Borane-Catalyzed Chemoselectivity-Controllable N-Alkylation and ortho C-Alkylation of Unprotected Arylamines Using Benzylic Alcohols

Article abstract of DOI:10.1021/acscatal.9b03038

An unprecedented protocol for the efficient and highly chemoselective alkylation of unprotected arylamines using alcohols catalyzed by B(C₆F₅)₃ has been developed. The reaction gives N-alkylated products and ortho C-alkylated products in different solvents in good chemoselectivities and yields. Control experiments and DFT calculations indicated that the borane underwent alcohol/arylamine exchange to ensure catalytic activity, and a possible mechanism involving a carbocation is proposed.

Full text of DOI:10.1021/acscatal.9b03038

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Letter
Borane Catalyzed Chemoselectivity-Controllable N-alkylation and
ortho C-alkylation of Unprotected Arylamines Using Benzylic Alcohols
Shanshui Meng, Xiaowen Tang, Xiang Luo, Ruibo Wu, Junling Zhao, and Albert Sun Chi Chan
ACS Catal., Just Accepted Manuscript • Publication Date (Web): 09 Aug 2019
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Borane Catalyzed Chemoselectivity-Controllable N-alkylation and
ortho C-alkylation of Unprotected Arylamines Using Benzylic
Alcohols
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Shan-Shui Meng*‡, Xiaowen Tang‡, Xiang Luo, Ruibo Wu, Jun-Ling Zhao*, Albert S. C. Chan*
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
KEYWORDS: Unprotected arylamine, N-alkylation, ortho C-alkylation, chemoselectivity-controllable, B(C6F5)3.
ABSTRACT: An unprecedented protocol for the efficient and highly chemoselective alkylation of unprotected arylamines using
alcohols catalyzed by B(C6F5)3 has been developed. The reaction gives N-alkylated products and ortho C-alkylated products in
different solvents in good chemoselectivities and yields. Control experiments and DFT calculations indicated that the borane
underwent alcohol/arylamine exchange to ensure catalytic activity, and a possible mechanism involving a carbocation is proposed.
Arylamines, which are important and fundamental compounds,
have unique significance in industrial, agricultural and
pharmaceutical chemistry.1 Alkylation is one of the most direct
and powerful tools for increasing the complexity of
arylamines.2 Numerous alkylating agents and methods have
been developed to enable the N-alkylation of arylamines.
However, traditional alkylating methods often generate
stoichiometric amounts of waste and salt contaminants.
Alcohols are a class of stable and widely available organic
compounds with low toxicity, making them ideal alternatives to
traditional alkylating agents. Since the first example of a
transitional-metal catalyzed alkylation of aniline using an
alcohol via the so-called “hydrogen borrowing” strategy was
reported, this area has been intensely explored (Scheme 1).3
However, this protocol has its natural limitations: 1) only
primary alcohols have been thoroughly investigated, and 2) the
alkylation is strictly limited to amino groups.
realize the alkylation, the catalyst must meet three basic
conditions: 1) acidic enough to activate the hydroxyl group; 2)
stable in wet and basic conditions; 3) able to dissociate from
amines. B(C6F5)3, a powerful nonmetallic Lewis acid catalyst,
has been elegantly applied in “frustrated Lewis pair” catalysis.8
Fu9 and Ingleson10 have both reported B(C6F5)3 -catalyzed N-
alkylations of amines using carboxylic acids or aldehydes in the
presence of an organosilane. In their reports, the borane
maintained its catalytic activity in the presence of arylamines
(Scheme 1). B(C6F5)3 has also been shown to activate hydroxyl
groups for various transformations of alcohols.11,12 The Li group
developed a high ortho-selective alkylation of phenols using
1,3-dienes catalyzed by B(C6F5)3 and studied the mechanism in
great detail.13 Zhang and Liu reported an elegant,
chemoselective and ortho-selective substitution of phenols with
diazoesters using the same catalyst.14 However, ortho-selective
alkylations of unprotected arylamines remain underdeveloped.
Herein, we report an unprecedented protocol for practical and
efficient N-alkylations and ortho C-alkylations of unprotected
arylamines with bulky alcohols (secondary and tertiary
alcohols) with controllable chemoselectivity catalyzed by
B(C6F5)3.
