Synthesis of Amidines from Amides Using a Nickel-Catalyzed Decarbonylative Amination through CO Extrusion Intramolecular Recombination Fragment Coupling

Article abstract of DOI:10.1002/chem.201702867

A catalytic synthesis of amidines from amides has been established for the first time. The newly developed CO extrusion recombination process takes advantage of an inexpensive nickel(II) catalyst and provides the corresponding amidines with high efficiency. The intramolecular fragment coupling shows excellent chemoselectivity, starts from readily available amides, and provides a valuable alternative amidine synthesis protocol.

Full text of DOI:10.1002/chem.201702867

A Journal of
Accepted Article
Title: Synthesis of Amidines from Amides using a Nickel Catalyzed
Decarbonylative Amination via CO Extrusion Intramolecular
Recombination Fragment Coupling
Authors: Magnus Rueping
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Chem. Eur. J. 10.1002/chem.201702867
Link to VoR: http://dx.doi.org/10.1002/chem.201702867
Supported by

10.1002/chem.201702867
Chemistry - A European Journal
COMMUNICATION
Synthesis of Amidines from Amides using a Nickel Catalyzed
Decarbonylative Amination via CO Extrusion Intramolecular
Recombination Fragment Coupling
Xiangqian Liu,[a] Huifeng Yue,[a] Jiaqi Jia,[a] Lin Guo[a] and Magnus Rueping*[a,b]
Abstract: A catalytic synthesis of amidines from amides has been
established for the first time. The newly developed CO extrusion
recombination process takes advantage of an inexpensive nickel(II)
catalyst and provides the corresponding amidines with high
efficiency. The intramolecular fragment coupling shows excellent
chemoselectivity, starts from readily available amides and provides a
valuable alternative amidine synthesis protocol.
the ester affording the corresponding morpholine amide
product.[13l] Additionally, very useful protocols for the direct
amidation of esters with N-methyl anilines[13j] and nitroarenes[13k]
were recently described. Interestingly, in the presence of an
excess of amine and nickel catalyst, activated amides can also
undergo a transamidation.[10e]
However, during our investigations, we noticed that when
N-methyl aniline was applied in reaction with phenyl quinoline-2-
carboxylate, significant amounts of a byproduct were formed in
addition to the amide product. This byproduct was analyzed to
be the corresponding amidine. Thus, we wondered whether it
would be possible to develop a general method in which
amidines are directly synthesized starting from esters or amides.
Interestingly, the formation of amidines starting from amides has
not been described before. In order to prevent the usage of
larger amounts of secondary amines and to circumvent the
typical formation of byproducts (i.e. phenols or amines when
starting from esters or activated amides) we decided to examine
an extrusion recombination fragment coupling strategy (Figure
1).
Amidines are highly important functional groups and are
part of various natural products, pharmaceutical agents,
agrochemical compounds, as well as materials.[1] In addition,
amidines are well established and found application as strong,
neutral organic bases[2] and as precursors in the synthesis of
structurally important heterocycles.[3] In recent years the
potential of amidines to act as nucleophilic organocatalysts has
also been recognized and successfully exploited in a wide range
of reactions, including asymmetric transformations.[4] Various
methods have been described for the synthesis of different
amidine derivatives.[5] Given their importance, straightforward
and general methods for the synthesis of N,N-disubstituted
semicyclic amidines are still highly desired.
Herein we describe an unconventional protocol for the
efficient synthesis of amidine derivatives through a nickel-
catalyzed intramolecular CO extrusion recombination reaction of
amide derivatives without the use of external amine nucleophiles.
Amides are key building blocks of proteins and are broadly
existing in natural and manufactured organic molecules.[6] In
sharp contrast with their natural abundance, methodologies to
functionalize the amide moieties are largely limited due to the
resonance stability of the amide bond.[6,7] Nevertheless, nickel
complexes[8] were recently found to activate amide substrates,[9-
11]
offering new opportunities for transformations, which were
previously not accessible via conventional protocols.
With the aim to expand the nickel-catalyzed inert bond
functionalization,[8-10,12,13] we recently developed direct
aminations of esters and amides with imines as nucleophiles.[13l]
The reactions provide primary amines but could not be extended
to secondary amines as these directly result in the amide
formation.[13l] For instance, use of secondary amines, such as
morpholine was reported to result in the aminolysis reaction of
[a]
[b]
Dr. X. Liu, H. Yue, J. Jia, L. Guo, Prof. Dr. M. Rueping
Institute of Organic Chemistry, RWTH Aachen University
Landoltweg 1, D-52074 Aachen, Germany
E-mail: magnus.rueping@rwth-aachen.de
Prof. Dr. M. Rueping
Figure 1. CO extrusion recombination protocol for the synthesis of amidines
from readily available amides.
