A Highly Efficient Dimeric Manganese-Catalyzed Selective Hydroarylation of Internal Alkynes

Article abstract of DOI:10.1002/anie.202004950

We have developed a general and site-predictable manganese-catalyzed hydroarylation of internal alkynes in the presence of water, under an air atmosphere without the involvement of ligand. The unique catalytic feature of this reaction is highlighted by comparison with other widely used transition metal catalysts including palladium, rhodium, nickel, or copper. The simple operation, high efficiency and excellent functional group compatibility make this protocol practical for more than 90 structurally diverse internal alkynes, overcoming the influence of both electronic and steric effect of alkynes. Its exclusive regio- and chemoselectivity originates from the unique reactivity of the manganese-based catalyst towards an inherent double controlled strategy of sterically hindered propargyl alcohols without the installing of external directing groups. Its synthetic robustness and practicality have been illustrated by the concise synthesis of bervastatin, a hypolipidemic drug, and late-stage modification of complex alkynes with precise regioselectivity.

Full text of DOI:10.1002/anie.202004950

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
International Edition Chemie
www.angewandte.org
Accepted Article
Title: A Highly Efficient Dimeric Manganese-Catalyzed Selective
Hydroarylation of Internal Alkynes
Authors: Jin Xie
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: Angew. Chem. Int. Ed. 10.1002/anie.202004950
Link to VoR: https://doi.org/10.1002/anie.202004950

Angewandte Chemie International Edition
10.1002/anie.202004950
COMMUNICATION
A Highly Efficient Dimeric Manganese-Catalyzed Selective
Hydroarylation of Internal Alkynes
Yubo Pang, Gengtu Liu, Congcong Huang, Xiang-Ai Yuan, Weipeng Li and Jin Xie*
[*]
Y. Pang, G. Liu, Prof. Dr. W. Li, Prof. Dr. J. Xie
State Key Laboratory of Coordination Chemistry, Jiangsu Key Laboratory of Advanced Organic Materials, Chemistry and Biomedicine Innovation Center
(ChemBIC), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023 (China)
http://hysz.nju.edu.cn/xie/ Email:xie@nju.edu.cn
C. Huang, Prof. Dr. X.-A. Yuan
School of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165 (China)
Supporting information for this article is given via a link at the end of the document. ((Please delete this text if not appropriate))
Abstract: We have developed
a
general and site-predictable
propargyl alcohols,[7] and d) late-stage -arylation of complex
manganese-catalyzed hydroarylation of internal alkynes in the
presence of water, under an air atmosphere without the involvement
of ligand. The unique catalytic feature of this reaction is highlighted by
comparison with other widely used transition metal catalysts including
palladium, rhodium, nickel or copper. The simple operation, high
efficiency and excellent functional group compatibility make this
protocol to be practical for more than 90 structurally diverse internal
alkynes, overcoming the influence of both electronic and steric effect
of alkynes. Its exclusive regio- and chemoselectivity originates from
the unique reactivity of the manganese-based catalyst towards an
inherent double controlled strategy of sterically hindered propargyl
alcohols without the installing of external directing groups. Its
synthetic robustness and practicality have been illustrated by the
concise synthesis of bervastatin, a hypolipidemic drug, and late-stage
modification of complex alkynes with precise regioselectivity.
internal alkynes bearing competing reaction sites.
Selective hydrofunctionalization of internal alkynes catalyzed by
transition metals is
a
powerful strategy to construct
multisubstituted alkenes, in which the chemo-, regio- and stereo-
selectivity are the key problem.[1] Arylboronic acids are
commercially abundant and easily handling reagents, which
recently have gained considerable momentum in selective
hydroarylation of alkynes.[2] For example, after much research
with palladium,[3a,3b] rhodium,[3c-f] copper[3g] and nickel[3h,3i]
catalysts, it is recognized that the utilization of electronic and
directing group strategy can normally control the regioselectivity
of hydroarylation but the inherent high reactivity of these metals
towards a wide range of useful functional groups simultaneously
compromises their chemoselectivities (Scheme 1a). On the other
hand, it requires several steps to install and remove the directing
group before and after reactions. The -arylated tertiary allyl
alcohols are versatile building blocks which provide access to
complex structures and are also structural motifs commonly found
in biologically important molecules (Scheme 1b).[4] However, a
general catalytic access to such kind of -arylated tertiary allyl
alcohols is still rarely reported to date. We questioned the
possibility of a direct -selective hydroarylation protocol of
sterically hindered tertiary propargyl alcohols with commercially
available arylboronic acids. The major challenge to development
of such a transformation involves: a) how to suppress the
competing -oxygen elimination side reactions,[5] b)
regioselectivity independent of the electronic effect of alkynes;[6]
c) the interference between multiple reactive functional groups in
Scheme 1. Transition metal-catalyzed selective hydroarylation of internal
alkynes with arylboronic acids.
Manganese is the third most naturally abundant transition
metal,[8] which generally has minimal toxicity and exhibits
[9]
excellent
functional
group
compatibility.
Recently,
manganese(I)-catalyzed C-H activation of directed arenes for
[10]
hydroarylation of alkynes has been successfully developed.
While powerful, the successful employment of a wide range of
structurally diverse and commercially available arylboronic acids
would significantly expand the chemical space and scope
limitation of directed arenes. To address this, our group reported
the first case of Mn(I)-catalyzed hydroarylation of 1,3-diynes with
[11a]
aromatic boronic acids.
However, its regioselectivity and
reactivity relies heavily on the electronic and steric effect of the
substituents respectively, which causes aliphatic propargyl
1
This article is protected by copyright. All rights reserved.

