Diboron-Mediated Rhodium-Catalysed Transfer Hydrogenation of Alkenes and Carbonyls

Article abstract of DOI:10.1002/ejoc.202000049

A diboron-mediated rhodium-catalysed transfer hydrogenation system using water as the hydrogen donor is developed. In addition to a series of alkenes with good functional group tolerance, this rhodium-based catalytic system also effectively reduces aldehydes and ketones. A plausible mechanism involving the Rh^I-catalysed hydrogen generation and Rh⁰-catalysed hydrogenation is proposed for the reaction.

Full text of DOI:10.1002/ejoc.202000049

A Journal of
Accepted Article
Title: Diboron-Mediated Rhodium-Catalysed Transfer Hydrogenation of
Alkenes and Carbonyls
Authors: Xiao Lin, Yuhan Wang, Yan Hu, Wanjiang Zhu, and Xiaowei
Dou
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: Eur. J. Org. Chem. 10.1002/ejoc.202000049
Link to VoR: http://dx.doi.org/10.1002/ejoc.202000049
Supported by

10.1002/ejoc.202000049
European Journal of Organic Chemistry
COMMUNICATION
Diboron-Mediated Rhodium-Catalysed Transfer Hydrogenation of
Alkenes and Carbonyls
Xiao Lin, Yuhan Wang, Yan Hu, Wanjiang Zhu and Prof. Dr. Xiaowei Dou*
Department of Chemistry, School of Science
China Pharmaceutical University
Longmian Avenue 639, Nanjing 211198, China
E-mail: dxw@cpu.edu.cn
Web: https://www.x-mol.com/groups/dou_xiaowei
Abstract:
A
diboron-mediated
rhodium-catalysed
transfer
hydrogenation system using water as the hydrogen donor is
developed. In addition to a series of alkenes with good functional
group tolerance, this rhodium-based catalytic system also effectively
reduces aldehydes and ketones. A plausible mechanism involving
the Rh(I)-catalysed hydrogen generation and Rh(0)-catalysed
hydrogenation is proposed for the reaction.
Transition-metal-catalysed hydrogenation is arguably one of the
most useful transformations in organic synthesis and catalysis.
In this type of reaction, hydrogen gas is usually employed as the
H donor, but its flammable nature and the operational issues
associated with its use can be troublesome, especially for bench
chemist. In this context, transfer hydrogenation,[1] which uses
alternative H donors other than hydrogen gas, has been
developed as an attractive approach. Among various H donors
in transfer hydrogenation, water is undoubtly the most
inexpensive and easy to handle one. Moreover, transfer
deuteration can be easily achieved by using deuterium oxide to
prepare valuable deuterated molecules. Therefore, development
of practical and versatile methods for transfer hydrogenation
with water is highly desirable.[2]
Scheme
1.
Diboron-mediated
transition-metal-catalysed
transfer
hydrogenation of alkenes and carbonyls with water.
The diboron reagents (e.g., B2(OH)4) are bench-stable,
nontoxic, and easy to handle, and they proved to be useful
reducing reagents in organic synthesis.[3] In recent years, there
has been a great interest in studying the diboron-mediated
transfer hydrogenation with water. Different metals including
palladium,[4] copper,[5] and ruthenium[6] have been explored to
catalyse this transformation, and it is found that the reactivity
and selectivity of the reaction are highly metal-dependent. For
example, the diboron/water system in concert with palladium
catalyst effective reduces unactivated alkenes,[4a] while the
copper catalyst promotes the formal reduction of the activated
alkenyl moiety of enones via a hydroboration-protodeboronation
pathway.[5a] Herein, we report our serendipitous finding that
rhodium is also able to effectively catalyse the diboron-mediated
transfer hydrogenation with water (Scheme 1). The current
rhodium catalytic system features the following advantages
compared with the established methods: 1) broad substrate
scope: it works well for both activated and unactivated alkenes,
as well as aldehydes and ketones; 2) better functional group
tolerance: for example, aryl bromide is sensitive to palladium
catalyst, but it is tolerated under the current system; 3)
controllable chemoselectivity: the selective reduction of enones
can be easily controlled via adjusting the amount of diboron
reagent. Thus, this rhodium-based catalytic system provides a
new tool for transfer hydrogenation with water.
