Manganese-Catalyzed N-Formylation of Amines by Methanol Liberating H2: A Catalytic and Mechanistic Study

Article abstract of DOI:10.1002/anie.201700681

The first example of a base metal (manganese) catalyzed acceptorless dehydrogenative coupling of methanol and amines to form formamides is reported herein. The novel pincer complex (iPr-PN^HP)Mn(H)(CO)₂ catalyzes the reaction under mild conditions in the absence of any additives, bases, or hydrogen acceptors. Mechanistic insight based on the observation of an intermediate and DFT calculations is also provided.

Full text of DOI:10.1002/anie.201700681

Angewandte
Communications
Chemie
International Edition: DOI: 10.1002/anie.201700681
German Edition: DOI: 10.1002/ange.201700681
Base-Metal Catalysis Hot Paper
Manganese-Catalyzed N-Formylation of Amines by Methanol
Liberating H : A Catalytic and Mechanistic Study
2
Subrata Chakraborty, Urs Gellrich, Yael Diskin-Posner, Gregory Leitus, Liat Avram, and
David Milstein*
[
12]
Abstract: The first example of a base metal (manganese)
methanol dehydrogenation. In 2011, Krische and co-work-
catalyzed acceptorless dehydrogenative coupling of methanol
ers reported an iridium-catalyzed direct CÀC bond coupling
and amines to form formamides is reported herein. The novel
of 1,1-disubstituted allenes and methanol to form homoallylic
neopentyl alcohols in which methanol dehydrogenation was
H
pincer complex (iPr-PN P)Mn(H)(CO) catalyzes the reac-
2
[12a]
tion under mild conditions in the absence of any additives,
bases, or hydrogen acceptors. Mechanistic insight based on the
observation of an intermediate and DFT calculations is also
provided.
considered to be a crucial step.
The groups of Beller,
Grꢀtzmacher, and Fujita as well as our own group reported on
the aqueous-phase dehydrogenation of methanol to generate
[
13–16]
H using pincer Ru and Ir catalysts.
2
An NHC/Ru complex
catalyzed dehydrogenative coupling of methanol and amines
to formamides with excess styrene as the hydrogen acceptor
was described by Glorius and co-workers (Scheme 1b).
F
ormamides are valuable intermediates in the synthesis of
[
1]
[17a]
pharmaceuticals, agrochemicals, dyes, and fragrances. They
[
2]
also serve as industrial solvents, and are useful reagents for
the Vilsmeier–Haack reaction and in the synthesis of
formamidines and isocyanates.
[3,4]
In addition, formyl moi-
eties are important amine protecting groups in peptide
[
5]
synthesis.
In general, an excess of the formylating reagent and the
corresponding amine is required for the synthesis of forma-
[
6]
mides. Several other methods have also been developed
[1c,7]
recently.
However, most of them suffer from toxicity
issues, expensive reagents, moisture sensitivity, poorly acces-
sible starting materials, long reaction times, and the gener-
[
8]
ation of copious waste. In terms of sustainability, an
attractive “green” route is the acceptorless dehydrogenative
coupling (ADC) of methanol with amines; methanol is an
abundant feedstock that can be obtained from renewable
[
9]
resources (biomass) and atmospheric CO2.
Acceptorless dehydrogenative couplings of alcohols to
form CÀC and CÀN bonds have emerged as a powerful
approach for various environmentally benign organic trans-
[
10]
formations.
However, catalytic dehydrogenation to the
aldehyde is considerably more problematic for methanol
Scheme 1. Synthetic strategies towards N-formamides.
À1
(
DH = 84 kJmol ) than for higher alcohols, such as ethanol
À1 [11]
(DH = 68 kJmol ),
and the generated formaldehyde is
very unstable towards decomposition to CO and hydrogen,
making dehydrogenative couplings using methanol challeng-
ing and less explored. There are only a few reports on
Gold-catalyzed aerobic N-formylation using methanol was
[
17b]
reported by the Asao group (Scheme 1c).