Using alcohols to obtain alkylated arylamines via
nucleophilic substitution is another option.4 Due to the poor
leaving ability of hydroxyl groups and the incompatibility
between catalysts and amines, few examples of such reactions
have been reported. In 2011, Saito and coworkers developed a
promising direct N-alkylation of amines with primary alcohols
catalyzed by an Fe/amino acid system.5 More recently, the
Sweeney group reported an elegant N-allylation of amines
catalyzed by nickel.6 Despite these precedents, there are many
problems in this area that must be addressed. N-Alkylations
with bulky alcohols, e.g., secondary and tertiary alcohols,
remain difficult.4e Moreover, to the best of our knowledge, the
synthesis of ortho C-alkylated anilines, which are important
motifs in ligands, still requires excess ZnCl2/HCl and harsh
reaction conditions.7 Therefore, a catalytic, efficient and
practical alkylation of arylamines using bulky alcohols is
challenging yet highly appealing, and developing the catalytic
alkylation with controllable chemoselectivity is also of interest.
Scheme 1. The methods of catalytic alkylation of arylamines
with alcohols.
1) N-alkylation of amine via "hydrogen borrowing" strategy
R2
R1 OH
Noble Metal Complexes
H2N
R1
R2
N
H
2) B(C6F5)3 catalyzed the reductive amination
O
O
R2
B(C6F5)3
Hydrogen Source
H2N
R1
or
R1
R1 OH
N
R2
H
Oxidized forms of alcohols
3) This work
R2
R2
R3
OH
R2
NH2
NH
R2
B(C6F5)3
HFIP
The main challenge in the direct catalytic alkylation of
amines with alcohols is that an “off-cycle species” can form
between the electron-rich arylamines and acidic catalysts.4,5 To
R1
R1
B(C6F5)3
CH3NO2
H2N
R1
R3
R1
R3
C-alkylation, >30 example, 54-90% yield N-alkylation, >24 example, 55-91% yield
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The initial investigation with model substrates 1a and 2a
Page 2 of 7
OMe
OH
R1 R2
1
NHPMP
R1 R2
B(C6F5)3 10 mol%
1
2
3
4
5
6
7
8
revealed the successful N-alkylation in 63% yield using 10
mol% B(C6F5)3 in toluene (Table 1, entry 1). The polar aprotic
solvent CH3NO2 gave a higher yield of 3a (entry 3), and an
unexpected ortho C-alkylation product (4a) was also isolated.
This exciting finding indicated that the challenging ortho C-
alkylation of arylamines might be achievable with this catalytic
system. The reaction did not proceed in ether or ester solvents
(entries 4 and 5). To further improve the yield of the N-
alkylation, the reaction was found to proceed smoothly under
ambient atmosphere, generating 3a in 86% yield after 48 h
(entry 6). We wondered if a weakly acidic environment might
promote the C-alkylation because the amino group would be
protonated and thus less reactive. Polyfluorinated alcohols,
which are protic nonnucleophilic solvents, have been utilized in
functional reactions of aromatic rings in previous reports.15 To
our delight, an obvious increase in the yield of 4a was observed
when CF3CH2OH was used (entry 7). A perfluorinated alcohol,
HFIP (1,1,1,3,3,3-hexafluoro-2-propanol), was found to be
superior, giving 71% yield of 4a with negligible N-alkylation
product (entry 9).16
CH3NO2, 120 C
H2N
2a
3
1
2
3a:
R =H, R =H, 86% yield
NHPMP
Me
NHPMP
1
2
3b:
3c:
3d:
3e:
R =H, R =2-CH3, 86% yield
1
2
R =4-F, R =4-F, 82% yield
R2
R1
1
2
R =H, R =4-Cl, 91% yield
1
2
3f: 67% yield
R =H, R =2-CF3, 0% yield
NHPMP
Me
NHPMP
NHPMP
Me
NHPMP
Me
9
H3C
3i:
F
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3g:
83% yield
NHPMP
3h:
3j:
59% yield
NHPMP
73% yield
67% yield
NPMP
S
NPMP
S
CN
O
O
3k:
3l:
3m:
3n:
72% yield
68% yield
78% yield
81% yield
Me
Ph
NHPMP
Ph NHPMP
NHPMP
Ph
Ph
Ph
[b]
[b]
[c]
3o:
3p:
3q:
63% yield
55% yield
62% yield
TABLES 1. Optimization of alkylation conditions.a
aReaction conditions: 1 (0.2 mmol), 2a (0.4 mmol), B(C6F5)3 (10
mol%), CH3NO2 (1 ml), 120 °C, 10 ml Schlenk tube, 24-48h.
Isolated yield. bCH3NO2 (0.5 ml), 85 °C. cDCE (0.5 ml), 85 °C.
