04 (m, 3H, Ar), 8.08 (dd, 1H, J = 6.8 and 2.1
(CDCl3)
 
61.9 (2CH, C2 and C5), 65.1 (2CH, C3 and C4), 69.5 Hz, Ar), 8.52 (s, 1H, H1’), 9.91 (s, 1H, NH); 13C NMR ((CD3)2SO)
(5CH, Cp), 94.8 (C, C1, C-N), 125.1 (CH, C6’), 127.3 (CH, C2’), 61.2 (2CH, C2 and C5), 64.0 (2CH, C3 and C4), 68.8 (5CH, Cp),
130.2 (CH, C5’), 131.8 (CH, C4’), 135.1 (C, C3’), 136.6 (C, C1’, C- 95.9 (C, C1, C-N), 124.3 (CH, Ar), 126.8 (CH, Ar), 127.5 (CH, Ar),
C=O), 164.3 (C, C=O). Crystal data for 2-3Cl. C17H14ClFeNO, M = 127.6 (CH, Ar), 127.6 (CH, Ar), 127.9 (CH, Ar), 128.9 (CH, Ar),
339.59, monoclinic, P 21/c, a = 14.4453(9), b = 10.4926(5), c = 132.1 (C, Ar), 132.1 (C, Ar), 134.1 (C, Ar), 164.9 (C, C=O).
10.0119(6) Å,

= 105.996(2) °, V = 1458.74(14) Å3, Z = 4, d =
N-(Ferrocenyl)ferrocenecarboxamide (2-Fc). The general
1.546 g cm-3, μ = 1.213 mm-1. A final refinement on F2 with procedure 1 starting from ferrocenecarboxamide (0.25 g) gave
3327 unique intensities and 193 parameters converged at 2-Fc (eluent: petroleum ether-AcOEt 50:50; Rf = 0.11) in 78%
ωR(F2) = 0.0720 (R(F) = 0.0310) for 2899 observed reflections yield (0.34 g) as an orange solid: mp 202-204 °C (lit.60 210-230
with I > 2σ(I). CCDC 2014642.
°C (dec.)); IR (ATR) 674, 692, 766, 809, 840, 877, 933, 1000,
N-Ferrocenyl-4-fluorobenzamide
procedure 1 starting from 4-fluorobenzamide (0.15 g) gave 2- 1385, 1411, 1453, 1484, 1554, 1633, 3102, 3315 cm-1; H NMR
(
2-4F). The general 1019, 1042, 1052, 1107, 1153, 1222, 1247, 1286, 1349, 1362,
1
This journal is © The Royal Society of Chemistry 20xx
New J. Chem., 2020, 00, 1-3 | 9
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New Journal of Chemistry
Page 10 of 15
ARTICLE
Journal Name
1
2
3
4
5
6
7
8
9
((CD3)2SO)

3.99 (br s, 2H, H3 and H4), 4.13 (s, 5H, Cp or Cp’), (C, C5’), 138.8 (CH, Cβ), 147.9 (C, Ca), 148.5 (C, Cb), 163.5 (C,
View Article Online
DOI: 10.1039/D0NJ03470C
4.21 (s, 5H, Cp or Cp’), 4.41 (t, 2H, J = 1.7 Hz, H3’ and H4’), 4.74 C=O).
(br s, 2H, H2 and H5), 4.91 (t, 2H, J = 1.7 Hz, H2’ and H5’), 8.92 N-Ferrocenyl-2-pyrrolidinone
(br s, 1H, NH); 13C NMR ((CD3)2SO)
60.6 (2CH, C2 and C5), procedure 1 starting from 2-pyrrolidinone (84 μL) gave 2-Pyrr
63.6 (2CH, C3 and C4), 68.3 (2CH, C2’ and C5’), 68.8 (5CH, Cp or (eluent: hexane-AcOEt 60:40) in 89% yield (0.24 g) as an
Cp’), 69.4 (5CH, Cp or Cp’), 70.2 (2CH, C3’ and C4’), 76.8 (C, C1’, orange solid: mp 126-128 °C; IR (ATR) 797, 828, 1000, 1021,
(2-Pyrr). The general

C-C=O), 96.4 (C, C1, C-N), 167.2 (C, C=O).
N-Ferrocenyl-2-thiophenecarboxamide
1101, 1212, 1297, 1382, 1416, 1495, 1682 cm-1; 1H NMR
The ((CD3)2CO) 2.12 (quint, 2H, J = 7.0 Hz, H4’), 2.35 (t, 2H, J = 7.0
(2-2Th).

10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
general procedure 1 starting from 2-thiophenecarboxamide Hz, H3’), 3.71 (t, 2H, J = 7.0 Hz, H5’), 4.00 (s, 2H, H3 and H4),
(0.14 g) gave 2-2Th (eluent: petroleum ether-AcOEt 80:20; Rf = 4.15 (s, 5H, Cp), 4.75 (s, 2H, H2 and H5); 13C NMR ((CD3)2CO)
0.30) in 93% yield (0.31 g) as an orange solid: mp 199-201 °C; 18.8 (CH2, C4’), 32.6 (CH2, C3’), 48.9 (CH2, C5’), 60.6 (2CH, C2
IR (ATR) 667, 724, 741, 753, 809, 824, 855, 931, 1001, 1020, and C5), 65.0 (2CH, C3 and C4), 69.3 (5CH, Cp), 97.9 (C, C1, C-
1032, 1049, 1080, 1106, 1218, 1250, 1285, 1353, 1368, 1387, N), 173.9 (C, C=O); MS (EI, 70 eV): 269 [M], 204 [M-Cp]. Crystal
1418, 1475, 1558, 1621, 3010, 3105, 3300 cm-1; 1H NMR data for 2-Pyrr. C14H15FeNO, M = 269.12, orthorhombic, P b c