In addition, an
ADC of ortho-aminobenzamides and methanol to quinazo-
linones in the presence of an Ir complex was reported by Li
[
18]
[
*] Dr. S. Chakraborty, Dr. U. Gellrich, Prof. Dr. D. Milstein
Department of Organic Chemistry
Weizmann Institute of Science
Rehovot, 76100 (Israel)
E-mail: david.milstein@weizmann.ac.il
and co-workers.
Ru-catalyzed ADCs of methanol with
amines to formamides were reported by Hong and Kanga
[
19a]
(Scheme 1d),
and very recently by Prakash and co-work-
[19b]
ers for N,N’-dimethylethylenediamine.
aforementioned elegant transformations are all based on
precious noble-metal catalysts.
Replacing expensive metal-based catalysts by earth-
abundant base-metal complexes (Fe, Co, Ni, Mn) in homoge-
neous catalysis is of much interest nowadays.
However, the
Dr. Y. Diskin-Posner, Dr. G. Leitus, Dr. L. Avram
Chemical Research Support
Weizmann Institute of Science
Rehovot, 76100 (Israel)
[20–23]
In fact,
Supporting information and the ORCID identification number(s) for
the author(s) of this article can be found under:
http://dx.doi.org/10.1002/anie.201700681.
considerable progress in catalysis by complexes of earth-
abundant metals has been made for various (de)hydrogen-
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ation reactions, including the dehydrogenation of aqueous
[
23a]
methanol to form H2 and CO2
couplings of methanol to form methyl formate
by iron complexes. Substantial efforts have also been made
and dehydrogenative
[
23b]
catalyzed
[
24–29]
towards the application of manganese
in (de)hydrogen-
ation reactions; manganese is the third most abundant metal
in the earthꢁs crust after iron and titanium.
Subsequent to our report on the dehydrogenative cou-
[
24a]
pling of alcohols and amines to give imines
Mn(PNPtBu) catalyst, several other reports on Mn-catalyzed
with a pincer
(
de)hydrogenation reactions appeared. Recently, C-alkyla-
[
33]
[
25a]
Figure 1. Molecular structure of 2. Thermal ellipsoids set at 50%
probability. Selected hydrogen atoms omitted for clarity. For bond
lengths, angles, and experimental details, see the Supporting Informa-
tion.
tions of ketones
alcohols
egies” were reported by Beller and co-workers. The groups of
Beller and Kempe independently developed ketone hydro-
genation reactions catalyzed by Mn pincer complexes,
and N-alkylations of amines using
based on so-called “borrowing hydrogen strat-
[
25b]
[
26]
including nitrile hydrogenation by Beller.
Beller
Very recently,
independently
worthy that this reaction proceeds in the absence of a hydro-
gen acceptor. GC analysis of the gases in the headspace
[
27a]
[27b]
and co-workers and our group
described the hydrogenation of esters to alcohols with
Mn(PNP) pincer complexes as the catalysts.
indicated the formation of H2. A small amount of
N-methylpiperidine (13%) was also observed, which results
To the best of our knowledge, the desirable ADC of
methanol and amines to form formamides catalyzed by
complexes of base metals has not been reported thus far.
Herein, we report such a reaction, which gave formamides as
the major products under mild conditions in the presence of
a new Mn complex. Mechanistic insight based on the
observation of an intermediate and DFT calculations is also
provided.
from reductive amination of the formaldehyde intermediate
[31]
with the amine in a borrowing hydrogen process. However,
when the reaction was carried out in an open system at reflux,
N-formylpiperidine was formed in only 35% yield after 24 h,
which might be due to the lower temperature, along with the
formation of an unidentified product; as expected,
N-methylation of piperidine was not observed (see the
Supporting Information, Table S1, entry 3).
Next, the scope of this unprecedented base-metal-cata-
lyzed ADC of methanol was probed with different amines. As
shown in Table 1, the cyclic secondary amines pyrrolidine and
morpholine were converted into the corresponding forma-
mides in moderate to good yields (entries 2 and 3). The
reaction of N-methylbenzylamine with methanol afforded
N-benzyl-N-methylformamide in 78% yield (entry 4).
