Synthesis of 1,1′-diacetylferrocene imines via catalytic oxo/imido heterometathesis

Article abstract of DOI:10.1016/j.jorganchem.2019.01.018

A novel C[dbnd]N bond forming strategy based on oxo/imido heterometathesis between N-sulfinylamines and ketones, catalyzed by a well-defined silica-supported Ti imido complex, was applied to prepare a series of hardly accessible 1,1’-diacetylferrocene ket

Full text of DOI:10.1016/j.jorganchem.2019.01.018

Accepted Manuscript
Synthesis of 1,1’-Diacetylferrocene imines via catalytic oxo/imido heterometathesis
Andrey V. Pichugov, Nikolai S. Bushkov, Liudmila V. Erkhova, Pavel A. Zhizhko,
Svetlana Ch Gagieva, Dmitry N. Zarubin, Nikolai A. Ustynyuk, Dmitry A. Lemenovskii,
Haojie Yu, Li Wang
PII:
S0022-328X(18)31040-4
DOI:
https://doi.org/10.1016/j.jorganchem.2019.01.018
JOM 20696
Reference:
To appear in: Journal of Organometallic Chemistry
Received Date: 30 December 2018
Revised Date: 21 January 2019
Accepted Date: 23 January 2019
Please cite this article as: A.V. Pichugov, N.S. Bushkov, L.V. Erkhova, P.A. Zhizhko, S.C. Gagieva,
D.N. Zarubin, N.A. Ustynyuk, D.A. Lemenovskii, H. Yu, L. Wang, Synthesis of 1,1’-Diacetylferrocene
imines via catalytic oxo/imido heterometathesis, Journal of Organometallic Chemistry (2019), doi: https://
doi.org/10.1016/j.jorganchem.2019.01.018.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
our customers we are providing this early version of the manuscript. The manuscript will undergo
copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please
note that during the production process errors may be discovered which could affect the content, and all
legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Synthesis of 1,1’-Diacetylferrocene Imines via Catalytic
Oxo/Imido Heterometathesis
Andrey V. Pichugov,†,‡ Nikolai S. Bushkov,†,§ Liudmila V. Erkhova,§ Pavel A. Zhizhko,†,* Svetlana
Ch. Gagieva,§ Dmitry N. Zarubin,†,* Nikolai A. Ustynyuk†, Dmitry A. Lemenovskii,§ Haojie Yu,¶ Li
Wang¶
† A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
Vavilov str., 28, 119991 Moscow (Russia)
‡ Higher Chemical College, D. Mendeleev University of Chemical Technology of Russia,
Miusskaya sq., 9, 125047 Moscow (Russia)
§ Department of Chemistry, Moscow State University, Vorob’evy Gory 1, 119992 Moscow (Russia)
¶ State Key Laboratory of Chemical Engineering, College of Chemical and Biological Engineering,
Zhejiang University, 310027 Hangzhou (People’s Republic of China)
E-mail: zhizhko@ineos.ac.ru
E-mail: zaroubine@ineos.ac.ru
Abstract
A novel C=N bond forming strategy based on oxo/imido heterometathesis between N-sulfinylamines
and ketones, catalyzed by a well-defined silica-supported Ti imido complex, was applied to prepare
a series of hardly accessible 1,1’-diacetylferrocene ketimines.
Introduction
During the sixty-year history, the chemistry of ferrocene and its derivatives developed extensively
and in a broad-spectrum manner [1]. Complexes based on 1,1'-bis(diphenylphosphino)ferrocene are
1