((CD3)2SO)  4.02 (t, 2H, J = 1.8 Hz, H3 and H4), 4.13 (s, 5H, Cp), a, a = 9.8360(12), b = 8.3860(10), c = 28.171(3) Å, V = 2323.6(5)
4.74 (t, 2H, J = 1.8 Hz, H2 and H5), 7.18 (dd, 1H, J = 4.8 and 3.8 Å3, Z = 8, d = 1.539 g cm-3, μ = 1.278 mm-1. A final refinement
Hz, H4’), 7.80 (dd, 1H, J = 5.1 and 0.9 Hz, H5’), 7.89 (d, 1H, J = on F2 with 2662 unique intensities and 154 parameters
3.4 Hz, H3’), 9.73 (br s, 1H, NH); 13C NMR ((CD3)2SO)

61.0 converged at ωR(F2) = 0.0832 (R(F) = 0.0352) for 2360
(2CH, C2 and C5), 64.0 (2CH, C3 and C4), 68.8 (5CH, Cp), 95.5 observed reflections with I > 2σ(I). CCDC 2014644.
(C, C1, C-N), 127.9 (CH, C4’), 128.4 (CH, C3’), 131.1 (CH, C5’), N-Ferrocenyl-2-azetidinone 2-Azet). The
140.2 (C, C2’, C-C=O), 159.4 (C, C=O); MS (EI, 70 eV): 311 [M], procedure 1 starting from 2-azetidinone (78 mg) gave 2-Azet
(
general
246 [M-Cp], 207.
(eluent: hexane-AcOEt 60:40) in 66% yield (0.17 g) as an
N-Ferrocenylisonicotinamide
(
2-4Py).61 The general orange solid: mp 136-138 °C; IR (ATR) 797, 809, 1002, 1017,
procedure 1 starting from isonicotinamide (0.13 g) gave 2-4Py 1157, 1339, 1353, 1378, 1408, 1509, 1728, 2903, 2967 cm-1; 1H
(eluent: petroleum ether-AcOEt 50:50; Rf = 0.11) in 49% yield NMR (CDCl3)
(0.16 g) as a red solid: mp 176-178 °C; IR (ATR) 662, 684, 751, Hz, H3’), 4.00 (s, 2H, H3 and H4), 4.21 (s, 5H, Cp), 4.47 (s, 2H,
814, 827, 841, 900, 933, 1002, 1018, 1036, 1065, 1106, 1130, H2 and H5); 13C NMR (CDCl3)
36.9 (CH2, C4’), 39.5 (CH2, C3’),
1222, 1289, 1349, 1367, 1389, 1409, 1473, 1496, 1548, 1598, 59.1 (2CH, C2 and C5), 64.7 (2CH, C3 and C4), 68.9 (5CH, Cp),
1645, 3100, 3301 cm-1; 1H NMR ((CD3)2SO)
4.05 (t, 2H, J = 1.7 94.4 (C, C1, C-N), 164.9 (C, C=O); MS (EI, 70 eV): 255 [M], 227,
 3.00 (t, 2H, J = 4.2 Hz, H4’), 3.43 (t, 2H, J = 4.2


Hz, H3 and H4), 4.14 (s, 5H, Cp), 4.80 (t, 2H, J = 1.7 Hz, H2 and 213. Crystal data for 2-Azet. C13H13FeNO, M = 255.09,
H5), 7.82 (d, 2H, J = 4.6 Hz, H3’ and H5’), 8.77 (br s, 2H, H2’ and monoclinic, P 21/c, a = 14.1641(13), b = 9.6057(8), c =
 61.3 (2CH, C2 and 8.2368(8) Å, 
H6’), 10.03 (s, 1H, NH); 13C NMR ((CD3)2SO) = 106.643(3) °, V = 1073.72(17) Å3, Z = 4, d =
C5), 64.2 (2CH, C3 and C4), 68.9 (5CH, Cp), 95.0 (C, C1, C-N), 1.578 g cm-3, μ = 1.378 mm-1. A final refinement on F2 with
121.3 (2CH, C3’ and C5’), 141.5 (C, C4’), 150.2 (2CH, C2’ and 2472 unique intensities and 146 parameters converged at
C6’), 163.2 (C, C=O); MS (EI, 70 eV): 306 [M], 241 [M-Cp]. ωR(F2) = 0.0629 (R(F) = 0.0224) for 2304 observed reflections
Crystal data for 2-4Py. C16H14FeN2O,
orthorhombic, P b c a, a = 10.5061(12), b = 9.9738(12), c =
M
=
306.14, with I > 2σ(I). CCDC 2014645.
N-Ferrocenyl-2-piperidinone
(2-Pipe). The general
25.333(3) Å, V = 2654.5(5) Å3, Z = 8, d = 1.532 g cm-3, μ = 1.131 procedure 1 starting from 2-piperidinone (97 μL) gave 2-Pipe
mm-1. A final refinement on F2 with 3011 unique intensities (eluent: hexane-AcOEt 60:40) in 46% yield (0.13 g) as an
and 184 parameters converged at ωR(F2) = 0.0959 (R(F) = orange solid: mp 104-106 °C; IR (ATR) 791, 825, 1000, 1167,
1
0.0413) for 2406 observed reflections with I > 2σ(I). These X- 1304, 1333, 1462, 1643, 2942 cm-1; H NMR ((CD3)2CO)
 1.80
ray data are as reported previously (XOTTIL, CCDC 1035326).61
3-(5-(1,3-Benzodioxolyl))-N-ferrocenylacrylamide 2-Acry). (t, 2H, J = 6.8 Hz, H3’), 3.71 (t, 2H, J = 5.9 Hz, H6’), 4.00 (t, 2H, J
The general procedure starting from 3-(5-(1,3- = 1.8 Hz, H3 and H4), 4.15 (s, 5H, Cp), 4.72 (t, 2H, J = 1.8 Hz, H2
benzodioxolyl))acrylamide (0.21 g) gave 2-Acry (eluent: and H5); 13C NMR ((CD3)2CO)
21.7 (CH2, C4’), 24.0 (CH2, C5’),
(quint, 2H, J = 6.1 Hz, H4’), 1.92 (quint, 2H, J = 5.9 Hz, H5’), 2.35
(
1