Exploring the scope further, dehydrogenative reactions of
methanol with various substituted primary benzylamines
were studied. The reaction of methanol with benzylamine,
H
[30]
Treatment of our previously reported iPr-PN P ligand 1
with Mn(CO) Br (1 equiv) at 908C in THF led to the
5
H
formation of the yellow Mn(iPr-PN P)(CO) Br complex (2)
2
Scheme 2. Synthesis of the manganese(I) complexes.
4
-methoxybenzylamine, and 4-methylbenzylamine afforded
the corresponding formamides in good yields (67–74%,
entries 5–7). Reactions of methanol with benzylic amines
bearing electron-withdrawing groups in the para position
in 86% yield (Scheme 2). Single crystals of 2 that were
suitable for X-ray diffraction were obtained by slow diffusion
of pentane into a saturated solution of the compound in
toluene at À308C. The molecular structure exhibits an
octahedral geometry with meridional coordination of the
(p-CF , p-Cl, p-F) afforded the corresponding formamides in
3
moderate yields (entries 8–10). The reaction of primary
amines is not limited to benzylamines. The reaction of
methanol and cyclohexylamine furnished N-cyclohexylfor-
mamide in 66% yield (entry 11). Similarly, N-(2-phenyl-
ethyl)formamide and
H
iPr-PN P ligand (Figure 1; see also the Supporting Informa-
tion).
The addition of NaHBEt (1 equiv) to a solution of 2 in
3
THF at room temperature furnished the monohydrido com-
N-butylformamide were obtained in 53 and 64% yield,
respectively, upon heating methanol and the corresponding
amines (entries 13 and 14). 1-Naphthylmethylamine was
formylated in 62% yield after 15 h (entry 12).
To gain insight into the mechanism of the manganese-
catalyzed ADC of methanol and amines, the amine complex 2
was reacted with tBuOK (1.2 equiv) in pentane at room
temperature. Deep red crystals of the amido species 4 were
obtained (Scheme 3; for full characterization, see the Sup-
porting Information), and its structure was confirmed by
X-ray diffraction (Scheme 3; see also the Supporting Infor-
H
plex (iPr-PN P)Mn(H)(CO) (3) in 88% yield (Scheme 2).
2
1
The H NMR spectrum of 3 displays a triplet at d = À5.5 ppm
2
(
t, J = 60 Hz, MnÀH), which corresponds to the hydride
PH
À1
ligand. The IR stretching bands at 1805 and 1879 cm in a 1:1
ratio correspond to the orthogonal carbonyl ligands of 3.
Complex 3 catalyzes the dehydrogenative coupling of
methanol and amines. Thus the reaction of piperidine
(
0.5 mmol) and 3 (2 mol%) in MeOH (1 mL) at 1108C in
a closed system resulted in the formation of N-formylpiper-
idine in 86% yield after 12 h (Table 1, entry 1). It is note-
2
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[
33]
Table 1: Acceptorless dehydrogenative formylation of amines with
methanol and catalyst 3.
mation). Employing the freshly prepared amido complex 4
2 mol%) as a catalyst in the dehydrogenative coupling of
[
a]
(
methanol and piperidine at 1108C yielded 72% of
N-formylpiperidine after 12 h (Table 1, entry 1, second row).
However, 4 turned out to be unstable at room temperature
(
stable at À308C for several hours), and was transformed into
[
a]
Entry
Amine
Product
t
Conv. Yield
the thermodynamically more stable light yellow metalated
complex 5 (Scheme 3) at room temperature in less than 12 h
or upon heating at 1108C for 30 min. Thus intramolecular
CÀH activation took place, involving cooperation between
[
b]
[b]
[h]
[%]
[%]
1
12
1
2
99
99
99
86
72
78
[
[
c]
1
d]
2
the metal center and the amido ligand of 4. Heating complex 3
at 1108C in THF also resulted in the formation of 5
2
3
14
97
61
(Scheme 3). Its structure was confirmed by X-ray diffrac-
[33]
tion
and detailed NMR spectroscopic studies (see the
24
99
50
Supporting Information). Complex 5 also catalyzed the
dehydrogenative coupling reaction, providing N-formylpiper-
idine in 78% yield after 12 h (Table 1, entry 1, third row).
