Chemo- and Regioselective Hydroarylation of Alkenes with Aromatic Amines Catalyzed by [Ph3C][B(C6F5)4]

Article abstract of DOI:10.1021/acs.orglett.8b01158

A nonmetal catalyst [Ph₃C][B(C₆F₅)₄] has been developed to catalyze hydroarylation reaction of alkenes with aromatic primary, secondary, and tertiary amines, which generated aniline derivatives in 32-98% yields. This method is applicable to a wide range of substrates, is highly chemo- and regioselective, and provides a simple and efficient approach for aniline derivative preparation.

Full text of DOI:10.1021/acs.orglett.8b01158

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Chemo- and Regioselective Hydroarylation of Alkenes with Aromatic
Amines Catalyzed by [Ph3C][B(C6F5)4]
Wenguo Zhu,† Qiu Sun,†,‡ Yaorong Wang,† Dan Yuan,*,† and Yingming Yao*,†
†Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Dushu
Lake Campus, Soochow University, Suzhou 215123, People’s Republic of China
‡School of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou 225002, People’s Republic of China
S
* Supporting Information
ABSTRACT: A nonmetal catalyst [Ph3C][B(C6F5)4] has
been developed to catalyze hydroarylation reaction of alkenes
with aromatic primary, secondary, and tertiary amines, which
generated aniline derivatives in 32−98% yields. This method is
applicable to a wide range of substrates, is highly chemo- and
regioselective, and provides a simple and efficient approach for
aniline derivative preparation.
niline derivatives have found widespread application in
and regioselective approach is highly desirable. We herein report
Anatural products, medicines, and organic functional the development of simple and readily available borate
[Ph3C][B(C6F5)4] as a metal-free catalyst for hydroarylation of
alkenes with primary, secondary, and tertiary aromatic amines
under relatively mild conditions.
materials. Tremendous efforts have been devoted to synthesizing
compounds bearing aniline motifs.1 Catalytic C−H addition of
anilines to alkenes is one of the most efficient and atom-
economical strategies to modify aniline skeletons. However,
classical Friedel−Crafts alkylation conditions2,3 are generally not
applicable in constructing aniline derivatives due to their
coordination with Lewis acid catalysts.4,5 Moreover, Friedel−
Crafts reactions usually furnish both ortho- and para-substitution
and require electron-deficient alkenes. Hence, the development
of suitable catalytic systems to promote direct and regioselective
C−H alkylation of anilines is an important task.
In the literature, some catalytic systems have been reported for
direct C−H alkylation reactions of anilines with C−C
unsaturated bonds.6,7 Transition metal catalysts include Rh,6a−c
Ru,6d Ir,6e Zn,6f Au,6g Y,6h and Ti complexes,6i which are mainly
precious metal based, and in general, require delicate design and
synthesis. Coates et al. employed CF3SO3H to catalyze ortho-
alkylation of primary anilines with styrenes at 160 °C.7e Stephan
et al. developed phosphonium cations as main group catalysts for
hydroarylation of olefins with secondary/tertiary anilines, giving
rise to para-substituted anilines.7i Arnold and Bergman reported
proton-catalyzed reactions of primary aniline and alkenes, which
afforded mixtures of hydroamination (N-alkylation) and hydro-
arylation (C-alkylation) products in varying ratios.7d Although
several catalysts have been developed for this important
transformation, current strategies suffer from some limitations:
(1) substrate scopes are limited to primary anilines,6a,b,e,f,i,7a−h
while reports on more basic secondary and tertiary amines are
rare;6c,d,g,h,7i−l (2) many protocols result in a mixture of
hydroamination (N-alkylation) and hydroarylation (C-alkyla-
tion) products, and the latter often consist of ortho- and para-
isomers;6a−c,e,f,i,7d−i (3) either aromatic alkenes7i or strong
electron-withdrawing groups on CC double bonds are
required for higher yields.7j−l Development of a highly chemo-
In a preliminary study, 10 mol % [Ph3C][B(C6F5)4] (TB)
catalyzed the reaction between styrene 1a and 1,2,3,4-
tetrahydroquinoline 2a at 100 °C, which furnished Markovnikov
addition product 3a with the ortho-C−H bond addition to
styrene in 83% yield (Table S1, entry 2). The identity of 3a was
confirmed by 1D and 2D NMR spectra in the Supporting
Information (SI). Optimization of reaction conditions includes
changing reaction temperatures, solvents, catalyst loadings,
substrate ratios, and borate reagents (Table S1), and the best
yield of 89% was obtained at 60 °C after 12 h reaction (Scheme
1). [PhNH3][B(C6F5)4] was reported to catalyze concurrent
Scheme 1. Optimal Conditions of Hydroarylation of Styrene
(1a) with 1,2,3,4-Tetrahydroquinoline (2a)
hydroamination and hydroarylation reactions of primary anilines
with alkenes.7d In our study, a low yield (31%) of hydroarylation
product was obtained in [PhNH3][B(C6F5)4]-catalyzed reac-
tions of secondary amines (Table S1, entry 13). Overall,
[Ph3C][B(C6F5)4] represents a most simple, active, and
Received: April 12, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b01158
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
chemo- and regioselective nonmetal catalyst that promotes
ortho-position reaction of secondary amines with simple alkenes.