King Abdullah University of Science and Technology (KAUST)
KAUST Catalysis Center (KCC), Thuwal, 23955-6900 (Saudi
Arabia)
E-mail: magnus.rueping@Kaust.edu.sa
Supporting information for this article is given via a link at the end of
the document.
We here report the first direct catalytic synthesis of amidines
starting from readily available amides. This procedure is based
on
a
new metal catalyzed insertion-decarbonylation-
[]
recombination reaction and neither requires an excess of the
This article is protected by copyright. All rights reserved.

10.1002/chem.201702867
Chemistry - A European Journal
COMMUNICATION
amine nucleophile nor the use of activated esters and amides
(Figure 1).
improves the transformation (entries 4-8). With IPr·HCl as ligand,
the desired product was isolated in 73% yield (entry 4). The use
of IMes·HCl and ICy·HCl provided similar results as IPr·HCl
(entries 6 and 8). Next, various bases and solvents were
evaluated and K3PO4 and toluene were found to be the optimal
choice (entries 4, 9-16). When we increased the reaction
temperature, the yield significantly increased to 97% (entry 18).
Gratifyingly, the transformation proceeded with excellent yields
of 97% and 93% in the presence of NiCl2 and NiBr2 as catalysts
(entries 19, 20). The desired product 2a was isolated in 84%
yield if the catalyst and ligand loadings were reduced to 5 mol%
NiCl2 and 10 mol% IPr·HCl, respectively (entry 21). However,
extending the reaction time under the same reaction conditions
improved the yield to 92% (entry 22). Control experiments
showed that no conversion into the desired product was
observed in the absence of the nickel catalyst and ligand and
the amide substrate was recovered (entries 23 and 24).
We initiated our investigation by evaluating various metal-ligand
complexes and were delighted to see that amidine formation
occurred when N-methyl-N-phenyl-2-quinolinecarboxamide (1a)
was reacted in the presence of Ni(cod)2 and K3PO4. Since
ligands play an essential role in the nickel-catalyzed cross-
coupling reactions via inert bond activation, a series of ligands
were tested in our new transformation. The use of monodentate
phosphine ligands showed promising results and the amidine
product 2a was isolated in 24% yield (Table 1, entries 1 and 2).
The bidentate phosphine ligand dcype did not promote the
transformation (entry 3).
Table 1. Optimization of the reaction conditions.[a]
Table 2. Substrate scope CO extrusion recombination fragment coupling of 2-
quinolinecarboxamides.[a]
Yield
Entry
[Ni] (mol%)
Ligand (mol%)
Solvent
(%)[b]
1
Ni(cod)2 (10)
Ni(cod)2 (10)
Ni(cod)2 (10)
Ni(cod)2 (10)
Ni(cod)2 (10)
Ni(cod)2 (10)
Ni(cod)2 (10)
Ni(cod)2 (10)
Ni(cod)2 (10)
Ni(cod)2 (10)
Ni(cod)2 (10)
Ni(cod)2 (10)
Ni(cod)2 (10)
Ni(cod)2 (10)
Ni(cod)2 (10)
Ni(cod)2 (10)
Ni(cod)2 (10)
Ni(cod)2 (10)
NiCl2 (10)
PCy3 (20)
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
iPr2O
24
24
-
2
P(nBu)3 (20)
dcype (10)
IPr·HCl (20)
SIPr·HCl (20)
IMes·HCl (20)
IiPr·HCl (20)
ICy·HCl (20)
IPr·HCl (20)
IPr·HCl (20)
IPr·HCl (20)
IPr·HCl (20)
IPr·HCl (20)
IPr·HCl (20)
IPr·HCl (20)
IPr·HCl (20)
IPr·HCl (20)
IPr·HCl (20)
IPr·HCl (20)
IPr·HCl (20)
IPr·HCl (10)
IPr·HCl (10)
IPr·HCl (20)
-
3
