Visible-Light-Promoted C-H Arylation by Merging Palladium Catalysis with Organic Photoredox Catalysis

Article abstract of DOI:10.1021/acs.joc.7b00140

The use of a dual palladium/organic photoredox catalytic system enables the directed arylation of arenes with aryldiazonium salts with a broad substrate scope at room temperature under mild reaction conditions. This study thus serves as not only an alternative route for the biaryl motifs but also a new example for the application of an organic photoredox catalyst.

Full text of DOI:10.1021/acs.joc.7b00140

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Article
Visible-light-promoted C–H arylation by mergering
palladium catalysis with organic photoredox catalysis
Jian Jiang, Wen-Man Zhang, Jian-Jun Dai, Jun Xu, and Hua-Jian Xu
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 17 Mar 2017
Downloaded from http://pubs.acs.org on March 17, 2017
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Visible-light-promoted C
–H arylation by mergering palladium catalysis with
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organic photoredox catalysis
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Jian Jiang, WenꢀMan Zhang, JianꢀJun Dai, Jun Xu, and HuaꢀJian Xu*
School of Biological and Medical Engineering, Hefei University of Technology, Hefei 230009, China
E-mail: hjxu@hfut.edu.cn
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RECEIVED DATE (will be automatically inserted after manuscript is accepted).
ABSTRACT: The use of a dual palladium/organic photoredox catalytic system enables the directed
arylation of arenes with aryldiazonium salts with broad substrate scope at room temperature under mild
reaction conditions. This study thus serves as not only an alternative route for the biaryl motifs but
also a new example for the application of organic photoredox catalyst.
INTRODUCTION
In recent years, visibleꢀlightꢀpromoted singleꢀelectron transfer (SET) by
photocatalysts has been recognized as a key step in organic synthesis.1 In this context,
photocatalyzed C–H arylation reaction using aryl diazonium salts has received much
attention and has made great progress.2 For instance, Sanford and coꢀworkers in 2011
described the ligandꢀdirected C–H arylation reactions by mergering palladium catalysis
with the Ruꢀbased visible light photoredox catalysis (Fig. 1a).2a Thereafter, König et al.
developed direct C–H arylations of heteroarenes using eosin Y as a photoredox catalyst
(Fig. 1b).2b More recently, Xiao and Rueping have reported C–H arylations of
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N
ꢀheteroarenes using [Ru(bpy)3]Cl2·6H2O and TiO2 as the photoredox catalysts,
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respectively (Fig. 1c).2c,d On the other hand, Fukuzumi et al. have demonstrated that 9,
10ꢀdihydro acridine (AcrH2) derivatives could act as efficient photocatalyst in
dehalogenation reactions.3
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Fig. 1 Deboronative cyanation by photoredox catalysis.
Inspired by these elegant works and recently reported dual transition metal (including
Pd,4 Au,5 Ni6)/photoredox catalysis, we envisioned that the AcrH2 could serve as a
photoredox catalyst for further elaboration with palladium catalyst thus enabling the C–H
arylation at mild conditions (Fig. 1d). This study not only provides an alternative route for
the formation of the biaryl motifs but also further highlights the use of AcrH2 for synthetic
applications under photoredox conditions.
RESULTS AND DISSCUSION
We started our investigations with acetanilide 1a as the model substrate. Extensive
studies were made to optimize the reaction conditions (Table 1). It was found that the C–H
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arylation product 3a was obtained in 86% (79% isolated) yield with 15 mol % of
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Pd(OAc)2, 10 mol % of 9, 10ꢀdihydroꢀ10ꢀethylacridine (AcrH2ꢀA), 3 equiv of
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phenyldiazonium tetrafluoroborate salt 2a in MeOH at room temperature (rt) under
visibleꢀlight irradiation from blue LEDs (λmax = 425 ± 15 nm) for 12 h (Table 1, entry 1).
Although the yields of 3a were inferior, the reactions could also be caused by other AcrH2
derivatives (Table 1, entries 2–6). We also tested some solvents including DCE, DCM,
DMF and CH3CN, but they were not effective (Table 1, entries 7–10). By employing
different light sources, blue LED was found to promote the reaction most efficiently (Table
1, entries 11–13). As expected, the control experiments clearly showed that Pd(OAc)2,
AcrH2 catalyst and light are essential for this reaction, as no or trace amount of the
arylation product was observed in the absence of the palladium catalyst, AcrH2 or blue
light irradiation (entry14–16). Use of 5 mol %, rather than 15 mol %, Pd(OAc)2 resulted in
a lower yield of the C–H arylation product (entry 17). Reducing the reaction time to 6 h
only led to a 45% yield of 3a (entry 17). As shown in entries 19 and 20, when 2 equiv and
1 equiv of 2a were used instead of 3 equiv of 2a, the yield of 3a decreased to 76% and
47%, respectively.
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Table 1. Optimization of the reaction conditionsa
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Entry
1
Variation from the standard conditions
none
Yield (%)b
86 (79)
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2
AcrH2ꢀB instead of A
AcrH2ꢀC instead of A
AcrH2ꢀD instead of A
AcrH2ꢀE instead of A
AcrH2ꢀF instead of A
DCE instead of MeOH
DCM instead of MeOH
DMF instead of MeOH
CH3CN instead of MeOH
36 W Green LED
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trace
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23 W White LED
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UV
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no blue light
trace
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no Pd(OAc)2
no AcrH2ꢀA
<10
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with 5 mol % Pd(OAc)2
6 h instead of 12 h
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with 2 equiv of 2a
with 1 equiv of 2a
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aStandard reaction conditions: 1a (0.2 mmol, 1 equiv), 2a (0.6 mmol, 3 equiv), Pd(OAc)2 (0.03 mmol, 15 mol %), AcrH2ꢀA (0.02
mmol, 10 mol %), MeOH (1.5 mL), under a N2 atmosphere, 12 h at room temperature with 36 W blue LEDs irradiation, unless
otherwise stated. bGC yields with benzophenone as an internal standard added after the reaction, isolated yield in parentheses.
After establishing the optimized conditions, we investigated the scope of the arylation
reaction with respect to the aryl diazonium salts substrates (Table 2a). A range of functional
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groups attached to the aromatic ring of the aryl diazonium substrate including methyl (3j, 3l),
tertꢀbutyl (3k), fluoro (3b), chloro (3c), bromo (3d), iodo (3e), esters (3g), ethers (3i) and
ketones (3h) were well tolerated. Notably, the use of easily decomposed substrate
4ꢀtrifluoromethylphenyldiazonium tetrafluoroborate can achieve a 77% yield of the arylated
product (3f). Next, we tested a series of substituted acetanilides (Table 2b).7 It was found that
a variety of acetanilides could be successfully transformed to the desired product in modest to
good yields (50–90%). orthoꢀ and metaꢀMethyl substituted acetanilides reacted with good
yields (3s, 3t). Notably, electronꢀwithdrawing group –CO2Et could well tolerated under the
reaction conditions and the corresponding product (3r) was provided in 50% yield. Also of
note, substrate containing the –CHO group was converted to the desired product 3q in useful
yield under the neutral reaction conditions. Again, aryl halide groups such as fluoro (3m),
iodo (3n) were also well compatible with the reaction. This feature could be useful for
providing great potential for orthogonal functionalization using crossꢀcoupling techniques.8
lastly, other groups such as benzoyl (3u–v), 2,4,6ꢀtrimethylbenzoyl (3w) and 2ꢀpyrrolidinone
(3x) can all be smoothly arylated in moderate to good yields (74ꢀ81%).
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a
Table 2. Substrate scope
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aThe reactions were conducted for 12 h on a 0.2 mmol scale. For details, please see the Supporting Information.
