Sustainable and Selective Alkylation of Deactivated Secondary Alcohols to Ketones by Non-bifunctional Pincer N-heterocyclic Carbene Manganese

Article abstract of DOI:10.1002/cssc.202000576

A sustainable and green route to access diverse functionalized ketones via dehydrogenative–dehydrative cross-coupling of primary and secondary alcohols is demonstrated. This borrowing hydrogen approach employing a pincer N-heterocyclic carbene Mn complex displays high activity and selectivity. A variety of primary and secondary alcohols are well tolerant and result in satisfactory isolated yields. Mechanistic studies suggest that this reaction proceeds via a direct outer-sphere mechanism and the dehydrogenation of the secondary alcohol substrates plays a vital role in the rate-limiting step.

Full text of DOI:10.1002/cssc.202000576

Chemistry–Sustainability–Energy–Materials
Accepted Article
Title: Sustainable and Selective Alkylation of Deactivated Secondary
Alcohols to Ketones by Non-bifunctional Pincer N-heterocyclic
Carbene Manganese
Authors: Xiao-bing Lan, Zongren Ye, Jiahao Liu, Ming Huang,
Youxiang Shao, Xiang Cai, Yan Liu, and Zhuofeng Ke
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: ChemSusChem 10.1002/cssc.202000576
Link to VoR: https://doi.org/10.1002/cssc.202000576
01/2020

10.1002/cssc.202000576
ChemSusChem
COMMUNICATION
Sustainable and Selective Alkylation of Deactivated Secondary
Alcohols to Ketones by Non-bifunctional Pincer N-heterocyclic
Carbene Manganese**
Xiao-Bing Lan,[a] Zongren Ye,[a] Jiahao Liu,[a] Ming Huang,[a] Youxiang Shao,[a] Xiang Cai,[c] Yan Liu,[b]*
and Zhuofeng Ke[a]*
synthetic intermediates.[5] Notably, nonprecious metals (such as
Fe, Co, Mn, Ni) have developed as catalysts and have made
significant progress in this reaction.[6] Particularly impressive is
the latest growth in manganese catalysis, since its reactivity
Abstract:
A sustainable and green route to access diverse
functionalized ketones via dehydrogenative-dehydrative cross-
coupling of primary and secondary alcohols is demonstrated under
mild reaction conditions. This borrowing hydrogen approach
employing a pincer N-heterocyclic carbene manganese complex
displays high activity and selectivity. A variety of primary and
secondary alcohols are well tolerant and result in satisfactory
isolated yields. Mechanistic studies suggest that this reaction
towards hydrogenation and dehydrogenation reactions was
7]
demonstrated in 2016.[6k,
Progress on the α-alkylation of
ketones, esters, or amides using primary alcohols has been
recently reported by Beller[6k], Milstein[6g], EI-Sepelgy[6e] and
Balaraman,[6a] etc. groups using manganese catalysts (Scheme
1a). Very recently, we have also reported a phosphine-free bis-
NHC manganese promoted α-alkylation of ketones with primary
alcohols to α-alkylated ketones.[8]
proceeds via
a
direct outer-sphere mechanism and the
dehydrogenation of the secondary alcohol substrates plays a vital
role in the rate-limiting step.
Carbon-carbon bonds formation plays a vital role in producing
organic compounds with structural complexity and diversity. In
diverse types of methodologies, the alkylation reaction provides
a fundamental tool toward the formation of C-C bonds.[1]
Traditional alkylation reactions, however, usually require
environmentally unfriendly organic or organometallic coupling
partners and large amounts of bases, and they generate copious
waste.[2] Although the borrowing hydrogen or hydrogen
autotransfer (BH/HA) methodology, using sustainable alcohol as
the reactant, has emerged as a powerful and green synthetic
strategy, providing a sustainable and green alternative to
conventional alkylation reactions for C−C bond formation,
expensive and toxic noble metal complexes (Ru, Ir, Pd, etc) or
expensive ligands are usually required.[3] Obviously, the
replacement of the precious metal catalysts by earth-abundant
alternatives with practical green ligands is a topic of current
interest for more sustainable processes.[4]
Recently, significant efforts have been devoted to the
synthesis of α-alkylated ketones via the α-alkylation of ketones
with primary alcohols as alkylating agents because the α-
alkylated ketones represent a class of compounds possessing a
broad spectrum of biological activities and are also used as key
[a]
[b]
X.-B. Lan, Z. Ye, J. Liu, M. Huang, Y. Shao, Prof. Dr. Z. Ke
School of Materials Science & Engineering, PCFM Lab, Sun Yat-sen
University, Guangzhou 510275, P. R. China
E-mail: kezhf3@mail.sysu.edu.cn
Prof. Dr. Y. Liu
School of Chemical Engineering and Light Industry, Guangdong
University of Technology, Guangzhou 510006, P. R. China
E-mail: yanliu@gdut.edu.cn
[c]
Prof. Dr. X. Cai
Scheme 1. Previous work and outline of the manganese-
Department of Light Chemical Engineering, Guangdong Polytechnic,
Foshan 528041, P. R. China
catalyzed BH/HA alkylation strategy.