4
73
42
62
46
62
44
56
32
-
5
6
7
8
9[c]
10[d]
11[e]
12[f]
13
71
64
67
32
79
97
97
93
84
92
-
14
THF
15
Dioxane
DMF
16
17[g]
18[h]
19[h]
20[h]
21[h]
22[i]
23[h]
24[h]
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
NiBr2 (10)
NiCl2 (5)
NiCl2 (5)
-
NiCl2 (10)
-
[a] Reaction conditions: 1a (0.25 mmol), [Ni] (0.025 mmol or 0.0125 mmol),
ligand (0.05 mmol or 0.025 mmol); K3PO4 (0.5 mmol), solvent (1.5 mL), sealed
tube, 150 °C, 16 h. [b] Yield after isolation. [c] K2CO3 (0.5 mmol) instead of
K3PO4. [d] Cs2CO3 (0.5 mmol) instead of K3PO4. [e] CsF (0.5 mmol) instead of
K3PO4. [f] KOtBu (0.5 mmol) instead of K3PO4. [g] 160 °C, 16 h. [h] 170 °C, 16
h. [i] 170 °C, 24 h. PCy3
= tricyclohexylphosphine, P(nBu)3 = tri-n-
butylphosphine, dcype = 1,2-bis (dicyclohexylphosphino)ethane, IPr·HCl = 1,3-
bis(2,6-diisopropyl-phenyl)imidazolium chloride, SIPr·HCl
diisopropylphenyl) imidazolinium chloride, IMes·HCl
trimethylphenyl)imidazolium chloride, IiPr·HCl = 1,3-di-iso-propylimidazolium
=
1,3-bis(2,6-
1,3-bis(2,4,6-
[a] Reaction conditions: 1 (0.25 mmol), NiCl2 (0.0125 mmol, 5 mol%), IPr·HCl
(0.05 mmol, 10 mol%), K3PO4 (0.5 mmol, 2.0 equiv), toluene (1.5 mL), sealed
reaction tube, 170 °C, 48 h. [b] NiCl2 (0.025 mmol, 10 mol%), IPr·HCl (0.05
mmol, 20 mol%) was used, 170 °C, 18 h. [c] NiCl2 (0.025 mmol, 10 mol%),
IPr·HCl (0.05 mmol, 20 mol%) was used, 170 °C, 48 h.
=
chloride, ICy·HCl = 1,3-dicyclohexylimidazolium chloride.
To our delight, further ligand examination showed that the
utilization of N-heterocyclic carbene (NHC) ligands dramatically
This article is protected by copyright. All rights reserved.

10.1002/chem.201702867
Chemistry - A European Journal
COMMUNICATION
Stimulated by these results, we next examined a series of 2-
quinolinecarboxamides to determine the scope of the
intramolecular fragment coupling (Table 2). In addition to the N-
Subsequently, we performed the new extrusion recombination
fragment coupling with various substituted 2-azinecarboxamides.
As shown in Table 3, the transformation of 1-iso-quinoline-
carboxamide (1n) was highly efficient and gave the product 2n
in a nearly quantitative yield. The electronic nature and the steric
properties of the pyridine moiety were also evaluated. Electron-
donating methyl substituents (1q-r) and the electron-withdrawing
methyl-N-phenyl-2-quinolinecarboxamide
(1a),
substrates
containing electron-donating methyl and methoxy substituents
(1b-d) or electron-withdrawing fluoride and trifluoromethyl
substitutes (1e, 1f) on the phenyl group of the 2-
quinolinecarboxamide underwent the reaction smoothly and
furnished the desired amidines 2b-f in good to excellent yields.
It should be mentioned that although protocols for the
functionalization of aryl methyl ethers and aryl fluorides under
nickel catalysis have been reported,[14] methoxy (1d) and fluoride
groups (1e) were found to be compatible with our conditions. In
addition, substrates bearing sensitive functional groups such as
ketone (1g), nitrile (1h), and amide (1i) on the phenyl moiety
were also successfully applied to give the desired amidine
product. When substrate 1i with two amide groups was applied
in the reaction, only the 2-azinecarboxamide was converted.