CHPh2
1a
Diphenylmethanol
H2N
OMe
MeO
NHCHPh2
MeO
NH2
B(C6F5)3 10 mol%
120 
2a
3a
4a
C
A series of alcohols was examined under the ortho C-
alkylation conditions (Scheme 3). Substituted benzhydrols gave
the ortho C-alkylated arylamines in HFIP (4a-4d, 71%-81%);
strangely, the C-alkylation with benzhydrols bearing electron-
donating groups was more efficient in CH3NO2 than in HFIP
(4e-4g). The electronic properties of the alcohol substrate is a
key factor in the ortho C-alkylation. The H-substituted and F-
substituted benzyl alcohols did not give the desired products,
but even the very weak electron-donating group CH3 could
facilitate the C-alkylation, generating the corresponding
product in moderate yield (4i, 56%). Other electron-rich benzyl
alcohols efficiently produced ortho-alkylation amines under the
optimal conditions (4j-4p, 53%-82%).
Entry
Solvent
yield%b (3a)
yield%b (4a)
1
toluene
1,2-dichloroethane
CH3NO2
63
62
71
0
<5
<5
12
0
2
3
4
THF
5
6c
Ethyl acetate
CH3NO2
0
0
86
24
27
<5
67
<5
36
30
71
<5
7
TFE
8
CF3CHOHCH3
HFIP
9
10c,d
CH3NO2
aReaction conditions: 1a (0.2 mmol), 2a (0.4 mmol), B(C6F5)3 (10
mol%), 15 ml sealed tube, 120 °C, 12h. Isolated yield. In 10 ml
Schlenk tube with an air-balloon, 48h. dAt 100 °C.
HFIP=1,1,1,3,3,3-hexafluoro-2-propanol.
b
c
Scheme 3. The alcohol substrate of ortho-selective C-
alkylation.a
OMe
With the optimal conditions in hand, we decided to explore
the alcohol scope of this N-alkylation. Diphenylmethanols with
electron-neutral and electron-donating groups were suitable for
the reaction (3b-d, 82-91%, Scheme 2). However, the desired
reaction did not occur for the alcohol with a strong electron-
withdrawing group (3e). For less reactive alcohols, 1-
phenylethan-1-ol and 1-phenylpropan-1-ol, the N-alkylation
still provided satisfactory results (3f-i, 59%-83%). Cyclic
alcohols were smoothly transformed into the corresponding
amines (3j 73%, 3k 67%). The functional group tolerance of
this system was also investigated (3l-n, 68-81%), and the
products were further oxidized to imines under the reaction
conditions (3m, 3n). α-Tertiary amines always attract
considerable interest due to their unique properties.17 However,
the catalytic alkylation of amines using tertiary alcohols is
rarely achieved because of the low reactivity of tertiary alcohols
and the elimination of the hydroxyl group. Luckily, the desired
transformations proceeded with satisfactory efficiencies with
little optimization of the conditions (3o-q, 55-63%).
OH
R2
B(C6F5)3 10 mol%
HFIP, 120 C
H2N
R1
H2N
OMe
R1
R2
1
2a
4
3
4
OMe
4a
: R =H, R = H, 71% yield
OMe
3
4
4b
4c
4d
4e
: R =H, R =2-CH3, 81% yield
H2N
3
4
H2N
R3
: R =4-F, R =4-F, 73% yield
3
4
: R =H, R =4-Cl, 81% yield
R4
3
4
b
: R =4-Me, R =4-Me, 76% yield
O
3
4
b
b
4f
4g
: 84% yield
: R =4-OMe, R =4-OMe, 90% yield
OMe
OMe
OMe
MeO
H2N
H2N
H2N
NH2
Me
Me
Me
S
Me
iPr
4h
4i
4j
4k
: 72% yield
: 86% yield
: 56% yield
OMe
: 53% yield
OMe
OMe
OMe
MeO
H2N
H2N
H2N
H2N
NH2
Me
Me
Me
Scheme 2. The alcohol scope of N-alkylation.a
S
MeO
OMe
4l
4m
4n
4o
4p
: 55% yield : 54% yield
: 62% yield
: 77% yield
: 82% yield
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aReaction conditions: 1 (0.2 mmol), 2a (0.4 mmol), B(C6F5)3 (10
R
R
HFIP,120 °
C
CH3NO2, 120 °
C
R
NH2
1
2
mol%), HFIP (1 ml), 15 ml sealed tube, 120 °C, 12h. Isolated yield.
NH2
NHCHPh2
bCH3NO2 (1 ml).