Different secondary amines and styrene were studied under
optimized conditions, and results are summarized in Scheme 2.
Scheme 3. Hydroarylation of Various Primary and Tertiary
Amines and Styrene Catalyzed by TB
a
Scheme 2. Hydroarylation of Various Secondary Amines and
a
Styrene Catalyzed by TB
a
Conditions: amines (0.5 mmol), styrene (1 mmol), TB (46 mg, 0.05
mmol), PhCl (2 mL), 80 °C, 24 h. Isolated yields based on amines.
3.0 equiv of styrene. 130 °C reaction temperature.
b
c
a
Conditions: amines (0.5 mmol), styrene (1 mmol), TB (46 mg, 0.05
mmol), PhCl (2 mL), 60 °C, 12 h. Isolated yields based on amines.
80 °C reaction temperature.
b
Table 1. Hydroarylation of 6-Methyl-1,2,3,4-
tetrahydroquinoline 2h and Styrene Derivatives Catalyzed by
a
TB
The reaction of N-methylaniline afforded desired product 3b
in 80% yield, while that of N-ethylaniline gave a lower yield of
44%, possibly due to increased steric hindrance.8 Similarly,
diphenyl amine resulted in 38% isolated yield of 3d. Substituted-
1,2,3,4-tetrahydroquinoline with either α- or aryl-substituent
gave rise to addition products 3e−h in 75−96% yields. Reactions
with indoline (2i) or indoline derivative (2j−m) were less
efficient and afforded products 3i and 3j−m in 45−73% yields.
No product was isolated from reactions of 1,2,3,4-tetrahydroi-
soquinoline or N-methyl-1-phenylmethanamine.
In addition to secondary amines, reactions of primary and
tertiary amines with styrene also proceeded at elevated
temperatures of 80−130 °C in the presence of TB and generated
hydroarylation products in 58−97% yields (Scheme 3).
Dialkylation reaction occurred to p-toluidine and generated
product 3n almost exclusively in 97% yield, while reaction of
aniline yielded trialkylation product 3o in a good yield of 82%. In
comparison, CF3SO3H-catalyzed alkylation of anilines required
high temperature of 160 °C.7e Tertiary anilines N,N-dimethylani-
line 2p and N,N,3-trimethylaniline 2q also reacted smoothly with
styrene, affording mixtures of mono- and dialkylated products
with high ortho-regioselectivity. This result is different with the
phosphonium cations-catalyzed alkylation of N,N-dimethylani-
line, which generated para-alkylation products.7i These two
methods thus complement each other. para-Substituted N,N-
dimethylaniline derivatives (2r−u) reacted efficiently at the
ortho-position in 80−90% yields, while reactions of ortho-
substituted N,N,2-trimethylaniline occurred at the other ortho-
position and afforded product 3v in a lower yield of 58%.
Reactions between 6-methyl-1,2,3,4-tetrahydroquinoline 2h
and a series of styrene derivatives were studied, and the results are
summarized in Table 1. Generally good yields of 89−99% were
a
Conditions: 1 (1 mmol), 2h (74 mg, 0.5 mmol), TB (46 mg, 0.05
b
mmol) in PhCl (2 mL) for 12 h, 60 °C, isolated yield. 1b/2h (1:1).
c
d
e
100 °C. 80 °C. 120 °C.
obtained with o-, m-, or p-substituted styrene. Reactions of
electron-rich styrenes proceeded at lower temperatures of 60−80
B
DOI: 10.1021/acs.orglett.8b01158
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Letter
°C (products 4b,c,e,i,m), while those of electron-deficient
styrenes required higher temperature of 100−120 °C (products
4f−h,j−l,n−p). For instance, 4-methoxystyrene 1b reacted with
2h in 97% yield at 60 °C, while no reaction occurred to 4-
nitrostyrene even at 130 °C. In addition, different positions of the
substituent seem to have some influence on the reaction
outcome. ortho-Substituted styrenes required elevated temper-
atures as compared to para-analogue (entry 1 vs 3). 1,1-
Disubstituted aromatic alkene α-methylstyrene 1q also worked
straightforwardly and led to a good yield of 96% (entry 4).