Angewandte Chemie International Edition
10.1002/anie.202004950
COMMUNICATION
alcohols gave only mixed regioisomeric products while sterically
hindered substrates are unreacted (Scheme 1c). Therefore, the
development of a more efficient, site-predictable and unified
efficiency. The reaction is clean and no side reactions of -oxygen
elimination to allenes, oxidation of boronic acids to phenol
derivatives or the homocoupling of boronic acids. Replacement of
hydroarylation protocol with Ar-B(OH)
2
is still highly desired for
2 8 2 5
Mn (CO) Br with 10 mol% Mn(CO) Br decreased the reaction
manganese catalysis owing to its undeveloped elementary
chemistry.
conversion and yield (82%). The use of other metals such as Pd,
Rh, Ni and Cu significantly decreases the conversion and also
results in undesired side reactions under our standard conditions
or the previously reported conditions. For example, with
To effect control of Mn(I)-catalyzed regioselectivity, we
proposed a double control strategy, which takes advantage of
both a steric effect and the influence of inherent hydroxyl group.
As shown in Scheme 1d, the  angle plays a crucial role in the
regioselectivity. In general, the smaller the  angle, the better -
regioselectivity. Consequently, this protocol offers the possibility
of adjusting the regioselectivity from the previous - to current -
position. When a tertiary alcohol motif was incorporated, only -
selectivity could be detected. Remarkably, the sterically hindered
propargyl alcohols are not only unreacted substrate under our
previous conditions[11] but also challenging alkynes in transition
metal-catalyzed selective hydrofunctionalization to construct
synthetically valuable tertiary allyl alcohols due to the facile -
oxygen elimination.[5] That the reaction is controlled by both a
steric effect and an inherent functional group (-OH) is supported
by the fact that introduction of a sterically hindered tert-butyl group
in this hydroarylation was unsuccessful (Scheme 1d). The
reaction is fast with a 15 min-2 h reaction time, has a broad scope
and simple operation, and proceeds under an air atmosphere.
More than 90 examples for both aliphatic and aromatic internal
alkynes as well as 1,3-enynes and 1,3-diynes have been
achieved. The use of manganese catalysts provides an excellent
functional group compatibility and allows for precise late-stage
modification of complex internal alkynes, which is difficult with
noble metal catalysts.
3 4
Pd(Ph P) as catalyst, the formation of allene (4) or biaryl (5)
[
3a]
byproducts is facilitated. Under the reaction conditions reported
by Reddy et al.,[ the use of a 10 mol% Ni(acac)
3i]
/Ph
P catalytic
2
3
combination leads to a complex reaction with only a moderate
yield (51%) of the desired product along with byproducts (4).
Comparison of these results using other transition metal catalysts
further highlights the unique reactivity of the manganese catalysts.
A control experiment indicates that no reaction occurs in the
absence of a transition metal catalyst.
We investigated the reaction scope with regard to internal
alkynes (Scheme 3). Besides propargyl alcohol, propargyl ether
is also a good kind of substrate (6). In general, this protocol has a
very broad scope and excellent functional group tolerance. A wide
range of structurally varied tertiary alcohols (1, 7-22), including
cyclic and acyclic tertiary alcohol motifs, can be incorporated into
aliphatic alkynes. The starting alkynes can uniformly undergo
manganese-catalyzed hydroarylation, largely uninfluenced by
structural changes. Heteroarenes in the tertiary alcohol had little
effect on the regioselectivity (16). A variety of substituted aliphatic
alkynes (23-40) were subjected to this protocol and found to
exhibit promising compatibility with functional groups. For
example, functional groups such as bromo (17, 28) and iodo (29)
that are sensitive in palladium or nickel catalysis, tolerate the
reaction conditions well. When the OTs-containing substrate (26)
was employed, a tandem hydroarylation and intramolecular
nucleophilic substitution readily occur to afford 8-phenyl-5-
oxaspiro[3.5]non-8-ene in 77% yield in 15 min.
Under the optimized reaction conditions, the desired product
(
3) is obtained in 95% yield in 15 min with 5 mol% dimeric
Mn (CO) Br as the catalyst under an air atmosphere (Scheme 2).
The addition of 10 equivalents of water improves the reaction
2
8
2
Scheme 2. Parallel comparison experiments with different transition metals. Standard conditions: Mn
2
(CO)
8
Br
2
(5 mol%), 1 (0.2 mmol), 2 (3 equiv), KHCO
3
(2.5
P)
o
o
equiv), H
2
O (10 equiv), toluene/pentane (v/v = 1:4), air atmosphere, 90 C, 15 min. [a] Mn(CO)
5
Br (10 mol%) instead of Mn
2
(CO) Br
8 2
(5 mol%), 90 C. [b] Pd(Ph
3
4
o
o
(5 mol%), AcOH (10 mol%), dioxane, 80 C. [c] [LRhCl]
2
(3 mol%), dppb (6 mol%), K
2
CO
3
(1.5 equiv), dioxane, 100 C. [d] CuOAc (5 mol%), MeOH, room temperature
o
[
e] Ni(acac)
2
3
(10 mol%), Ph P (10 mol%), Cs
2
CO
3
(20 mol%), dioxane/EtOH (v/v = 4:1), 90 C. dppb = 1,4-bis(diphenylphosphino)butane; L = 1,5-cyclooctadiene.
2
This article is protected by copyright. All rights reserved.