Encouraged by the results of the experiments with acetanilides, we turned our attention to the
arylation of aromatic C–H bonds with weak weaklyꢀcoordinating directing groups (Table 3).9
Under optimal conditions, the reaction of benzamides derivatives (4a–k) with either
electronꢀwithdrawing (5b–c) or –donating (5d–g) groups provided the desired product in 37–78%
yields. Additionally, the naphthyl (5j) could also be well compatible.
Table 3. Substrate scope of benzamidesa
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O
A
10 mol % AcrH2-
O
N2BF4
Me
15 mol % Pd(OAc)2
N
Me
Ar
H
+
N
Ar
H
36 W blue LED
1.5 mL MeOH, r.t., 12 h
H
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4a-k
2a
5a-k
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O
O
O
O
Me
Me
Me
Me
N
N
N
N
H
H
H
H
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Cl
Br
Me
5a
, 72%
5b
, 37%
5c
, 43%
5d
, 78%
O
O
Me
O
O
Me
Me
Me Me
Me
N
H
N
H
N
N
H
H
MeO
tBu
5e
, 58%
5f
,71%
5g
, 77%
5h
, 58%
O
O
O
tBu
Me
Me
N
N
N
H
H
H
5i
, 63%
5j
5k
, 81%
, 51%
aThe reactions were conducted for 12 h on a 0.2 mmol scale. For details, please see the Supporting Information
Preliminary mechanistic studies were next conducted to gain more insight into the
mechanism (Fig. 2). Firstly, the intramolecular kinetic isotope effect (KIE) experiments (kH/kD =
1.3) show that the C–H bond cleavage might not be the rate determining step (Fig. 2a).10
Reactions in the presence of 1,1ꢀdiphenylethene 6 as a radical inhibitor showed no formation of
arylated product 3a and phenyl radical trapping product 7 could be observed instead in a 85%
isolated yield (Fig. 2b). These results indicated that the reaction should proceed with the
intermediate of an aryl radical. In addition, we also examined the reactivity of palladacycle
complex 8 under the photocatalytic conditions (Fig. 2c). Indeed, the desired product could be
isolated in a 75% yield. Importantly, only a 9% yield of 3a was obtained in the absence of AcrH2,
highlighting the role of AcrH2 as the photocatalyst. Furthermore, quantum yield Φ of the reaction
was measured to be 6.5 (please see the Supporting Information). This indicates the mechanism for
the current reaction involves a radical chain process.11
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Fig. 2 Preliminary mechanism research.
Based on the above experiments and previous reports,2a,b we propose the possible
mechanism depicted in Fig. 3. Upon irradiation with blue light, the reaction of
aryldiazonium tetrafluoroborate salts
2
with photoexcited AcrH2* initially generates
to afford the Pd(III)
. Then, B is further oxidized by AcrH2 via SET process, producing Pd(IV)
AcrH2 and an aryl radical that reacts with palladacycle
A
intermediate
intermediate
B
C
and regenerating the photocatalyst AcrH2. Finally, the reductive elimination
and regenerate the Pd(II) catalyst.
of intermediate C furnishes the arylated product
D
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Fig. 3 Proposed reaction mechanism.
CONCLUSIONS
In summary, we have developed a novel palladium/AcrH2 dual catalytic system for the C(sp2)
C–H arylation under mild reaction conditions. In this study, various synthetically relevant
functional groups, including halides, esters, amides, ethers, ketones, and aldehydes can be well
compatible. Preliminary mechanistic studies support the proposed reaction pathway. Further
investigation of the AcrH2 catalyst in combination with transitionꢀmetal catalyst to achieve new
transformations is ongoing in our laboratory.
EXPERIMENT SECTION
General Information
All reagents were used as received from commercial sources unless specified otherwise, or
prepared as described in the literature. CH3CN, CH2Cl2, DMF and MeOH were purchased from
SigmaꢀAldrich and used without any purification. Acetone and ether was purchased from
Sinopharm Chemical Reagent. Pd(OAc)2 was purchased from Adamas. H NMR, 13C NMR, 19F
1
NMR spectra were recorded on a Bruker Advance 600 spectrometer at the ambient temperature in
CDCl3, d6ꢀDMSO. Data for 1H NMR are reported as follows: chemical shift (δ ppm), multiplicity,
integration, and coupling constant (Hz). Data for 13C NMR are reported in terms of chemical shift
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(δ ppm). Data for 19F NMR are reported in terms of chemical shift (δ ppm). Gas
ChromatographyꢀMass Spectrometer (GCꢀMS) analyses were performed on a Thermo Trace 1300
ISQ Series GCꢀMS System. GCꢀMS method: initial temp.: 50 °C (hold for 1 min), rate: 20 °C/min,
final temp.: 250 °C (hold for 10 min). High resolution mass spectra were obtained on an
HRMSꢀTOF spectrometer. After elution, the plate was visualized under UV illumination at 254
nm for UV active materials Column chromatography was performed using 50ꢀ500 mesh silica gel.
Organic solutions were concentrated under reduced pressure on a BUCHI rotary evaporator. Flash
column chromatographic purification of products was accomplished using forcedꢀflow
chromatography on silica gel (200ꢀ300 mesh).
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General procedure A (GPA): synthesis of 10-ethyl-9,10-dihydroacridine
To a 250 mL roundꢀbottomed flask was charged with acridineꢀ9(10H)ꢀone (7.333 g, 25.0 mmol)
in THF (100 mL), BH3·THF solution (1.0 M in THF; 50 mL, 50.0 mmol) added drop wise and the
mixture was refluxed for 4 h under Ar atmosphere. On completion (checked by TLC) the mixture
was cooled to 0ꢀ5 °C and brine (100 mL) was cautiously added followed by 2 N NaOH aq. (25
mL). The organic layer was separated, and the aqueous layer was extracted with Et2O (50 mL).
The collected organic layers were washed with conc. aq. NaHCO3 (50 mL), dried over MgSO4 and
evaporated. The reaction mixture was concentrated and purified by flash column chromatography
to afford 9, 10ꢀdihydroacridine as a light yellowish powder. A Schlenkꢀtube equipped with a
magnetic stirrer was evacuated and refilled with argon, then charged with a solution of acridane
(1.812 g, 10 mmol) in THF (40 mL). A solution of nꢀBuLi (2.5 M in hexanes; 4.4 mL, 11 mmol)
was added dropꢀwise at 0ꢀ5 °C and the mixture stirred for 1 h, followed by the addition of
ethylbromide (0.74 mL, 10 mmol) in THF (10 mL). The mixture was then stirred at 0ꢀ5 °C for
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additional 2 h and then at room temperature overnight. The reaction was quenched by pouring on
H2O (100 mL), and the product was extracted with EtOAc (3 × 100 mL). The organic layers were
washed with brine (60 mL), dried over MgSO4, The reaction mixture was concentrated and
purified by flash column chromatography to afford Nꢀethylacridane as a white solid.12
General procedure B (GP B): synthesis of compounds 2
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To a 100 mL flask containing HCl (6 mL) and H2O (6 mL) was added aniline (0.025 mol). Aniline
hydrochloride crystals were formed at 0ꢀ5 °C using ice bath, and then sodium nitrite (1.8 g) in
H2O (4 mL) was added droꢀpwise in 5 min interval of time, followed by addition of sodium
tetrafluoroborate (4 g) in H2O (8 mL). The reaction mixture was allowed to stir for another 10 min
at temperature below 5 °C. The arenediazonium salt solid was filtered out and then washed with of
5% sodium tetrafluoroborate (3 × 10 mL), followed by methanol (2 × 15 mL). The crude product
was purified by recrystallization with acetone and cold diethyl ether, and dried under vacuum.13
General procedure C (GP C): synthesis of compounds 1b-i
Some substrates were directly purchased from commercial sources and the others were prepared
by methods below.