petroleum ether-AcOEt 50:50; Rf = 0.58) in 76% yield (0.30 g) 34.2 (CH2, C3’), 49.9 (CH2, C6’), 63.0 (2CH, C2 and C5), 64.9
as a red solid: mp 175-177 °C; IR (ATR) 700, 723, 749, 811, 855, (2CH, C3 and C4), 69.4 (5CH, Cp), 101.3 (C, C1, C-N), 169.2 (C,
878, 933, 973, 1000, 1039, 1102, 1133, 1187, 1218, 1250, C=O); MS (EI, 70 eV): 283 [M], 218 [M-Cp]. Crystal data for 2-
1358, 1369, 1387, 1410, 1447, 1487, 1504, 1561, 1601, 1649, Pipe. C15H17FeNO, M = 283.14, orthorhombic, P b c a, a =
1733, 2885, 3079, 3288 cm-1; 1H NMR ((CD3)2SO)

4.00 (t, 2H, J 10.0250(13), b = 8.8225(10), c = 27.727(3) Å, V = 2452.3(5) Å3,
= 1.9 Hz, H3 and H4), 4.11 (s, 5H, Cp), 4.67 (t, 2H, J = 1.9 Hz, H2 Z = 8, d = 1.534 g cm-3, μ = 1.215 mm-1. A final refinement on F2
and H5), 6.08 (s, 2H, CH2), 6.51 (d, 1H, J = 15.6 Hz, H), 6.97 (d, with 2793 unique intensities and 163 parameters converged at
1H, J = 8.1 Hz, H7’), 7.10 (dd, 1H, J = 8.1 and 1.4 Hz, H6’), 7.16 ωR(F2) = 0.0724 (R(F) = 0.0305) for 2385 observed reflections
(d, 1H, J = 1.4 Hz, H4’), 7.42 (d, 1H, J = 15.6 Hz, Hβ), 9.49 (s, 1H, with I > 2σ(I). CCDC 2014646.
NH); 13C NMR ((CD3)2SO)

60.9 (2CH, C2 and C5), 64.0 (2CH, C3
N-(Ferrocenyl)hexahydro-2-azepinone
(2-Azep).
The
and C4), 68.8 (5CH, Cp), 95.4 (C, C1, C-N), 101.4 (CH2), 106.2 general procedure 1 starting from hexahydro-2-azepinone
(CH, C4’), 108.6 (CH, C7’), 120.1 (CH, Cα), 123.3 (CH, C6’), 129.2 (0.12 g) gave 2-Azep (eluent: hexane-AcOEt 60:40) in 32% yield
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(95 mg) as an orange solid: mp 102-104 °C; IR (ATR) 710, 803, chloro-N-methylbenzamide (0.95 g) gave 2-3ClMe (eluent:
View Article Online
967, 1032, 1185, 1215, 1258, 1385, 1410, 1466, 1643, 2928 petroleum ether-AcOEt 70:30; Rf = 0.53)DiOnI:1120%.10y3i9e/lDd0(N2J20534m70gC)
1
cm-1; H NMR ((CD3)2CO)
 1.66 (quint, 2H, J = 4.8 Hz, H4’), as a red solid: mp 138-140 °C; IR (ATR) 666, 683, 728, 760, 806,
1.75-1.81 (m, 4H, H5’ and H6’), 2.55-2.58 (m, 2H, H3’), 3.90- 853, 891, 917, 1001, 1027, 1050, 1106, 1130, 1222, 1295,
1
3.92 (m, 2H, H7’), 4.01 (t, 2H, J = 1.8 Hz, H3 and H4), 4.17 (s, 1331, 1354, 1369, 1411, 1478, 1563, 1631, 2928 cm-1; H NMR
5H, Cp), 4.54 (t, 2H, J = 1.8 Hz, H2 and H5); 13C NMR ((CD3)2CO) ((CD3)2SO)


3.43 (br s, 3H, Me), 4.03 (s, 2H, H3 and H4), 3.87-
24.4 (CH2, C4’), 29.4 and 30.2 (2CH2, C5’ and C6’), 38.7 (CH2, 4.21 (br s, 2H, H2 and H5), 4.28 (s, 5H, Cp), 7.12 (br s, 1H, Ar),
C3’), 52.0 (CH2, C7’), 63.7 (2CH, C2 and C5), 64.9 (2CH, C3 and 7.22 (br s, 1H, Ar), 7.29 (br s, 1H, Ar), 7.39 (br s, 1H, Ar); 13C
C4), 69.4 (5CH, Cp), 101.9 (C, C1, C-N), 174.8 (C, C=O); MS (EI, NMR ((CD3)2SO) 38.6 (CH3), 64.1 (2CH, C2 and C5), 64.8 (2CH,
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70 eV): 297 [M], 232 [M-Cp]. Crystal data for 2-Azep. C3 and C4), 68.8 (5CH, Cp), 102.1 (C, C1, C-N), 126.5 (CH, Ar),
C16H19FeNO, M = 297.17, monoclinic, C 2/c, a = 20.788(3), b = 127.7 (CH, Ar), 129.4 (CH, Ar), 129.7 (CH, Ar), 132.5 (C, Ar),
13.387(2), c = 10.5242(13) Å,
 = 114.189(4) °, V = 2671.6(7) 138.4 (C, Ar), 168.0 (C, C=O); MS (EI, 70 eV): 353 [M], 288 [M-
Å3, Z = 8, d = 1.478 g cm-3, μ = 1.119 mm-1. A final refinement Cp]. Crystal data for 2-3ClMe. C18H16ClFeNO, M = 353.62,
on F2 with 3051 unique intensities and 172 parameters triclinic, P –1, a = 10.3749(11), b = 11.6955(13), c = 13.3758(12)
converged at ωR(F2) = 0.0696 (R(F) = 0.0288) for 2630 Å,
observed reflections with I > 2σ(I). CCDC 2014647.