This interesting chemoselectivity provides opportunities to
realize a selective amide to amidine interconversion in more
complex substrates (see below). With regard to aniline derived
amides, the more steric N-ethyl and N-butyl-substituted aniline
amides 1j and 1k could also be effectively converted. Moreover,
indoline (1l) and 1,2,3,4-tetrahydroquinolines (1m) reacted
smoothly to give the corresponding products in excellent yields.
trifluoromethyl substituent (1t) did not show
a significant
influence on the reaction outcome and the corresponding
products were obtained in good yields. When substrates 1p and
1s bearing methyl and trifluoromethyl substituents in the ortho
position were submitted to the amination reaction, the products
were obtained in moderate to good yields. Furthermore, the
pyrazinecarboxamide (1u) and quinoxalinecarboxamide (1v)
underwent the conversion smoothly and were converted into the
corresponding products in excellent yields.
In order to confirm our proposed reaction path for the amide to
amidine interconversion (Scheme 1c), we performed an
experiment in which a 1:1 mixture of substrates 1d and 1n was
subjected to the optimized reaction conditions (Scheme 2a).
After reaction, we isolated products 2d and 2n exclusively,
which indicates that the reaction takes place intramolecularly.
Compounds 2a and 2w (Scheme 2b) which would theoretically
result from an intermolecular reaction have not been observed.
Table 3. Substrate scope of 2-azinecarboxamides for the decarbonylative
amination.[a]
Scheme 2. Simultaneous reaction of substrates 1d and 1n.
To demonstrate the utility of our new methodology, several
experiments were performed. In terms of the scalability of the
method, the extrusion recombination fragment coupling was
conducted on a 5 mmol (1.3 gram) scale as shown in Scheme
3a. In the presence of 5 mol% NiCl2, the N-methyl-N-phenyl-2-
quinolinecarboxamide (1a) was converted into the N-methyl-N-
phenyl-2-quinolinamine (2a) in 68% yield. The reduction of
amide to amine with organometallic hydrides or silane/siloxane,
paired with this new extrusion recombination fragment coupling,
provides opportunities to synthesize bis-amino products
sequentially, as demonstrated in Scheme 3b. Firstly, 2,4-
pyridinedicarboxylic acid (3) underwent amidation via carboxylic
chloride and produced the bis-amide product 4 in 97% yield.
Subjection of bis-amide 4 to our new intramolecular fragment
coupling protocol afforded amidoamine 5 in 91% yield without
disturbing the secondary amide moiety. Subsequently, exposing
amidoamine 5 to the siloxane/Lewis acid system led to the
reduction of the secondary amide and gave the desired bis-
[a] Reaction conditions: 1 (0.25 mmol), NiCl2 (0.0125 mmol, 5 mol%), IPr·HCl
(0.05 mmol, 10 mol%), K3PO4 (0.5 mmol, 2.0 equiv), toluene (1.5 mL), sealed
reaction tube, 170 °C, 48 h. [b] NiCl2 (0.025 mmol, 10 mol%), IPr·HCl (0.05
mmol, 20 mol%) was used, 170 °C, 18 h. [c] NiCl2 (0.025 mmol, 10 mol%),
IPr·HCl (0.05 mmol, 20 mol%) was used, 170 °C, 48 h.
This article is protected by copyright. All rights reserved.

10.1002/chem.201702867
Chemistry - A European Journal
COMMUNICATION
amino product 6 in 98% yield (86% over three steps starting
from bis-carboxylic acid 3).
[2]
D. Margetic, Physico-Chemical Properties of Organosuperbases in
Superbases for Organic
Synthesis: Guanidines, Amidines,
Phosphazenes and Related Organocatalysts, (Ed.: T. Ishikawa), 2009,
John Wiley & Sons, pp. 9-48.
[3]
[4]
A. A. Aly, A. M. Nour-El-Din, ARKIVOC 2008, 153-194.
a) J. E. Taylor, S. D. Bull, J. M. J. Williams, Chem. Soc. Rev. 2012, 41,
2109-2121; b) For initial work on the use of amidinium ions as chiral
catalysts, see: T. Schuster, M. Bauch, G. Dürner, M. W. Göbel, Org.
Lett. 2000, 2, 179-181
[5]
a) P. J. Dunn, Amidines and N-Aryl Amidines in Comprehensive
Organic Functional Group Transformations II; (Eds.: I. Katritzky, R.
Taylor), Elsevier: Oxford, U.K., 2005; Vol. 5, pp 655-699; b) T. R. M.
Rauws, B. U. W. Maes, Chem. Soc. Rev. 2012, 41, 2463-2497; c) G.
Kantin, M. Krasavin, Curr. Org. Chem. 2016, 20, 1370-1388; d) K.
