B(C6F5)3-Catalyzed Highly Stereoselective Hydrogenation of Unfunctionalized Tetrasubstituted Olefins

Article abstract of DOI:10.1021/acs.orglett.9b02512

A metal-free hydrogenation of unfunctionalized tetrasubstituted olefins were successfully realized using a combination of B(C₆F₅)₃ and Ph₂NMe catalyst. The corresponding products were afforded in 58-98% yields with up to >99:1 cis/trans selectivity.

Full text of DOI:10.1021/acs.orglett.9b02512

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
B(C6F5)3‑Catalyzed Highly Stereoselective Hydrogenation of
Unfunctionalized Tetrasubstituted Olefins
Yun Dai,†,‡ Xiangqing Feng,*,†,‡ and Haifeng Du*,†,‡
†Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of
Chemistry, Chinese Academy of Sciences, Beijing 100190, China
‡University of Chinese Academy of Sciences, Beijing 100049, China
S
* Supporting Information
ABSTRACT: A metal-free hydrogenation of unfunctionalized
tetrasubstituted olefins were successfully realized using a combina-
tion of B(C6F5)3 and Ph2NMe catalyst. The corresponding
products were afforded in 58−98% yields with up to >99:1 cis/
trans selectivity.
complex and B(C6F5)3 adduct was developed by Ison’s
he catalytic hydrogenation of olefins is one of the most
Tfundamental and important transformations in synthetic group, and the catalyst could effectively catalyze the hydro-
genation of monosubstituted olefins, geminal substituted
olefins, and vicinal disubstituted olefins. The tetrasubstituted
olefin tetramethylethylene was also suitable for this trans-
formation and gave a 13% yield.8c In addition, Li, Wang, and
co-workers reported an HB(C6F5)2-mediated hydroboration
and σ-bond metathesis of mono-, di-, or trisubstituted olefins,
and tetramethylethylene in 2013.8d To date, the metal-free
hydrogenation of unfunctionalized tetrasubstituted olefins is
still an unsolved problem and presents a great challenge.
As part of our research interest in the FLP catalysis,9 the
hydrogenation of several types of unsaturated compounds such
as imines,10 N-heterocycles,11 naphthylamines,12 and alkynes13
has been successfully realized. On the basis of these results, we
will further devote our efforts to the difficult and challenging
hydrogenation of unfunctionalized tetrasubstituted olefins.
Herein, we reported our preliminary results on the metal-free
highly stereoselective hydrogenation of indenes and 1,2-
dihydronapthalenes.
chemistry and has been widely applied in pharmaceuticals,
agrochemicals, material chemistry, and chemical industries.1
Among the olefins, the unfunctionalized tetrasubstituted ones
are undoubtedly the least reactive class of olefins, which may
attribute to their steric hindrance and lack of the coordination
heteroatoms.2 Transition-metal catalysts such as Ru,3 Rh,4 and
Ir,5 have been predominant in catalytic hydrogenation and
asymmetric hydrogenation of unfunctionalized olefins, and
have made great progress. However, metal-free hydrogenation
of these substrates is still in its infancy.6 The emergence and
development of frustrated Lewis pairs chemistry7 provided a
new opportunity for metal-free catalytic hydrogenation of
unfunctionalized olefins. In 2013, Grimme and Stephan
reported an Et2O·B(C6F5)3 FLP catalyst, which could activate
H2 and catalyze the hydrogenation of 1,1-diphenylethylene and
anthracene.8a In 2015, the hydrogenation of olefins was
realized with a combination of electrophilic fluorophospho-
nium cation and diaryl amines or diaryl silylamines catalyst
(Scheme 1).8b In 2016, an oxorhenium diamidopyridine
Initially, the hydrogenation of 2,3-dimethyl-1H-indene (1a)
14
was examined using B(C6F5)3 (2a) (20 mol %) as a catalyst
in CH2Cl2 at 100 °C for 24 h. Without Lewis base, the reaction
could not carry out. With Ph3P (3a) and Ph3N (3b) as Lewis
bases, the reduction product 4a was afforded in 16% and 79%
conversion, respectively (Scheme 2).
Scheme 1. Frustrated Lewis Pairs Catalyzed Hydrogenation
of Unfunctionalized Olefins
Because the amine−Lewis base exhibited significantly higher
activity than the phosphine−Lewis base, a variety of amines
were screened as Lewis bases as shown in Table 1. A series of
diaryl- and dialkylamines 3c−j were attempted, and it was
found that dialkylamines (3i and 3j) and the amines with
larger steric hindrance (3d and 3f) led to lower reactivities
(Table 1, entries 1−8). The reaction could not be conducted
using N-methylaniline (3k) as a Lewis base (Table 1, entry 9).
With N,N-dimethylaniline (3l), 50% conversion was achieved,
Received: July 19, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b02512
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
screened in the hydrogenation, accompanied by weakened
Lewis acidity, and the reaction activity gradually decreased.
B(C6F5)3 (2a) gave a quantitative conversion, but B(p-