[**]
We thank the NSFC (21673301, 21973113, and 21977019), the
Guangdong Natural Science Funds for Distinguished Young Scholar
(No. 2015A030306027), the Tip-top Youth Talents of Guangdong
Special Support Program (No.20153100042090537), GDHVPS(2017),
and the Fundamental Research Funds for the Central Universities.
Supporting information for this article is available on the WWW under
http://www.angewandte.org.
More significantly, using sustainable secondary and primary
alcohols as starting materials, α-alkylated ketones can be
furnished via direct dehydrogenative and dehydrative coupling
and borrowing hydrogen. It is an intriguing process because
This article is protected by copyright. All rights reserved.

10.1002/cssc.202000576
ChemSusChem
COMMUNICATION
alcohol can be obtained from abundant and indigestible
biomass.[9] The major challenge is that the alkylation of
secondary alcohols with primary alcohols often leads to mixtures
of the β-alkylated alcohols and the β-alkylated ketones,
1). To our delight, the cross-coupling product 3aa could be
detected with 45-92 % yields. Only trace amount of product was
formed when the reaction was carried out in the absence of the
catalyst. These results indicated that C1 was the most effective
one among the evaluated complexes. With these gratifyingly
results in mind, we further optimized the reaction conditions
using C1 in combination with different bases and solvents (Table
1, more details see the Supporting Information, Table S1).
Performing the reaction in t-AmOH resulted in a satisfactory
result (entry 9, Table 1). The manganese and base loading
could be lowered to 1 mol % and 30 mol % respectively (entries
10-12, Table 1). In control experiments performed in the
absence of catalyst, or without both catalyst and base, no cross-
coupling product was observed, indicating that catalyst and base
are essential for the reaction (entries 13-14, Table 1). An inert
atmosphere seemed to be necessary (entry 15, Table 1). GC
analysis indicated the formation of H2 as side product (Figure S1,
SI).
presenting a tricky selectivity issue (Scheme 2).[10] Very recently,
11]
Kempe,[4k,
EI-Sepelgy[12] and Yu[13] et. al. reported the β-
alkylation of secondary alcohols with primary alcohols to provide
β-alkylated alcohols using manganese complexes (Scheme 1b).
On the other hand, the β-alkylation of secondary alcohols with
methanol to provide β-methylated alcohols using manganese
complexes were also reported by Leitner and Kempe et. al.[14]
Therefore, from
a sustainable chemistry standpoint, the
alternative formation of α-alkylated ketones from secondary and
primary alcohols is highly attractive in terms of high selectivity,
efficiency, and more environmentally benign conditions.
Table 1. Optimization of the reaction conditions
Yield
of 3aa
(%)b
92
56
45
81
6
65
0
0
96
94
92
93(88)
0
0
42
10
Ratio of
3aa/3aa*
(%)c
Cat.
(mol%)
Base
(eq.)
Run
Solvent
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15d
16e
17f
C1 (2)
C2 (2)
C3 (2)
C4 (2)
-------
C1 (2)
C1 (2)
C1 (2)
C1 (2)
C1 (1)
C1 (1)
C1 (1)
C1 (1)
-------
NaOH (0.5)
NaOH (0.5)
NaOH (0.5)
NaOH (0.5)
NaOH (0.5)
NaOH (0.5)
NaOH (0.5)
NaOH (0.5)
NaOH (0.5)
NaOH (0.5)
NaOH (0.4)
NaOH (0.3)
--------------
NaOH (0.3)
NaOH (0.3)
NaOH (0.3)
NaOH (0.3)
Toluene
Toluene
Toluene
Toluene
Toluene
1,4-dioxane
DMSO
95:5
81:19
78:22
93:7
50:50
98:2
Scheme 2. The origin of selectivity challenges: the alkylation of
secondary alcohols with primary alcohols.