The acetanilide substrates were prepared by acylation of the corresponding aniline, which were
directly purchased from commercial sources. Aniline (10.0 mmol) was dissolved in 20 mL DCM,
then NEt3 (30.0 mmol) was added directly. The solution was cooled to 0 °C and stirred for 5 min
under the protection of nitrogen. Then acetyl chloride (15.0 mmol) was added to the solution in
dropꢀwise for about 15 min at 0 °C. Then the solution was stirred at room temperature. The
reaction was monitored by TLC to achieve full conversion, then was quenched by saturated NaCl
(aq), extracted by EtOAc for three times, dried over Na2SO4, and evaporated in vacuum to afford
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the crude product, which was further purified by flash chromatography on silica gel with
petroleum ethyl acetate/petroleum ether to give high yield of corresponding acetanilide 1b-i.14
General procedure D (GP D): synthesis of compounds 4b-j
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Some substrates were directly purchased from commercial sources and the others were prepared
by methods below.
Preparation of amides from acid chloride: RNH2 methanol solution (33.3%) (1.5 equiv.), acid
chloride (1.0 equiv.), Et3N (2.0 equiv.) and Et2O (0.5 M) were added into a round bottom flask
capped with a septum. The mixture was stirred at room temperature. After 1 h, the crude reaction
mixture was extracted with Et2O, purified by flash chromatography to yield a white solid 4b-j.15
General procedure E (GP E): synthesis of compounds [D5]-1a
The Nꢀ(phenylꢀd5) acetamide was prepared by acylation of the benzenꢀd5ꢀamine, which were
directly purchased from commercial sources. At room temperature, benzenꢀd5ꢀamine (10.0 mmol)
was dissolved in 20 mL DCM, then NEt3 (30.0 mmol) was added directly. The solution was
cooled to 0 °C and stirred for 5 min under the protection of nitrogen. Then acetyl chloride (15.0
mmol) was added to the solution in dropꢀwise for about 15 min at 0 °C. Then the solution was
stirred at room temperature. The reaction was monitored by TLC to achieve full conversion, then
was quenched by saturated NaCl (aq), extracted by EtOAc for three times, dried over Na2SO4, and
evaporated in vacuum to afford the crude product, which was further purified by flash
chromatography on silica gel with petroleum ethyl acetate/petroleum ether to give high yield of
Nꢀ(phenylꢀd5)acetamide.14
General procedure F (GP F): synthesis of compounds 8
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To a dried three neck round bottom flask were added acetanilide 1a (540.6 mg, 4.0 mmol) and
palladium (II) acetate (449.0 mg, 2.0 mmol). The flask was sealed and degassed with nitrogen for
three times and toluene (7.0 mL) was added via syringe directly. The reaction mixture was put into
an oil bath of 120 °C and refluxed with stirring for 1 h under N2 atmosphere. Then the precipitate
from the reaction mixture was filtered immediately when the solution was still hot and washed
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with
toluene
for
several
times
to
give
greenish
yellow
solid
[diꢀµꢀacetatoꢀbis(2ꢀacetaminophenylꢀ2C,O) dipalladium(II)] 8 after removing the solvent under
vacuum.14
General procedure G (GP G): synthesis of compounds 3a-x
In glove box, acetanilide 1a (27.0 mg, 0.2 mmol), aryl diazonium tetrafluoroborate 2 (115.2 mg,
0.6 mmol), palladium (II) acetate (6.9 mg, 0.03 mmol) and AcrH2-A (4.2 mg, 0.02 mmol) were
added into a strictly dried Schlenk tube. Then MeOH was added. The reaction mixture was stirred
for 12 h at room temperature with irradiation of 36 W blue LED. Upon completion, the reaction
mixture was purified by column chromatography (silica gel, ethyl acetate/petroleum ether) yielded
the desired product.
General procedure H (GP H): synthesis of compounds 5a-k
In glove box, Nꢀphenylacetamide 4a (27.0 mg, 0.2 mmol), aryl diazonium tetrafluoroborate 2
(115.2 mg, 0.6 mmol), palladium (II) acetate (6.9 mg, 0.03 mmol) and AcrH2-A (4.2 mg, 0.02
mmol) were added into a strictly dried Schlenk tube. Then MeOH was added. The reaction
mixture was stirred for 12 h at room temperature with irradiation of 36 W blue LED.. Upon
completion, the reaction mixture was purified by column chromatography (silica gel, ethyl
acetate/petroleum ether) yielded the desired product.
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10-ethyl-9,10-dihydroacridine (AcrH2ꢀA): Prepared according to GP A, AcrH2-A was afford as
a white solid. Physical data were in accordance with literature data.11 1H NMR (600 MHz, CDCl3)
δ 7.25 – 7.19 (m, 2H), 7.16 (d, J = 6.3 Hz, 2H), 6.96 (d, J = 8.2 Hz, 2H), 6.92 (dd, J = 11.2, 7.2 Hz,
2H), 4.03 – 3.98 (m, 4H), 1.43 (t, J = 7.0 Hz, 3H). 13C NMR (151 MHz, CDCl3) δ 141.7, 128.0,
126.8, 123.2, 120.1, 112.0, 40.0, 32.7, 11.5.
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N-(4-fluorophenyl)acetamide (1b): Prepared according to GP C from 4ꢀfluoroaniline and acetyl
chloride, 1b was obtained as a white solid. 1H NMR (600 MHz, CDCl3) δ 7.49 – 7.44 (m, 2H),
7.43 (s, 1H), 6.99 (t, J = 8.5 Hz, 2H), 2.15 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 168.4, 160.2,
158.5, 133.8, 121.8 (d, J = 7.9 Hz), 115.6, 115.5, 24.3.
N-(4-iodophenyl)acetamide (1c): Prepared according to GP C from 4ꢀiodoaniline and acetyl
chloride, 1c was obtained as a white solid. 1H NMR (600 MHz, CDCl3) δ 7.61 (d, J = 8.3 Hz, 2H),
7.28 (d, J = 8.3 Hz, 2H), 7.23 (s, 1H), 2.17 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 168.2, 137.9,
137.6, 121.6, 87.4, 24.6.
N-(4-methoxyphenyl)acetamide (1d): Prepared according to GP C from 4ꢀmethoxyaniline and
acetyl chloride, 1d was obtained as a white solid. 1H NMR (600 MHz, CDCl3) δ 7.60 (s, 1H), 7.38
(d, J = 8.9 Hz, 2H), 6.83 (d, J = 8.5 Hz, 2H), 3.77 (s, 3H), 2.13 (s, 3H). 13C NMR (151 MHz,
CDCl3) δ 168.4, 156.3, 130.9, 121.9, 113.9, 55.4, 24.2.
Ethyl 4-acetamidobenzoate (1e): Prepared according to GP C from ethyl 4ꢀaminobenzoate and
acetyl chloride, 1e was obtained as a white solid. 1H NMR (600 MHz, CDCl3) δ 8.00 (d, J = 8.5
Hz, 2H), 7.59 (d, J = 8.3 Hz, 3H), 4.35 (q, J = 7.1 Hz, 2H), 2.20 (s, 3H), 1.38 (t, J = 7.1 Hz, 3H).
13C NMR (151 MHz, CDCl3) δ 168.4, 166.1, 141.9, 130.7, 125.9, 118.7, 60.8, 24.7, 14.3.
