Yb(OTf) 3-Mediated Regioselective Hydroamination of Ynamides with Anilines and p -Toluenesulfonamide

Article abstract of DOI:10.1055/a-1488-4467

A rare-earth salt Yb(OTf) ₃-catalyzed regioselective hydroamination of ynamides with anilines and p -toluenesulfonamide has been developed. This protocol provided facile access to a diverse range of amidines with good functional group tolerance in moderate to high yields.

Full text of DOI:10.1055/a-1488-4467

Submission Date:
Accepted Date:
Publication Date:
2021-03-23
2021-04-21
2021-04-21
Accepted Manuscript
Synthesis
Yb(OTf)3-mediated regioselective hydroamination of ynamides with anilines
or p-toluenesulfonamide
Xiaobao Zeng, Qingyun Gu, Wenjing Dai, Yushan Xie, Xinyi Liu, Guixia Wu.
Affiliations below.
DOI: 10.1055/a-1488-4467
Please cite this article as: Zeng X, Gu Q, Dai W et al. Yb(OTf)3-mediated regioselective hydroamination of ynamides with anilines or
p-toluenesulfonamide. Synthesis 2021. doi: 10.1055/a-1488-4467
Conflict of Interest: The authors declare that they have no conflict of interest.
This study was supported by National College Students Innovation and Entrepreneurship Training Program, 202010304044Z, the
Start-Up Funding for Research of Nantong University, 03081231, the Large Instruments Open Foundation of Nantong University,
KFJN2175; KFJN2176
Abstract:
A rare-earth salts Yb(OTf)3-catalyzed regioselective hydroamination of ynamides with anilines or p-toluenesulfonamide has
been developed. This protocol provided facile access to a diverse range of amidines with good group functional group tolerance
in moderate to high yield.
Corresponding Author:
Xiaobao Zeng, Nantong University, School of Pharmacy, Nantong City, China, zengxb@ntu.edu.cn
Affiliations:
Xiaobao Zeng, Nantong University, School of Pharmacy, Nantong City, China
Qingyun Gu, Nantong University, School of Pharmacy, Nantong, China
Wenjing Dai, Nantong University, School of Pharmacy, Nantong City, China
[…]
Guixia Wu, Nantong University, School of Pharmacy, Nantong City, China
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Synthesis
Paper
Yb(OTf)3-mediated regioselective hydroamination of ynamides with
anilines or p-toluenesulfonamide
Xiaobao Zeng*
Qingyun Gu
Wenjing Dai
Yushan Xie
Xinyi Liu
Guixia Wu
School of Pharmacy, Nantong University, 19 Qixiu Road,
Nantong, Jiangsu Province 226001, People's Republic of China.
E-mail: zengxb@ntu.edu.cn
Click here to insert a dedication.
Received:
blocks.12 Consequently, considerable efforts have been devoted to
accessing these compounds.13 Among them, direct hydroamination of
ynamides with amines is an efficient protocol to generate amidines.
For instance, Skrydstrup and coworkers innovatively developed an
efficient Au-catalyzed intermolecular hydroamination reaction of
ynamides with primary aromatic amines to regioselectively afford
numerous N-arylimines in 2009 (Scheme 2a),8c the strategy was
Accepted:
Published online:
DOI:
Abstract A rare-earth salts Yb(OTf)3-catalyzed regioselective hydroamination of
ynamides with anilines or p-toluenesulfonamide has been developed. This protocol
provided facile access to a diverse range of amidines with good group functional
group tolerance in moderate to high yield.
Key words Rare-earth salts, Hydroamination, Ynamides, Amidines, Amide
further applied in the intermolecular annulation reaction to
4b
synthesize indoles3e-g and quinolones4a,
. Similarly, Cai and
coworkers reported the first heterogeneous Au/Ag-catalyzed
regiospecific hydroamination of ynamides with anilines.8h Catalyst-
free hydroamination of N, N-disulfonyl ynamides with amines was
also reported by Cao and coworkers. (Scheme 2b).8f, 8g It was worthy
to note that the protocol is compatible with both primary aromatic
amines and secondary aliphatic amines, affording various N-
sulfonylamidines in good yields. In 2014, t-BuONa-mediated
hydroamination of terminal ynamides to regioselectively afford
various (Z)-N-(2-aminovinyl)-sulfonamide was developed by Dodd
and coworkers (Scheme 2c).8i Later, Meng and coworkers disclosed a
AgOTf-catalyzed addition of sulfonyl hydrazones with ynamides to
synthesize functionalized α-amino alkenyl-substituted hydrazine
products in good yields (Scheme 2d).8d Recently, Ni-catalyzed
hydroamination of ynamides with secondary aromatic amines to
generate various substituted ethene-1,1-diamine compounds was
reported by Wei and coworkers (Scheme 2e).8j The same group also