= 109.852(3),
 = 100.413(3),  = 91.180(4) °, V = 1495.5(3)
Å3, Z = 4, d = 1.571 g cm-3, μ = 1.187 mm-1. A final refinement
N,N-Diferrocenylacetamide
(2-AcFc).
The
general on F2 with 6806 unique intensities and 399 parameters
procedure 1 starting from N-ferrocenylacetamide (0.27 g) gave converged at ωR(F2) = 0.1001 (R(F) = 0.0391) for 6090
2-AcFc (eluent: hexane-AcOEt 60:40) in 8% yield (36 mg) as an observed reflections with I > 2σ(I). CCDC 2014650.
orange solid: mp 171-173 °C; IR (ATR) 800, 818, 1001, 1017,
1106, 1226, 1280, 1312, 1363, 1455, 1672, 2928, 3103 cm-1; 1H specified in the product description, 1.0 mmol), CuI (0.19 g, 1.0
NMR (CDCl3) 1.99 (s, 3H, Me), 4.06 (s, 10H, Cp), 4.11 (s, 4H, mmol), tBuOK (0.11 g, 2.0 mmol) and the amide (1.1 mmol)
H3 and H4), 4.44 (s, 4H, H2 and H5); 13C NMR (CDCl3)
24.4 were introduced in a degassed Schlenk tube and dissolved in
General procedure 2. Iodoferrocene (1; unless otherwise


(CH3), 64.6 (4CH, C3 and C4), 66.6 (4CH, C2 and C5), 69.7 DMSO (2 mL). The reaction mixture was stirred under argon
(10CH, Cp), 102.9 (2C, C1, C-N), 171.1 (C, C=O); MS (EI, 70 eV): and heated at 90 °C for 14 h. It was then allowed to cool to
427 [M], 207. The NMR data are as reported previously.24 room temperature before addition of water (10 mL). After
Crystal data for 2-AcFc. C22H21Fe2NO, M = 427.10, monoclinic, extraction with AcOEt (3 x 20 mL), drying over MgSO4 and
P 21/n, a = 17.0141(13), b = 10.6656(9), c = 20.1450(16) Å,

=
evaporation of the solvent under reduced pressure, the
107.428(3) °, V = 3487.8(5) Å3, Z = 8, d = 1.627 g cm-3, μ = 1.674 coupling product was purified by chromatography over silica
mm-1. A final refinement on F2 with 8038 unique intensities gel (the eluent is given in the product description).
and 471 parameters converged at ωR(F2) = 0.0853 (R(F) =
N-(Ferrocenyl)trifluoroacetamide
(2-CF3). The general
0.0341) for 6945 observed reflections with I > 2σ(I). CCDC procedure 2 starting from trifluoroacetamide (0.11 g) gave 2-
2014648.
N-Ferrocenyl-3-methoxy-N-methylbenzamide
CF3 (eluent: petroleum ether-AcOEt 90:10; Rf = 0.48) in 56%
2- yield (0.165 g) as an orange solid: mp 37-38 °C; IR (ATR) 802,
(
3OMeMe). The general procedure 1, but on a 5 mmol scale, 821, 903, 1001, 1106, 1144, 1170, 1256, 1314, 1474, 1559,
starting from 3-methoxy-N-methylbenzamide (0.90 g) gave 2- 1701, 3106, 3325 cm-1; 1H NMR ((CD3)2CO)
4.08 (t, 2H, J = 2.0
3OMeMe (eluent: petroleum ether-AcOEt 70:30; Rf = 0.36) in Hz, H3 and H4), 4.16 (s, 5H, Cp), 4.76 (t, 2H, J = 2.0 Hz, H2 and
9% yield (165 mg) as a red glue oil: IR (ATR) 663, 693, 745, 788, H5), 9.93 (br s, 1H, NH); 13C NMR ((CD3)2CO)
62.6 (2CH, C2


819, 877, 932, 1009, 1041, 1105, 1123, 1160, 1216, 1249, and C5), 65.8 (2CH, C3 and C4), 70.1 (5CH, Cp), 93.5 (m, C, C1,
1288, 1333, 1353, 1367, 1429, 1452, 1483, 1580, 1599, 1634, C-N), 117.0 (q, C, J = 288 Hz, CF3), 155.3 (q, C, J = 39.1 Hz, C=O);
1
2835, 2936, 3090 cm-1; H NMR ((CD3)2SO)
   -75.6; MS (EI, 70
3.42 (br s, 3H, 19F NMR ((CD3)2CO) -76.1; 19F NMR (CDCl3)
1
Me), 3.66 (s, 3H, OMe), 4.01 (s, 2H, H3 and H4), 4.11 (br s, 2H, eV): 297 [M]. The H NMR data are similar to those reported
H2 and H5), 4.26 (s, 5H, Cp), 6.74 (br s, 2H, H2’ and H6’), 6.90 previously.58 Crystal data for 2-CF3. C12H10F3FeNO, M = 297.06,
(d, 1H, J = 6.6 Hz, H4’), 7.18 (br s, 1H, H5’); 13C NMR ((CD3)2SO) monoclinic, P 21/c, a = 15.261(3), b = 7.4670(11), c =

39.0 (CH3, NMe), 55.5 (CH3, OMe), 64.3 (2CH, C2 and C5), 10.2018(16) Å, 
= 109.261(6) °, V = 1097.5(3) Å3, Z = 4, d =
65.1 (2CH, C3 and C4), 69.2 (5CH, Cp), 102.8 (C, C1, C-N), 113.6 1.798 g cm-3, μ = 1.400 mm-1. A final refinement on F2 with
(CH, C2’), 115.9 (CH, C4’), 120.5 (CH, C6’), 129.4 (CH, C5’), 2466 unique intensities and 166 parameters converged at
138.2 (C, C1’, C-C=O), 159.0 (C, C3’, C-OMe), 169.8 (C, C=O). ωR(F2) = 0.0720 (R(F) = 0.0333) for 2147 observed reflections
Crystal data for 2-3OMeMe. C19H19FeNO2, M = 349.20, with I > 2σ(I). CCDC 2014638.
monoclinic, P 21, a = 8.9424(5), b = 9.3918(6), c = 18.8587(12)
General procedure 3. The N-ferrocenylbenzamide (1.0
Å,