ACCEPTED MANUSCRIPT
known to exhibit high activity in homogeneous catalysis and their chiral analogs have been used
with success in enantioselective catalysis [1a]. For medical applications, of most interest are
ferrocene derivatives which showed anticancer effect [2]. Materials with practically valuable
properties have been synthesized based on ferrocene, among which are redox switchable molecular
systems [3], molecular recognition and sensing materials [4], metallocene molecular gears [5],
molecular machines [6] and other nanovehicles [7], and rod-like ferrocenylmesogenes [8]. Ferrocene
chemistry is well-established and routes for binding heteroatoms (O, N, P, S etc.) either directly to
the ring carbon atom or to the side-chain Cα atom have been developed. However certain derivatives
remain difficult to access due to specific features of the ferrocene core. For instance, ferrocenyl-
based amines [9] are not easily available because the standard route to aromatic amines (nitration
followed by reduction) cannot be applied due to oxidation of the ferrocene core under nitration
conditions [10]. Nucleophilic addition to imines or their reduction is an alternative general strategy
for amine preparation. This route seems particularly attractive in the ferrocene chemistry because
acetyl (and other alkanoyl/arenoyl) derivatives are readily accessible. However, we were surprised
to find that ferrocenyl-based ketimines are very difficult to obtain via classical condensation of
ketone and amine [11]. Even with the simplest anilines the reactions require tedious multiday
procedures and give only moderate yields (Scheme 1, a) [11c]. Significant improvement is achieved
by the use of TiCl4 as a homogeneous catalyst (Scheme 1, b) [12]. It should be also noted that
ferrocenylketone hydrazones can be obtained via trialkylaluminum-assisted condensation [13].
2

ACCEPTED MANUSCRIPT
Scheme 1. Comparison of different methods for the preparation of 1,1’-diacetylferrocene imines.
Scheme 2. Catalytic cycle of oxo/imido heterometathesis between N-sulfinylamines and ketones.
We have recently elaborated an alternative X=N bond forming strategy based on the catalytic
oxo/imido heterometathesis reactions [14]. In particular, we have previously shown that oxo and
3

ACCEPTED MANUSCRIPT
imido complexes of early transition metals catalyze imidation of carbonyl compounds with
N-sulfinylamines according to the catalytic cycle shown in Scheme 2. This reaction represents a
novel water-free method for preparation of imines and proved useful in preparation of ketimines that
are difficult to access via classical acid-catalyzed condensation (e.g. employing poorly nucleophilic
amines or acid-sensitive substrates). Herein we report that this approach is also very efficient in the
case of acetyl derivatives of ferrocene (Scheme 1, c) and show that oxo/imido heterometathesis
catalyzed by a well-defined silica-supported Ti imido complex (≡SiO)Ti(NtBu)(Me2Pyr)(py)2
(Ti/SiO2, Me2Pyr = 2,5-dimethylpyrrolyl, py = pyridine) provides a straightforward access to a wide
range of imines of 1,1’-diacetylferrocene.
Results and Discussion
Ti/SiO2 heterogeneous catalyst was designed using the Surface Organometallic Chemistry
approach [15]. Its preparation was described previously and includes grafting of the imido complex
Ti(NtBu)(Me2Pyr)2(py)2 onto a surface of silica partially dehydroxylated at 700°C (SiO2-700) to give
a well-defined silica-supported Ti imido complex (≡SiO)Ti(NtBu)(Me2Pyr)(py)2 (Scheme 3), that
was fully characterized by IR and solid-state NMR spectroscopy, as well as by elemental and mass
balance analyses [14a]. This catalyst was found to be significantly more active towards imidation of
carbonyl compounds with N-sulfinylamines as compared to the other previously reported systems
based on V, Mo, and Ta. This observation is in agreement with the general reactivity trend
recognized in transition metal imido chemistry, where the most reactive imides are found when
going to the left across the d-block of the Periodic table [16]. Immobilization of the catalyst on the
surface of the support plays an essential role, since it prevents the deactivation of the active species
via the formation of catalytically inert µ-oxo bridged oligomers at the step of the formation of Ti=O
intermediate (Scheme 2).
4