0:0
0:0
Except for the limited progress in phosphine manganese
CH3CN
t-AmOH
t-AmOH
t-AmOH
t-AmOH
t-AmOH
t-AmOH
t-AmOH
t-AmOH
t-AmOH
>99:1
>99:1
>99:1
>99:1
0:0
0:0
97:3
92:8
93:7
promoted homogeneous β-alkylation of secondary alcohols to
14, 15]
give α-alkylated ketones,[6g,
α-alkylated ketones were
synthesized by direct dehydrogenative coupling of secondary
alcohols with primary alcohols using heterogeneous or
homogeneous Ru, Ir, Ag, and Cu catalysts.[16] Thus, it would be
desirable to develop a practical, economical, phosphine-free and
green alkylation process for the formation of α-alkylated ketones
using environmentally friendly first-row transition metals. Based
on our recent progress in practical N-heterocyclic carbene (NHC)
manganese catalysis and the encouraging results have been
reported very recently on the manganese pincer complexes.[4k, 8]
We envision that non-bifunctional NHC-based pincer-type
C1 (1)
C1 (1)
C1 (1)
58
[a] Reaction conditions: 1a (0.5 mmol), 2a (0.6 mmol), solvent (1.0 mL), at
110 oC for 6 h. [b] The yield was determined by GC with 1,4-Di-tert-
butylbenzene as an internal standard, Isolated yield in parentheses. [c] Ratio
were determined using GC analysis. [d] Performed in air. [e] 1 mol% trityl
hexachloroantimonate was added. [f] 0.5 mol% trityl hexachloroantimonate
was added.
manganese complex may be
a
promising catalyst for
sustainable coupling between secondary alcohols and primary
alcohols, due to the merit of NHC ligands in easy accessibility,
environmental benignancy, stability, and tunable structure.[17] In
this context, herein, we report a sustainable and high selective
β-alkylation of secondary alcohols to give α-alkylated ketones
catalyzed by a practical pincer NHC manganese catalysis
(Scheme 1c).
Having the optimal reaction conditions in hand, the scope of
the reaction was explored (Table 2). Various substituted primary
alcohols all resulted in highly selective formation of
corresponding ketones. It was found that benzyl alcohols with
electron-donating substituents, including 3-methyl benzyl alcohol,
4-methyl benzyl alcohol, and 4-methoxy benzyl alcohol
efficiently proceeded to desired ketones 3ab-3ad in 89-90%
yields (Table 2). However, benzyl alcohols bearing an electron-
withdrawing substituent at the para position, such as F, Cl, and
Br, showed a negative electronic effect, resulting in products
3ae-3ag in 88-56% yields. Interestingly, the strong electron-
At the start of this study, the coupling of 1-phenylethanol (1a)
and benzyl alcohol (2a) was chosen as a model reaction (Table
1). Pincer-type manganese complexes were prepared following
the Luca’s report.[18] Note that all of these pincer-type
manganese complexes are both air- and moisture-stable and
could be stored in brown glass vials beyond 30 days and no
obvious decrease of catalytic activity was observed. An initial
attempt control experiments were conducted (entries 1-5, Table
This article is protected by copyright. All rights reserved.

10.1002/cssc.202000576
ChemSusChem
COMMUNICATION
withdrawing trifluoromethyl substituent can also be tolerated.
2,6-Dimethylbenzyl alcohol exhibited obvious steric impact on
the yield of 3al (66%), while 2-methyl benzyl alcohol and 2-
naphthalenemethanol efficiently underwent the reaction with 1a,
forming 3ak and 3am in 95% and 90% yields, respectively.
Heteroatom-containing substrates showed negative effects,
resulting in products 3an (71%), 3ao (72%), and 3ap (63%).
With a higher catalyst loading (2 mol%), heterocyclic alcohols
containing thiophene, furan, and pyridine moiety, also reacted
with 1a to give 3aq-3as in 33-58% yields (Table 2). In these
cases, the catalyst might be partially deactivated by the
yields (81-86%). Various halo groups such as F, Cl, Br, and CF3
could be tolerant on the aryl group of 1-arylethanols (3fa-3ja, 87-
46%, Table 3). Interestingly, 1-(1-naphthyl)ethanol efficiently
reacted with 2a to afford 3ka (84%), while an obvious steric
effect was revealed with an ortho-substituent (3la, 54%, Table 3).