reported Zn(OTf)2-catalyzed hydroamination of ynamides with
primary aromatic amines during our preparation of this manuscript.
The protocol features facile reaction conditions and broad substrate
scope.8k Although considerable developments have been achieved in
the hydroamination of ynamides, to the best of our knowledge, the
amines employed in the process above are mainly aromatic amines,
while TsNH2 has never been explored. What’s more, the incorporation
of rare-earth element to effect synthetically useful hydroamination
has gained increasing attention in recent years.14 As part of our
continuous interests in the application of functionalized alkenes and
The exploration of synthetic utilities of functionalized alkynes has
constantly been the focus of organic chemists.1 As one of the most
popular subclass of functionalized alkynes, ynamides have displayed
distinctive reactivity due to the possible delocalization of lone pair by
an electron-withdrawing group attached at the nitrogen atom, thus
rendering them synthetically attractive synthons in organic synthesis
owing to the better balance between increased stability and
reactivity.2 In the past decades, they have widely been applied in
transition-metal involved and metal-free transformations to
construct various prominent structures such as indoles,3 quinolones,4
pyridines,5 pyroles,6 benzofurans,7 amidines8, enamides9 and other
compounds10 (Scheme 1).
Scheme 1 Resonance structures of ynamides and their application in organic
synthesis
On the other hand, hydroamination of alkynes is a powerful strategy
for the synthesis of amidines,11 which have been characterized as
efficient coordinating ligands and versatile functional building
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Synthesis
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alkynes,15 we reported herein Yb(OTf)3-catalyzed hydroamination of
ynamides with ArNH2 or TsNH2 for the preparation of amidines.
vast array of para-substituted aromatic amines were tested to
a) Au-catalyzed hydroamination of ynamides with primary aromatic amines
afford the corresponding products 3aa-f mostly with high yields.
The electronic effect had clear impact on the reaction, resulting
3af with reduced yield compared with 3aa-c. The positional
change of ortho-, meta- and para-substituents had little effect on
the protocol, affording 3ab, 3ag and 3aj in satisfied yield.
Substrates with halide substituents like chlorine, fluorine and
iodine underwent the reaction smoothly to produce the
corresponding compounds in good yields (3ad, 3ah-i). Notably,
free hydroxyl group at the meta-position of the phenyl ring was
also tolerated in the reaction to afford 3al in 78% yield. Apart
from mono-phenyl substituted substrates, di- and tri-phenyl
substituted aromatic amines were also suitable substrates (3am-
n).
R
EWG
R'
GWE
R
N
(PPh3)AuNTf2
DCM, rt
N
R'
+
Ar NH2
N
Ar
b) Catalyst-free hydroamination of N, N-disulfonyl ynamides
PhO2S
Ph
PhO2S
N
R1
DCM, rt
R2
NH
R2
N
Ph
+
N
R1
PhO2S
c) Metal-free hydroamination of ynamides with indoles
GWE
tBuONa
R
N
N
H
+
N
DMF, 3Å MS, rt
N
R
EWG
H
d) Ag-catalyzed hydroamination of ynamides with sulfonyl hydrazones
Ar'
N
Ts
N
GWE
Table 1 Optimization of conditions.a
Ar'
N
Ts
AgOTf
N
+
N
Ar
EWG
H
K2CO3, DCE, 40 o
C
N
R
Ar
R
e) Ni-catalyzed hydroamination of ynamides with secondary aromatic amines
R
EWG
GWE
R
Ni(OTf)2
N
Ar
R1
N
R'
+
N
Ar
toluene, 80 o
C
H
N
R1
R'
f) Zn-catalyzed hydroamination of ynamides with aromatic amines
Entry Catalyst
[mol%]
Solvent
Temp.
[oC]
Yield[%]b
R
EWG
GWE
Zn(OTf)2
N
N
R'
+
Ar
NH2
toluene, 80 o
C
R
N
Ar
R'
1
2
3
4
5
6
7
8
9
BF3·OEt2 (10)
DCE
DCE
DCE
DCE
DCE
85
85
85
85
85
85
85
85
85
66
This work
R1 NH2
R
EWG
FeCl3 (10)
35
GWE
Yb(OTf)3
N
N
R'
+
DCE, 85 o
C
R1N
R
Bi(OTf)3 (10)
Zn(OTf)2 (10)
Yb(OTf)3 (10)
43
R'
Scheme 2 Hydroamination of ynamides and their application in organic
synthesis
57
89
Mg(OTf)2 (10) DCE
trace
45
We commenced our investigation by choosing 2a (0.3 mmol) and
1a (2 equiv.) as model substrates, BF3·Et2O (10 mol%) as catalyst
in 2 mL DCE at 85 oC under air atmosphere. Gratifyingly, the
desired product 3aa could be obtained in 66% yield (Table 1,
entry 1). Subsequently, various Lewis acids were screened
including FeCl3, Bi(OTf)3, Zn(OTf)2 and Yb(OTf)3, showing that
the reaction was compatible with most Lewis acid catalyst to