ACCEPTED MANUSCRIPT
Scheme 3. Preparation of Ti/SiO2 catalyst.
The catalyst was tested in the imidation of 1,1’-diacetylferrocene with different N-sulfinylamines
(Table 1). The reactions were carried out in boiling toluene and monitored by IR spectroscopy to
ensure the disappearance of the carbonyl C=O band at 1676 cm−1 and the appearance of the C=N
band in 1640–1620 cm−1 region. Evolution of SO2 serves as a driving force for shifting the
equilibrium, quantitative conversions being reached in most reactions. In certain cases, separation of
the heterogeneous catalyst and crystallization from toluene/heptane straightforwardly gave the
analytically pure product; however, in some cases additional recrystallization was required, which
lowered the final yield. It should be noted that N-sulfinylamines, used as a source of the imido
group, are readily available compounds that can be prepared from the corresponding anilines in
nearly quantitative yields by treatment with SOCl2 [17].
Table 1. Preparation of 1,1’-diacetylferrocene imines by oxo/imido heterometathesis.
#
ArNSO
Ti, mol%a
Time
Yieldb
1
2
3
1
1
1
30 min
1 h
90%
93%
77%
1.5 h
5

ACCEPTED MANUSCRIPT
4
5
6
7
8
9
1
1
1
2
2
3
3 h
72%
43%c
76%
71%
81%
65%
4 h
3 h
30 min
2.5 h
2 h
10
11
3
2 h
64%c
3
5
1.5 h
4 h
46%c
55%c
12
a
Per carbonyl group (based on the total Ti content in the catalyst as determined by elemental
analysis, 0.23 mmol/g). b Isolated yield. c Additional recrystallization was required.
While the influence of electronic effects in N-sulfinylaniline is not obvious from this data, steric
factor clearly plays a key role in the reaction. While ortho-non-substituted N-sulfinylanilines reacted
smoothly at 1 mol% catalyst loading, ortho-substituted N-sulfinylanilines typically required higher
catalyst loadings to reach quantitative conversions, up to 5 mol% in the case of very bulky
tribromophenylaniline derivative (entry 12). It should be noted that the imines of extremely poorly
nucleophilic polyhalogenated anilines (entries 10–12) are often challenging to obtain even in the
case of ordinary ketones. Thus, the isolation of the corresponding acetylferrocene derivatives
demonstrates the remarkable potential of oxo/imido heterometathesis reactions in preparation of
difficult imines, even though lower yields were observed in these cases (possibly due to higher
propensity of these compounds to hydrolysis which complicated their crystallization).
6

ACCEPTED MANUSCRIPT
We have shown that oxo/imido heterometathesis catalyzed by silica-supported Ti imido complex
and employing N-sulfinylamines as imidating agents serves as a powerful imidation methodology
and allows for the efficient and high-yielding preparation of ketimines of 1,1’-diacetylferrocene that
are difficult to access via classical methods.
Experimental Section
The catalyst Ti/SiO2 was prepared as described before [14a]. Catalytic runs were performed under
argon atmosphere using standard Schlenk techniques. Toluene was distilled from Na/benzophenone
and stored over activated 3 Å MS. Importantly, CDCl3 should be distilled from CaH2 in order to
remove the acidic impurities that facilitate decomposition of ferrocene derivatives in chloroform
(poor quality NMR spectra were sometimes obtained if CDCl3 was only distilled from usually
recommended P2O5). 1,1’-diacetylferrocene was synthesized according to a standard procedure.
N-sulfinylanilines were prepared according to standard procedures using Merck SOCl2 (“for
synthesis” grade) and freshly distilled or recrystallized anilines [17]. 1H, 13C, 19F NMR spectra were
recorded using Bruker Avance 400 and Agilent 400-MR spectrometers. Chemical shifts (δ) are
1
given in ppm and coupling constants (J) in Hz. H chemical shifts were referenced relative to the
13
residual solvent peak: 7.26 (CHCl3 in CDCl3). C chemical shifts were referenced relative to the
solvent peak: 77.00 (CDCl3). 19F spectra were referenced externally to CFCl3. Monitoring of the
reactions by IR spectroscopy was performed using Specord M82 spectrometer. IR spectra of isolated
products were recorded in KBr pellets on a Bruker Tensor 37 FTIR spectrometer. Wavenumbers are
given in cm−1. Elemental analysis was performed at the Laboratory of Microanalysis of the INEOS
RAS.
General procedure for the preparation of imines. A double-neck Schlenk flask was charged
under argon with Ti/SiO2, dry toluene, 1,1’-diacetylferrocene and N-sulfinylamine, and the mixture
was stirred under reflux. The reaction was monitored by IR spectroscopy by taking aliquots of the
7