Ostrowska, A. Kolasa; Product Subclass 8: N-Alkyl, N-Aryl-, and N-
Hetaryl-Substituted Amidines (Imidamides) in Science of Synthesis,
(Ed.: A. Charette), 2005; Vol. 22, pp. 379-488.
[6]
[7]
[8]
The Amide Linkage: Structural Significance in Chemistry, Biochemistry,
and Materials Science (Eds.: A. Greenberg, C. M. Breneman, J. F.
Liebman). Wiley, New York, 2003.
a) L. Pauling, R. B. Corey, H. R. Branson, Proc. Natl Acad. Sci. U. S. A.
1951, 37, 205-211; b) L. Pauling, The Nature of the Chemical Bond,
Cornell University Press, Ithaca, 1960.
a) Nickel Catalysts in Comprehensive Organic Synthesis (Eds.: P.
Knochel, G. A. Molander), 2nd Ed., Elsevier: Oxford, 2014, Vol 3; b)
Metal-Catalyzed Cross-Coupling Reactions and More (Eds.: A. de
Meijere, S. Bräse, M. Oestreich) WILEY-VCH, Weinheim, 2014; c) New
Trends in Cross-Coupling Theory and Applications (Ed. T. J Colacot),
RSC Catalysis Series 2015; d) V. P. Ananikov, ACS Catal. 2015, 5,
1964-1971; e) M. Tobisu, N. Chatani, Acc. Chem. Res. 2015, 48, 1717-
1726.
Scheme 3. Gram-scale reaction and synthetic application.
[9]
a) G. Meng, S. Shi, M. Szostak, Synlett 2016, 27, 2530-2540; b) J. E.
Dander, N. K. Garg, ACS Cat. 2017, 7, 1413-1423; c) C. Liu, M.
Szostak, Chem. Eur. J. 2016, 23, 7157-7173.
In summary, we have developed an efficient extrusion
recombination fragment coupling of amides via
a nickel-
catalyzed C–N activation. The new protocol allows the amide to
amidine interconversion without reducing reagents, the use of
esters, activated amines or an additional amine source. The high
chemoselectivity of our amidine synthesis protocol, paired with
the reduction of amide to amine, offers opportunities to access
more complex substrates with multiple amino groups. Compared
to traditional amidine synthesis procedures, the new protocol
distinguishes itself by its high atom efficiency, the use of readily
available amides and low amounts of an inexpensive nickel(II)
catalyst and, thus the new fragment coupling strategy provides a
viable alternative for the synthesis of amidines.
[10] For Ni-catalyzed transformations of amides: Esterification: a) L. Hie, N.
F. F. Nathel, T. K. Shah, E. L. Baker, X. Hong, Y. F. Yang, P. Liu, K. N.
Houk, N. K. Garg, Nature 2015, 524, 79-83; b) L. Hie, E. L. Baker, S. M.
Anthony, J. N. Desrosiers, C. Senanayake, N. K. Garg, Angew. Chem.
Int. Ed. 2016, 55, 15129-15132; c) T. Deguchi, H.-L. Xin, H. Morimoto,
T. Ohshima, ACS Catal. 2017, 7, 3157-3161; d) J. E. Dander, N. A.
Weires, N. K. Garg. Org. Lett. 2016, 18, 3934–3936; Transamidation: e)
E. L. Baker, M. M. Yamano, Y. Zhou, S. M. Anthony, N. K. Garg, Nat.
Commun. 2016, 7, 11554; Ketone formations: f) N. A. Weires, E. L.
Baker, N. K. Garg, Nat. Chem. 2016, 8, 75-79; g) B. J. Simmons, N. A.
Weires, J. E. Dander, N. K. Garg, ACS Catal. 2016, 6, 3176-3179; h) S.
Shi, M. Szostak, Chem. Eur. J. 2016, 22, 10420-10424; i) S. Shi, M.
Szostak, Org. Lett. 2016, 18, 5872-5875; arylation, borylation and
amination: j) S. Shi, G. Meng, M. Szostak, Angew. Chem., Int. Ed. 2016,
55, 6959-6963; k) J. Hu, Y. Zhao, J. Liu, Y. Zhang, Z. Shi, Angew.
Chem., Int. Ed. 2016, 55, 8718-8722; reductive reactions: l) A. Dey, S.
Sasmal, K. Seth, G. K. Lahiri, D. Maiti, ACS Catal. 2017, 7, 433-437; m)
H. Yue, L. Guo, S.-C. Lee, X. Liu, M. Rueping, Angew. Chem. Int. Ed.
2017, 56, 3972-3976. n) B. J. Simmons, M. Hoffmann, J. Hwang, M. K.