furnish 3aa in moderate yields, among which Yb(OTf)3 was
proved to be superior than other catalyst to afford 3aa in 89%.
However, a trace amount of 3aa was obtained using Mg(OTf)2
(entries 2-6). The effect of solvent was subsequently investigated.
Lower yield was observed when reaction was conducted in
toluene or DMF, while no desired products was detected in 1,4-
dioxane and CH3CN. By continuous lowering the amount of
Yb(OTf)3 to 5 mol%, the yield of 3aa was significantly reduced to
71% (entry 11). Next, the substrates proportion of 1a:2a was
evaluated. By reducing the ration of 1a:2a to 1.5:1, the yield of
3aa was reduced to 77%, while further increasing the ration to
3:1 didn’t lead to a better yield (entries 12, 13). Furthermore,
continuous elevating the reaction temperature to 110 oC or
lowering the reaction temperature to 60 oC was detrimental to
the reaction, resulting in a lower yield (entries 14, 15). Finally,
the optimum conditions were determined as entry 5.
Yb(OTf)3 (10)
Yb(OTf)3 (10)
Yb(OTf)3 (10)
toluene
DMF
35
1,4-
dioxane
n.r.
10
11
12c
13d
14
15
Yb(OTf)3 (10)
Yb(OTf)3 (5)
Yb(OTf)3 (10)
Yb(OTf)3 (10)
Yb(OTf)3 (10)
Yb(OTf)3 (10)
CH3CN
DCE
DCE
DCE
DCE
DCE
85
85
85
85
110
60
n.r.
71
77
88
68
63
a Unless otherwise stated, reactions were carried out on a 0.3 mmol scale of 2a, 1a
(2 equiv.), catalyst (10 mol%) and solvent (2 mL) at 85 oC for 2 h in a sealed tube
under air.
b Isolated products.
c 1a:2a = 1.5:1.
d 1a:2a = 3:1.
Subsequently, the scope of ynamides was examined (Scheme 3).
The results demonstrated that substrates with phenyl, methyl
and allyl moiety at the nitrogen position were readily
transformed into desired products, albeit with lower yield (3ao-
q). Similarly, by switching tosyl group at the nitrogen position to
With the optimal reaction conditions established, the generality
of the anilines and ynamides was explored (Scheme 3). Firstly, a
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methyl sulfonyl and 4-nitrobenzene sulfonyl, the reaction
proceeded smoothly to produce 3ar and 3as in 81% and 46%
yield. Ynamides bearing methyl and bromo group at the para-
position of phenyl ring were also subjected to the reaction to
furnish 3at-u in good yields. However, no reaction was detected
with 1o-q under standard reaction conditions.
with benzamide was completely shut down under the standard
conditions.
Based on the results obtained above and previous reports,2k, 2m
a
plausible mechanism was proposed as shown in Scheme 5.
Initially, the highly active ketenimine intermediate A was formed
by the interaction of Yb(OTf)3 with the triple bond of ynamide 1a.
Nucleophilic addition of aniline 2a onto the ketenimine A would
then lead to nitrenium ion intermediate B, followed by proton
transfer process to afford intermediate C, which underwent
tautomerization to afford amidine 3aa and regenerate Yb(OTf)3
to complete the cycle.
Scheme 4 Substrates scope of TsNH2 and ynamides. Reaction conditions: 2 (0.3
mmol), TsNH2 (2 equiv.), Yb(OTf)3 (10 mol%) and DCE (2 mL) at 85 oC for 2 h in
a sealed tube under air; Isolated Yields.
Scheme 3 Substrates scope of anilines and ynamides. Reaction conditions: 2
(0.3 mmol), 1 (2 equiv.), Yb(OTf)3 (10 mol%) and DCE (2 mL) at 85 oC for 2 h in
a sealed tube under air; Isolated Yields.
Inspired by the results obtained with aromatic amines, we were
next intrigued to apply the present protocol for the
hydroamination with TsNH2, resulting 5aa in 73% yield (Scheme
4). Pleasantly, ynamides with variation at the nitrogen position
including methyl, allyl, methyl sulfonyl and 4-nitrobenzene
sulfonyl were all tolerated to deliver 5ab-d in moderate to good
yield, while 5ae was obtained in relative lower yield. Ynamide
with bromine group at the phenyl ring was also viable substrates
for the reaction to afford 5af in 81% yield. However, the reaction
Scheme 5 Plausible mechanism
Although the mechanism proposed above seems to be reasonable
based on previous report, control experiments were also
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(E)-N-benzyl-2-phenyl-N'-(p-tolyl)-N-tosylacetimidamide
108.1 mg (77%); Yellow oil;
(3ab).
conducted to further verify the mechanism. Firstly, the reaction
was conducted with 2a as substrate under standard reaction
conditions in the absence of aniline 1a, compound 6 was isolated
in 38% yield (Scheme 6, equation 1). Compound 6 was then
subjected to the reaction with 2 equiv. of aniline 1a under