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N-(m-tolyl)pivalamide (1f): Prepared according to GP C from mꢀtoluidine and pivaloyl chloride,
1f was obtained as a white solid. 1H NMR (600 MHz, CDCl3) δ 7.43 (s, 1H), 7.28 (d, J = 7.4 Hz,
2H), 7.20 (t, J = 7.8 Hz, 1H), 6.92 (d, J = 7.5 Hz, 1H), 2.34 (s, 3H), 1.31 (s, 9H). 13C NMR (151
MHz, CDCl3) δ 176.5, 138.8, 137.9, 128.7, 124.9, 120.5, 116.9, 39.5, 27.6, 21.4.
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N-phenylbenzamide (1g): Prepared according to GP C from aniline and benzoyl chloride, 1g was
obtained as a white solid. 1H NMR (600 MHz, CDCl3) δ 7.87 (d, J = 7.5 Hz, 3H), 7.65 (d, J = 7.9
Hz, 2H), 7.55 (t, J = 7.3 Hz, 1H), 7.48 (t, J = 7.6 Hz, 2H), 7.37 (t, J = 7.8 Hz, 2H), 7.16 (t, J = 7.4
Hz, 1H). 13C NMR (151 MHz, CDCl3) δ 165.7, 137.9, 135.0, 131.8, 129.1, 128.7, 126.9, 124.5,
120.1.
N-(p-tolyl)benzamide (1h): Prepared according to GP C from pꢀtoluidine and benzoyl chloride,
1h was obtained as a white solid. 1H NMR (600 MHz, CDCl3) δ 7.87 (dd, J = 15.5, 8.6 Hz, 3H),
7.53 (t, J = 7.6 Hz, 3H), 7.46 (dd, J = 10.9, 4.3 Hz, 2H), 7.16 (d, J = 8.1 Hz, 2H), 2.34 (s, 3H). 13C
NMR (151 MHz, CDCl3) δ 165.6, 135.3, 135.1, 134.2, 131.6, 129.5, 128.7, 126.9, 120.3, 20.8.
2,4,6-trimethyl-N-phenylbenzamide (1i): Prepared according to GP C from aniline and
2,4,6ꢀtrimethylbenzoyl chloride, 1i was obtained as a white solid. 1H NMR (600 MHz, CDCl3) δ
7.61 (d, J = 7.9 Hz, 2H), 7.40 (s, 1H), 7.37 (t, J = 7.6 Hz, 2H), 7.16 (t, J = 7.4 Hz, 1H), 6.88 (s,
2H), 2.35 (s, 6H), 2.31 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 168.7, 138.8, 137.8, 134.9, 134.2,
129.1, 128.3, 124.5, 119.7, 21.1, 19.1.
N-(phenyl-d5)acetamide ([D5]-1a): Prepared according to GP E from benzenꢀd5ꢀamine and
1
acetyl chloride, [D5]-1a was obtained as a yellow solid. H NMR (600 MHz, CDCl3) δ 7.67 (s,
1H), 2.16 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 168.5, 137.7, 128.4 (t, J = 24.9 Hz), 123.7 (t, J
= 24.9 Hz), 119.5 (t, J = 24.4 Hz), 24.5.
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4-chloro-N-methylbenzamide (4b): Prepared according to GP D from 4ꢀchlorobenzoyl chloride
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6
7
1
and methanamine methanol solution (33.3%), 4b was obtained as a white solid. H NMR (600
8
9
MHz, CDCl3) δ 7.70 (d, J = 8.5 Hz, 2H), 7.40 (d, J = 8.5 Hz, 2H), 6.15 (s, 1H), 3.01 (d, J = 4.8 Hz,
3H). 13C NMR (151 MHz, CDCl3) δ 167.1, 137.6, 128.8, 128.3, 107.4 , 26.8.
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4-bromo-N-methylbenzamide (4c): Prepared according to GP D from 4ꢀbromobenzoyl chloride
1
and methanamine methanol solution (33.3%), 4c was obtained as a white solid. H NMR (600
MHz, CDCl3) δ 7.62 (d, J = 8.5 Hz, 2H), 7.55 (d, J = 8.5 Hz, 2H), 6.26 (s, 1H), 2.99 (d, J = 4.8 Hz,
3H). 13C NMR (151 MHz, CDCl3) δ 167.2, 133.5, 131.7, 128.4, 125.9, 26.8.
N,4-dimethylbenzamide (4d): Prepared according to GP D from 4ꢀmethylbenzoyl chloride and
1
methanamine methanol solution (33.3%), 4d was obtained as a white solid. H NMR (600 MHz,
CDCl3) δ 7.65 (d, J = 8.0 Hz, 2H), 7.21 (d, J = 6.7 Hz, 2H), 6.20 (s, 1H), 2.99 (dd, J = 5.7, 3.3 Hz,
3H), 2.38 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 168.1, 141.6, 131.8, 129.1, 126.8, 26.7, 21.3.
4-methoxy-N-methylbenzamide (4e): Prepared according to GP D from 4ꢀmethoxybenzoyl
chloride and methanamine methanol solution (33.3%), 4e was obtained as a white solid. 1H NMR
(600 MHz, CDCl3) δ 7.72 (d, J = 8.7 Hz, 2H), 6.90 (dd, J = 8.8, 2.2 Hz, 2H), 6.14 (s, 1H), 3.83 (d,
J = 1.5 Hz, 3H), 2.98 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 167.7, 162.1, 128.6, 126.9, 113.7,
55.4, 26.7.
4-(tert-butyl)-N-methylbenzamide (4f): Prepared according to GP D from 4ꢀ(tertꢀbutyl)benzoyl
chloride and methanamine methanol solution (33.3%), 4f was obtained as a white solid. 1H NMR
(600 MHz, CDCl3) δ 7.69 (d, J = 8.3 Hz, 2H), 7.43 (d, J = 8.3 Hz, 2H), 6.18 (s, 1H), 3.00 (s, 3H),
1.33 (s, 9H).13C NMR (151 MHz, CDCl3) δ 168.1, 154.8, 131.8, 126.6, 125.4, 34.9, 31.1, 26.7.
N,2-dimethylbenzamide (4g): Prepared according to GP D from 2ꢀmethylbenzoyl chloride and
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methanamine methanol solution (33.3%), 4g was obtained as a white solid. 1H NMR (600 MHz,
CDCl3) δ 7.29 (dd, J = 12.7, 7.3 Hz, 2H), 7.21 – 7.12 (m, 2H), 5.92 (s, 1H), 2.96 – 2.92 (m, 3H),
2.40 (d, J = 5.1 Hz, 3H). 13C NMR (151 MHz, CDCl3) δ 170.8, 136.5, 135.9, 130.9, 129.7, 126.6,
125.6, 26.5, 19.7.
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N-(tert-butyl)benzamide (4h): Prepared according to GP D from benzoyl chloride and
2ꢀmethylpropanꢀ2ꢀamine, 4h was obtained as a white solid. 1H NMR (600 MHz, CDCl3) δ 7.71 (d,
J = 8.3 Hz, 2H), 7.46 (t, J = 7.3 Hz, 1H), 7.41 (t, J = 7.7 Hz, 2H), 5.88 (d, J = 44.4 Hz, 1H), 1.48
(s, 9H). 13C NMR (151 MHz, CDCl3) δ 166.9, 131.0, 128.4, 126.6, 107.3, 51.6, 28.9.
N-methyl-2-naphthamide (4i): Prepared according to GP D from 2ꢀnaphthoyl chloride and
1
methanamine methanol solution (33.3%), 4i was obtained as a white solid. H NMR (600 MHz,
CDCl3) δ 8.28 (s, 1H), 7.91 – 7.80 (m, 4H), 7.54 (dt, J = 19.8, 7.1 Hz, 2H), 6.40 (s, 1H), 3.07 (d, J
= 4.7 Hz, 3H). 13C NMR (151 MHz, CDCl3) δ 168.3, 134.7, 132.7, 131.9, 128.9, 128.4, 127.7,
127.5, 127.2, 126.7, 123.5, 26.9.