Significantly, treatment of 4 with methanol (2 equiv) in
C D at room temperature resulted in instant formation of
4
5
6
15
14
12
99
99
99
78
70
67
6
6
a new complex that exhibited broad resonances in the
1
31
1
H NMR spectrum and two broad P{ H} NMR signals at
d = 55 and 85 ppm. Upon conducting the experiment in
7
8
9
18
12
12
14
99
83
99
99
74
71
56
57
3
1
[
D ]toluene with methanol (1 equiv), the P NMR spectrum
8
2
at À308C exhibited two sharp doublets at d = 57.1 ( J
=
PP
2
1
42 Hz) and 88.7 ppm ( J = 142 Hz), attributable to
PP
methoxy complex 6 (Scheme 4). A sharp signal at d =
1
1
0
1
12
15
93
99
66
62
1
2
1
1
3
4
24
15
99
97
53
64
[a] Reaction conditions: Amine (0.5 mmol), MeOH (1 mL), 3
(
0.01 mmol), heated in a 100 mL closed Fischer–Porter tube at 1108C.
[b] Yields and conversions determined by GC or NMR analysis using
toluene or meta-xylene as the internal standard. The conversions are
based on amine consumption. [c] Complex 4 as the catalyst. [d] Complex
5
as the catalyst. Differences in yield and conversion indicate the
formation of the N-methylated amine and also an unidentified side
product.
Scheme 4. Plausible mechanism for the acceptorless dehydrogenative
coupling of methanol and amines. DGvib+rot values calculated at the
SMD(MeOH)-TPSS-D3BJ/def2-TZVPP//BP86-D3/def2-SV(P) level of
theory are given in square brackets. The transition state TS6’/3 is shown
in the inset.
1
3
.9 ppm in the H NMR spectrum (À308C) was assigned to
a proton of the methoxy ligand. Another sharp minor
resonance at d = 3.1 ppm, overlapping with other resonances,
was due to free methanol. Irradiation of the signal at d =
3
.9 ppm (1D NOE study at À308C) led to an NOE
enhancement of the resonances at d = 3.1 ppm, indicating
exchange with free methanol. H NMR spectroscopy of the
2
Scheme 3. Reactivity of complexes 2 and 3.
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reaction of amido complex 4 with CD OD (1 equiv) at À308C
Molecular Design. D.M. holds the Israel Matz Professorial
Chair of Organic Chemistry. S.C. thanks the Swiss Friends of
the Weizmann Institute of Science Committee for a generous
postdoctoral fellowship.
3
revealed signals at d = 3.9 and 3.1 ppm (see the Supporting
Information) for the coordinated methoxy ligand and free
methanol. The NÀD signal was not detected, likely because of
overlap with CD O signals. These results represent a rare
3
direct observation of an alkoxy intermediate in OÀH
activation by an amido-amine metal–ligand cooperation Conflict of interest
[
28]
(
MLC). However, 6 turned out to be unstable, and removal
of the solvent regenerated amido complex 4 along with
The authors declare no conflict of interest.
a small amount of free ligand and an unidentified product
3
1
1
with P{ H} NMR resonances at d = 71 and 96 ppm. Complex
required excess methanol and longer reaction times (3 h) to
Keywords: dehydrogenation · formylation · manganese ·
methanol · pincer complexes
5
form methoxy complex 6 at room temperature (see the
Supporting Information). In addition, when complex 5 was
heated in methanol at 1008C, partial formation of hydrido
complex 3 was observed after 30 min, and after 1 h, it was
converted into methoxy complex 6.
[
1] a) B. C. Chen, M. S. Bednarz, R. Zhao, J. E. Sundeen, P. Chen, Z.
Shen, A. P. Skoumbourdis, J. C. Barrish, Tetrahedron Lett. 2000,
41, 5453; b) K. Kobayashi, S. Nagato, M. Kawakita, O. Mor-
ikawa, H. Konishi, Chem. Lett. 1995, 24, 575; c) A. Tlili, E.