standard conditions, no desired product was detected in the
reaction, and starting material compound 6 remained intact, to
further exclude the possibility that 3aa could be obtained by
condensation of 1a with the hydrolysed product 6 from 2a
(equation 2).
1H NMR (400MHz, CDCl3) δ 7.74–7.72 (m, 2H), 7.34–7.32 (m, 2H), 7.21–
7.09 (m, 6H), 7.05–6.97 (m, 4H), 6.79–6.77 (m, 2H), 6.35–6.33 (m, 2H),
4.64 (s, 2H), 3.88 (s, 2H), 2.45 (s, 3H), 2.27 (s, 3H).
13C NMR (100 MHz, CDCl3) δ 155.7, 145.5, 144.1, 135.8, 135.3, 134.8,
132.9, 129.6, 129.5, 129.2, 128.8, 128.3, 128.1, 128.0, 127.2, 126.4, 119.3,
51.0, 37.6, 21.6, 20.8.
HRMS m/z (ESI) calcd. for C29H28N2O2SNa (M + Na)+ 491.1764, found
491.1766.
(E)-N-benzyl-N'-(4-methoxyphenyl)-2-phenyl-N-tosylacetimidamide
(3ac).
120.5 mg (83%); Yellow oil;
1H NMR (400MHz, CDCl3) δ 7.74–7.72 (m, 2H), 7.33–7.31 (m, 2H), 7.20–
7.06 (m, 6H), 7.02–7.00 (m, 2H), 6.80–6.75 (m, 4H), 6.39–6.37 (m, 2H),
4.65 (s, 2H), 3.90 (s, 2H), 3.74 (s, 3H), 2.45 (s, 3H).
13C NMR (100 MHz, CDCl3) δ 156.0 (2C), 144.1, 141.3, 135.8, 135.3, 134.8,
129.4, 129.1, 128.8, 128.3, 128.1, 128.0, 127.2, 126.4, 120.5, 114.3, 55.4,
51.0, 37.5, 21.6.
HRMS m/z (ESI) calcd. for C29H28N2O3S (M + H)+ 485.1893, found
485.1895.
Scheme 6 Control experiments
(E)-N-benzyl-N'-(4-chlorophenyl)-2-phenyl-N-tosylacetimidamide
(3ad).
3. Conclusion
124.4 mg (85%); off-white solid; mp 120–122 °C;
1H NMR (400MHz, CDCl3) δ 7.72–7.70 (m, 2H), 7.31–7.29 (m, 2H), 7.20–
7.13 (m, 6H), 7.11–7.07 (m, 2H), 7.04–7.02 (m, 2H), 6.76–6.74 (m, 2H),
6.33–6.31 (m, 2H), 4.68 (s, 2H), 3.84 (s, 2H), 2.42 (s, 3H).
In conclusion, we have developed a Lewis acid Yb(OTf)3-
catalyzed hydroamination reaction for the synthesis of a wide
range of amidines from ynamides with ArNH2 or TsNH2. The
broad functional group tolerance and usage of cheap catalyst has
made it a practical method to access these valuable compounds.
Further exploration of this methodology is ongoing in our lab.
13C NMR (100 MHz, CDCl3) δ 155.9, 146.5, 144.2, 135.8, 135.3, 134.4,
129.4, 128.9, 128.8, 128.7, 128.5, 128.4, 128.0 (2C), 127.3, 126.5, 120.8,
50.8, 37.4, 21.5.
HRMS m/z (ESI) calcd. for C28H25ClN2O2S (M + H)+ 489.1398, found
489.1398.
The experimental section has no title; please leave this line here.
Ethyl
(E)-4-((1-((N-benzyl-4-methylphenyl)sulfonamido)-2-
phenylethylidene)amino)benzoate (3ae).
General information
All 1H NMR (400 MHz) and 13C NMR (100 MHz) spectra were recorded in
CDCl3. TMS was used as an internal reference and J values are given in Hz.
HR-MS were obtained on a Bruker micrOTOF-Q II spectrometer. PE is
petroleum ether (60–90 oC). All ynamides (2a-h)8 are known compounds.
They were prepared according to the reported procedures. Unless
otherwise noted, materials obtained from commercial suppliers were
used without further purification.
135.7 mg (86%); white solid; mp 110–112 °C;
1H NMR (400MHz, CDCl3) δ 7.92–7.90 (m, 2H), 7.74–7.72 (m, 2H), 7.33–
7.31 (m, 2H), 7.22–7.14 (m, 4H), 7.12–7.08 (m, 2H), 7.06–7.04 (m, 2H),
6.78–6.76 (m, 2H), 6.43–6.41 (m, 2H), 4.70 (s, 2H), 4.31 (q, J = 7.1 Hz, 2H),
3.83 (s, 2H), 2.44 (s, 3H), 1.34 (t, J = 7.1 Hz, 3H).
13C NMR (100 MHz, CDCl3) δ 166.1, 155.2, 152.0, 144.3, 135.7, 135.2,
134.2, 130.6, 129.4, 128.8, 128.4, 128.3, 128.0 (2C), 127.3, 126.6, 125.5,
119.2, 60.6, 50.9, 37.6, 21.5, 14.2.
Preparation and characterizations of compounds 3aa-u, 5aa-f
A mixture of amines (1a-q, 2 equiv. 0.6 mmol), ynamides (2a-h, 0.3
mmol), Yb(OTf)3 (16 mg, 0.03 mmol, 10 mol%) in DCE (2 mL) was stirred
at 85 °C for 2 h (monitored by TLC). After it was cooled down to room
temperature, the reaction was quenched by the slow addition of a
saturated solution of Na2CO3. The mixture was poured into water (15 mL)
and was extracted with EtOAc (3 x 15 mL). The combined organic layers
were washed with brine (2 x 15 mL) and dried over MgSO4. The solvent
was removed by vacuum and the residue was purified by column
chromatography (10% EtOAc in PE) to give the corresponding products
3aa-u.
HRMS m/z (ESI) calcd. for C31H30N2O4S (M + H)+ 527.1999, found
527.1997.
(E)-N-benzyl-N'-(4-nitrophenyl)-2-phenyl-N-tosylacetimidamide
(3af).
58.4 mg (39%); Yellow solid; mp 146–148 °C;
1H NMR (400MHz, CDCl3) δ 8.07–8.05 (m, 2H), 7.73–7.71 (m, 2H), 7.36–
7.33 (m, 2H), 7.26–7.07 (m, 8H), 6.76–6.74 (m, 2H), 6.44–6.42 (m, 2H),
4.77 (s, 2H), 3.82 (s, 2H), 2.48 (s, 3H).
13C NMR (100 MHz, CDCl3) δ 155.4, 153.8, 144.6, 143.6, 135.8, 135.5,