N-methyl-[1,1'-biphenyl]-4-carboxamide (4j): Prepared according to GP
D
from
[1,1'ꢀbiphenyl]ꢀ4ꢀcarbonyl chloride and methanamine methanol solution (33.3%), 4j was obtained
as a white solid. 1H NMR (600 MHz, CDCl3) δ 7.84 (d, J = 8.3 Hz, 2H), 7.64 (d, J = 8.1 Hz, 2H),
7.60 (d, J = 7.3 Hz, 2H), 7.45 (t, J = 7.6 Hz, 2H), 7.38 (t, J = 7.4 Hz, 1H), 6.29 (s, 1H), 3.04 (d, J
= 4.6 Hz, 3H). 13C NMR (151 MHz, CDCl3) δ 167.9, 144.2, 140.0, 133.3, 128.8, 127.9, 127.3,
127.2, 127.2, 26.8.
N-([1,1'-biphenyl]-2-yl)acetamide (3a): Prepared according to GP G from acetanilide (27 mg,
0.2 mmol) and PhN2BF4 (115.2 mg, 0.6 mmol). The resulting mixture was purified by flash
chromatography (PE : EA = 5 : 1) to give the desired product as a white solid (32.1 mg, 76%
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yield). Physical data were in accordance with literature data.16 Mp 120
–121 °C. H NMR (600
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8
9
MHz, CDCl3) δ 8.25 (d, J = 8.2 Hz, 1H), 7.49 (t, J = 7.4 Hz, 2H), 7.42 (t, J = 7.3 Hz, 1H), 7.37 (t,
J = 7.2 Hz, 3H), 7.25 (d, J = 7.4 Hz, 1H), 7.17 (dd, J = 14.4, 6.7 Hz, 2H), 2.02 (s, 3H). 13C NMR
(151 MHz, CDCl3) δ 168.3, 138.1, 134.5, 132.1, 130.0, 129.2, 129.0, 128.4, 127.9, 124.4, 121.6,
24.6.
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N-(4'-fluoro-[1,1'-biphenyl]-2-yl)acetamide (3b): Prepared according to GP G from acetanilide
(27 mg, 0.2 mmol) and pꢀFC6H4N2BF4 (126.0 mg, 0.6 mmol). The resulting mixture was purified
by flash chromatography (PE : EA = 5 : 1) to give the desired product as a white solid (25.6 mg,
1
56% yield). Physical data were in accordance with literature data.16 Mp 119
–
120 °C. H NMR
(600 MHz, CDCl3) δ 8.19 (d, J = 8.1 Hz, 1H), 7.37 (d, J = 7.6 Hz, 1H), 7.36 – 7.31 (m, 2H), 7.21
(d, J = 7.3 Hz, 1H), 7.17 (t, J = 8.3 Hz, 3H), 7.05 (s, 1H), 2.03 (s, 3H). 13C NMR (151 MHz,
CDCl3) δ 168.3, 163.2, 161.6, 134.6, 134.0 (d, J = 3.4 Hz), 134.0 (d, J = 3.4 Hz), 131.4, 130.9 (d,
J = 8.1 Hz), 130.9 (d, J = 8.1 Hz), 130.0, 128.5, 124.5, 122.0, 116.1, 115.9, 24.5. 19F NMR (564
MHz, CDCl3) δ ꢀ113.87.
N-(4'-chloro-[1,1'-biphenyl]-2-yl)acetamide (3c): Prepared according to GP G from acetanilide
(27 mg, 0.2 mmol) and pꢀClC6H4N2BF4 (135.6 mg, 0.6 mmol). The resulting mixture was purified
by flash chromatography (PE : EA = 5 : 1) to give the desired product as a white solid (43.1 mg,
1
88% yield). Physical data were in accordance with literature data.7l Mp 134
–
135 °C. H NMR
(600 MHz, CDCl3) δ 8.19 (d, J = 8.0 Hz, 1H), 7.46 (d, J = 8.1 Hz, 2H), 7.38 (t, J = 7.5 Hz, 1H),
7.31 (d, J = 8.1 Hz, 2H), 7.23 – 7.15 (m, 2H), 7.01 (s, 1H), 2.03 (s, 3H). 13C NMR (151 MHz,
CDCl3) δ 168.2, 136.6, 134.5, 134.0, 131.3, 130.5, 129.9, 129.2, 128.7, 124.6, 122.2, 24.4.
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N-(4'-bromo-[1,1'-biphenyl]-2-yl)acetamide (3d): Prepared according to GP G from acetanilide
(27 mg, 0.2 mmol) and pꢀBrC6H4N2BF4 (162.5 mg, 0.6 mmol). The resulting mixture was purified
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by flash chromatography (PE : EA = 5 : 1) to give the desired product as a white solid (49.1 mg,
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85% yield). Physical data were in accordance with literature data.7l Mp 132
–133 °C. H NMR
(600 MHz, CDCl3) δ 8.15 (d, J = 8.2 Hz, 1H), 7.60 (d, J = 8.0 Hz, 2H), 7.37 (t, J = 7.3 Hz, 1H),
7.24 (d, J = 8.1 Hz, 2H), 7.19 (q, J = 7.1 Hz, 2H), 7.08 (s, 1H), 2.03 (s, 3H). 13C NMR (151 MHz,
CDCl3) δ 168.3, 137.0, 134.3, 132.1, 131.4, 130.8, 129.8, 128.7, 124.7, 122.4, 122.1, 24.4.
N-(4'-iodo-[1,1'-biphenyl]-2-yl)acetamide (3e): Prepared according to GP G from acetanilide
(27 mg, 0.2 mmol) and pꢀIC6H4N2BF4 (190.7 mg, 0.6 mmol). The resulting mixture was purified
by flash chromatography (PE : EA = 5 : 1) to give the desired product as a white solid (43.8 mg,
65% yield). Mp 137–
138 °C. 1H NMR (600 MHz, CDCl3) δ 8.19 (d, J = 8.0 Hz, 1H), 7.81 (d, J =
7.8 Hz, 2H), 7.38 (t, J = 6.8 Hz, 1H), 7.23 – 7.15 (m, 2H), 7.12 (d, J = 7.8 Hz, 2H), 7.00 (s, 1H),
2.04 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 168.2, 138.1, 137.7, 134.4, 131.4, 131.0, 129.8,
128.7, 124.6, 122.3, 93.8, 24.5. HRMS (ESI) m/z calcd for C14H13INO [M+H]+: 338.0036; found:
338.0039.
N-(4'-(trifluoromethyl)-[1,1'-biphenyl]-2-yl)acetamide (3f): Prepared according to GP G from
acetanilide (27 mg, 0.2 mmol) and pꢀCF3C6H4N2BF4 (156.0 mg, 0.6 mmol). The resulting mixture
was purified by flash chromatography (PE : EA = 5 : 1) to give the desired product as a white
solid (43.0 mg, 77% yield). Physical data were in accordance with literature data.16 Mp
1
118–
119 °C. H NMR (600 MHz, CDCl3) δ 8.16 (d, J = 8.2 Hz, 1H), 7.74 (d, J = 7.9 Hz, 2H),
7.51 (d, J = 7.8 Hz, 2H), 7.41 (t, J = 7.3 Hz, 1H), 7.25 – 7.19 (m, 2H), 6.99 (s, 1H), 2.04 (s, 3H).