Blondiaux, X. Frogneux, T. Cantat, Green Chem. 2015, 17, 157;
d) R. Hett, Q. K. Fang, Y. Gao, S. A. Wald, C. H. Senanayake,
Org. Process Res. Dev. 1998, 2, 96.
With these experimental results in hand, we became
interested in elucidating whether the benzylic CH group is
involved in H liberation in the actual catalytic transforma-
2
tion. Therefore, DFT calculations at the SMD(MeOH)-TPSS-
D3BJ/def2-TZVPP//BP86-D3/def2-SV(P) level of theory
were carried out (Scheme 4). In agreement with the exper-
imental results, 5 was predicted to be thermodynamically
[
2] K. Weissermel, H.-J. Arpe, Industrial Organic Chemistry, 3rd ed.,
translated by C. R. Lindley, Wiley-VCH, Weinheim, 1997.
À1
more stable than 4 by 9.7 kcalmol . The reaction of 4 or 5
[3] a) I. M. Downie, M. J. Earle, H. Heaney, K. F. Shuhaibar,
Tetrahedron 1993, 49, 4015; b) S. Jones, C. J. A. Warner, Org.
Biomol. Chem. 2012, 10, 2189; c) S. B. Jagtap, S. B. Tsogoeva,
Chem. Commun. 2006, 4747.
[4] a) Y. Han, L. Cai, Tetrahedron Lett. 1997, 38, 5423; b) M. K.
Faraj, U.S. Patent 5686645, 1997.
with methanol gives rise to methoxy complex 6. Hydrogen
abstraction from the methoxy ligand by b-hydride elimination
requires dissociation of the NH group and the formation of
[32]
the agostic intermediate 6’. Formaldehyde and the hydrido
complex 3 are generated by this b-hydride elimination with
[
5] P. G. M. Wuts, Greeneꢀs Protective Groups in Organic Synthesis,
th ed., Wiley, Hoboken, NJ, 2014, p. 991.
À1
a barrier of 11.6 kcalmol with respect to 4 and free
5
methanol. H2 liberation from 3, involving two methanol
[6] C. J. Gerack, L. McElwee-White, Molecules 2014, 19, 7689.
[7] a) L. Zhang, Z. Han, X. Zhao, Z. Wang, K. Ding, Angew. Chem.
Int. Ed. 2015, 54, 6186; Angew. Chem. 2015, 127, 6284; b) C.
Das Neves Gomes, O. Jacquet, C. Villiers, P. Thuery, M. Eph-
ritikhine, T. Cantat, Angew. Chem. Int. Ed. 2012, 51, 187; Angew.
Chem. 2012, 124, 191; c) C. Federsel, A. Boddien, R. Jackstell, R.
Jennerjahn, P. J. Dyson, R. Scopelliti, G. Laurenczy, M. Beller,
Angew. Chem. Int. Ed. 2010, 49, 9777; Angew. Chem. 2010, 122,
9971; d) T. Ishida, M. Haruta, ChemSusChem 2009, 2, 538; e) P.
Preedasuriyachai, H. Kitahara, W. Chavasiri, H. Sakurai, Chem.
Lett. 2010, 39, 1174; f) T. M. El Dine, D. Evans, J. Rouden, J.
Blanchet, Chem. Eur. J. 2016, 22, 5894.
molecules as a proton shuttle, requires only a low activation
À1
energy (8.1 kcalmol with respect to 4). In contrast, the
transition state for H liberation involving the benzylic CH
2
À1
group was found to be higher in energy (41.8 kcalmol with
respect to 4). According to these computations, this transition
state cannot be stabilized by additional methanol molecules,
most likely owing to the fact that the benzylic CH group is not
capable of forming hydrogen bonds to the methanol mole-
cules. The formed formaldehyde reacts with the amine to
generate a hemiaminal, which liberates hydrogen in another
catalytic cycle to give the formamide (Scheme 4).
[
8] G. A. Olah, L. Ohannesian, M. Arvanaghi, Chem. Rev. 1987, 87,
71.