133.9, 129.6, 128.6 (2C), 128.3 (2C), 128.2, 127.6, 126.9, 124.9, 119.9,
50.9, 37.8, 21.7.
The similar procedure was used for the preparation of products 5aa–f.
(E)-N-benzyl-N',2-diphenyl-N-tosylacetimidamide (3aa).8e
121.2 mg (89%); White solid; mp 94-96 °C;
HRMS m/z (ESI) calcd. for C28H25N3O4S (M + H)+ 500.1639, found
500.1637.
1H NMR (400MHz, CDCl3) δ 7.75–7.73 (m, 2H), 7.35–7.32 (m, 2H), 7.25–
7.20 (m, 3H), 7.18–7.07 (m, 5H), 7.03–6.98 (m, 3H), 6.79–6.77 (m, 2H),
6.43–6.41 (m, 2H), 4.65 (s, 2H), 3.87 (s, 2H), 2.46 (s, 3H).
(E)-N-benzyl-2-phenyl-N'-(o-tolyl)-N-tosylacetimidamide
123.6 mg (88%); white solid; mp 86-88 °C;
(3ag).
13C NMR (100 MHz, CDCl3) δ 155.6, 148.0, 144.1, 135.8, 135.3, 134.7,
129.5, 129.2, 129.0, 128.8, 128.4, 128.1, 128.0, 127.2, 126.4, 123.5, 119.4,
51.0, 37.7, 21.6.
1H NMR (400MHz, CDCl3) δ 7.78–7.76 (m, 2H), 7.30–7.28 (m, 2H), 7.20–
7.11 (m, 6H), 7.07–7.00 (m, 4H), 6.93–6.85 (m, 3H), 6.22 (m, 1H), 4.77 (s,
2H), 3.79 (s, 2H), 2.42 (s, 3H), 1.76 (s, 3H).
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13C NMR (100 MHz, CDCl3) δ 155.3, 146.7, 144.1, 136.2, 135.9, 134.6,
130.3, 129.5, 129.2, 128.3, 128.2, 128.1, 128.0, 127.6, 127.2, 126.5, 126.3,
123.6, 118.9, 50.9, 37.7, 21.5, 17.8.
125.8 mg (87%); off-white solid; mp 95-97 °C;
1H NMR (400MHz, CDCl3) δ 7.81–7.79 (m, 2H), 7.30–7.27 (m, 2H), 7.21–
7.12 (m, 6H), 7.07–7.05 (m, 2H), 7.00–6.96 (m, 2H), 6.91–6.89 (m, 2H),
6.87-6.80 (m, 1H), 4.93 (s, 2H), 3.70 (s, 2H), 2.43 (s, 3H), 1.63 (s, 6H).
HRMS m/z (ESI) calcd. for C29H28N2O2S (M + H)+ 469.1944, found
469.1945.
13C NMR (100 MHz, CDCl3) δ 155.4, 145.5, 144.1, 136.9, 136.8, 134.4,
129.5, 129.2, 128.4, 128.3, 128.2, 128.0, 127.4, 127.2, 126.9, 126.8, 123.2,
50.8, 37.7, 21.6, 18.1.
(E)-N-benzyl-N'-(2-fluorophenyl)-2-phenyl-N-tosylacetimidamide
(3ah).
124.6 mg (88%); Colorless oil;
HRMS m/z (ESI) calcd. for C30H30N2O2S (M + H)+ 483.2101, found
483.2102.
1H NMR (400MHz, CDCl3) δ 7.77-7.75 (m, 2H), 7.31-7.29 (m, 2H), 7.21-
7.11 (m, 4H), 7.09-6.94 (m, 7H), 6.78-6.76 (m, 2H), 6.46-6.36 (m, 1H), 4.67
(s, 2H), 3.91 (s, 2H), 2.41 (s, 3H).
(E)-N-benzyl-2-phenyl-N-tosyl-N'-(3,4,5-
trimethoxyphenyl)acetimidamide (3an).
13C NMR (100 MHz, CDCl3) δ 158.3, 151.8 (q, JC-F = 243 Hz), 144.1, 135.7,
135.6, 135.0, 134.3, 129.5, 129.1, 128.7, 128.3, 128.0, 127.9, 127.2, 126.4,
124.6 (q, JC-F = 7 Hz), 124.3 (q, JC-F = 3 Hz), 122.3, 115.8 (q, JC-F = 20 Hz),
51.0, 38.5, 21.5.
129.0 mg (79%); Yellow oil;
1H NMR (400MHz, CDCl3) δ 7.75–7.73 (m, 2H), 7.34–7.32 (m, 2H), 7.21–
7.09 (m, 6H), 7.07–7.06 (m, 2H), 6.82–6.80 (m, 2H), 5.53 (s, 2H), 4.71 (s,
2H), 3.89 (s, 2H), 3.76 (s, 3H), 3.66 (s, 6H), 2.44 (s, 3H).
HRMS m/z (ESI) calcd. for C28H25FN2O2S (M + H)+ 473.1694, found
473.1696.
13C NMR (100 MHz, CDCl3) δ 155.7, 153.3, 144.1, 144.0, 135.9, 135.4,
134.8, 133.8, 129.4, 128.9, 128.8, 128.2, 128.1, 127.9, 127.2, 126.4, 96.6,
60.8, 55.8, 51.0, 37.7, 21.5.
(E)-N-benzyl-N'-(2-iodophenyl)-2-phenyl-N-tosylacetimidamide
(3ai). 8c
HRMS m/z (ESI) calcd. for C31H32N2O5S (M + H)+ 545.2105, found
146.2 mg (84%); Yellow oil;
545.2103.
1H NMR (400MHz, CDCl3) δ 7.84–7.82 (m, 2H), 7.75–7.73 (m, 1H), 7.30–
7.28 (m, 2H), 7.23–7.12 (m, 9H), 6.89–6.88 (m, 2H), 6.71–6.67 (m, 1H),
6.25–6.23 (m, 1H), 4.83 (s, 2H), 3.80 (s, 2H), 2.43 (s, 3H).
(E)-N,N',2-triphenyl-N-tosylacetimidamide (3ao).
88.4 mg (67%); White solid; mp 88-90 °C;
1H NMR (400MHz, CDCl3) δ 7.78–7.76 (m, 2H), 7.37–7.33 (m, 1H), 7.28–
7.25 (m, 6H), 7.20–7.19 (m, 3H), 7.05–6.97 (m, 3H), 6.85–6.84 (m, 2H),
6.73–6.71 (m, 2H), 3.36 (s, 2H), 2.43 (s, 3H).
13C NMR (100 MHz, CDCl3) δ 156.6, 149.5, 144.1, 138.9, 136.4, 136.2,
134.6, 129.5, 128.9, 128.8, 128.4 (3C), 128.1, 127.3, 126.6, 124.8, 120.0,
90.1, 50.8, 38.1, 21.6.
13C NMR (100 MHz, CDCl3) δ 154.6, 147.9, 143.6, 136.7, 136.6, 134.8,
130.6, 129.8, 129.0, 128.9, 128.8, 128.6, 128.5, 128.4, 126.6, 123.5, 119.9,
35.8, 21.6.
(E)-N-benzyl-2-phenyl-N'-(m-tolyl)-N-tosylacetimidamide (3aj).
96.9 mg (69%); White solid; mp 91-93 °C;
1H NMR (400MHz, CDCl3) δ 7.74–7.73 (m, 2H), 7.32–7.30 (m, 2H), 7.19–
7.07 (m, 7H), 7.03–7.01 (m, 2H), 6.82–6.78 (m, 3H), 6.27–6.19 (m, 2H),
4.65 (s, 2H), 3.88 (s, 2H), 2.43 (s, 3H), 2.25 (s, 3H).
HRMS m/z (ESI) calcd. for C27H24N2O2S (M + H)+ 441.1631, found
441.1633.
(E)-N-methyl-N',2-diphenyl-N-tosylacetimidamide (3ap).8e
13C NMR (100 MHz, CDCl3) δ 155.4, 147.9, 144.0, 138.7, 135.8, 135.3,