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13C NMR (151 MHz, CDCl3) δ 168.3, 142.0, 134.3, 131.4, 129.9, 129.6, 129.1, 125.9, 125.9,
124.9, 124.8, 123.0, 122.8, 24.4. 19F NMR (564 MHz, CDCl3) δ ꢀ62.63.
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Ethyl 2'-acetamido-[1,1'-biphenyl]-4-carboxylate (3g): Prepared according to GP G from
acetanilide (27 mg, 0.2 mmol) and pꢀCOOEtC6H4N2BF4 (158.4 mg, 0.6 mmol). The resulting
mixture was purified by flash chromatography (PE : EA = 5 : 1) to give the desired product as a
white solid (44.1 mg, 78% yield). Mp 130–131 °C. 1H NMR (600 MHz, CDCl3) δ 8.20 (d, J = 8.1
Hz, 1H), 8.15 (d, J = 7.9 Hz, 2H), 7.46 (d, J = 7.9 Hz, 2H), 7.40 (t, J = 7.7 Hz, 1H), 7.26 – 7.18 (m,
2H), 7.03 (s, 1H), 4.42 (q, J = 7.1 Hz, 2H), 2.02 (s, 3H), 1.42 (t, J = 7.2 Hz, 3H). 13C NMR (151
MHz, CDCl3) δ 168.2, 166.1, 142.8, 134.4, 130.2, 130.0, 129.8, 129.2, 129.0, 124.7, 122.4, 107.3,
61.2, 24.4, 14.3. HRMS (ESI) m/z calcd for C17H18NO3 [M+H]+: 284.1281; found: 284.1285.
N-(4'-acetyl-[1,1'-biphenyl]-2-yl)acetamide (3h): Prepared according to GP G from acetanilide
(27 mg, 0.2 mmol) and pꢀC2H3OC6H4N2BF4 (140.4 mg, 0.6 mmol). The resulting mixture was
purified by flash chromatography (PE : EA = 5 : 1) to give the desired product as a white solid
(23.8 mg, 47% yield). Physical data were in accordance with literature data.17 Mp 193–194 °C. 1H
NMR (600 MHz, CDCl3) δ 8.17 (d, J = 8.1 Hz, 1H), 8.05 (d, J = 8.0 Hz, 2H), 7.48 (d, J = 7.9 Hz,
2H), 7.40 (t, J = 7.5 Hz, 1H), 7.26 – 7.18 (m, 2H), 7.06 (s, 1H), 2.65 (s, 3H), 2.03 (s, 3H). 13C
NMR (151 MHz, CDCl3) δ 197.4, 168.3, 143.2, 136.4, 134.4, 131.6, 129.8, 129.4, 129.0, 128.9,
124.8, 122.6, 26.6, 24.4.
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N-(4'-methoxy-[1,1'-biphenyl]-2-yl)acetamide (3i): Prepared according to GP G from
acetanilide (27 mg, 0.2 mmol) and pꢀMeOC6H4N2BF4 (133.2 mg, 0.6 mmol). The resulting
mixture was purified by flash chromatography (PE : EA = 5 : 1) to give the desired product as a
white solid (31.3 mg, 65% yield). Physical data were in accordance with literature data.16 Mp
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133–134 °C. 1H NMR (600 MHz,CDCl3) δ 8.25 (d, J = 8.0 Hz, 1H), 7.34 (t, J = 7.7 Hz, 1H), 7.29
(d, J = 8.1 Hz, 2H), 7.22 (d, J = 7.3 Hz, 1H), 7.18 – 7.09 (m, 2H), 7.01 (d, J = 8.1 Hz, 2H), 3.87 (s,
3H), 2.03 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 168.1, 159.3, 134.8, 131.7, 130.3, 130.2, 130.1,
128.1, 124.2, 121.4, 114.4, 55.3, 24.6.
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N-(4'-methyl-[1,1'-biphenyl]-2-yl)acetamide (3j): Prepared according to GP G from acetanilide
(27 mg, 0.2 mmol) and pꢀMeC6H4N2BF4 (123.6 mg, 0.6 mmol). The resulting mixture was
purified by flash chromatography (PE : EA = 5 : 1) to give the desired product as a white solid
(26.6 mg, 59% yield). Physical data were in accordance with literature data.16 Mp 103–104 °C. 1H
NMR (600 MHz,CDCl3) δ 8.26 (d, J = 8.2 Hz, 1H), 7.35 (t, J = 7.8 Hz, 1H), 7.29 (d, J = 7.8 Hz,
2H), 7.27 (s, 1H), 7.26 – 7.24 (m, 1H), 7.23 (d, J = 7.4 Hz, 1H), 7.17 (dd, J = 15.1, 7.5 Hz, 2H),
2.43 (s, 3H), 2.03 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 168.2, 137.7, 135.0, 134.6, 132.0, 130.0,
129.7, 129.0, 128.1, 124.2, 121.4, 24.6, 21.1.
N-(4'-(tert-butyl)-[1,1'-biphenyl]-2-yl)acetamide (3k): Prepared according to GP G from
acetanilide (27 mg, 0.2 mmol) and pꢀtertꢀbutylC6H4N2BF4 (148.8 mg, 0.6 mmol). The resulting
mixture was purified by flash chromatography (PE : EA = 5 : 1) to give the desired product as a
white solid (27.8 mg, 52% yield). Physical data were in accordance with literature data.16 Mp
93–94 °C. 1H NMR (600 MHz, CDCl3) δ 8.27 (d, J = 8.2 Hz, 1H), 7.50 (d, J = 7.9 Hz, 2H), 7.37 –
7.30 (m, 3H), 7.24 (d, J = 6.9 Hz, 2H), 7.17 (t, J = 7.4 Hz, 1H), 2.05 (s, 3H), 1.38 (s, 9H). 13C
NMR (151 MHz, CDCl3) δ 168.3, 150.9, 134.9, 134.5, 131.9, 130.1, 128.8, 128.1, 126.0, 124.3,
121.5, 34.6, 31.2, 24.6.
N-(2'-methyl-[1,1'-biphenyl]-2-yl)acetamide (3l): Prepared according to GP G from acetanilide
(27 mg, 0.2 mmol) and 2ꢀMeC6H4N2BF4 (123.6 mg, 0.6 mmol). The resulting mixture was
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mg, 71% yield). Physical data were in accordance with literature data.18 Mp 125–126 °C. H
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NMR (600 MHz, CDCl3) δ 8.34 (d, J = 8.1 Hz, 1H), 7.38 (t, J = 7.7 Hz, 1H), 7.34 (s, 2H), 7.32 –
7.27 (m, 1H), 7.18 (d, J = 7.7 Hz, 1H), 7.14 (t, J = 9.0 Hz, 2H), 6.79 (s, 1H), 2.10 (s, 3H), 1.95 (s,
3H). 13C NMR (151 MHz, CDCl3) δ 168.0, 136.9, 136.7, 135.2, 131.1, 130.5, 129.9, 129.6, 128.4,
128.3, 126.3, 123.8, 120.6, 24.6, 19.6.
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N-(5-fluoro-[1,1'-biphenyl]-2-yl)acetamide (3m): Prepared according to GP
G from
Nꢀ(4ꢀfluorophenyl)acetamide (30.6 mg, 0.2 mmol) and PhN2BF4 (115.2 mg, 0.6 mmol). The
resulting mixture was purified by flash chromatography (PE : EA = 5 : 1) to give the desired
product as a white solid (32.1 mg, 70% yield). Physical data were in accordance with literature
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data.16 Mp 135–136 °C. H NMR (600 MHz, CDCl3) δ 8.19 – 8.12 (m, 1H), 7.49 (t, J = 7.4 Hz,
2H), 7.43 (t, J = 7.3 Hz, 1H), 7.35 (d, J = 7.4 Hz, 2H), 7.05 (dd, J = 15.6, 9.1 Hz, 2H), 6.97 (d, J =
8.6 Hz, 1H), 2.01 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 168.3, 159.1 (d, J = 244.5 Hz), 137.0 (d,
J = 1.1 Hz), 134.5 (d, J = 7.6 Hz), 130.5 (d, J = 2.7 Hz), 129.1, 128.9, 128.3, 123.9 (d, J = 8.1 Hz),
116.6 (d, J = 22.9 Hz), 114.8 (d, J = 21.9 Hz), 24.3. 19F NMR (564 MHz, CDCl3) δ ꢀ117.95.