= 94.385(2) °, V = 1579.22(17) Å3, Z = 4, d = 1.469 g cm-3, μ mmol) was dissolved in THF (8 mL) and treated by NaH (~60%
= 0.964 mm-1. A final refinement on F2 with 6715 unique dispersion in mineral oil; 0.12 g, 3.0 mmol). After 15 min at
intensities and 419 parameters converged at ωR(F2) = 0.1996 room temperature, MeI (0.43 g, 0.19 mL, 3.0 mmol) was added
(R(F) = 0.0804) for 6266 observed reflections with I > 2σ(I). and the reaction mixture was stirred for 0.5 h at room
CCDC 2014649.
temperature. It was then cooled to 0 °C before addition of
3-Chloro-N-ferrocenyl-N-methylbenzamide
(2-3ClMe). The water (10 mL). After extraction with AcOEt (3 x 20 mL) and
general procedure 1, but on a 5 mmol scale, starting from 3- drying over MgSO4, the product was purified by
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chromatography over silica gel (the eluent is given in the
product description).

= 99.381(2),

= 91.4120(10),

= 109.2600(10) °, V =
View Article Online
-1
3
-3
DOI: 10.1039/D0NJ03470C
1950.30(13) Å , Z = 4, d = 1.463 g cm , μ = 0.925 mm . A final
N-Ferrocenyl-N-methylbenzamide (
2-PhMe). The general refinement on F2 with 8850 unique intensities and 505
procedure 2 starting from N-ferrocenylbenzamide (0.31 g) parameters converged at ωR(F2) = 0.0730 (R(F) = 0.0321) for
gave 2-PhMe (eluent: petroleum ether-AcOEt 70:30) in 96% 7363 observed reflections with I > 2σ(I). CCDC 2014652.
yield (0.31 g) as an orange solid: mp 132-134 °C; IR (ATR) 670,
701, 726, 762, 793, 816, 826, 926, 1008, 1028, 1055, 1105, ferrocenylbenzamide
1132, 1155, 1180, 1223, 1293, 1333, 1354, 1368, 1402, 1422, ferrocenylbenzamide
N-Benzyl-3-(2,5-dimethoxyphenyl)-N-
(2-PF1).
N-benzyl-3-chloro-N-
(
2-3ClBn
;
0.21 g, 0.5 mmol), 2,5-
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1446, 1487, 1574, 1598, 1628, 1979, 2854, 2923, 3031, 3095 dimethoxybenzeneboronic acid (0.14 g, 0.75 mmol),
1
cm-1; H NMR (CDCl3)

3.53 (s, 3H, Me), 3.96 (s, 2H, H3 and palladium(II)
acetate
(1.1
mg,
5
μmol),
2-
H4), 4.00 (br s, 2H, H2 and H5), 4.23 (s, 5H, Cp), 7.19-7.30 (m, dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (SPhos; 4.1
5H, Ph); 13C NMR (CDCl3)
38.9 (CH3, NMe), 64.2 (2CH, C2 and mg, 10 μmol) and tripotassium phosphate (0.21 g, 1.0 mmol)

C5), 65.0 (2CH, C3 and C4), 69.1 (5CH, Cp), 102.9 (C, C1, C-N), were charged in a degassed Schlenk. Tetrahydrofuran (1.0 mL)
127.8 and 128.5 (CH, C2’ and C6’, and CH, C3’ and C5’), 129.8 was added and the reaction mixture was heated at 60 °C for 14
(CH, C4’), 136.3 (C, C1’, C-C=O), 171.0 (C, C=O); MS (EI, 70 eV): h. The reaction mixture was cooled to room temperature.
319 [M], 254 [M-Cp], 207. The IR and 1H NMR data are as Water (5 mL) was added and the reaction mixture was
reported previously.62 Crystal data for 2-PhMe. C18H17FeNO, M extracted with AcOEt (3 x 10 mL). The combined organic layers
= 319.17, monoclinic, P 21/c, a = 9.6323(9), b = 10.0838(12), c = were dried over MgSO4, filtrated over cotton wool and
15.0175(18) Å,

= 95.784(4) °, V = 1451.2(3) Å3, Z = 4, d = concentrated under reduced pressure. Purification by column
1.461 g cm-3, μ = 1.036 mm-1. A final refinement on F2 with chromatography over silica gel (eluent: petroleum ether-
3316 unique intensities and 191 parameters converged at AcOEt-Et3N 69:30:1) gave 2-PF1 in 24% yield (0.14 g) as an
ωR(F2) = 0.0699 (R(F) = 0.0263) for 3050 observed reflections orange solid: Rf (petroleum ether-AcOEt 80:20) = 0.37; mp 58-
with I > 2σ(I). CCDC 2014651.
60 °C; IR (ATR) 697, 718, 808, 908, 999, 1025, 1040, 1052,
N-Ferrocenyl-3-methoxy-N-methylbenzamide
3OMeMe). The general procedure
ferrocenyl-3-methoxybenzamide (0.34 g) gave 2-3OMeMe (CDCl3)
(
2- 1106, 1149, 1178, 1216, 1259, 1307, 1336, 1374, 1407, 1475,
2
starting from N- 1502, 1578, 1602, 1637, 2249, 2832, 2932 cm-1; 1H NMR