As part of our ongoing efforts on the Rh(I)-catalysed conjugate
addition of organoborons to alkenes,[7] we investigated the Rh(I)-
catalysed addition of diborons to CF3-activated alkene 1a,
aiming to achieve the conjugate borylation of this -aryl
substituted substrate, which remains a formidable task in
borylation of trifluoromethyl alkenes.[8] To our surprise, no
conjugate borylation product was detected during our
investigation, but reduction of 1a was observed. As shown in
Table 1, the reaction between trifluoromethyl alkene 1a and
tetrahydroxydiboron 2a proceeded smoothly in the presence of
rhodium catalyst under mild reaction conditions in aqueous THF,
giving the reduced product 3a in high yield (86%, entry 1). Other
diboron reagents including bis(neopentylglycolate) diboron
B2(neop)2 and bis(catecholate) diboron B2(cat)2 also worked well,
but bis(pinacolate) diboron B2(pin)2 was found to be ineffective
(entries 2−4). The coordinating ligand on rhodium was crucial for
the catalytic activity, and bis(phosphine) ligands were found to
be not suitable for this catalytic system (entries 5−6). Control
experiments revealed that the rhodium catalyst was essential, as
no conversion of 1a was observed without catalyst (entry 7). The
use of triethylamine as the base was also necessary for the high
yield of the reaction (entries 8−10). The reaction did not proceed
under anhydrous conditions, validating the important role of
water as the H donor (entry 11, B2(cat)2 was used to avoid the
introduction of water from B2(OH)4). It is noteworthy that the
1
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000049
European Journal of Organic Chemistry
COMMUNICATION
defluorination product, which can be generated via -F
With the established reaction conditions for transfer
hydrogenation of trifluoromethyl alkenes, the scope of this
catalytic transformation was studied, and the results are
summarized in Scheme 2 (isolated yields of products were
shown). In addition to the -aryl substituted trifluoromethyl
alkenes, the current catalytic system also efficiently reduced
the -alkyl substituted substrates (3b and 3c). Moreover, the
,-disubstituted trifluoromethyl alkenes were also suitable in
this system, producing the corresponding ,-disubstituted
trifluoromethyl alkanes in high yields (3d−3g). Considering the
easy preparation of trifluoromethyl alkenes, the current method
elimination from the alkyl-rhodium species,[9] was not observed.
Table 1. Rhodium-catalysed reduction of trifluoromethyl alkene 1a with
diboron/water.[a]
provides
a
useful approach to accessing functionalized
trifluoromethyl alkanes.[10]
Entry
1
Variation from standard conditions
none
Yield [%][b]
86
<5
71
81
<5
<5
<5
35
78
<5
<5
2
B2(pin)2 instead of B2(OH)4
B2(neop)2 instead of B2(OH)4
B2(cat)2 instead of B2(OH)4
binap instead of cod
dppe instead of cod
w/o [RhCl(cod)]2
3
4
5
6
7
8
w/o Et3N
9
Cs2CO3 instead of Et3N
pyridine instead of Et3N
w/o H2O[c]
10
11
[a] Standard conditions: 1a (0.20 mmol), 2a (0.30 mmol), [RhCl(cod)]2 (5 mol,
2.5 mol%), and Et3N (0.60 mmol) in THF/H2O (2.0 mL/0.05 mL) at 30 oC for 12
h. [b] Isolated yield of 3a. [c] B2(cat)2 was used for anhydrous conditions.
Scheme 3. Scope of alkenes and carbonyls. [a] 2.5 equiv. B2(OH)4 was used.
[b] EtOH was used as the solvent.
Scheme 2. Substrate scope of trifluoromethyl alkenes.
2
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000049
European Journal of Organic Chemistry
COMMUNICATION
With the success achieved on transfer hydrogenation of
trifluoromethyl alkenes, we further explored the generality of the
rhodium-based catalytic system for other types of substrates. As
shown in Scheme 3 (isolated yields of products were shown),
the ester or amide-activated alkenyl substrates, including those
bearing aryl chloride or aryl bromide moieties, worked well under
the standard conditions (5a−5f). The catalytic system was also
suitable for the reduction of ,-disubstituted substrate (5g) and
cyclic substrate (5h). Both cyclic and acyclic ,-unsaturated
ketones can be reduced to saturated ketones under the
standard conditions (5i−5j). Furthermore, we were delighted to
achieve the reduction of the keto moiety with an excess amount
of diboron reagent (5k−5l).[11] The utility of the current catalytic
system for transfer hydrogenation of carbonyls was then next
explored, and both aldehydes and ketones were found to be
suitable substrates (5m−5r). Finally, the unactivated alkenes
were investigated, and the transfer hydrogenation reaction
worked very well (5s−5v). The wide scope and good functional
group tolerance distinguish the current method from other known.
formation of hydrogen gas: oxidation of rhodium(I) to diboron
generates the rhodium(III) intermediate,[12] which reacts with
water and produces hydrogen gas upon reductive elimination.
The second cycle is the rhodium black-catalysed hydrogenation:
in the presence of hydrogen gas, the cyclooctadiene-ligated
rhodium(I) catalyst is reduced to rhodium black, which then
catalyses the hydrogenation of alkenes and carbonyls.[13]
Scheme 4. Transfer deuteration with D2O.