134.7, 129.4, 129.1, 128.7 (2C), 128.2, 128.0, 127.9, 127.1, 126.3, 124.2,
120.0, 116.4, 50.9, 37.6, 21.5, 21.3.
87.3 mg (77%); White solid; mp 106-108 °C;
1H NMR (400MHz, CDCl3) δ 7.65–7.63 (m, 2H), 7.28–7.19 (m, 7H), 7.10–
6.99 (m, 3H), 6.63–6.61 (m, 2H), 4.03 (s, 2H), 3.10 (s, 3H), 2.40 (s, 3H).
HRMS m/z (ESI) calcd. for C29H28N2O2S (M + H)+ 469.1944, found
469.1946.
13C NMR (100 MHz, CDCl3) δ 157.3, 148.0, 143.9, 135.6, 134.9, 129.3,
129.0, 128.6 (2C), 127.8, 126.6, 123.5, 119.7, 37.0, 35.6, 21.5.
(E)-N-benzyl-N'-(3-nitrophenyl)-2-phenyl-N-tosylacetimidamide
(3ak).
(E)-N-allyl-N',2-diphenyl-N-tosylacetimidamide (3aq).
72.7 mg (60%); Yellow oil;
94.3 mg (63%); Yellow solid; mp 104-106 °C;
1H NMR (400MHz, CDCl3) δ 7.74–7.72 (m, 2H), 7.27–7.19 (m, 7H), 7.08–
7.00 (m, 3H), 6.61–6.59 (m, 2H), 5.55–5.46 (m, 1H), 5.15–5.03 (m, 2H),
4.19–4.18 (m, 2H), 3.90 (s, 2H), 2.41 (s, 3H).
1H NMR (400MHz, CDCl3) δ 7.84–7.81 (m, 1H), 7.75–7.73 (m, 2H), 7.37–
7.32 (m, 3H), 7.27–7.23 (m, 3H), 7.17–7.12 (m, 6H), 6.74–6.72 (m, 2H),
6.67–6.65 (m, 1H), 4.78 (s, 2H), 3.82 (s, 2H), 2.49 (s, 3H).
13C NMR (100 MHz, CDCl3) δ 155.4, 147.9, 143.8, 135.8, 134.8, 132.9,
129.1, 128.9 (2C), 128.4, 128.3, 126.7, 123.5, 119.6, 118.2, 49.7, 37.0, 21.5.
13C NMR (100 MHz, CDCl3) δ 156.7, 148.9, 148.6, 144.6, 135.9, 135.5,
134.0, 129.7, 129.6, 128.6 (2C), 128.3 (2C), 128.2, 127.6, 126.9, 125.8,
118.1, 114.7, 50.9, 37.5, 21.7.
HRMS m/z (ESI) calcd. for C24H24N2O2S (M + H)+ 405.1631, found
HRMS m/z (ESI) calcd. for C28H25N3O4S (M + H)+ 500.1639, found
405.1633.
500.1637.
(E)-N-benzyl-N-(methylsulfonyl)-N',2-diphenylacetimidamide
(3ar).8e
(E)-N-benzyl-N'-(3-hydroxyphenyl)-2-phenyl-N-tosylacetimidamide
(3al).
91.9 mg (81%); White solid; mp 88-90 °C;
1H NMR (400MHz, CDCl3) δ 7.33–7.21 (m, 10H), 7.07–6.99 (m, 3H), 6.74–
6.72 (m, 2H), 4.84 (s, 2H), 3.81 (s, 2H), 3.08 (s, 3H).
110.0 mg (78%); White solid; mp 100-102 °C;
1H NMR (400MHz, CDCl3) δ 7.72–7.70 (m, 2H), 7.30–7.28 (m, 2H), 7.18–
6.98 (m, 9H), 6.78–6.76 (m, 2H), 6.48–6.46 (m, 1H), 5.98–5.97 (m, 2H),
5.67 (brs, 1H), 4.63 (s, 2H), 3.84 (s, 2H), 2.40 (s, 3H).
13C NMR (100 MHz, CDCl3) δ 156.0, 147.9, 136.5, 134.5, 129.1, 128.7, 128.6
(2C), 127.9, 127.6, 126.9, 123.7, 119.7, 50.0, 41.7, 36.3.
13C NMR (100 MHz, CDCl3) δ 156.3, 155.6, 149.3, 144.3, 135.6, 135.0,
134.5, 130.0, 129.5, 129.0, 128.6, 128.3, 128.0 (2C), 127.2, 126.4, 111.8,
110.6, 106.6, 50.9, 37.6, 21.5.
(E)-N-benzyl-N-((4-nitrophenyl)sulfonyl)-N',2-
diphenylacetimidamide (3as).
66.9 mg (46%); Yellow solid; mp 124-126 °C.
HRMS m/z (ESI) calcd. for C28H26N2O3S (M + H)+ 471.1737, found
471.1737.
1H NMR (400MHz, CDCl3) δ 8.31–8.29 (m, 2H), 8.00–7.98 (m, 2H), 7.27–
7.16 (m, 8H), 7.06–7.02 (m, 3H), 6.89–6.87 (m, 2H), 6.52–6.50 (m, 2H),
4.76 (s, 2H), 3.78 (s, 2H).
(E)-N-benzyl-N'-(2,6-dimethylphenyl)-2-phenyl-N-
tosylacetimidamide (3am).
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13C NMR (100 MHz, CDCl3) δ 155.1, 150.1, 147.3, 144.7, 135.4, 134.0,
129.7, 129.2, 128.7, 128.6, 128.5, 128.0, 127.7, 126.9, 124.0, 123.7, 119.4,
50.8, 36.8.
1H NMR (400MHz, CDCl3) δ 7.84–7.82 (m, 2H), 7.36–7.28 (m, 8H), 7.24–
7.22 (m, 2H), 7.17–7.16 (m, 2H), 4.86 (s, 2H), 4.57 (s, 2H), 2.98 (s, 3H), 2.43
(s, 3H).
HRMS m/z (ESI) calcd. for C27H23N3O4S (M + H)+ 486.1482, found
486.1485.
13C NMR (100 MHz, CDCl3) δ 166.6, 143.5, 138.6, 135.5, 132.6, 129.4,
129.3, 129.1, 128.3, 128.0, 127.6, 126.7, 126.6, 49.6, 42.8, 38.6, 21.6.
(E)-N-benzyl-N'-phenyl-2-(p-tolyl)-N-tosylacetimidamide
(3at).
HRMS m/z (ESI) calcd. for C23H24N2O4S2 (M + H)+ 457.1250, found
103.9 mg (74%); White solid; mp 94–96 °C;
457.1251.
1H NMR (400MHz, CDCl3) δ 7.75–7.73 (m, 2H), 7.33–7.31 (m, 2H), 7.23–
7.18 (m, 3H), 7.16–7.12 (m, 2H), 7.06–6.97 (m, 3H), 6.91–6.89 (m, 2H),
6.69–6.67 (m, 2H), 6.44–6.42 (m, 2H), 4.67 (s, 2H), 3.81 (s, 2H), 2.45 (s,
3H), 2.30 (s, 3H).
N-benzyl-N-((4-nitrophenyl)sulfonyl)-2-phenyl-N'-
tosylacetimidamide (5ae).
50.7 mg (30%); Yellow solid; mp 118–120 °C;
1H NMR (400MHz, CDCl3) δ 7.94–7.91 (m, 2H), 7.74–7.72 (m, 2H), 7.48–
7.45 (m, 2H), 7.40–7.32 (m, 8H), 7.18–7.17 (m, 2H), 7.06–7.04 (m, 2H),
4.97 (s, 2H), 4.39 (s, 2H), 2.53 (s, 3H).
13C NMR (100 MHz, CDCl3) δ 155.7, 148.0, 144.0, 136.0, 135.9, 135.4,
131.5, 129.4, 129.0, 128.9 (2C), 128.6, 128.1, 128.0, 127.1, 123.4, 119.5,
50.9, 37.1, 21.6, 21.0.
13C NMR (100 MHz, CDCl3) δ 165.2, 150.1, 144.1, 144.0, 138.1, 135.1,
132.1, 129.6, 129.5, 129.3 (2C), 128.3, 127.9, 127.8, 127.1, 126.3, 123.4,