CHPh2
6
2
5
3
4
5
6
7
8
9
C-alkylation productc
N-alkylation productb
Trisubstituted aromatics, which are important frameworks,
appear frequently in organic ligands, functionalized
organometallic compounds and polymeric materials.18 The
appealing bis C-alkylation products could be isolated in high
yields (Scheme 4, 4q-4t, 73%-87%) from this C-alkylation
system when the ratio of alcohols to amines was changed to
2.1:1.
Aniline substrate
H3C
NH2
6b
H3C
NH2
H3C
NHCH(Ph)2
74% yield
CHPh2
2b
5b: 81% yield
iPr
NH2
6c
iPr
NH2
iPr
NHCH(Ph)2
78% yield
CHPh2
2c
2d
5c: 81% yield
Scheme 4. The alcohol substrate of ortho, ortho' bis C-
tBu
NH2
CHPh2
NH2
10
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6d
tBu
NH2
NH2
tBu
NHCH(Ph)2
alkylation.a
81% yield
5d: 90% yield
R1
PhO
6e
PhO
PhO
NHCH(Ph)2
73% yield
CHPh2
2e
2f
5e: 88% yield
R2
BnO
NH2
OH
6f
B(C6F5)3 10 mol%
HFIP, 120 C
BnO
NH2
BnO
NHCH(Ph)2
78% yield
H2N
OMe
H2N
OMe
R2
CHPh2
R1
5f: 91% yield
H3C
H3C
H3C
R2
R1
6g
NH2
NH2
NHCH(Ph)2
1 ( 2.1 equiv)
2a ( 1 equiv)
4
67% yield
H3C
CHPh2
CHPh2
H3C
H3C
H3C
H3C
OMe
OMe
2g
2h
5g: 79% yield
H3C
6h
NH2
Me
NH2
NH2
H3C
NHCH(Ph)2
72% yield
NH2
CH3
NH2
CH3
Me
5h: 77% yield
CHPh2
NH2
Cl
6i
Cl
Cl
NHCH(Ph)2
b
c
4q
: 83% yield (17% yield)
4r
: 87% yield
OMe
Cl
55% yield
Cl
2i
CH3
Cl
OMe
5i: 76% yield
CH3
F
F
6j
NH2
H3C
CH3
mixture products
74% yield
NH2
NH2
NH2
CHPh2
tBu
2j
tBu
6k
NH2
F
F
OMe
OMe
mixture products
NH2
72% yield
c
4s
: 82% yield
4t
CHPh2
: 73% yield
2k
aThe reaction was carried out under the specified conditions.
Isolated yield. bReaction conditions: 1 (0.2 mmol), 2a (0.4 mmol),
B(C6F5)3 (10 mol%), CH3NO2 (1 ml), 120 °C, 10 ml Schlenk tube.
cReaction conditions: 1 (0.2 mmol), 2a (0.4 mmol), B(C6F5)3 (10
mol%), HFIP (1 ml), 15 ml sealed tube, 120 °C.
aReaction conditions: 1 (0.42 mmol), 2a (0.2 mmol), B(C6F5)3 (10
mol%, 0.02 mmol), HFIP (1 ml), 15 ml sealed tube, 120 °C, 12h.
Isolated yield. bThe ratio between 1a and 2a was 1:1. cdr = 1:1.
Different arylamines gave both the desired N-alkylation
and C-alkylation products in high yields (Scheme 5). Different
electron-neutral and electron-donating substituents at the 4-
position were well tolerated (5b-5f, 81%-91%; 6b-6f, 73%-
81%). To ensure that the C-alkylation is ortho-selective, 3,5-
dimethylaniline was evaluated and generated 6g in high yield
and excellent site selectivity. The ortho-alkylation was more
likely to occur at a less hindered position (6h). 2-Substituted
arylamines also gave excellent ortho selectivity in the C-
alkylation under the optimal conditions (6j, 74%; 6k, 72%);
however, a mixture of unknown compounds was generated
when the reactions were conducted under the N-alkylation
conditions.
To provide more insight into the reaction, complex I
(B(C6F5)3-NH2PMP) was synthesized, and the structure was
confirmed by single-crystal X-ray analysis (Scheme 6). In a
previous report, the generation of an “off-cycle species”
between the amine and Lewis catalyst would limit the
reaction,4,5 but in our system, the N-alkylation and C-alkylation
could be catalyzed by complex I, and similar results were
achieved. Control experiments indicated that a SN1 pathway
was more reasonable in the alkylated reaction (see Supporting
Information).