3.68 (s, 3H, C2”-OMe), 3.77 (s, 3H, C5”-OMe), 3.96 (s,
(eluent: petroleum ether-AcOEt 70:30; Rf = 0.36) in 88% yield 2H, H3 and H4), 4.00 (br s, 2H, H2 and H5), 4.22 (s, 5H, Cp),
(33 mg) as a red glue oil. The analyses are as reported before 5.38 (br s, 2H, CH2), 6.66 (d, 1H, J = 2.9 Hz, H6”), 6.83 (dd, 1H, J
in the present paper.
= 8.9 and 2.9 Hz, H4”), 6.88 (d, 1H, J = 8.9 Hz, H3”), 7.27-7.31
N-Benzyl-3-chloro-N-ferrocenylbenzamide
(
2-3ClBn). (m, 2H, H5’ and H6’), 7.35-7.38 (m, 3H, H3”, H4” and H5”),
Sodium hydride (60% in mineral oil, 0.33 g, 7.5 mmol) was 7.39-7.41 (m, 3H, H2’ and H2”), 7.53 (d, 1H, J = 7.6 Hz, H4’); 13
C
added to a solution of 3-chloro-N-ferrocenylbenzamide (2-3Cl
;
NMR (CDCl3)  55.7 (CH2), 56.0 (CH3, C5”’-OMe), 56.5 (CH3,
0.85 g, 2.5 mmol) and tetrabutylammonium bromide (80 mg, C2”’-OMe), 64.7 (2CH, C2 and C5), 64.9 (2CH, C3 and C4), 69.2
0.25 mmol) in tetrahydrofuran (40 mL) at room temperature, (5CH, Cp), 104.3 (C, C1, C-N ferrocenyl), 113.1 (CH, C3”’), 113.8
and the reaction mixture was stirred for 15 min. Benzyl (CH, C4”’), 116.5 (CH, C6”’), 126.8 (C2” and C6”), 127.2 (CH,
bromide (0.89 mL, 7.5 mmol) was added and the reaction C6’), 127.3 (CH, C4”), 127.6 (CH, C5’), 128.9 (2CH, C3” and C5”),
mixture was stirred at room temperature for 3 h. Water (20 129.4 (CH, C2’), 131.0 (C, C3’), 131.4 (CH, C4’), 136.1 (C, C1’, C-
mL) was added and the reaction mixture was extracted with C=O), 138.0 (C, C1”’), 138.7 (C, C1”, C-CH2), 150.9 (C, C2”’),
AcOEt (3 x 20 mL). The combined organic layers were dried 153.9 (C, C5’”), 170.8 (C, C=O).
over MgSO4, filtrated over cotton wool and concentrated
N-Benzyl-N-ferrocenyl-3-(N-morpholino)benzamide
(2-
under reduced pressure. Purification by chromatography over PF2). N-benzyl-3-chloro-N-ferrocenylbenzamide (2-3ClBn; 0.21
silica gel (eluent: petroleum ether-AcOEt 90:10 to 70:30) gave g, 0.5 mmol), palladium(II) acetate (1.1 mg, 5 μmol), 2-
2-3ClBn in 90% yield (0.97 g) as an orange solid: Rf (petroleum dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (SPhos; 4.1
ether-AcOEt 80:20) = 0.40; mp 129-131 °C; IR (ATR) 664, 695, mg, 10 μmol) and sodium tert-butoxide (64 mg, 0.65 mmol)
719, 744, 758, 794, 823, 845, 881, 898, 923, 1001, 1016, 1026, were charged in a degassed Schlenk. Morpholine (52.5 µL) and
1076, 1104, 1233, 1293, 1311, 1333, 1349, 1377, 1404, 1421, tetrahydrofuran (1.0 mL) were added and the reaction mixture
1456, 1475, 1495, 1566, 1631, 1645, 3096 cm-1; 1H NMR was heated at 85 °C for 14 h. The reaction mixture was cooled
(CDCl3)
 3.90 (br s, 2H, H2 and H5), 3.95 (s, 2H, H3 and H4), to room temperature. Water (5 mL) was added and the
4.20 (s, 5H, Cp), 5.35 (br s, 2H, CH2), 7.14-7.15 (m, 2H, Ar), reaction mixture was extracted with AcOEt (3 x 10 mL). The
7.27-7.32 (m, 2H, Ar), 7.34 (s, 1H, H2’), 7.39-7.40 (m, 4H, H2”, combined organic layers were dried over MgSO4, filtrated over
H3”, H5” and H6”); 13C NMR (CDCl3)
 55.8 (CH2), 64.8 (2CH, C2 cotton wool and concentrated under reduced pressure.
and C5), 65.1 (2CH, C3 and C4), 69.3 (5CH, Cp), 103.7 (C, C1, C- Purification by column chromatography over silica gel (eluent:
N), 126.6 (CH, Ar), 126.8 (CH, Ar), 127.4 (2CH, C2” and C6”), petroleum ether-AcOEt-Et3N 69:30:1; Rf = 0.19) gave 2-PF2 in
128.7 (CH, Ar), 128.9 (2CH, C3” and C5”), 129.1 (CH, C2’), 130.1 79% yield (0.19 g) as an orange solid: mp 66-68 °C; IR (ATR)
(CH, Ar), 134.0 (C, C3’, C-Cl), 138.1 (C, Ar), 138.4 (C, Ar), 169.3 664, 695, 747, 792, 817, 864, 920, 946, 1000, 1028, 1069,
(C, C=O). Crystal data for 2-3ClBn. C24H20ClFeNO, M = 429.71, 1106, 1120, 1146, 1242, 1263, 1305, 1338, 1374, 1408, 1439,
1
triclinic, P –1, a = 10.9882(5), b = 12.9018(5), c = 14.8228(5) Å, 1475, 1576, 1598, 1638, 2855, 2959 cm-1; H NMR (CDCl3)