Angewandte Chemie International Edition
10.1002/anie.202004950
COMMUNICATION
2 8 2 3
Scheme 3. Substrate scope about internal alkynes. Standard conditions: Mn (CO) Br (5 mol%), propargyl alcohol (0.2 mmol), boronic acid 2 (3 equiv), KHCO
(2.5 equiv), H
2
O (10 equiv), toluene/pentane (v/v = 1:4), air atmosphere, 90 oC, 15 min-2 hours, please see the Supporting Information for detailed reaction
conditions.
3
This article is protected by copyright. All rights reserved.

Angewandte Chemie International Edition
10.1002/anie.202004950
COMMUNICATION
enyne alcohols, which are versatile
building blocks in organic synthesis. We
found that the introduction of another
alkyne motif in the substrate had no
effect on the regioselectivity (45). The
regio-, chemo- and stereo-selectivity can
be predicted in different kinds of aliphatic
and aromatic alkynes regardless of the
substitution effect and electronic effect.
Aromatic
boronic
acids
are
commercially available and are a class of
widely used synthetic reagents.[2] Under
the optimized reaction conditions,
a
number of readily available boronic acids
have been examined in this manganese-
catalyzed
hydroarylation
protocol
(
Scheme 4). Both the electron-rich and
electron-poor functional groups in the
ortho-, meta- and para-position of the
phenyl ring are tolerated, affording the
desired products (50-74) in yields as high
to 91%. In general, boronic acids bearing
electron-poor functional groups give
better results than those with electron-
rich functional groups. Compounds with
a wide array of functional groups, such as
halides (52, 54, 57, 68-70), electron-
donating tertiary amines (55) and ethers
(
53, 64), and electron-deficient carbonyl
groups (56, 62) and nitro groups (58) as
well as trifluoromethyl groups (63, 71) are
compatible
with
this
reaction.
Furthermore, the reactive styrene (65)
can keep intact in this protocol. In general,
arylboronic acids with strongly electron-
poor groups are sensitive to basic
conditions, and are prone to undergo
protodemetalation.[12] However, they are
good
coupling
partners
under
manganese catalysis, and they deliver
the hydroarylation products (71-74) in 46-
8
6% yield. Notably, the use of acetonitrile
instead of water may either increase the
solubility of arylboronic acids or slow
down the protodemetalation rate in some
cases and thus affords a better result (54,
5
6, 58, 72, 75-77, 79, 83-85). Nitrogen-,
oxygen- and sulfur-containing
heteroaromatic boronic acids are
effective coupling partners, and can
furnish the desired products (75-82) in
Scheme 4. Scope for arylboronic acid. Standard conditions: Mn
2
(CO)
8 2
Br (5 mol%), propargyl alcohol 1 (0.2
mmol), arylboronic acids (3 equiv), KHCO
3
(2.5 equiv), H
2
O (10 equiv), toluene/pentane (v/v = 1:4), air
o
atmosphere, 90 C, 15 min-2 hours. [a] MeCN (3 equiv) was used to replace water. [b] The reactions are
o
performed at 70 C. Please see the Supporting Information for detailed reaction conditions.
4
1-86%
yield.
acids
Several
derived
complex
from
arylboronic
Furthermore, as shown in Scheme 3, both electron-rich terminal and internal alkenes
biologically important pharmaceutical
chemicals, such as phenylalanine (83),
estrone (84), and fenofibrate (85) can be
(
21, 22, 36 and 39) which are potential reaction sites can keep intact. The selenium-
substituted aliphatic alkyne (33) is also compatible with the reaction, and gives rise to the