Hydroarylation of 1,2,3,4-tetrahydroquinoline with aliphatic
olefins, i.e., norbornene, cyclohexadiene, and linear alkenes, were
explored under established conditions, and the results are
summarized in Table 2. Good yields of 95 and 74% were isolated
2
Figure 1. Plot of ([amine]0 − [amine]2)/2 versus time (h) for the
hydroarylation reaction of styrene 1a and 6-methyl-1,2,3,4-tetrahy-
droquinoline 2h. Conditions: [1a]0 = 1.6665 mol·L−1, [2h]0 = 0.3333
mol·L−1, 10 mol % of TB, PhCl, 100 °C, detected by GC with n-
2
Table 2. Hydroarylation Reactions of 1,2,3,4-
■
hexadecane as internal standard. R = 0.9963 (black ); plot of [amine]0
− [amine] versus time (h). Conditions: [1a]0 = 1.25 mol·L−1, [2h]0 =
Tetrahydroquinoline and Aliphatic/Internal Olefins
a
−1
2
●
0.25 mol·L , 10 mol % of TB, PhCl, 100 °C. R = 0.9986 (red ).
Catalyzed by TB
To gain more insight into the mechanism of the hydro-
arylation reaction, monitoring by 11B and 19F NMR spectroscopy
was conducted, which revealed no change of the [B(C6F5)4]
anion signals, and rules out the participation of borate in the
catalytic process.7i Moreover, kinetic study of N-methyl aniline
and d5-N-methyl aniline was conducted in parallel. The kinetic
isotope effect was determined to be 2.3 (Figure S3), suggesting
C−H bond cleavage as the rate-determining step.
Two possible mechanisms are proposed for the [Ph3C][B-
(C6F5)4]-catalyzed hydroarylation reaction. The trityl cation may
first react with the aromatic amine substrate to form an anilinium
salt (Scheme S1), followed by protonation of alkenes to generate
a carbocation.9 This mechanism, however, does not explain
reactions of tertiary amines. Alternatively, the trityl cation may
first activate the alkene (Scheme 4).7i In both pathways,
Scheme 4. Plausible Mechanism
a
Conditions: 1 (1 mmol), 2h (74 mg, 0.5 mmol), TB (46 mg, 0.05
b
mmol) in PhCl (2 mL) 12 h. Isolated yield. Olefin/1,2,3,4-
tetrahydroquinoline = 5:1, 24 h.
from reactions of cyclic alkenes norbornene and cyclohexadiene
(entry 1 and 2), respectively, while lower yields of 40 and 32%
were obtained from linear alkenes 1-octene and 1-hexene (entry
3 and 4), respectively, albeit with a higher ratio of alkene to
amine. Acyclic internal alkene β-methylstyrene reacted straight-
forwardly at 130 °C and generated product 4v in 90% yield
(entry 5), while the bulkier substrate stilbene did not react (entry
6).
A linear plot of ln([1a]0/[1a]) versus time reveals a first-order
dependence on styrene concentration (Figure S2). The order of
amine 2h was found to be fractional, as the plots suggest reverse-
first-order at a higher concentration of 0.33 mol·L−1, whereas
zero-order at a lower concentration of 0.25 mol·L−1 (Figure 1).
Overall, the rate law is deduced as ν ≈ [styrene]1[amine]n (n =
−1−0).
nucleophilic addition leads to C−C bond formation,10 and
subsequent proton transfer regenerates aryl rings, as well as trityl
cations. High concentration amine may interact with trityl
cations, decreasing their nucleophilicity, which slows the
reaction. Both mechanisms are plausible, and further con-
firmation cannot be made based on the current results.
In conclusion, nonmetal catalyst [Ph3C][B(C6F5)4] has been
developed for hydroarylation of a wide range of alkenes with
aromatic primary, secondary, and tertiary amines. One hundred
C
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good yields of 32−98%. A kinetic study revealed a fractional-
order dependence on amine concentration, while first-order on
alkene concentration. This method provides a simple and
efficient method to prepare aniline derivatives, and the work
complements the literature methods. Further development of
catalytic C−H bond functionalization is in progress.
ASSOCIATED CONTENT
■
́
48, 7642. (i) Perez, M.; Mahdi, T.; Hounjet, L. J.; Stephan, D. W. Chem.
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* Supporting Information
Commun. 2015, 51, 11301. (j) Paras, N. A.; MacMillan, D. W. C. J. Am.
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The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.8b01158.
1
Characterization of hydroarylation products, H and 13C
NMR spectra, and details of kinetic study (PDF)
(8) (a) Sun, Q.; Wang, Y.; Yuan, D.; Yao, Y.; Shen, Q. Chem. Commun.
2015, 51, 7633. (b) Sun, Q.; Wang, Y.; Yuan, D.; Yao, Y.; Shen, Q.
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AUTHOR INFORMATION
■
Corresponding Authors
*E-mail:yuandan@suda.edu.cn.
*E-mail: yaoym@suda.edu.cn.
ORCID
Yingming Yao: 0000-0001-9841-3169
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We gratefully acknowledge financial support from the National
Natural Science Foundation of China (Grants 21402135 and
21674070), the Project of Scientific and Technologic Infra-
structure of Suzhou (SZS201708), and PAPD.
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DOI: 10.1021/acs.orglett.8b01158
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