6
In conclusion, we have demonstrated that N-formyl-
amines can be formed by acceptorless dehydrogenative
couplings of methanol and amines that were catalyzed by
a base-metal (manganese) catalyst for the first time. The
reaction proceeds without any additives using the pincer
[
9] a) http://www.methanol.org/Methanol-Basics.aspx; b) P. Galin-
do Cifre, O. Badr, Energy Convers. Manage. 2007, 48, 519.
[10] C. Gunanathan, D. Milstein, Science 2013, 341, 249.
[
11] a) K. Tani, A. Iseki, T. Yamagata, Chem. Commun. 1999, 1821;
b) W.-H. Lin, H.-F. Chang, Catal. Today 2004, 97, 181; c) M.
Qian, M. A. Liauw, G. Emig, Appl. Catal. A 2003, 238, 211.
12] a) J. Moran, A. Preetz, R. A. Mesch, M. J. Krische, Nat. Chem.
H
catalyst (iPr-PN P)Mn(H)(CO)2 (3) under homogeneous
[
conditions. A plausible mechanism is provided that is based
on the rare direct observation of an intermediate that is
formed by OÀH bond activation of methanol by metal–ligand
2011, 3, 287; b) L. K. M. Chan, D. L. Poole, D. Shen, M. P. Healy,
T. J. Donohoe, Angew. Chem. Int. Ed. 2014, 53, 761; Angew.
Chem. 2014, 126, 780; c) S. Ogawa, Y. Obora, Chem. Commun.
2014, 50, 2491; d) D. Morton, D. J. Cole-Hamilton, J. Chem. Soc.
Chem. Commun. 1988, 1154; e) S. Shinoda, T. Yamakawa, J.
Chem. Soc. Chem. Commun. 1990, 1511; f) Y. Li, H. Li, H. Junge,
M. Beller, Chem. Commun. 2014, 50, 14991.
cooperation.
Acknowledgements
[
13] a) M. Nielsen, E. Alberico, W. Baumann, H.-J. Drexler, H.
Junge, S. Gladiali, M. Beller, Nature 2013, 495, 85; b) A. Monney,
E. Barsch, P. Sponholz, H. Junge, R. Ludwig, M. Beller, Chem.
Commun. 2014, 50, 707.
This research was supported by the Israel Science Foundation,
the MINERVA Foundation, and the Kimmel Center for
4
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Angewandte
Communications
Chemie
[
[
[
[
14] R. E. Rodrꢂguez-Lugo, M. Trincado, M. Vogt, F. Tewes, G.
Santiso-Quinones, H. Grꢀtzmacher, Nat. Chem. 2013, 5, 342.
15] P. Hu, Y. Diskin-Posner, Y. Ben-David, D. Milstein, ACS Catal.
[23] a) E. Alberico, P. Sponholz, C. Cordes, M. Nielsen, H.-J. Drexler,
W. Baumann, H. Junge, M. Beller, Angew. Chem. Int. Ed. 2013,
52, 14162; Angew. Chem. 2013, 125, 14412; b) E. A. Bielinski, M.
Fçrster, Y. Zhang, W. H. Bernskoetter, N. Hazari, M. C.
Holthausen, ACS Catal. 2015, 5, 2404.
2014, 4, 2649.
16] K. Fujita, R. Kawahara, T. Aikawa, R. Yamaguchi, Angew.
Chem. Int. Ed. 2015, 54, 9057; Angew. Chem. 2015, 127, 9185.
17] a) N. Ortega, C. Richter, F. Glorius, Org. Lett. 2013, 15, 1776;
b) S. Tanaka, T. Minato, E. Ito, M. Hara, Y. Kim, Y. Yamamoto,
N. Asao, Chem. Eur. J. 2013, 19, 11832.
[24] a) A. Mukherjee, A. Nerush, G. Leitus, L. J. W. Shimon, Y.
Ben David, N. A. Espinosa Jalapa, D. Milstein, J. Am. Chem.
Soc. 2016, 138, 4298; b) M. Mastalir, M. Glatz, N. Gorgas, B.
Stçger, E. Pittenauer, G. Allmaier, L. F. Veiros, K. Kirchner,
Chem. Eur. J. 2016, 22, 12316.