12 | New J. Chem., 2020, 00, 1-3
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7. F. Monnier and M. Taillefer, Angew. Chem. Int. Ed., 2009, 48,
3.01 (t, 4H, J = 4.8 Hz, 2CH2-N morpholino), 3.80 (t, 4H, J = 4.8
Hz, 2CH2-O), 3.92 (s, 2H, H3 and H4), 3.96 (br s, 2H, H2 and
H5), 4.19 (s, 5H, Cp), 5.33 (br s, 2H, CH2-N benzyl), 6.82 (d, 1H,
J = 7.8 Hz, H6’), 6.85 (dd, 1H, J = 7.8 and 2.4 Hz, H4’), 6.87 (s,
1H, H2’), 7.12 (t, 1H, J = 7.8 Hz, H5’), 7.27-7.29 (m, 1H, H4”),
View Article Online
6954-6971.
DOI: 10.1039/D0NJ03470C
8. F. Monnier and M. Taillefer, Top. Organomet. Chem., 2013, 46,
173-204.
9. C. Sambiagio, S. P. Marsden, A. J. Blacker and P. C. McGowan,
Chem. Soc. Rev., 2014, 43, 3525-3550.
10. A. Klapars, J. C. Antilla, X. Huang and S. L. Buchwald, J. Am.
Chem. Soc., 2001, 123, 7727-7729.
11. G. J. Sherborne, S. Adomeit, R. Menzel, J. Rabeah, A. Brückner,
M. R. Fielding, C. E. Willans and B. N. Nguyen, Chem. Sci., 2017,
8, 7203-7210.
7.36-7.39 (m, 4H, H2”, H3”, H5” and H6”); 13C NMR (CDCl3)