HC6F4)3 (2b) gave a much lower conversion. With B(2,4,6-
F3-C6H2)3 (2c), there was no predicted product (Table 2,
Scheme 2. Initial Study on Hydrogenation of 2,3-Dimethyl-
1H-indene 1a
a
Table 2. Optimization of Reaction Conditions
a
Table 1. Evaluation of Lewis Base 3
b
temp
(°C)
time conv
entry
1
borane (x mol %)
solvent
CH2Cl2
(h)
(%)
B(C6F5)3 (2a)
(20 mol %)
B(p-HC6F4)3 (2b)
(20 mol %)
100
100
100
24
100
2
3
CH2Cl2
CH2Cl2
24
24
61
c
B(2,4,6-F3−C6H2)3(2c)
nr
(20 mol %)
4
5
6
7
8
9
10
11
12
13
2a (20 mol %)
2a (20 mol %)
2a (20 mol %)
2a (20 mol %)
2a (20 mol %)
2a (20 mol %)
2a (20 mol %)
2a (10 mol %)
2a (10 mol %)
2a (10 mol %)
2a (10 mol %)
2a (10 mol %)
2a (10 mol %)
CH2Cl2
CHCl3
ClCH2CH2Cl
BrCH2CH2Br
Cl2CHCHCl2
toluene
hexane
CH2Cl2
CH2Cl2
CH2Cl2
60
60
60
60
60
60
60
60
100
120
120
120
120
5
5
5
5
5
100
33
3
c
nr
85
10
5
5
c
nr
24
24
24
24
24
24
57
80
100
70
83
100
d
14
15
16
CH2Cl2
CH2Cl2
CH2Cl2
e
f
a
All reactions were carried out with 1a (0.1 mmol), B(C6F5)3 (2a)
(20 mol %), Ph2NMe (3m) (20 mol %), and H2 (40 bar) in solvent
b
1
(0.5 mL) unless otherwise noted. Determined by crude H NMR.
c
d
e
No reaction. 1a (0.5 mmol) in CH2Cl2 (2.5 mL). 1a (0.5 mmol) in
CH2Cl2 (1.0 mL). 1a (0.5 mmol) in CH2Cl2 (0.5 mL).
f
entries 1−3). The solvents influenced the reaction activity
significantly, CH2Cl2 was the optimal one, and the hydro-
genation product could be afforded in quantitative conversion
at 60 °C for 5 h (Table 2, entries 4−10). Reducing the catalyst
loading to 10 mol %, higher temperature was need to maintain
the reactivity, and full conversion could be obtained at 120 °C
(Table 2, entries 11−13). On a larger scale, it was found that a
higher concentration gave a better reactivity (Table 2, entries
14−16).
Under the optimal reaction conditions, we investigated the
scope of the B(C6F5)3-Ph2NMe catalyzed hydrogenation of
unfunctionalized tetrasubstituted olefins, and the results are
summarized in Scheme 3. For five-membered ring substrates
1a−m, the reactions went well and gave satisfactory isolated
yields and up to >99/1 cis/trans selectivity. 1,2-Dialkyl-
substituted alkenes showed better reactivity but lower cis/
trans selectivity than the 1-alkyl-2-Ph or the 1-Ph-2-alkyl ones;
the latter usually need a longer reaction time. The aromatic
ring-substituted substrates 1n−p were also examined, and
electron-withdrawing substituted compound 1p gave relatively
poor reactivity and selectivity with 20 mol % catalyst in 150 °C
for 48 h. For six-membered ring substrates 1q−t, lower yields
and poor stereoselectivities were achieved. A 1 mmol scale
hydrogenation of 2,3-dimethyl-1H-indene (1a) was further
examined, and the compound 4a was afforded in 96% yield
with 96/4 cis/trans selectivity (Scheme 4).
a
All reactions were carried out with 1a (0.1 mmol), B(C6F5)3 (2a)
(20 mol %), Lewis base 3 (20 mol %), and H2 (40 bar) in CH2Cl2
b
(0.5 mL) at 100 °C for 24 h unless otherwise noted. Determined by
c
d
e
crude 1H NMR. 10 mol % Lewis base was used. No reaction. The
reaction was performed for 5 h.
while N-methyl-N-phenylaniline (3m) could give completely
conversion in 5 h (Table 1, entries 10−12). Subsequently, the
alkyl group and the substituents on the aromatic rings on the
N-alkyl-N-arylanilines were investigated, Ph2NMe (3m) was
still proven to be the optimal Lewis base (Table 1, entries 12−
18).
The conditions of metal-free hydrogenation of 2,3-dimethyl-
1H-indene (1a) were further examined. The boranes 2 were
B
DOI: 10.1021/acs.orglett.9b02512
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
transfer from the hydridoborate moiety to liberate the
hydrocarbon 4 and regenerate the B(C6F5)3 2a.
Scheme 3. Hydrogenation of Unfunctionalized
Tetrasubstituted Olefins 1
In summary, we have demonstrated a metal-free hydro-
genation of indenes and 1,2-dihydronapthalenes using a
borane-amine FLP catalyst. The corresponding reductants
were achieved in 58−98% yields with up to >99:1 cis/trans
selectivity. Further work will be devoted to explore efficient
chiral catalyst for the asymmetric versions and expand this
methodology to other substrates.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.9b02512.
Experimental procedures for metal-free hydrogenation,
characterization of substrates and products, and NMR
spectra (PDF)
AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: fxq@iccas.ac.cn.
*E-mail: haifengdu@iccas.ac.cn.
ORCID
Xiangqing Feng: 0000-0003-1739-925X
Haifeng Du: 0000-0003-0122-3735
Notes
The authors declare no competing financial interest.
a
b
c
48 h. With 20 mol % of B(C6F5)3 (2a) and Ph2NMe (3m). 150
ACKNOWLEDGMENTS
d
■
°C. 36 h.
We are grateful for generous financial support from the
National Natural Science Foundation of China (21871269 and
21521002).
Scheme 4. 1 Mmol Scale Hydrogenation of 1a
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Org. Lett. XXXX, XXX, XXX−XXX