As a result, this catalytic cross-coupling is sensitive to the steric
hindrance of the secondary alcohols. The α-tetralol, 1-
ferrocenylethanol was alkylated by 2a to give 3ma and 3na in
51% and 56% yields, respectively. Furthermore, thiophene and
furan containing heteroaromatic secondary alcohols were also
found to be viable coupling partners, delivering the product 3oa-
coordination of the heteroatom to the metal center of the catalyst. 3pa in moderate yields. However, attempts to perform alkylation
Middle-chain aliphatic primary alcohols exhibited lower
reactivities than those of the benzyl alcohols, and their reactions
with 1a were conducted under the relatively harsh conditions,
forming the target products 3at−3av in 67−76% yields. These
results have revealed that benzyl alcohols are more reactive
than aliphatic primary alcohols in the studied β-alkylation of
secondary alcohols.
of non-benzylic primary alcohols with secondary alcohols
(saturated aliphatic alcohols) were unsuccessful, yielding only
trace amounts of products (Scheme S2).
Table 3. Reaction scope of secondary alcohols.
Table 2. Reaction scope of primary alcohols.
[a] Reaction conditions: 1 (0.5 mmol), 2 (0.6 mmol), C1 (1 mol%),
o
NaOH (30 mol%), t-AmOH (1 mL), at 110 C for 6 h, isolated
yield. [b] C1 (2 mol%), NaOH (50 mol%).
To gain insight into the reaction mechanism, a number of
control experiments were performed (Scheme 3a, more details
see the Supporting Information, Scheme S3). In the presence of
NaOH, the condensation of benzaldehyde with acetophenone
afforded chalcone 3aa** in 80% yields (Scheme 3a). Transfer
hydrogenation of chalcone 3aa** could be achieved with 1a or
2a as the hydrogen source (Scheme 3a). These results indicate
the reaction proceeds via condensation and borrowing hydrogen
processes. In order to obtain further mechanistic insight, we
performed deuterium-labeling experiments (Scheme 3b, more
details see the Supporting Information, Scheme S4). In this case,
the aprotic solvent toluene was used instead of t-amyl alcohol to
avoid additional H/D exchange. All the deuterium-labeling
experimental results show deuterium atoms did not incorporate
at the α-position and mostly distributed in the β-positions
[a] Reaction conditions: 1 (0.5 mmol), 2 (0.6 mmol), C1 (1 mol%),
NaOH (30 mol%), t-AmOH (1 mL), at 110 C for 6 h, isolated
o
yield. [b] C1 (2 mol%), NaOH (50 mol%). [c] C1 (5 mol%), NaOH
(50 mol%), 130 oC.
Subsequently, a wide range of secondary alcohols was also
studied and the results are summarized in Table 3. Various
electron-rich or electron-deficient 1-arylethanols were effectively
transferred into the corresponding ketones 3ba-3ea in high
This article is protected by copyright. All rights reserved.

10.1002/cssc.202000576
ChemSusChem
COMMUNICATION
(Scheme 3b, more details see the Supporting Information,
Scheme S4). These results imply that a similar mechanism to
our previously observed of a direct outer-sphere mechanism.[18]
Subsequently, the progress of model reaction between 1a and
2a as a function of time was investigated (see the Supporting
Information for details, Figure S2). The kinetic isotope effect
(KIE = 2.31) and kinetic profiles results suggested that the
dehydrogenation of the alcohol substrates is most likely the rate-
limiting step (RDS).
To confirm Mn-H species, several attempts were made to
trace metal hydride by 1H-NMR experiments. Unfortunately,
hydride trapping was not successful, we only observed the
aldehyde formation (1H-NMR=9.6 ppm; see SI). The failure of
1
direct observation of Mn-H species by H-NMR may result from
their thermodynamic instability or the high reactivity of the Mn-H
species under the reaction conditions. According to literature,[19]
we observed that the addition of stoichiometric amounts of trityl
cation inhibited catalysis and the addition of smaller quantities of
trityl cation led to proportional decreases in reactivity (entries 13-
14, Table 1), which indicated the Mn-H could be involved in the
catalytic cycle.