49.3 (2CH2, CH2-N morpholino), 55.7 (CH2, CH2-N benzyl), 64.5
(2CH, C2 and C5), 64.9 (2CH, C3 and C4), 66.9 (2CH2, CH2-O
morpholino), 69.2 (5CH, Cp), 104.1 (C, C1), 116.0 (CH, C2’),
117.5 (CH, C4’), 120.3 (CH, C6’), 126.8 and 128.9 (2CH, C2” and
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25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
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52
53
54
55
56
57
58
59
60
C6”, and 2CH, C3” and C5”), 127.2 (CH, C4”), 128.7 (CH, C5’), 12. A. Klapars, X. Huang and S. L. Buchwald, J. Am. Chem. Soc.,
2002, 124, 7421-7428.
13. E. R. Strieter, B. Bhayana and S. L. Buchwald, J. Am. Chem. Soc.,
2009, 131, 78-88.
14. E. R. Strieter, D. G. Blackmond and S. L. Buchwald, J. Am. Chem.
Soc., 2005, 127, 4120-4121.
15. J. W. Tye, Z. Weng, A. M. Johns, C. D. Incarvito and J. F. Hartwig,
J. Am. Chem. Soc., 2008, 130, 9971-9983.
137.0 (C, C1’, C-C=O), 138.8 (C, C1”, C-CH2 benzyl), 150.8 (C,
C3’, C-N morpholino), 171.0 (C, C=O).
Conclusions
Thus, while it is not suitable to forge C-N bonds between
iodoferrocene and partners such as benzylamine, pyrazole and
16. I. Güell and X. Ribas, Eur. J. Org. Chem., 2014, 2014, 3188-3195.
imidazole, our protocol allows for the coupling of 17. M. Rovira, L. Jašiková, E. Andris, F. Acuña-Parés, M. Soler, I.
Güell, M.-Z. Wang, L. Gómez, J. M. Luis, J. Roithová and X. Ribas,
Chem. Commun., 2017, 53, 8786-8789.
18. X. Ribas and I. Güell, Pure Appl. Chem., 2014, 86, 345-360.
19. A. Casitas and X. Ribas, Chem. Sci., 2013, 4, 2301-2318.
iodoferrocene with primary and cyclic secondary amides to
rapidly deliver libraries of ferrocene amide derivatives. It is
complementary to the method developed by Bolm to create C-
N bonds between iodoferrocene and azoles or, as we have
20. S.-L. Zhang, L. Liu, Y. Fu and Q.-X. Guo, Organometallics, 2007,
shown in the present paper, between iodoferrocene and an
26, 4546-4554.
acetamide bearing electron-withdrawing groups. Extension of
these results to the copper-catalysed amidation with
substituted iodoferrocenes is currently under investigation in
the lab and will be reported in due course.
21. K. K. Gurjar and R. K. Sharma, ChemCatChem, 2017, 9, 862-869.
22. M. Sato, S. Ebine and S. Akabori, Synthesis, 1981, 472-473.
23. C. Metallinos, J. John, J. Zaifman and K. Emberson, Adv. Synth.
Catal., 2012, 354, 602-606.
24. M. Herberhold, M. Ellinger and W. Kremnitz, J. Organomet.
Chem., 1983, 241, 227-240.
25. B. Bildstein, M. Malaun, H. Kopacka, K.-H. Ongania and K.
Wurst, J. Organomet. Chem., 1999, 572, 177-187.
26. S. Özçubukçu, E. Schmitt, A. Leifert and C. Bolm, Synthesis,
2007, 389-392.
27. P. Srinivas, S. Prabhakar, F. Chevallier, E. Nassar, W. Erb, V.
Dorcet, V. Jouikov, P. Radha Krishna and F. Mongin, New J.
Chem., 2016, 40, 9441-9447.
28. T. Jernei, S. Bȍsze, R. Szabó, F. Hudecz, K. Majrik and A.
Csámpai, Tetrahedron, 2017, 73, 6181-6192.
29. J. Yin and S. L. Buchwald, Org. Lett., 2000, 2, 1101-1104.
30. B. P. Fors, P. Krattiger, E. Strieter and S. L. Buchwald, Org. Lett.,
2008, 10, 3505-3508.
31. B. P. Fors, K. Dooleweerdt, Q. Zeng and S. L. Buchwald,
Tetrahedron, 2009, 65, 6576-6583.
32. C. A. Fleckenstein and H. Plenio, Chem. Soc. Rev., 2010, 39, 694-
711.
33. C. A. Fleckenstein and H. Plenio, Organometallics, 2007, 26,
2758-2767.
34. M. W. Hooper, M. Utsunomiya and J. F. Hartwig, J. Org. Chem.,
2003, 68, 2861-2873.
35. J. Alonso, N. Halland, M. Nazare, O. R'Kyek, M. Urmann and A.
Lindenschmidt, Eur. J. Org. Chem., 2011, 234-237.
36. H. Xu and C. Wolf, Chem. Commun., 2009, 1715-1717.
37. D. P. Phillips, X.-F. Zhu, T. L. Lau, X. He, K. Yang and H. Liu,
Tetrahedron Lett., 2009, 50, 7293-7296.
38. R. Hosseinzadeh, M. Tajbakhsh, M. Mohadjerani and H.
Mehdinejad, Synlett, 2004, 1517-1520.
39. W. Deng, Y.-F. Wang, Y. Zou, L. Liu and Q.-X. Guo, Tetrahedron
Lett., 2004, 45, 2311-2315.
Conflicts of interest
There are no conflicts to declare.
Acknowledgements
This work was supported by the Université de Rennes 1 and
CNRS. The authors would like to thank Rennes Métropole for a
doctoral mobility fellowship (L. K.). We gratefully acknowledge
the Fonds Européen de Développement Régional (FEDER; D8
Venture Bruker AXS diffractometer). This research has been
performed as part of the Indo-French ‘Joint Laboratory for
Natural Products and Synthesis towards Affordable Health’.
Notes and references
1. I. Goldberg, Ber. Dtsch. chem. Ges., 1906, 39, 1691-1692.
2. A. M. Thomas, A. Sujatha and G. Anilkumar, Mini-Rev. Org.
Chem., 2015, 12, 3-23.
3. I. P. Beletskaya and A. V. Cheprakov, Organometallics, 2012, 31,
7753-7808.
4. J. Bariwal and E. Van der Eycken, Chem. Soc. Rev., 2013, 42,
9283-9303.
5. A. R. Muci and S. L. Buchwald, Top. Curr. Chem., 2002, 219, 131-
209.
6. P. Ruiz-Castillo and S. L. Buchwald, Chem. Rev., 2016, 116,
12564-12649.
This journal is © The Royal Society of Chemistry 20xx
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New Journal of Chemistry
Page 14 of 15
ARTICLE
Journal Name
1
2
3
4
5
6
7
8
9
40. R. Amara, G. Bentabed-Ababsa, M. Hedidi, J. Khoury, H. Awad,
E. Nassar, T. Roisnel, V. Dorcet, F. Chevallier, Z. Fajloun and F.
Mongin, Synthesis, 2017, 49, 4500-4516.
41. M.-G. Wang, H. Yu, J. Wu and Z.-C. Shang, Synthesis, 2013, 45,
1955-1964.
42. D. M. Nguyen and D. H. Miles, Synth. Commun., 2009, 39, 2829-
2836.
43. H. Chen, Y.-X. Wang, Y.-X. Luan and M. Ye, Angew. Chem., Int.
Ed., 2020, 59, 9428-9432.
View Article Online
DOI: 10.1039/D0NJ03470C
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
44. G. R. Kracke, M. R. VanGordon, Y. V. Sevryugina, P. J. Kueffer, K.
Kabytaev, S. S. Jalisatgi and M. F. Hawthorne, ChemMedChem,
2015, 10, 62-67.
45. X. F. Liu, R. F. Li, X. Fu, H. Shen, M. Wen and X. Feng, Russ. J.
Coord. Chem., 2018, 44, 353-358.
46. T. Kovacevic, M. Mesic, A. Avdagic and M. Zegarac, Tetrahedron
Lett., 2018, 59, 4180-4182.
47. M. Sugahara and T. Ukita, Chem. Pharm. Bull., 1997, 45, 719-
721.
48. H. E. Gottlieb, V. Kotlyar and A. Nudelman, J. Org. Chem., 1997,
62, 7512-7515.
49. M. S. Inkpen, S. Du, M. Driver, T. Albrecht and N. J. Long, Dalton
Trans., 2013, 42, 2813-2816.
50. A. Zirakzadeh, A. Herlein, M. A. Gross, K. Mereiter, Y. Wang and
W. Weissensteiner, Organometallics, 2015, 34, 3820-3832.
51. E. A. Schmittling and J. S. Sawyer, Tetrahedron Lett., 1991, 32,
7207-7210.
52. R. Peters and D. F. Fischer, Org. Lett., 2005, 7, 4137-4140.
53. L. G. Czaplewski, I. Collins, E. A. Boyd, D. Brown, S. P. East, M.
Gardiner, R. Fletcher, D. J. Haydon, V. Henstock, P. Ingram, C.
Jones, C. Noula, L. Kennison, C. Rockley, V. Rose, H. B.
Thomaides-Brears, R. Ure, M. Whittaker and N. R. Stokes,
Bioorg. Med. Chem. Lett., 2009, 19, 524-527.
54. G. M. Sheldrick, Acta Crystallogr., Sect. A, 2015, 71, 3-8.
55. G. M. Sheldrick, Acta Crystallogr., Sect. C, 2015, 71, 3-8.
56. L. J. Farrugia, J. Appl. Crystallogr., 1997, 30, 565.
57. L. Barišic, M. Čakic, K. A. Mahmoud, Y.-n. Liu, H.-B. Kraatz, H.
Pritzkow, S. I. Kirin, N. Metzler-Nolte and V. Rapić, Chem. Eur. J.,
2006, 12, 4965-4980.
58. T.-a. Okamura, K. Sakauye, M. Doi, H. Yamamoto, N. Ueyama
and A. Nakamura, Bull. Chem. Soc. Jpn., 2005, 78, 1270-1278.
59. G. R. Knox, P. L. Pauson, D. Willison, E. Solčániová and S. Toma,
Organometallics, 1990, 9, 301-306.
60. K. Heinze and D. Siebler, Z. Anorg. Allg. Chem., 2007, 633, 2223-
2233.
61. E. Patterson, B. Brautigam, W. Farnsworth, M. Eric, G. Wu and S.
Contakes, Inorg. Chem. Commun., 2015, 51, 36-39.
62. R. Damrauer, J. Organometal. Chem., 1971, 32, 121-126.
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TOC
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O
Cl
CuI
K3PO4
DMEDA
O
I
N
H
Fe
Fe
O
N
Dioxane
90 °C
14 h
9
N
Fe
(85% yield)
CH2Ph
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A general copper-promoted amidation of iodoferrocene is described toward original scaffolds
that can be further functionalized by cross-coupling reactions.
1