One important advantage of the transfer hydrogenation with
water is that the transfer deuteration can be easily achieved by
using cheap deuterium oxide. In the current rhodium catalytic
system, the transfer deuteration was also feasible. As shown in
Scheme 4, both alkenyl and carbonyl substrates were reduced
with high levels of deuterium incorporation. The scrambling of
deuterium in 5s-d2 indicates the involvement of a rhodium
hydride species during the catalytic process, which can lead to
Scheme 5. Mechanistic studies and proposed mechanism.
In summary, we have developed a rhodium catalytic system
that catalyses the diboron-mediated transfer hydrogenation with
water. The new system features broad substrate scope, good
functional group tolerance, and controllable chemoselectivity.
This rhodium-based catalytic system provides a new tool for
transfer hydrogenation.
the observed scrambling via
a
migratory insertion/ -H
elimination/regio-reversed reinsertion process.
There are two important experimental phenomena observed
during the study. The first one is the fast formation of hydrogen
gas bubbles at the initial stage of the reaction; and the second
one is the fast formation of rhodium black during the reaction
process. To gain insight into the possible reaction mechanism,
several control experiments were conducted in Scheme 5 based
on the aforementioned observations. Control experiments
showed that the rhodium(I) catalyst was essential for the
production of hydrogen gas. Both rhodium(I) catalyst and
rhodium black were found to catalyse the hydrogenation of 4s
with hydrogen gas, however, rhodium black was not able to
catalyse the transfer hydrogenation with diboron as the reducing
reagent. Based on the experimental results and literature
precedents, a plausible mechanism for the current catalytic
system is proposed (Scheme 5). The first cycle accounts for the
Acknowledgements
We are grateful for the generous financial support from the
“Double First-Class” University project (CPU2018GY35) of China
Pharmaceutical University and the “Six Talent Peaks Plan” of
Jiangsu Province.
Keywords: Rhodium • Transfer Hydrogenation • Diboron •
Alkenes • Carbonyls
3
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000049
European Journal of Organic Chemistry
COMMUNICATION
[1]
[2]
For a comprehensive review, see: D. Wang, D. Astruc, Chem. Rev.
2015, 115, 6621−6686.
a) E. Shirakawa, H. Otsuka, T. Hayashi, Chem. Commun. 2005, 5885–
5886; b) T. Sato, S. Watanabe, H. Kiuchi, S. Oi, Y. Inoue, Tetrahedron
Lett. 2006, 47, 7703–7705; c) A. G. Campaña, R. E. Estévez, N.
Fuentes, R. Robles, J. M. Cuerva, E. Buñuel, D. Cárdenas, J. E. Oltra,
Org. Lett. 2007, 9, 2195–2198; d) O. Muhammad, S. U. Sonavane, Y.
Sasson, M. Chidambaram, Catal. Lett. 2008, 125, 46–51; e) K. Li, R.
Khan, X. Zhang, Y. Gao, Y. Zhou, H. Tan, J. Chen, B. Fan, Chem.
Commun. 2019, 55, 5663–5666; f) X. Hu, G. Wang, C. Qin, X. Xie, C.
Zhang, W. Xu, Y. Liu, Org. Chem. Front. 2019, 6, 2619–2623; g) G.
Shen, J. Chen, D. Xu, X. Zhang, Y. Zhou, B. Fan, Org. Lett. 2019, 21,
1364–1367; h) C.-Q. Zhao, Y.-G. Chen, H. Qiu, L. Wei, P. Fang, T.-S.
Mei, Org. Lett. 2019, 21, 1412–1416.
[3]
For a review, see: a) E. C. Neeve, S. J. Geier, I. A. I. Mkhalid, S. A.
Westcott, T. B. Marder, Chem. Rev. 2016, 116, 9091–9161. For
selected examples, see: b) Y.-T. Xia, X.-T. Sun, L. Zhang, K. Luo, L.
Wu, Chem. Eur. J. 2016, 22, 17151–17155; c) K. Yang, Q. Song,
Green Chem. 2016, 18, 932–936. d) G. Gao, J. Yan, K. Yang, F. Chen,
Q. Song, Green Chem. 2017, 19, 3997–4001. e) D. Chen, G. Xu, Q.
Zhou, L. W. Chung, W. Tang, J. Am. Chem. Soc. 2017, 139, 9767–
9770; f) H.-C. Du, N. Simmons, J. C. Faver, Z. Yu, M. Palaniappan, K.
Riehle, M. M. Matzuk, Org. Lett. 2019, 21, 2194–2199; g) F. Takahashi,
K. Nogi, T. Sasamori, H. Yorimitsu, Org. Lett. 2019, 21, 4739–4744.
a) S. P. Cummings, T.-N. Le, G. E. Fernandez, L. G. Quiambao, B. J.
Stokes, J. Am. Chem. Soc. 2016, 138, 6107–6110; b) Q. Xuan, Q.