desired product in 57% yield. The non-conjugated diyne alcohol (40) can undergo a double
hydroarylation process to furnish the corresponding product in a satisfactory yield. This
protocol can overcome the electronic effects of alkyne substituents. Besides the aliphatic
alkynes, aromatic and heteroaromatic alkynes (41-47) are competent substrates which
deliver the -arylated alkenes predictably. Importantly, the 1,3-enyne (48) and 1,3-diyne
applied
in
late-stage
reactions.
Unfortunately, when the alkenyl and alkyl
boronic acids were employed, no desired
products can be observed.
(
49) are also good substrates for the stereoselective construction of 1,3-diene and 1,3-
4
This article is protected by copyright. All rights reserved.

Angewandte Chemie International Edition
10.1002/anie.202004950
COMMUNICATION
Although it can be concluded that
manganese-catalyzed hydroarylation of
internal alkynes has good selectivity and
good functional group tolerance, its late-
stage application represents
a new
challenge since the complex substrates
can affect the selectivity of the reaction.
To demonstrate the synthetic practicality
of the reaction, we applied the strategy
shown in Scheme 5a for the late-stage
hydroarylation of a series of complex
bioactive molecules, giving products 86-
9
5.
Importantly,
introduction
of
heteroatom-containing substituents has
little influence on the regioselectivity and
a wide range of functional groups are
entirely compatible. Interestingly, the
unsaturated alkenes (90, 91 and 95) can
keep intact in manganese-catalyzed
hydroaylation. For the unsymmetrical
internal alkynes, manganese-catalyzed
hydroarylation strategy provides
a
precise and powerful tool for the
construction of multisubstituted alkenes,
thus revealing its synthetic robustness.
Bervastatin is a hypolipidemic drug
active that is used against centrum
cerebrovascular diseases. As shown in
Scheme 5b, application of manganese-
catalyzed hydroarylation to the internal
alkyne (96) can produce the trisubstituted
alkene (97) in 63% yield (2 mmol scale).
Importantly, it is different from palladium
catalysis and no Suzuki coupling reaction
occurs. Subsequent intramolecular C-O
coupling with a tertiary alcohol and C-C
coupling with an alkenyltin reagent can
deliver bervastatin (100) in 40% total
yield. As illustrated in Scheme 5c, the
alkenyl tertiary alcohols are also very
useful building blocks. They can undergo
a series of downstream transformations
of both the hydroxyl group and the
carbon-carbon double bond (102-107),
enhancing its value in organic synthesis.
In conclusion, we have developed
an operationally simple and practical
hydroarylation protocol of sterically
hindered tertiary propargyl alcohols with
commercially available aromatic boronic
acids enabled by a dimeric manganese
catalyst, affording a wide range of highly
functionalized alkenes in moderate to
good yields. The reactions are very
efficient and are completed in 15 min to 2
h
under an air atmosphere in the
presence of water and produce
essentially no byproducts. With
manganese catalysis, the regio-, chemo-
and stereoselectivity of internal alkynes
can be predicted and are independent of
Scheme 5. Synthetic application. Please see the Supporting Information for detailed reaction conditions.
5
This article is protected by copyright. All rights reserved.