49.7, 39.0, 21.6.
HRMS m/z (ESI) calcd. for C29H28N2O2S (M + H)+ 469.1944, found
469.1945.
(E)-N-benzyl-2-(4-bromophenyl)-N'-phenyl-N-tosylacetimidamide
(3au).
HRMS m/z (ESI) calcd. for C28H25N3O6S2 (M + H)+ 564.1258, found
564.1259.
130.9 mg (82%); Yellow solid; mp 118–120 °C;
N-benzyl-2-(4-bromophenyl)-N,N'-ditosylacetimidamide (5af).
1H NMR (400MHz, CDCl3) δ 7.75–7.73 (m, 2H), 7.37-7.35 (m, 2H), 7.27–
7.20 (m, 3H), 7.17–7.13 (m, 4H), 7.05–6.99 (m, 3H), 6.62–6.60 (m, 2H),
6.43–6.42 (m, 2H), 4.59 (s, 2H), 3.86 (s, 2H), 2.46 (s, 3H).
148.2 mg (81%); Yellow solid; mp 104–106 °C;
1H NMR (400MHz, CDCl3) δ 7.68–7.66 (m, 2H), 7.35–7.25 (m, 9H), 7.10–
7.06 (m, 4H), 6.83–6.81 (m, 2H), 4.90 (s, 2H), 4.41 (s, 2H), 2.47 (s, 3H), 2.41
(s, 3H).
13C NMR (100 MHz, CDCl3) δ 155.6, 147.9, 144.3, 135.2, 134.9, 133.6,
131.3, 131.0, 129.7, 129.2, 129.1, 128.0, 127.8, 127.4, 123.8, 120.4, 119.2,
51.3, 37.6, 21.6.
13C NMR (100 MHz, CDCl3) δ 164.8, 145.1, 143.5, 138.4, 135.4, 135.0, 131.9
(2C), 129.8, 129.3, 129.2, 128.9, 128.4, 127.8, 127.0, 126.7, 121.3, 50.4,
38.5, 21.7, 21.6.
HRMS m/z (ESI) calcd. for C28H25BrN2O2S (M + H)+ 533.0893, found
533.0895.
HRMS m/z (ESI) calcd. for C29H27BrN2O4S2 (M + H)+ 611.0668, found
611.0669.
N-benzyl-2-phenyl-N,N'-ditosylacetimidamide (5aa).
116.5 mg (73%); White solid; mp 112–114 °C;
1H NMR (400MHz, CDCl3) δ 7.74–7.72 (m, 2H), 7.33–7.28 (m, 7H), 7.26–
7.25 (m, 3H), 7.15–7.13 (m, 2H), 7.04–7.02 (m, 2H), 6.98–6.93 (m, 2H),
4.93 (s, 2H), 4.39 (s, 2H), 2.47 (s, 3H), 2.40 (s, 3H).
N-benzyl-2-phenyl-N-tosylacetamide (6)16
72.0 mg (38%); White solid; mp 123−125 °C
1H NMR (400MHz, CDCl3) δ. 7.64 (d, J = 8.4 Hz, 2H), 7.36–7.29 (m, 5H),
7.27–7.22 (m, 5H), 6.99–6.97 (m, 2H), 5.07 (s, 2H), 3.86 (s, 2H), 2.42 (s,
3H).
13C NMR (100 MHz, CDCl3) δ 165.2, 144.9, 143.3, 138.6, 135.8, 135.1,
132.8, 129.2, 129.1, 129.0, 128.9, 128.7, 127.9, 127.8, 127.3, 127.0, 126.4,
49.9, 39.1, 21.7, 21.6.
13C NMR (100 MHz, CDCl3) δ. 171.2, 144.9, 136.5, 136.4, 133.1, 129.6,
129.2, 128.6, 128.5, 127.9, 127.7, 127.6, 127.1, 49.6, 42.8, 21.6.
HRMS m/z (ESI) calcd. for C29H28N2O4S2 (M + H)+ 533.1563, found
533.1565.
N-methyl-2-phenyl-N,N'-ditosylacetimidamide (5ab).
97.1 mg (71%); White solid; mp 86–88 °C;
1H NMR (400MHz, CDCl3) δ 7.76–7.74 (m, 2H), 7.34–7.29 (m, 4H), 7.28–
7.25 (m, 3H), 7.08–7.02 (m, 4H), 4.52 (s, 2H), 3.22 (s, 3H), 2.45 (s, 3H), 2.37
(s, 3H).
Funding Information
13C NMR (100 MHz, CDCl3) δ 165.4, 144.7, 143.2, 138.7, 134.9, 132.6,
129.1, 129.1, 128.9, 128.2, 128.1, 127.2, 126.8, 39.2, 34.1, 21.5 (2C).
This study was supported by National College Students Innovation and
Entrepreneurship Training Program (202010304044Z), the Jiangsu’s
Mass Entrepreneurship and Innovation Program, the Start-Up Funding for
Research of Nantong University (03081231), and the Large Instruments
Open Foundation of Nantong University (KFJN2175; KFJN2176)
HRMS m/z (ESI) calcd. for C23H24N2O4S2 (M + H)+ 457.1250, found
457.1252.
N-allyl-2-phenyl-N,N'-ditosylacetimidamide (5ac).
Acknowledgment
95.4 mg (66%); Yellow solid; mp 76–78 °C;
We would like to thank the Analysis Center of Nantong University for the
Large Instruments Open Foundation.
1H NMR (400MHz, CDCl3) δ 7.76–7.74 (m, 2H), 7.38–7.36 (m, 2H), 7.32–
7.30 (m, 2H), 7.27–7.24 (m, 3H), 7.03–7.01 (m, 4H), 5.83–5.72 (m, 1H),
5.27–5.17 (m, 2H), 4.46 (s, 2H), 4.37 (dt, J = 4.9, 1.7 Hz, 2H), 2.46 (s, 3H),
2.38 (s, 3H).
Supporting Information
13C NMR (100 MHz, CDCl3) δ 164.9, 144.7, 143.2, 138.6, 135.2, 132.8,
132.4, 129.1, 129.0, 128.9, 128.7, 127.8, 127.3, 126.9, 118.2, 48.6, 38.7,
21.6, 21.5.
YES (this text will be updated with links prior to publication)
Primary Data
HRMS m/z (ESI) calcd. for C25H26N2O4S2 (M + H)+ 483.1407, found
483.1408.
NO (this text will be deleted prior to publication)
N-benzyl-N-(methylsulfonyl)-2-phenyl-N'-tosylacetimidamide (5ad).
References
112.2 mg (82%); White solid; mp 96–98 °C;
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Template for SYNTHESIS © Thieme Stuttgart · New York
2021-04-21
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Supplementary Information for
Yb(OTf)3-Mediated regioselective hydroamination of
ynamides with anilines or p-toluenesulfonamide
Xiaobao Zeng,* Qingyun Gu, Wenjing Dai, Yushan Xie, Xinyi Liu, and
Guixia Wu
School of Pharmacy, Nantong University, 19 Qixiu Road, Nantong,
Jiangsu Province 226001, People's Republic of China