ACCEPTED MANUSCRIPT
reaction mixture until complete disappearance of the carbonyl C=O band at 1676 cm−1. The catalyst
was filtered off in air using a glass filter and the product was isolated by crystallization from the
appropriate solvent and dried in vacuum. Crystallization was typically performed under argon,
however most of the products do not show evidence of decomposition upon short exposure to air.
Acknowledgements
This work was supported by Russian Foundation for Basic Research (grant 18-53-53014).
Supporting Information
Details on the preparation and characterization of compounds 1–12.
References
[1]
[2]
(a) Ferrocenes: Homogeneous Catalysis, Organic Synthesis, Materials Science (Eds.: A.
Togni, T. Hayashi), VCH, 1995;
(b) L. Wang, H. Yu, Synthesis, Properties and Applications of Ferrocene-Based Derivatives,
Polymers and Hydrogels, Springer, 2018.
(a) C.G. Hartinger, N. Metzler-Nolte, P.J. Dyson, Organometallics 31 (2012) 5677-5685;
(b) J. Spencer, J. Amin, M. Wang, G. Packham, S.S.S. Alwi, G.J. Tizzard, S.J. Coles, R.M.
Paranal, J.E. Bradner, T.D. Heightman, ACS Med. Chem. Lett. 2 (2011) 358-362;
(c) V.N. Babin, Y.A. Belousov, V.I. Borisov, V.V. Gumenyuk, Y.S. Nekrasov, L.A.
Ostrovskaya, I.K. Sviridova, N.S. Sergeeva, A.A. Simenel, L.V. Snegur, Russ. Chem. Bull.
63 (2014) 2405-2422.
[3]
(a) G. Grelaud, G. Argouarch, M.P. Cifuentes, M.G. Humphrey, F. Paul, Tetrahedron 69
(2013) 3316-3322;
(b) E.M. Broderick, N. Guo, C.S. Vogel, C. Xu, J. Sutter, J.T. Miller, K. Meyer, P.
Mehrkhodavandi, P.L. Diaconescu, J. Am. Chem. Soc. 133 (2011) 9278-9281.
8

ACCEPTED MANUSCRIPT
[4]
R. Sun, L. Wang, H. Yu, Z.-u. Abdin, Y. Chen, J. Huang, R. Tong, Organometallics 33
(2014) 4560-4573.
[5]
[6]
[7]
A.M. Stevens, C.J. Richards, Tetrahedron Lett. 38 (1997) 7805-7808.
G. Rapenne, G. Jimenez-Bueno, Tetrahedron 63 (2007) 7018-7026.
Y. Shirai, J.-F. Morin, T. Sasaki, J.M. Guerrero, J.M. Tour, Chem. Soc. Rev. 35 (2006)
1043-1055.
[8]
(a) C. Imrie, P. Engelbrecht, C. Loubser, C.W. McCleland, Appl. Organomet. Chem. 15
(2001) 1-15;
(b) T. Chen, D. Wang, L.-H. Gan, Y. Matsuo, J.-Y. Gu, H.-J. Yan, E. Nakamura, L.-J. Wan,
J. Am. Chem. Soc. 136 (2014) 3184-3191;
(c) O.N. Kadkin, E.H. Kim, S.Y. Kim, M.-G. Choi, Polyhedron 28 (2009) 1301-1307;
(d) M.V. Makarov, D.A. Lemenovskii, A.E. Bruce, M.R.M. Bruce, V.P. Dyadchenko, Liq.
Cryst. 33 (2006) 485-494.
[9]
(a) F.S. Arimoto, A.C. Haven, J. Am. Chem. Soc. 77 (1955) 6295-6297;
(b) E.M. Acton, R.M. Silverstein, J. Org. Chem. 24 (1959) 1487-1490;
(c) G.R. Knox, P.L. Pauson, J. Chem. Soc. (1961) 4615-4618;
(d) A. Shafir, M.P. Power, G.D. Whitener, J. Arnold, Organometallics 19 (2000) 3978-3982.
[10] H. Grubert, K.L. Rinehart, Tetrahedron Lett. 1 (1959) 16-17.
[11] (a) C. López, J. Sales, X. Solans, R. Zquiak, J. Chem. Soc., Dalton Trans. (1992) 2321-2328;
(b) R. Bosque, C. López, J. Sales, X. Solans, M. Font-Bardía, J. Chem. Soc., Dalton Trans.
(1994) 735-745;
(c) R. Bosque, C. López, X. Solans, M. Font-Bardia, Organometallics 18 (1999) 1267-1274;
(d) T.-Y. Lee, P.-R. Chiang, M.-C. Tsai, C.-Y. Lin, J.-H. Huang, J. Mol. Struct. 935 (2009)
102-109.
9