Jackl, N. K. Garg, Org. Lett. 2017, 19, 1910-1913; o) J. Hu, M. Wang, X.
Pu, Z. Shi, Nat. Commun. 2017, 8, 14993.
Acknowledgements
H. Yue and L. Guo were supported by the China Scholarship
Council.
Keywords: • synthetic methods • C-N activation • amine • amide
[11] Further recent applications of amides: Pd-catalyzed ketone formations:
a) G. Meng, M. Szostak, Org. Lett. 2015, 17, 4364-4367; b) X. Li, G.
Zou, Chem. Commun. 2015, 51, 5089-5092; c) X. Li, G. Zou, J.
Organomet. Chem. 2015, 794, 136-145; d) G. Meng, M. Szostak, Org.
Biomol. Chem. 2016, 14, 5690-5707; e) C. Liu, G. Meng, Y. Liu, R. Liu,
R. Lalancette, R. Szostak, M. Szostak, Org. Lett. 2016, 18, 4194-4197;
f) G. Meng, S. Shi, M. Szostak, M. ACS Catal. 2016, 6, 7335-7339; g)
H. Wu, M. Cui, J. Jian, Z. Zheng, Adv. Synth. Catal. 2016, 358, 3876-
3880; h) M. Cui, H. Wu, J. Jian, H. Wang, C. Liu, S. Daniel, Z. Zeng,
Chem. Commun. 2016, 52, 12076-12079; i) P. Lei, G. Meng, M.
Szostak, ACS Catal. 2017, 7, 1960-1965; j) Liu, Y. Liu, R. Liu, R.
Lalancette, R. Szostak, M. Szostak, Org. Lett. 2017, 19, 1434-1437; k)
Pd-catalyzed olefine additions: d) A. Yada, S. Okajima, M. Murakami, J.
Am. Chem. Soc. 2015, 137, 8708-8711; l) G. Meng, M. Szostak, Angew.
Chem., Int. Ed. 2015, 54, 14518-14522; m) C. Liu, G. Meng, M.
Szostak, J. Org. Chem. 2016, 81, 12023-12030; Rhodium catalyzed
• nickel catalysis
[1]
a) The Chemistry of Amidines and Imidates, (Eds.: S. Pathai, Z.
Rappoport), John Wiley & Sons, Chichester, 1991; b) J. V. Greehills, P.
Lue, Amidines and Guanidines in Progress in Medicinal Chemistry, Vol.
30 (Eds.: G. P. Ellis, D. K. Luscombe), Elsevier Science Publishers,
New York, 1993, chapter 5, pp. 203–326; c) T. Ishikawa, T. Kumamoto,
Amidines in Organic Synthesis in Superbases for Organic Synthesis:
Guanidines, Amidines, Phosphazenes and Related Organocatalysts,
(Ed.: T. Ishikawa), 2009, John Wiley & Sons, pp 49-91; d) T. Kumamoto,
Amidines and Guanidines in Natural Products and Medicines in
Superbases for Organic
Synthesis: Guanidines, Amidines,
Phosphazenes and Related Organocatalysts, (Ed.: T. Ishikawa), 2009,
John Wiley & Sons, pp. 295-299.
This article is protected by copyright. All rights reserved.

10.1002/chem.201702867
Chemistry - A European Journal
COMMUNICATION
arylations: n) G. Meng, M. Szostak, Org. Lett. 2016, 18, 796-799; k) H.
Wu, T. Liu, M. Cui, Y. Li, J. Jian, H. Wang, Z. Zeng, Org. Biomol. Chem.
2017, 15, 536-540.
[12] Fur further examples of Ni-catalyzed reactions from our group, see: a)
M. Leiendecker, C. C. Hsiao, L. Guo, N. Alandini, M. Rueping, Angew.
Chem. Int. Ed. 2014, 53, 12912-12915; b) L. Guo, M. Leiendecker, C.-C.
Hsiao, C. Baumann, M. Rueping, Chem. Commun. 2015, 51, 1937-
1940; c) M. Leiendecker, A. Chatupheeraphat, M. Rueping, Org. Chem.
Front. 2015, 2, 350-353; d) X. Liu, C.-C. Hsiao, I. Kalvet, M.