On the basis of our experimental observations and literature
precedents,[6e, 8, 10a, 20] a plausible reaction pathway is proposed
in Scheme 3c. Initially, catalyst C1 reacts with a base to
generate an unsaturated reactive species C1-1, which is similar
to previous reports.[6e, 12] The resulted active intermediate C1-1
then reacts with primary or secondary alcohols to provide an
alkoxo manganese intermediates (C1-2 and C1-3). An outer
sphere hydride elimination may result in the formation of ketone
intermediate
A
and aldehyde intermediate B. Both
dehydrogenation reactions converge to provide the manganese
hydride intermediate C1-4 for the subsequent hydrogenation. A
base mediated cross-aldol condensation between A and B in
situ produces the α,β-unsaturated ketone 3aa**, which
undergoes selective 1,4-hydrogenation by metal hydride C1-4 to
from enol (isomerization to ketone), instead of 1,2-hydrogenation
of the C=O bond to alcohols. An additional molecule of H2 will
also be released during the whole catalytic cycle.
Figure 1. Free energy profile for C1-catalyzed alkylation of 1a
with 2a. Free energies are given in kcal/mol
DFT calculations were performed to further understand the
reaction mechanism. As shown in Figure 1, the reactive
intermediate C1-2 or C1-3 promotes the hydride elimination
through transition state TS1 (19.6 kcal/mol) or TS2 (25.4
kcal/mol), respectively, via an outer-sphere manner, liberating A
or B, generating manganese hydride species C1-4. As
compared with primary alcohol, secondary alcohol is crucial in
the dehydrogenation stage. Then the enone, which is formed by
the aldol condensation between aldehyde and ketone, is
Scheme 3. Mechanistic considerations. Isolated Yields.
This article is protected by copyright. All rights reserved.

10.1002/cssc.202000576
ChemSusChem
COMMUNICATION
Cavallo, M. Rueping, O. El-Sepelgy, ChemSusChem 2019, 12, 3083-
3088; g) K. Polidano, B. D. W. Allen, J. M. J. Williams, L. C. Morrill,
ACS Catal. 2018, 8, 6440-6445; h) A. Mukherjee, D. Milstein, ACS
Catal. 2018, 8, 11435-11469; i) W. Liu, B. Sahoo, K. Junge, M. Beller,
Acc. Chem. Res. 2018, 51, 1858-1869; j) V. G. Landge, A. Mondal, V.
Kumar, A. Nandakumar, E. Balaraman, Org. Biomol. Chem. 2018, 16,
8175-8180; k) F. Kallmeier, R. Kempe, Angew. Chem. Int. Ed. 2018, 57,
46-60; l) G. A. Filonenko, R. van Putten, E. J. M. Hensen, E. A. Pidko,
Chem. Soc. Rev. 2018, 47, 1459-1483; m) B. Maji, M. Barman,
Synthesis 2017, 49, 3377-3393; n) F. Freitag, T. Irrgang, R. Kempe,
Chem. Eur. J. 2017, 23, 12110-12113.
reduced by the manganese hydride species C1-4 through
transition state TS3 (18.9 kcal/mol) to furnish the α,β-saturated
ketone as the final product. DFT studies suggested that the RDS
should the dehydrogenation of the alcohol substrates, which is in
good accordance with the deuterium-labeling experiments and
the observed KIE effect.
In summary, we have developed an efficient and green
approach to access diverse functionalized ketones via borrowing
hydrogen strategy, with sustainable primary and secondary
alcohols as starting materials, using a phosphine-free pincer
type NHC-Mn catalyst. This sustainable approach displays high
activity and selectivity, and broad substrate scope of various
primary and secondary alcohols under mild reaction conditions
by using a low catalyst loading, a catalytic amount of cheap
base, and t-amyl alcohol solvent at relatively mild temperature.
Mechanistic studies suggested an outer-sphere mechanism for
this non-bifunctional pincer NHC-Mn system and the
dehydrogenation of the secondary alcohol substrates plays a
vital role in the rate-limiting step.
[5] For selected examples and reviews, see: a) J. Sklyaruk, J. C. Borghs, O.
El-Sepelgy, M. Rueping, Angew. Chem. Int. Ed. 2019, 58, 775-779; b) A.
Bruneau-Voisine, L. Pallova, S. Bastin, V. César, J.-B. Sortais, Chem.
Commun. 2019, 55, 314-317; c) N. R. Bennedsen, R. L. Mortensen, S.
Kramer, S. Kegnæs, J. Catal. 2019, 371, 153-160; d) L. Rakers, F.
Schäfers, F. Glorius, Chem. Eur. J. 2018, 24, 15529-15532; e) L. M.