Scheme 6. The reaction catalyzed by complex I.
Scheme 5. The scope of arylamines.a
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carbocation is stabilized by the p-π conjugated system of 2a via
Page 4 of 7
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2
3
4
5
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a cation-π interaction. The atom distances involved with the
following nucleophilic attack are 3.48 Å for C-N and 3.09 Å for
C-C, which are consistent with the both the N-alkylation and C-
alkylation occurring simultaneously. However, the free energy
profile of the two alkylation steps indicates that N-alkylation is
toluene
120 C
B(C6F5)3
1:1
2a
complex-I
1a, complex-I
10 mol%
absolutely
favored
over
the
C-alkylation
both
MeO
MeO
NH2
MeO
NHCHPh2
CH3NO2, 120 C
thermodynamically and kinetically. The N-alkylation is highly
exothermic by 20.8 kcal/mol and was shown to be barrierless
by our potential energy surface scan (Figure S2, see the
Supporting Information), while the C-alkylation is slightly
exothermic by 8.7 kcal/mol with a barrier of 5.2 kcal/mol. It
seems that the N-alkylation could be the sole dominant pathway
in our system. In the latter stage of the catalytic cycle, proton
transfer from ammonium N-alkylation intermediate IV1 to B2 is
endergonic by 2.0 kcal/mol without a reaction barrier;
conversely, a rearomatization process involving a proton
transfer from C-alkylation intermediate IV2 to B2 is highly
exothermic by 16.4 kcal/mol with a negligible barrier of 0.1
kcal/mol. These significant thermodynamic differences
facilitate the C-alkylation pathway. After the proton transfer
process, hydroxide-coordinated catalyst B2 is reverted to water-
coordinated complex B3. The coordinating free energy of the
water molecule and B(C6F5)3 is -6.0 kcal/mol, indicating that
thermodynamically favored complex I can be generated rapidly
via an exchange of arylamine 1a and water. To further
illuminate the chemoselectivity in different solvents, the
interactions of 2a with solvent molecules are investigated10a,20
and the electrostatic potential surfaces of HFIP-2a, 2a and
CH3NO2-2a complex are displayed in Figure 2C. The arylamine
2a is hydrogen-bonding acceptor in solvent HFIP making the
amine group electron-deficient, which can be a severe obstacle
for N-alkylation, and the reaction is more likely to undergo C-
alkylation pathway. But in CH3NO2, the arylamine 2a turns into
hydrogen-bonding donor and the amine group is much more
electron-rich, which enhances the N-alkylation giving a higher
yield of N-alkylated product.
2a
3a
, 85% yield
CHPh2
NH2
9
1a, complex-I
10 mol%
NH2
MeO
10
11
12
13
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60
HFIP, 120 C
2a
4a
, 64% yield
The B(C6F5)3-catalyzed alkylation of arylamines with
alcohols is assumed to proceed through four steps as shown in
Figure 1: (1) alcohol/amine exchange of complex I generates
catalyst-alcohol complex II; (2) dissociation of complex II
delivers the carbocation; (3) nucleophilic attack of the
carbocation by the arylamine produces the N-/C-alkylation
intermediates; (4) protolysis of the σ-complex intermediates
produces the final N-/C-alkylation products and regenerates
B(C6F5)3. To verify the feasibility of our proposed catalytic
cycle, density functional theory (DFT) calculations with the
M06-2X19 functional were conducted to evaluate the energy
profile and configurational information of the catalytic process.
The reaction between model substrates diphenylmethanol (1a)
and p-anisidine (2a) in toluene was chosen as the model
reaction. Moreover, the temperature was set to 393.15 K, which
is consistent with the actual reaction conditions. More
computational details are described in the Supporting
Information.
Figure 1. Plausible mechanism of the alkylation.
B(C6F5)3
ArNH2
H2O
F
F
F
(A)
F
OHB(C6F5)3
F
F
H
N
C6F5
B
R1
R1
H
R1
I
F
OH
F
NH2
NH2
or
R2
F
H
R2
Ph
R2
Ph
IV1
IV2
NH2
R1
R2
NH2
(C) 5.5e-2
(B)
R1
Ph
R2
H
O
B(C6F5)3
III
Ph
II
OHB(C6F5)3
The free energy profile and pivotal transition states along
the proposed reaction path are shown in Figure 2, and all
structures involved in the catalytic cycle are shown in Figure S1
(see the Supporting Information). The coordination of B(C6F5)3
and 2a is highly exothermic by 16.9 kcal/mol, while the
coordination with 1a is slightly endergonic by 2.4 kcal/mol.