Song, Org. Lett. 2016, 18, 4250–4253; c) D. P. Ojha, K. Gadde, K. R.
Prabhu, Org. Lett. 2016, 18, 5062–5065; d) Y. Zhou, H. Zhou, S. Liu, D.
Pi, G. Shen, Tetrahedron 2017, 73, 3898–3904; e) K. A. Korvinson, H.
K. Akula, C. T. Malinchak, D. Sebastian, W. Wei, T. A. Khandaker, M. R.
Andrzejewska, B. Zajc, M. K. Lakshman, Adv. Synth. Catal. 2019, doi:
10.1002/adsc.201901099.
[4]
[5]
a) W. Ding, Q. Song, Org. Chem. Front. 2016, 3, 14–18; b) D. Pi, H.
Zhou, Y. Zhou, Q. Liu, R. He, G. Shen, Y. Uozumi, Tetrahedron 2018,
74, 2121–2129; c) H. Bao, B. Zhou, H. Jin, Y. Liu, J. Org. Chem. 2019,
84, 3579–3589; d) X. Han, J. Hu, C. Chen, Y. Yuan, Z. Shi, Chem.
Commun. 2019, 55, 6922–6925.
[6]
[7]
Y. Wei, C. Zhao, Q. Xuan, Q. Song, Org. Chem. Front. 2017, 4, 2291–
2295.
a) L. Yin, J. Xing, Y. Wang, Y. Shen, T. Lu, T. Hayashi, X. Dou, Angew.
Chem. Int. Ed. 2019, 58, 2474–2478; b) J. Yao, N. Liu, L. Yin, J. Xing, T.
Lu, X. Dou, Green Chem. 2019, 21, 4946–4950; c) J. Yao, L. Yin, Y.
Shen, T. Lu, T. Hayashi, X. Dou, Org. Lett. 2018, 20, 6882–6885; d) J.
Huang, N. Liu, T. Lu, X. Dou, Adv. Synth. Catal. 2018, 360, 3466–3470.
a) P. Gao, C. Yuan, Y. Zhao, Z. Shi, Chem 2018, 4, 2201–2211; b) R.
Kojima, S. Akiyama, H. Ito, Angew. Chem. Int. Ed. 2018, 57, 7196–
7199.
[8]
[9]
a) T. Miura, Y. Ito, M. Murakami, Chem. Lett. 2008, 37, 1006–1007; b)
Y. Huang, T. Hayashi, J. Am. Chem. Soc. 2016, 138, 12340–12343; c)
Y. J. Jang, D. Rose, B. Mirabi, M. Lautens, Angew. Chem. Int. Ed. 2018,
57, 16147–16151.
[10] a) N. J. W. Straathof, S. E. Cramer, V. Hessel, T. Noël, Angew. Chem.
Int. Ed. 2016, 55, 15549–15553; b) S. Choi, Y. J. Kim, S. M. Kim, J. W.
Yang, S. W. Kim, E. J. Cho, Nat. Commun. 2014, 5, 4881–4887.
[11] Reduction of carbonyls was achieved with other diboron reagents in the
absence of a metal catalyst, but tetrahydroxydiboron did not work in
those systems, see: a) M. Flinker, H. Yin, R. W. Juhl, E. Z. Eikeland, J.
Overgaard, D. U. Nielsen, T. Skrydstrup, Angew. Chem. Int. Ed. 2017,
56, 15910–15915; b) Q. Xuan, C. Zhao, Q. Song, Org. Biomol. Chem.
2017, 15, 5140–5144.
[12] For examples involving oxidative addition of B2(OR)4 to rhodium, see: a)
P. Nguyen, G. Lesley, N. J. Taylor, T. B. Marder, Inorg. Chem. 1994, 33,
4623–4624; b) S. Trudeau, J. B. Morgan, M. Shrestha, J. P. Morken, J.
Org. Chem. 2005, 70, 9538–9544; c) J. Ramírez, A. M. Segarra, E.
Fernández, Tetrahedron: Asymmetry 2005, 16, 1289–1294; d) N. Hu, G.
Zhao, Y. Zhang, X. Liu, G. Li, W. Tang, J. Am. Chem. Soc. 2015, 137,
6746–6749.
[13] H. Miyamura, A. Suzuki, T. Yasukawa, S. Kobayshi, J. Am. Chem. Soc.
2018, 140, 11325–11334.
4
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000049
European Journal of Organic Chemistry
COMMUNICATION
Entry for the Table of Contents
Transfer Hydrogenation: A diboron-mediated rhodium-catalysed transfer hydrogenation system using water as the hydrogen donor
is developed. The new system features broad substrate scope, good functional group tolerance, and controllable chemoselectivity.
This rhodium-based catalytic system provides a new tool for transfer hydrogenation.
5
This article is protected by copyright. All rights reserved.