Kabadwal, J. Das, D. Banerjee, Chem. Commun. 2018, 54, 14069-
14072; f) X. N. Cao, X. M. Wan, F. L. Yang, K. Li, X. Q. Hao, T. Shao, X.
Zhu, M. P. Song, J. Org. Chem. 2018, 83, 3657-3668; g) C. B. Reddy,
R. Bharti, S. Kumar, P. Das, ACS Sustainable Chem. Eng. 2017, 5,
9683-9691; h) P. Piehl, M. Pena-Lopez, A. Frey, H. Neumann, M. Beller,
Chem. Commun. 2017, 53, 3265-3268; i) L. Guo, X. Ma, H. Fang, X. Jia,
Z. Huang, Angew. Chem. Int. Ed. 2015, 54, 4023-4027; j) M. S. Kwon,
N. Kim, S. H. Seo, I. S. Park, R. K. Cheedrala, J. Park, Angew. Chem.
Int. Ed. 2005, 44, 6913-6915; k) K. Taguchi, H. Nakagawa, T.
Hirabayashi, S. Sakaguchi, Y. Ishii, J. Am. Chem. Soc. 2004, 126, 72-
73.
Keywords: alcohol · borrowing hydrogen · N-heterocyclic
carbene · manganese · alkylation· pincer
[6] For selected examples and reviews, see: a) J. Rana, V. Gupta, E.
[1] For selected examples and reviews, see: a) T. Irrgang, R. Kempe, Chem.
Rev. 2019, 119, 2524-2549; b) M. B. Dambatta, K. Polidano, A. D.
Northey, J. M. J. Williams, L. C. Morrill, ChemSusChem 2019, 12, 2345-
2349; c) L. Bettoni, S. Gaillard, J.-L. Renaud, Org. Lett. 2019, 21, 8404-
8408; d) G. Zhang, T. Irrgang, T. Dietel, F. Kallmeier, R. Kempe, Angew.
Chem. Int. Ed. 2018, 57, 9131-9135; e) W. Ma, S. Cui, H. Sun, W. Tang,
D. Xue, C. Li, J. Fan, J. Xiao, C. Wang, Chem. Eur. J. 2018, 24, 13118-
13123; f) A. Corma, J. Navas, M. J. Sabater, Chem. Rev. 2018, 118,
1410-1459; g) F. Huang, Z. Liu, Z. Yu, Angew. Chem. Int. Ed. 2016, 55,
862-875; h) X. Quan, S. Kerdphon, P. G. Andersson, Chem.Eur. J.
2015, 21, 3576-3579; i) Y. Obora, ACS Catal. 2014, 4, 3972-3981; j) Y.
Li, D. Xue, W. Lu, C. Wang, Z.-T. Liu, J. Xiao, Org. Lett. 2014, 16, 66-
69; k) C. Gunanathan, D. Milstein, Science 2013, 341, 1229712; l) G.
Guillena, D. J. Ramón, M. Yus, Angew. Chem. Int. Ed. 2007, 46, 2358-
2364.
Balaraman, Dalton Trans. 2019, 48, 7094-7099
; b) J. Das, M.
Vellakkaran, D. Banerjee, J. Org. Chem. 2019, 84, 769-779; c) L.
Bettoni, C. Seck, M. D. Mbaye, S. Gaillard, J.-L. Renaud, Org. Lett.
2019, 21, 3057-3061; d) S. P. Midya, J. Rana, J. Pitchaimani, A.
Nandakumar, V. Madhu, E. Balaraman, ChemSusChem 2018, 11,
3911-3916; e) Y. K. Jang, T. Krückel, M. Rueping, O. El-Sepelgy, Org.
Lett. 2018, 20, 7779-7783; f) J. Das, K. Singh, M. Vellakkaran, D.
Banerjee, Org. Lett. 2018, 20, 5587-5591; g) S. Chakraborty, P. Daw, Y.
Ben David, D. Milstein, ACS Catal. 2018, 8, 10300-10305; h) M. K.
Barman, A. Jana, B. Maji, Adv. Synth. Catal. 2018, 360, 3233-3238; i) G.
Zhang, J. Wu, H. Zeng, S. Zhang, Z. Yin, S. Zheng, Org. Lett. 2017, 19,
1080-1083; j) C. Seck, M. D. Mbaye, S. Coufourier, A. Lator, J.-F.