[
18] F. Li, L. Lu, P. Liu, Org. Lett. 2016, 18, 2580.
[
19] a) B. Kanga, S. H. Hong, Adv. Synth. Catal. 2015, 357, 834; b) J.
Kothandaraman, S. Kar, R. Sen, A. Goeppert, G. A. Olah, G. K.
Surya Prakash, J. Am. Chem. Soc. 2017, 139, 2549.
[25] a) M. PeÇa-Lꢃpez, P. Piehl, S. Elangovan, H. Neumann, M.
Beller, Angew. Chem. Int. Ed. 2016, 55, 14967; Angew. Chem.
2016, 128, 15191; b) S. Elangovan, J. Neumann, S. Jean-Baptiste,
K. Junge, C. Darcel, M. Beller, Nat. Commun. 2016, 7, 12641.
[26] a) S. Elangovan, C. Topf, S. Fischer, H. Jiao, A. Spannenberg, W.
Baumann, R. Ludwig, K. Junge, M. Beller, J. Am. Chem. Soc.
2016, 138, 8809; b) F. Kallmeier, T. Irrgang, T. Dietel, R. Kempe,
Angew. Chem. Int. Ed. 2016, 55, 11806; Angew. Chem. 2016, 128,
11984.
[27] a) S. Elangovan, M. Garbe, H. Jiao, A. Spannenberg, K. Junge,
M. Beller, Angew. Chem. Int. Ed. 2016, 55, 15364; Angew. Chem.
2016, 128, 15590; b) N. A. Espinosa-Jalapa, A. Nerush, L. J. W.
Shimon, G. Leitus, L. Avram, Y. Ben-David, D. Milstein, Chem.
Eur. J. 2016, DOI: 10.1002/chem.201604991.
[28] A Mn-catalyzed methanol dehydrogenation reaction was
recently reported, see: M. Andꢄrez-Fernꢅndez, L. K. Vogt, S.
Fischer, W. Zhou, H. Jiao, M. Garbe, S. Elangovan, K. Junge, H.
Junge, R. Ludwig, M. Beller, Angew. Chem. Int. Ed. 2017, 56,
559; Angew. Chem. 2017, 129, 574.
[29] a) M. Mastalir, M. Glatz, E. Pittenauer, G. Allmaier, K.
Kirchner, J. Am. Chem. Soc. 2016, 138, 15543; b) N. Deibl, R.
Kempe, Angew. Chem. Int. Ed. 2017, 56, 1663; Angew. Chem.
2017, 129, 1685; c) D. H. Nguyen, X. Trivelli, F. Capet, J.-F. Paul,
F. Dumeignil, R. M. Gauvin, ACS Catal. 2017, 7, 2022.
[30] S. Chakraborty, G. Leitus, D. Milstein, Angew. Chem. Int. Ed.
2017, 56, 2074; Angew. Chem. 2017, 129, 2106.
[
20] For recent reviews on catalysis by Fe and Ni complexes, see: a) I.
Bauer, H.-J. Knçlker, Chem. Rev. 2015, 115, 3170; b) R. H.
Morris, Acc. Chem. Res. 2015, 48, 1494; c) P. J. Chirik, Acc.
Chem. Res. 2015, 48, 1687; d) S. Chakraborty, P. Bhattacharya, H.
Dai, H. Guan, Acc. Chem. Res. 2015, 48, 1995; e) W. McNeill, T.
Ritter, Acc. Chem. Res. 2015, 48, 2330; f) D. Benito-Garagorri,
K. Kirchner, Acc. Chem. Res. 2008, 41, 201; g) T. Zell, D.
Milstein, Acc. Chem. Res. 2015, 48, 1979, and references therein.
21] a) C. Bornschein, S. Werkmeister, B. Wendt, H. Jiao, E.
Alberico, W. Baumann, H. Junge, K. Junge, M. Beller, Nat.
Commun. 2014, 5, 4111; b) S. Chakraborty, G. Leitus, D.
Milstein, Chem. Commun. 2016, 52, 1812; c) J. A. Garg, S.