This suggests that amine-coordinated catalyst complex I is
thermodynamically stable; nevertheless, alcohol-amine
exchange is also feasible. The subsequent alcohol activation is
still endergonic by 11.2 kcal/mol with a barrier of 12.7
kcal/mol, indicating that intermediate complex III is metastable
and that the formation of the carbocation is the rate-limiting
step. In the initial stage of the arylamine alkylation, the
-5.5e-2
Figure 2. (A) Gibbs free energy profile of B(C6F5)3-catalyzed
alkylation of 2a with 1a. (B) 3D-structures of the transition states
involved in the reaction process. (C) Electrostatic potential surfaces
of HFIP-2a, 2a and CH3NO2-2a complex.
In conclusion, efficient N-alkylations and ortho C-
alkylations of arylamines with controllable chemoselectivity
catalyzed by B(C6F5)3 using alcohols has been developed. The
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Yu, Z. Substitution of alcohols by N-nucleophiles via transition metal-
chemoselectivity is controlled by the solvent; CH3NO2 gives N-
alkylation products, while HFIP, which is protic, is essential for
C-alkylation. The reaction features a wide substrate scope and
provides convenient access to advanced arylamines.
Mechanistic studies and DFT calculations suggest that the
reaction might proceed through a four-step mechanism, and the
feasibility of N-alkylation and ortho C-alkylation is well
demonstrated.
catalyzed dehydrogenation. Chem. Soc. Rev. 2015, 44, 2305-2329.
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Secondary and Primary Alcohols via a Carbocationic Pathway. Adv.
Synth. Catal. 2018, 360, 730 –737.
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ASSOCIATED CONTENT
The Supporting Information is available free of charge on the ACS
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Publications
website.
Experimental details, GCMS, and NMR spectra of
products (PDF)
Crystallographic data for Complex I (CIF)
AUTHOR INFORMATION
Corresponding Author
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Catalyzed Hydrosilylation of Alkenes. J. Am. Chem. Soc. 2017, 139,
9439-9442; (d) Cherian, A. E.; Domski, G. J.; Rose, J. M.; Lobkovsky,
E. B.; Coates, G. W. Acid-Catalyzed ortho-Alkylation of Anilines with
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[8] (a) Stephan, D. W. J. Am. Chem. Soc. 2015, 137, 10018-10032; (b)
Stephan, D. W.; Erker, G. Angew. Chem. Int. Ed. 2015, 54, 6400 –
6441; (c) Oestreich, M.; Hermeke, J.; Mohr, J. Chem. Soc. Rev. 2015,
44, 2202-2220.
[9] (a) Fu, M.-C.; Shang, R.; Cheng, W.-M.; Fu, Y. Boron-Catalyzed
N-Alkylation of Amines using Carboxylic Acids. Angew. Chem. Int.
Ed. 2015, 54, 9042-9046; (b) Zhang, Q.; Fu, M.-C.; Yu, H.-Z.; Fu, Y.
Mechanism of Boron-Catalyzed N-Alkylation of Amines with
Carboxylic Acids. J. Org. Chem. 2016, 81, 6235-6243; (c) Pan, Y.;
Luo, Z.; Han, J.; Xu, X.; Chen, C.; Zhao, H.; Xu, L.; Fan, Q.; Xiao, J.
B(C6F5)3-Catalyzed Deoxygenative Reduction of Amides to Amines
Corresponding Author
mengshsh@mail.sysu.edu.cn; zhaojling3@mail.sysu.edu.cn;
chenxz3@mail.sysu.edu.cn.
Author Contributions
The manuscript was written through contributions of all authors. /
All authors have given approval to the final version of the
manuscript. / ‡ S.-S. Meng and X. Tang contributed equally.
Notes
The authors declare no competing financial interests.
ACKNOWLEDGMENT
We are grateful to the Research Foundation for Natural Science
Foundation of Guangdong Province (2018A0303130178) and
Advanced Talents of Sun Yat-sen University (36000-18821101)
for financial support of this program. We thank Prof. Yong Liang
for the kind suggestion of reaction mechanism.
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N-alkylation
NH
NH2
Ar
>24 example, 55-91% yield
>30 example, 54-90% yield
R
CH3NO2
R
OH
Ar
R
B(C6F5)3
OMe
C-alkylation
HFIP
NH2
R
R
8
Ar
9
No metallic catalyst
No protect group
High chemoselectivity
Borad scope
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