Angewandte Chemie International Edition
10.1002/anie.202004950
COMMUNICATION
M. Beller, Angew. Chem. Int. Ed. 2016, 55, 14967–14971; c) H. Wang,
I. Choi, T. Rogge, N. Kaplaneris, L. Ackermann, Nat. Catal. 2018, 1,
9
9
2
93–1001; d) X. Yang, C. Wang, Angew. Chem. Int. Ed. 2018, 57,
23−928; e) Y. Wang, Z. Shao, K. Zhang, Q. Liu, Angew. Chem. Int. Ed.
018, 57, 15143-15147; f) M. K. Barman, S. Waiba, B. Maji, Angew.
substitution effect and electronic effect of alkynes. This
manganese-catalyzed hydroarylation strategy will expedite
synthesis of synthetically versatile alkenes and benefit future
drug discovery research.
Chem. Int. Ed. 2018, 57, 9126-9130; g) G. Zhang, H. Zeng, J. Wu, Z.
Yin, S. Zheng, J. C. Fettinger, Angew. Chem. Int. Ed. 2016, 55, 14369–
14372.
[
10] Selected examples: a) B.-W. Zhou, H. Chen, C. Wang, J. Am. Chem.
Soc. 2013, 135, 1264−1267; b) R.-Y. He, Z.-T. Huang, Q.-Y. Zheng, C.
Wang, Angew. Chem. Int. Ed. 2014, 53, 4950–4953; c) Q. Lu, S.
Greßies, F. J. R. Klauck, F. Glorius, Angew. Chem. Int. Ed. 2017, 56,
Acknowledgements
We thank the National Natural Science Foundation of China
6660–6664; d) L. A. Hammarback, I. P. Clark, I. V. Sazanovich, M.
(
21971108, 21702098 and 21703118), the Natural Science
Towire, A. Robinson, F. Clarke, S. Meyer, I. J. S. Fairlamb, J. M. Lynam,
Nat. Catal. 2018, 1, 830–840; e) Y. Yang, Q. Zhang, J. Shi, Y. Fu, Acta
Chimica Sinica 2016, 74, 422-428; f) S.-Y. Chen, X.-L. Han, J.-Q. Wu,
Q. Li, Y. Chen, H. Wang, Angew. Chem. Int. Ed. 2017, 56, 9939-9943;
g) C. Wang, A. Wang, M. Rueping, Angew. Chem. Int. Ed. 2017, 56,
Foundation of Jiangsu Province (BK20190006 and
BK20190285), “Innovation & Entrepreneurship Talents Plan” of
Jiangsu Province, ‘‘Jiangsu Six Peak Talent Project’’, Shandong
Provincial Natural Science Foundation (No. ZR2017MB038),
“
1000-Youth Talent Plan” and start-up funds from Nanjing
9935-9938; h) S. Cembellín, T. Dalton, T. Pinkert, F. Schäfers, F.
University for financial support. The DFT calculation is supported
by High Performance Computing Center of Qufu Normal
University. Professor Stephen Hashmi at Heidelberg University
and Prof. Chengjian Zhu at Nanjing University are warmly
acknowledged for the insightful manuscript discussion and
generous support.
Glorius, ACS Catal. 2020, 10, 197-202; i) G. Zheng, J. Sun, Y. Xu, S.
Zhai, X. Li, Angew. Chem. Int. Ed. 2019, 58, 5090-5094.
[
[
11] a) Z.-F. Yan, X.-A. Yuan, Y. Zhao, C. Zhu, J. Xie, Angew. Chem. Int. Ed.
2018, 57, 12906–12910; b) D. Wang, J. Dong, W. Fan, X.-A. Yuan, J.
Han, J. Xie, Angew. Chem. Int. Ed. DOI: 10.1002/anie.201916305.
12] P. A. Cox, A. G. Leach, A. D. Campbell, G. C. Jones, J. Am. Chem. Soc.
2016, 138, 9145–9157.
Keywords: alkyne • arylation • homogeneous catalysis •
manganese • selectivity
[
1]
Selected examples: a) L. Wang, J.-M. Lear, S.-M. Rafferty, S.-C. Fosu,
D.-A. Nagib, Science 2018, 362, 225–229; b) Z.-P. Zhang, K. Tanaka,
J.-Q. Yu, Nature 2017, 543,538–542; c) D. W. Robbins, J. Hartwig,
Science 2011, 333, 1423–1427; c) C. Vovard-Le Bray, S. Derien, P.