N-(5-iodo-[1,1'-biphenyl]-2-yl)acetamide (3n): Prepared according to GP
G
from
Nꢀ(4ꢀiodophenyl)acetamide (52.2 mg, 0.2 mmol) and PhN2BF4 (115.2 mg, 0.6 mmol). The
resulting mixture was purified by flash chromatography (PE : EA = 5 : 1) to give the desired
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product as a white solid (33.7 mg, 50% yield). Mp 128–129 °C. H NMR (600 MHz, CDCl3) δ
8.09 (d, J = 8.6 Hz, 1H), 7.65 (d, J = 8.7 Hz, 1H), 7.61 – 7.55 (m, 1H), 7.49 (t, J = 7.4 Hz, 2H),
7.44 (t, J = 7.5 Hz, 1H), 7.35 (t, J = 10.7 Hz, 2H), 7.10 (s, 1H), 2.00 (s, 3H). 13C NMR (151 MHz,
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CDCl3) δ 168.1, 138.4, 137.2, 136.5, 134.6, 134.0, 129.2, 129.0, 128.4, 123.1, 87.6, 24.6. HRMS
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(ESI) m/z calcd for C14H13INO [M+H]+: 338.0036; found: 338.0033.
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N-(5-methyl-[1,1'-biphenyl]-2-yl)acetamide (3o): Prepared according to GP
G from
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Nꢀ(pꢀtolyl)acetamide (29.8 mg, 0.2 mmol) and PhN2BF4 (115.2 mg, 0.6 mmol). The resulting
mixture was purified by flash chromatography (PE : EA = 5 : 1) to give the desired product as a
white solid (31.9 mg, 71% yield). Physical data were in accordance with literature data.16 Mp
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120–121 °C. H NMR (600 MHz, CDCl3) δ 8.07 (d, J = 8.3 Hz, 1H), 7.47 (t, J = 7.4 Hz, 2H),
7.40 (t, J = 7.3 Hz, 1H), 7.36 (d, J = 7.6 Hz, 2H), 7.18 (d, J = 8.4 Hz, 1H), 7.08 (d, J = 14.5 Hz,
2H), 2.35 (s, 3H), 2.01 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 168.1, 138.3, 134.0, 132.4, 132.0,
130.5, 129.1, 128.9, 128.8, 127.7, 122.0, 24.3, 20.8.
N-(5-methoxy-[1,1'-biphenyl]-2-yl)acetamide (3p): Prepared according to GP G from
Nꢀ(4ꢀmethoxyphenyl)acetamide (33.0 mg, 0.2 mmol) and PhN2BF4 (115.2 mg, 0.6 mmol). The
resulting mixture was purified by flash chromatography (PE : EA = 5 : 1) to give the desired
product as a white solid (36.1 mg, 75% yield). Physical data were in accordance with literature
data.7l Mp 113–114 °C. 1H NMR (600 MHz, CDCl3) δ 7.97 (d, J = 8.9 Hz, 1H), 7.46 (t, J = 7.4 Hz,
2H), 7.40 (t, J = 7.4 Hz, 1H), 7.36 (d, J = 7.1 Hz, 2H), 7.01 (s, 1H), 6.90 (dd, J = 8.9, 2.9 Hz, 1H),
6.80 (d, J = 2.8 Hz, 1H), 3.80 (s, 3H), 1.99 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 168.4, 156.3,
138.1, 134.7, 128.9, 128.8, 127.8, 127.5, 124.3, 115.3, 113.3, 55.4, 24.1.
N-(5-formyl-[1,1'-biphenyl]-2-yl)acetamide (3q): Prepared according to GP
G from
Nꢀ(4ꢀformylphenyl)acetamide (32.6 mg, 0.2 mmol) and PhN2BF4 (115.2 mg, 0.6 mmol). The
resulting mixture was purified by flash chromatography (PE : EA = 5 : 1) to give the desired
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product as a white solid (38.7 mg, 81% yield). Mp 128–129 °C. H NMR (600 MHz, CDCl3) δ
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9.92 (s, 1H), 8.60 (d, J = 8.0 Hz, 1H), 7.86 (d, J = 8.5 Hz, 1H), 7.75 (s, 1H), 7.53 (t, J = 7.4 Hz,
2H), 7.47 (t, J = 7.4 Hz, 1H), 7.42 (d, J = 11.7 Hz, 1H), 7.38 (d, J = 7.1 Hz, 2H), 2.05 (s, 3H). 13C
NMR (151 MHz, CDCl3) δ 190.9, 168.3, 140.3, 136.5, 131.9, 131.1, 130.7, 129.4, 129.0, 128.7,
124.1, 120.3, 24.8. HRMS (ESI) m/z calcd for C15H14NO2 [M+H]+: 240.1019; found: 240.1017.
Ethyl 6-acetamido-[1,1'-biphenyl]-3-carboxylate (3r): Prepared according to GP G from ethyl
4ꢀacetamidobenzoate (41.4 mg, 0.2 mmol) and PhN2BF4 (115.2 mg, 0.6 mmol). The resulting
mixture was purified by flash chromatography (PE : EA = 5 : 1) to give the desired product as a
white solid (28.3 mg, 50% yield). Mp 137–138 °C. 1H NMR (600 MHz, CDCl3) δ 8.48 (d, J = 6.9
Hz, 1H), 8.04 (d, J = 8.7 Hz, 1H), 7.92 (s, 1H), 7.52 (t, J = 7.4 Hz, 2H), 7.45 (t, J = 7.0 Hz, 1H),
7.39 (t, J = 10.7 Hz, 2H), 7.32 (s, 1H), 4.36 (q, J = 7.0 Hz, 2H), 2.03 (s, 3H), 1.37 (t, J = 6.9 Hz,
3H). 13C NMR (151 MHz, CDCl3) δ 168.2, 166.0, 138.8, 137.0, 131.4, 130.0, 129.3, 129.2, 128.4,
125.7, 124.2, 120.0, 60.8, 24.8, 14.3. HRMS (ESI) m/z calcd for C17H18NO3 [M+H]+: 284.1281;
found: 284.1284.
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N-(3-methyl-[1,1'-biphenyl]-2-yl)acetamide (3s): Prepared according to GP
G from
Nꢀ(oꢀtolyl)acetamide (29.8 mg, 0.2 mmol) and PhN2BF4 (115.2 mg, 0.6 mmol). The resulting
mixture was purified by flash chromatography (PE : EA = 5 : 1) to give the desired product as a
white solid (40.5 mg, 90% yield). Physical data were in accordance with literature data.7l Mp
127–128 °C. 1H NMR (600 MHz, CDCl3) δ 7.40 (t, J = 7.4 Hz, 2H), 7.36 – 7.30 (m, 3H), 7.26 (d,
J = 5.0 Hz, 2H), 7.19 – 7.15 (m, 1H), 6.64 (s, 1H), 2.31 (s, 3H), 1.98 (s, 3H).13C NMR (151 MHz,
CDCl3) δ 169.2, 139.6, 139.5, 136.8, 132.6, 130.1, 129.0, 128.8, 128.3, 127.8, 127.3, 23.0, 18.5.