4. 1H NMR and 13C NMR spectra of compounds 3aa-u, 5aa-f
1H NMR spectrum of 3aa
13C NMR spectrum of 3aa

1H NMR spectrum of 3ab
13C NMR spectrum of 3ab

1H NMR spectrum of 3ac
13C NMR spectrum of 3ac

1H NMR spectrum of 3ad
13C NMR spectrum of 3ad

1H NMR spectrum of 3ae
13C NMR spectrum of 3ae

1H NMR spectrum of 3af
13C NMR spectrum of 3af

1H NMR spectrum of 3ag
13C NMR spectrum of 3ag

1H NMR spectrum of 3ah
13C NMR spectrum of 3ah

1H NMR spectrum of 3ai
13C NMR spectrum of 3ai

1H NMR spectrum of 3aj
13C NMR spectrum of 3aj

1H NMR spectrum of 3ak
13C NMR spectrum of 3ak

1H NMR spectrum of 3al
13C NMR spectrum of 3al

1H NMR spectrum of 3am
13C NMR spectrum of 3am

1H NMR spectrum of 3an
13C NMR spectrum of 3an

1H NMR spectrum of 3ao
13C NMR spectrum of 3ao

1H NMR spectrum of 3ap
13C NMR spectrum of 3ap

1H NMR spectrum of 3aq
13C NMR spectrum of 3aq

1H NMR spectrum of 3ar
13C NMR spectrum of 3ar

1H NMR spectrum of 3as
13C NMR spectrum of 3as

1H NMR spectrum of 3at
13C NMR spectrum of 3at

1H NMR spectrum of 3au
13C NMR spectrum of 3au