Lohier, A. Poater, T. R. Ward, S. Gaillard, J.-L. Renaud, ChemCatChem
2017, 9, 4410-4416; k) M. Peña-López, P. Piehl, S. Elangovan, H.
Neumann, M. Beller, Angew. Chem. Int. Ed. 2016, 55, 14967-14971; l)
N. Deibl, R. Kempe, J. Am. Chem. Soc. 2016, 138, 10786-10789; m) S.
Elangovan, J.-B. Sortais, M. Beller, C. Darcel, Angew. Chem. Int. Ed.
2015, 54, 14483-14486.
[2] a) F.A. Carey, R.J .Sundberg, Advanced Organic Chemistry Part B:
Reactions and Synthesis, 5th ed., Springer, New York, 2007, pp. 1–62;
b) Modern Carbonyl Chemistry (Eds.: J. Otera), Wiley-VCH, Weinheim,
2000; c) D. Caine in Comprehensive Organic Chemistry, Vol. 3 (Eds.: B.
M. Trost, I. Fleming,G .Pattenden), Pergamon, Oxford, 1991, pp. 1–63.
[3] For selected examples and reviews, see: a) S. Genc, S. Gunnaz, B.
Cetinkaya, S. Gulcemal, D. Gulcemal, J. Org. Chem. 2018, 83, 2875-
2881; b) S. Shee, B. Paul, D. Panja, B. C. Roy, K. Chakrabarti, K.
Ganguli, A. Das, G. K. Das, S. Kundu, Adv. Synth. Catal. 2017, 359,
3888-3893; c) R. Mamidala, S. Samser, N. Sharma, U. Lourderaj, K.
Venkatasubbaiah, Organometallics 2017, 36, 3343-3351; d) P. Liu, R.
Liang, L. Lu, Z. Yu, F. Li, J. Org. Chem. 2017, 82, 1943-1950; e) G.
Chelucci, Coord. Chem. Rev. 2017, 331, 1-36; f) C. Schlepphorst, B.
Maji, F. Glorius, ACS Catal. 2016, 6, 4184-4188; g) D. Shen, D. L.
Poole, C. C. Shotton, A. F. Kornahrens, M. P. Healy, T. J. Donohoe,
Angew. Chem. Int. Ed. 2015, 54, 1642-1645; h) D. Wang, K. Zhao, C.
Xu, H. Miao, Y. Ding, ACS Catal. 2014, 4, 3910-3918; i) S. Ogawa, Y.
Obora, Chem. Commun. 2014, 50, 2491-2493; j) L. Guo, Y. Liu, W. Yao,
X. Leng, Z. Huang, Org. Lett. 2013, 15, 1144-1147; k) Y. Iuchi, Y.
Obora, Y. Ishii, J. Am. Chem. Soc. 2010, 132, 2536-2537.
[7] S. Elangovan, J. Neumann, J. B. Sortais, K. Junge, C. Darcel, M. Beller,
Nat. Commun. 2016, 7, 12641.
[8] X.-B. Lan, Z. Ye, M. Huang, J. Liu, Y. Liu, Z. Ke, Org. Lett. 2019, 21,
8065-8070.
[9] a) S. Michlik, R. Kempe, Nature Chem. 2013, 5, 140; b) C. O. Tuck, E.
Pérez, I. T. Horváth, R. A. Sheldon, M. Poliakoff, Science 2012, 337,
695-699; c) T. P. Vispute, H. Zhang, A. Sanna, R. Xiao, G. W. Huber,
Science 2010, 330, 1222-1227.
[10] a) S. Thiyagarajan, C. Gunanathan, J. Am. Chem. Soc. 2019, 141,
3822-3827; b) B. Pandey, S. Xu, K. Ding, Org. Lett. 2019, 21, 7420-
7423; c) M. V. Jiménez, J. Fernández-Tornos, F. J. Modrego, J. J.
Pérez-Torrente, L. A. Oro, Chem. Eur. J. 2015, 21, 17877-17889.
[11] N. Deibl, R. Kempe, Angew. Chem. Int. Ed. 2017, 56, 1663-1666.
[12] O. El-Sepelgy, E. Matador, A. Brzozowska, M. Rueping,
ChemSusChem 2019, 12, 3099-3102.
[13] T. Liu, L. Wang, K. Wu, Z. Yu, ACS Catal. 2018, 8, 7201-7207.
[14] a) M. Schlagbauer, F. Kallmeier, T. Irrgang, R. Kempe, Angew. Chem.