Leiendecker, L. Guo, F. Schoenebeck, M. Rueping, Angew. Chem. Int.
Ed. 2016, 55, 6093-6098; e) L. Guo, C.-C. Hsiao, H. Yue, X. Liu, M.
Rueping, ACS Catal. 2016, 6, 4438-4442; f) L. Guo, X. Liu, C.
Baumann, M. Rueping, Angew. Chem. Int. Ed. 2016, 55, 15415-15419;
g) L. Fan, J. Jia, H. Hou, Q. Lefebvre, M. Rueping, Chem. Eur. J. 2016,
22, 16437-16440; h) H. Yue, L. Guo, X. Liu, M. Rueping, Org. Lett.
2017, 19, 1788-1791; i) W. Srimontree, A. Chatupheeraphat, H.-H. Liao,
M. Rueping, Org. Lett. 2017, 19, 3091-3094; j) X. Liu, J. Jia, M.
Rueping, ACS Catal. 2017, 7, 4491-4496.
[13] For the Ni-catalyzed synthesis of ethers starting from esters: a) R.
Takise, R. Isshiki, K. Muto, K. Itami, J. Yamaguchi, J. Am. Chem. Soc.
2017, 139, 3340-3343. related Ni-catalyzed ester activations, for:
arylations: b) K. Amaike, K. Muto, J. Yamaguchi, K. Itami, J. Am. Chem.
Soc. 2012, 134, 13573-13576; c) K. Muto, J. Yamaguchi, D. G. Musaev,
K. Itami, Nat. Commun. 2015, 6, 7508; d) L. Meng, Y. Kamada, K. Muto,
J. Yamaguchi, K. Itami, Angew. Chem., Int. Ed. 2013, 52, 10048-10051;
e) N. A. LaBerge, J. A. Love, Eur. J. Org. Chem. 2015, 5546-5553; f) K.
Amaike, K. Itami, J. Yamaguchi, Chem.-Eur. J. 2016, 22, 4384-4388;
borylation and silylation: g) L. Guo, A. Chatupheeraphat, M. Rueping,
Angew. Chem., Int. Ed. 2016, 55, 11810-11813; h) L. Guo, M. Rueping,
Chem. Eur. J. 2016, 22, 16787-16790; i) X. Pu, J. Hu, Y. Zhao, Z. Shi,
ACS Catal. 2016, 6, 6692-6698; amidation: j) L. Hie, N. F. Fine Nathel,
X. Hong, Y. F. Yang, K. N. Houk, N. K. Garg, Angew. Chem., Int. Ed.
2016, 55, 2810-2814; k) C. W. Cheung, M. L. Ploeger, X. Hu, Nat.
Commun. 2017, 8, 14878; amination: l) H. Yue, L. Guo, H.-H. Liao, Y.
Cai, C. Zhu, M. Rueping, Angew. Chem. Int. Ed. 2017, 56, 4282-4285;
computational studies: m) X. Hong, Y. Liang, K. N. Houk, J. Am. Chem.
Soc. 2014, 136, 2017-2025; n) Q. Lu, H. Yu, Y. Fu, J. Am. Chem. Soc.
2014, 136, 8252-8260; o) A. N. Desnoyer, F. W. Friese, W. Chiu, M. W.
Drover, B. O. Patrick, J. A. Love, Chem. Eur. J. 2016, 22, 4070-4077.
[14] a) J. Cornella, C. Zarate, R. Martin, Chem. Soc. Rev. 2014, 43, 8081-
8097; b) M. Tobisu, N. Chatani, Acc. Chem. Res. 2015, 48, 1717-1726.
This article is protected by copyright. All rights reserved.

10.1002/chem.201702867
Chemistry - A European Journal
COMMUNICATION
Entry for the Table of Contents (Please choose one layout)
Layout 2:
COMMUNICATION
Xiangqian Liu, Huifeng Yue, Jiaqi Jia,
Lin Guo and Magnus Rueping*
Page No. – Page No.
Synthesis of Amidines from Amides using
a Nickel Catalyzed Decarbonylative
Amination via CO Extrusion Intramolecular
Recombination Fragment Coupling
Text for Table of Contents
A nickel-catalyzed intramolecular decarbonylative amination of amide derivatives has been established for the first time. This
unconventional amination process takes advantage of an inexpensive nickel(II) catalyst and a carbene ligand and provides the
corresponding amidines with high efficiency.
This article is protected by copyright. All rights reserved.