ACCEPTED MANUSCRIPT
[12] H.-X. Wang, R.-Q. Gao, X.-L. Yang, L. Wan, H.-F. Wu, F.-Y. Geng, R. Jin, Polyhedron 26
(2007) 1037-1044.
[13] B. Bildstein, P. Denifl, Synthesis 1994 (1994) 158-160.
[14] (a) P.A. Zhizhko, A.V. Pichugov, N.S. Bushkov, F. Allouche, A.A. Zhizhin, D.N. Zarubin,
N.A. Ustynyuk, Angew. Chem. Int. Ed. 57 (2018) 10879-10882;
(b) P.A. Zhizhko, A.A. Zhizhin, O.A. Belyakova, Y.V. Zubavichus, Y.G. Kolyagin, D.N.
Zarubin, N.A. Ustynyuk, Organometallics 32 (2013) 3611-3617;
(c) P.A. Zhizhko, A.A. Zhizhin, D.N. Zarubin, N.A. Ustynyuk, Mendeleev Commun. 22
(2012) 64-66;
(d) P.A. Zhizhko, A.A. Zhizhin, D.N. Zarubin, N.A. Ustynyuk, D.A. Lemenovskii, B.N.
Shelimov, L.M. Kustov, O.P. Tkachenko, G.A. Kirakosyan, J. Catal. 283 (2011) 108-118;
(e) A.A. Zhizhin, D.N. Zarubin, N.A. Ustynyuk, Mendeleev Commun. 19 (2009) 165-166;
(f) A.A. Zhizhin, D.N. Zarubin, N.A. Ustynyuk, Tetrahedron Lett. 49 (2008) 699-702.
[15] C. Copéret, A. Comas-Vives, M.P. Conley, D.P. Estes, A. Fedorov, V. Mougel, H. Nagae, F.
Núñez-Zarur, P.A. Zhizhko, Chem. Rev. 116 (2016) 323-421.
[16] (a) W.A. Nugent, R.J. McKinney, R.V. Kasowski, F.A. Van-Catledge, Inorg. Chim. Acta 65
(1982) L91-L93;
(b) W.A. Nugent, J.M. Mayer, Metal–Ligand Multiple Bonds, Wiley, New York, 1988;
(c) D.E. Wigley, Prog. Inorg. Chem. 42 (1994) 239-482.
[17] (a) A. Michaelis, Justus Liebigs Ann. Chem. 274 (1893) 200-266;
(b) G. Kresze, A. Maschke, R. Albrecht, K. Bederke, H.P. Patzschke, H. Smalla, A. Trede,
Angew. Chem. Int. Ed. 1 (1962) 89-98;
(c) A. Meller, W. Maringgele, H. Fetzer, Chem. Ber. 113 (1980) 1950-1961.
10

ACCEPTED MANUSCRIPT
Oxo/imido heterometathesis provides a novel catalytic C=N bond forming strategy;
N-sulfinylamines as convenient imidating agents;
Efficient synthesis of hardly accessible 1,1’-diacetylferrocene ketimines.