Int. Ed. 2020, 59, 1485-1490; b) A. Kaithal, P. van Bonn, M. Hölscher,
W. Leitner, Angew. Chem. Int. Ed. 2020, 59, 215-220; c) A. Kaithal, L.-L.
Gracia, C. Camp, E. A. Quadrelli, W. Leitner, J. Am. Chem. Soc. 2019,
141, 17487-17492.
[4] For selected examples and reviews, see: a) V. Yadav, V. G. Landge, M.
Subaramanian, E. Balaraman, ACS Catal. 2020, 10, 947-954; b) M.
Subaramanian, S. P. Midya, P. M. Ramar, E. Balaraman, Org. Lett.
2019, 21, 8899-8903; c) B. G. Reed-Berendt, K. Polidano, L. C. Morrill,
Org. Biomol. Chem. 2019, 17, 1595-1607; d) S. S. Gawali, B. K. Pandia,
C. Gunanathan, Org. Lett. 2019, 21, 3842-3847; e) J. C. Borghs, M. A.
Tran, J. Sklyaruk, M. Rueping, O. El-Sepelgy, J. Org. Chem. 2019, 84,
7927-7935; f) J. C. Borghs, L. M. Azofra, T. Biberger, O. Linnenberg, L.
[15] S. S. Gawali, B. K. Pandia, S. Pal, C. Gunanathan, ACS Omega 2019,
4, 10741-10754.
This article is protected by copyright. All rights reserved.

10.1002/cssc.202000576
ChemSusChem
COMMUNICATION
[16] a) Y. Qiu, Y. Zhang, L. Jin, L. Pan, G. Du, D. Ye, D. Wang, Org. Chem.
Front. 2019, 6, 3420-3427; b) D. W. Tan, H. X. Li, D. L. Zhu, H. Y. Li, D.
J. Young, J. L. Yao, J. P. Lang, Org. Lett. 2018, 20, 608-611; c) A. R.
Sahoo, G. Lalitha, V. Murugesh, C. Bruneau, G. V. M. Sharma, S.
Suresh, M. Achard, J. Org. Chem. 2017, 82, 10727-10731; d) R. Wang,
J. Ma, F. Li, J. Org. Chem. 2015, 80, 10769-10776; e) S. Musa, L.
Ackermann, D. Gelman, Adv. Synth. Catal. 2013, 355, 3077-3080; f) K.
Shimizu, R. Sato, A. Satsuma, Angew. Chem. Int. Ed. 2009, 48, 3982-
3986.
[17] E. Peris, Chem. Rev. 2018, 118, 9988-10031.
[18] a) T. H. T. Myren, A. M. Lilio, C. G. Huntzinger, J. W. Horstman, T. A.
Stinson, T. B. Donadt, C. Moore, B. Lama, H. H. Funke, O. R. Luca,
Organometallics 2019, 38, 1248-1253; b) D. S. McGuinness, V. C.
Gibson, J. W. Steed, Organometallics 2004, 23, 6288-6292.
[19] J. R. Carney, B. R. Dillon, L. Campbell, S. P. Thomas, Angew. Chem.
Int. Ed. 2018, 57, 10620-10624.
[20] Z. Ke, Y. Li, C. Hou, Y. Liu, in Phys. Sci. Rev. 2018, 3 (10), No.
20170038.
This article is protected by copyright. All rights reserved.

10.1002/cssc.202000576
ChemSusChem
COMMUNICATION
COMMUNICATION
Xiao-Bing Lan, Zongren Ye, Jiahao Liu,
Ming Huang, Youxiang Shao, Xiang Cai,
Yan Liu,* and Zhuofeng Ke* Page No. –
Page No.
Sustainable and Selective Alkylation of
Deactivated Secondary Alcohols to
Ketones by Non-bifunctional Pincer N-
heterocyclic Carbene Manganese
A sustainable and green route to access diverse functionalized ketones via
dehydrogenative-dehydrative cross-coupling of primary and secondary alcohols is
demonstrated under mild reaction conditions. This borrowing hydrogen approach
employing a pincer N-heterocyclic carbene manganese complex displays high activity
and selectivity. A variety of primary and secondary alcohols are well tolerant and
result in satisfactory isolated yields. Mechanistic studies suggest that this reaction
proceeds via a direct outer-sphere mechanism and the dehydrogenation of the
secondary alcohol substrates plays a vital role in the rate-limiting step.
This article is protected by copyright. All rights reserved.