Dixneuf, Angew. Chem. Int. Ed. 2009, 48, 1439-1442; d) C.-Q. Wang,
C. Feng, T.-P. Loh, Asian J. Org. Chem. 2016, 5, 1002-1007
[
[
2]
3]
Y. Yamamoto, Catalytic alkyne hydroarylation using arylboron reagents,
aryl halides, and congeners. Wiley-VCH, 2018, Chap. 8, pp. 307-325.
Selected examples: a) C. O. Oh, H. H. Jung, K. S. Kim, N. Kim, Angew.
Chem. Int. Ed. 2003, 42, 805–808; b) Z. Liu, J. Derosa, K. M. Engle, J.
Am. Chem. Soc. 2016, 138, 13076–13081; c) K. Fagnou, M. Lautens,
Chem. Rev. 2003, 103, 169−196; d) T. Hayashi, K. Inoue, N. Taniguchi,
M. Ogasawara, J. Am. Chem. Soc. 2001, 123, 9918-9919; e) W.-Y.
Wang, H. Qian, S.-M. Ma, Chin. J. Chem. 2020, 38, 331-345; f) A.-N.
Qin, H. Qian, Q. Chen, S.-M. Ma, Chin. J. Chem. 2020, 38, 372-382; g)
Y. Yamamoto, N. Kirai, Y. Harada, Chem. Commun. 2008, 2010–2012;
h) E. Shirakawa, G. Takahashi, T. Tsuchimoto, Y. Kawakami, Chem.
Commun. 2001, 2688–2689; i) M. H. Babu, G. R. Kumar, R. Kantc, M.
S. Reddy, Chem. Commun. 2017, 53, 3894–3897.
[
[
4]
5]
a) Z. Werner, R. Peter, H. R. Graham, T. Stephan, WO2004052816 A1,
2004; b) E. F. Oliveira, D. S. Martins, A. M. Ribeiro, N. F. Brás, N. S.
Cerqueira, S. F. Sousa, M. J. Ramos, P. A. Fernandes, Expert Opin.
Ther Pat. 2016, 11, 1257–1272; c) R. E. Dolle, B. L. Bourdonnec, G.-H.
Chu, WO2005159438 A1, 2005.
Selected examples: a) M. Sen, P. Dahiya, J. R. Premkumar, B.
Sundararaju, Org. Lett. 2017, 19, 3699-3702; b) N. Liu, Y. L. Zhi, J. Yao,
J. H. Xing, T. Lu, X.-W. Dou, Adv. Synth. Catal. 2018, 360, 642–646.
A. Arcadia, S. Cacchi, F. Marinellia, Tetrahedron 1985, 41, 5121-5131.
H.-W. Qian, D.-Y. Huang, Y.-Y. Bi, G.-B. Yan, Adv. Synth. Catal. 2019,
[
[
6]
7]
361, 3240-3280.
[
[
8]
9]
Recent reviews: a) P. Gandeepan, T. Müller, D. Zell, G. Cera, S.
Warratz, L. Ackermann, Chem. Rev. 2019, 119, 2192-2452; b) J. R.
Carney, B. R. Dillon, S. P. Thomas, Eur. J. Org. Chem. 2016, 3912–
3929; c) Y.-Y. Hu, B.-W. Zhou, C. Wang, Acc. Chem. Res. 2018, 51,
816−827; d) C. Wang, Synlett 2013, 24, 1606-1613; e) W. Liu, J. T.
Groves, Acc. Chem. Res. 2015, 48, 1727-1735; f) Z. Yan, C. Zhu, J. Xie,
Synlett 2019, 30, 124-128.
Selected examples: a) A. Kumar, N. A. Espinosa-Jalapa, G. Leitus, Y.
Diskin-Posner, L. Avram, D. Milstein, Angew. Chem. Int. Ed. 2017, 56,
14992−14996; b) M. Pena-Lopez, P. Piehl, S. Elangovan, H. Neumann,
6
This article is protected by copyright. All rights reserved.

Angewandte Chemie International Edition
10.1002/anie.202004950
COMMUNICATION
Entry for the Table of Contents
Insert graphic for Table of Contents here.
2
H O Does A Favor: Manganese(I) can achieve a highly efficient and practical hydroarylation of challenging sterically hindered
propargyl alcohols despite of the substitution effect under air atmosphere in the presence of water. The precise regioselectivity
represents a significant step-forward towards the hydrofunctionalization of internal alkynes.
researcher Twitter usernames: XIE Group NJU @GroupXie
7
This article is protected by copyright. All rights reserved.