Chakraborty, Y. Ben-David, D. Milstein, Chem. Commun. 2016,
[
52, 5285; d) F. Schneck, M. Assmann, M. Balmer, K. Harms, R.
Langer, Organometallics 2016, 35, 1931; e) T. Zell, Y. Ben-
David, D. Milstein, Angew. Chem. Int. Ed. 2014, 53, 4685;
Angew. Chem. 2014, 126, 4773; f) S. Werkmeister, K. Junge, B.
Wendt, E. Alberico, H. Jiao, W. Baumann, H. Junge, F. Gallou,
M. Beller, Angew. Chem. Int. Ed. 2014, 53, 8722; Angew. Chem.
2014, 126, 8867; g) S. Chakraborty, H. Dai, P. Bhattacharya, N. T.
Fairweather, M. S. Gibson, J. A. Krause, H. Guan, J. Am. Chem.
Soc. 2014, 136, 7869.
[
22] For Co-catalyzed (de)hydrogenation, see: a) G. Zhang, B. L.
Scott, S. K. Hanson, Angew. Chem. Int. Ed. 2012, 51, 12102;
Angew. Chem. 2012, 124, 12268; b) G. Zhang, S. K. Hanson, Org.
Lett. 2013, 15, 650; c) G. Zhang, K. V. Vasudevan, B. L. Scott,
S. K. Hanson, J. Am. Chem. Soc. 2013, 135, 8668; d) S. Rçsler, J.
Obenauf, R. Kempe, J. Am. Chem. Soc. 2015, 137, 7998; e) T.-P.
Lin, J. C. Peters, J. Am. Chem. Soc. 2014, 136, 13672; f) R. P. Yu,
J. M. Darmon, C. Milsmann, G. W. Margulieux, S. C. E. Stieber,
S. DeBeer, P. J. Chirik, J. Am. Chem. Soc. 2013, 135, 13168;
g) T. J. Korstanje, J. I. van der Vlugt, C. J. Elsevier, B. de Bruin,
Science 2015, 350, 298; h) S. M. Jeletic, M. T. Mock, A. M.
Appel, J. C. Linehan, J. Am. Chem. Soc. 2013, 135, 11533; i) C.
Federsel, C. Ziebart, R. Jackstell, W. Baumann, M. Beller, Chem.
Eur. J. 2012, 18, 72; j) N. Deibl, R. Kempe, J. Am. Chem. Soc.
[31] D. van der Waals, L. E. Heim, C. Gedig, F. Herbrik, S. Vallazza,
M. H. G. Prechtl, ChemSusChem 2016, 9, 2343.
[32] No barrier for the methanol addition to 4 or 5 with respect to the
separated reactants could be identified by relaxed potential
energy surface scans. A barrier resulting from solvent reorgan-
ization effects, intractable by DFT computations, cannot be
excluded.
[33] CCDC 1528327 (2), 1528328 (5), and 1528329 (4) contain the
supplementary crystallographic data for this paper. These data
are provided free of charge by The Cambridge Crystallographic
Data Centre.
2016, 138, 10786; k) A. Mukherjee, D. Srimani, S. Chakraborty,
Manuscript received: January 19, 2017
Y. Ben-David, D. Milstein, J. Am. Chem. Soc. 2015, 137, 8888.
Final Article published: && &&, &&&&
Angew. Chem. Int. Ed. 2017, 56, 1 – 6
ꢀ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!

Angewandte
Communications
Chemie
Communications
Base-Metal Catalysis
S. Chakraborty, U. Gellrich,
Y. Diskin-Posner, G. Leitus, L. Avram,
D. Milstein*
&&&& — &&&&
Manganese-Catalyzed N-Formylation of
Back to basics: An acceptorless dehy-
drogenative coupling of methanol and
amines to form formamides that is
catalyzed by a well-defined manganese
pincer complex (see scheme) is reported.
Mechanistic insight based on the obser-
vation of an intermediate and density
functional calculations is also provided.
Amines by Methanol Liberating H : A
2
Catalytic and Mechanistic Study
6
www.angewandte.org
ꢀ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2017, 56, 1 – 6
These are not the final page numbers!