N-(4-methyl-[1,1'-biphenyl]-2-yl)pivalamide (3t): Prepared according to GP
G from
Nꢀ(mꢀtolyl)pivalamide (38.2 mg, 0.2 mmol) and PhN2BF4 (115.2 mg, 0.6 mmol). The resulting
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mixture was purified by flash chromatography (PE : EA = 5 : 1) to give the desired product as a
white solid (47.8 mg, 82% yield). Physical data were in accordance with literature data.19 Mp
77–78 °C. 1H NMR (600 MHz, CDCl3) δ 8.24 (s, 1H), 7.48 (t, J = 7.5 Hz, 2H), 7.46 (s, 1H), 7.41
(t, J = 7.4 Hz, 1H), 7.35 (d, J = 7.7 Hz, 2H), 7.14 (d, J = 7.7 Hz, 1H), 6.98 (d, J = 7.7 Hz, 1H),
2.40 (s, 3H), 1.10 (s, 9H). 13C NMR (151 MHz, CDCl3) δ 176.3, 138.4, 138.1, 134.8, 129.4, 129.4,
129.4, 128.9, 127.8, 124.6, 121.4, 39.7, 27.3, 21.4.
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N-([1,1'-biphenyl]-2-yl)benzamide (3u): Prepared according to GP G from Nꢀphenylbenzamide
(39.4 mg, 0.2 mmol) and PhN2BF4 (115.2 mg, 0.6 mmol). The resulting mixture was purified by
flash chromatography (PE : EA = 5 : 1) to give the desired product as a white solid (43.1 mg, 79%
yield). Physical data were in accordance with literature data.17 Mp 84–85 °C. 1H NMR (600 MHz,
CDCl3) δ 8.55 (d, J = 8.2 Hz, 1H), 8.03 (s, 1H), 7.61 (d, J = 8.1 Hz, 2H), 7.52 (t, J = 7.3 Hz, 2H),
7.50 – 7.42 (m, 5H), 7.39 (t, J = 7.4 Hz, 2H), 7.31 (d, J = 7.5 Hz, 1H), 7.23 (t, J = 7.5 Hz, 1H). 13C
NMR (151 MHz, CDCl3) δ 164.9, 138.0, 134.9, 134.7, 132.3, 131.6, 129.9, 129.3, 129.2, 128.7,
128.5, 128.1, 126.7, 124.3, 121.1.
N-(5-methyl-[1,1'-biphenyl]-2-yl)benzamide (3v): Prepared according to GP
G from
Nꢀ(pꢀtolyl)benzamide (42.2 mg, 0.2 mmol) and PhN2BF4 (115.2 mg, 0.6 mmol). The resulting
mixture was purified by flash chromatography (PE : EA = 5 : 1) to give the desired product as a
white solid (41.3 mg, 72% yield). Mp 123–124 °C. 1H NMR (600 MHz,CDCl3) δ 8.39 (d, J = 8.2
Hz, 1H), 7.94 (s, 1H), 7.61 (d, J = 7.5 Hz, 2H), 7.51 (t, J = 7.5 Hz, 2H), 7.47 (d, J = 7.4 Hz, 1H),
7.46 – 7.42 (m, 3H), 7.39 (t, J = 7.7 Hz, 2H), 7.24 (s, 1H), 7.13 (s, 1H), 2.39 (s, 3H). 13C NMR
(151 MHz, CDCl3) δ 164.9, 138.1, 134.8, 134.0, 132.4, 132.2, 131.6, 130.5, 129.3, 129.1, 129.0,
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128.7, 128.0, 126.7, 121.3, 20.9. HRMS (ESI) m/z calcd for C20H18NO [M+H]+: 288.1383; found:
288.1386.
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N-([1,1'-biphenyl]-2-yl)-2,4,6-trimethylbenzamide (3w): Prepared according to GP G from
2,4,6ꢀtrimethylꢀNꢀphenylbenzamide (47.8 mg, 0.2 mmol) and PhN2BF4 (115.2 mg, 0.6 mmol).
The resulting mixture was purified by flash chromatography (PE : EA = 5 : 1) to give the desired
product as a white solid (51.0 mg, 81% yield). Physical data were in accordance with literature
data.20 Mp 124–125 °C. 1H NMR (600 MHz, CDCl3) δ 8.47 (d, J = 8.2 Hz, 1H), 7.46 (t, J = 7.7
Hz, 1H), 7.42 (t, J = 7.5 Hz, 2H), 7.39 – 7.34 (m, 3H), 7.28 (d, J = 7.4 Hz, 1H), 7.26 – 7.20 (m,
2H), 6.81 (s, 2H), 2.27 (s, 6H), 2.25 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 168.8, 138.6, 138.0,
134.8, 134.5, 134.1, 132.9, 130.3, 129.2, 128.9, 128.4, 128.2, 127.9, 124.6, 122.1, 21.0, 19.0.
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1-([1,1'-biphenyl]-2-yl)pyrrolidin-2-one (3x): Prepared according to GP
G
from
1ꢀphenylpyrrolidinꢀ2ꢀone (32.2 mg, 0.2 mmol) and PhN2BF4 (115.2 mg, 0.6 mmol). The resulting
mixture was purified by flash chromatography (PE : EA = 5 : 1) to give the desired product as a
white solid (35.1 mg, 74% yield). Physical data were in accordance with literature data.21 Mp
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127–128 °C. H NMR (600 MHz, CDCl3) δ 7.41 (d, J = 7.4 Hz, 2H), 7.39 – 7.38 (m, 4H), 7.36
(dd, J = 13.1, 4.3 Hz, 2H), 7.32 (d, J = 7.3 Hz, 1H), 3.20 (t, J = 7.0 Hz, 2H), 2.42 (t, J = 8.0 Hz,
2H), 1.89 – 1.83 (m, 2H). 13C NMR (151 MHz, CDCl3) δ 175.6, 139.5, 139.0, 136.2, 130.7,
128.4, 128.3, 128.3, 128.2, 127.9, 127.5, 50.1, 31.1, 18.9.
N-methyl-[1,1'-biphenyl]-2-carboxamide (5a): Prepared according to GP
H
from
Nꢀmethylbenzamide (27.1 mg, 0.2 mmol) and PhN2BF4 (115.2 mg, 0.6 mmol). The resulting
mixture was purified by flash chromatography (PE : EA = 2:1) to give the desired product as a
white solid (30.4 mg, 72% yield). Physical data were in accordance with literature data.22 Mp
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166–167 °C. H NMR (600 MHz, CDCl3) δ 7.68 (d, J = 7.6 Hz, 1H), 7.47 (t, J = 7.4 Hz, 1H),
7.44 – 7.39 (m, 5H), 7.37 (d, J = 8.1 Hz, 2H), 5.23 (s, 1H), 2.67 (d, J = 4.9 Hz, 3H). 13C NMR
(151 MHz, CDCl3) δ 170.2, 140.0, 139.2, 135.6, 130.1, 128.7, 128.5, 127.7, 127.5, 26.6.
5-chloro-N-methyl-[1,1'-biphenyl]-2-carboxamide (5b): Prepared according to GP H from
4ꢀchloroꢀNꢀmethylbenzamide (33.8 mg, 0.2 mmol) and PhN2BF4 (115.2 mg, 0.6 mmol). The
resulting mixture was purified by flash chromatography (PE : EA = 2 : 1) to give the desired
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product as a white solid (18.1 mg, 37% yield). Mp 152–153 °C. H NMR (600 MHz, CDCl3) δ
7.57 (d, J = 8.7 Hz, 1H), 7.55 – 7.51 (m, 2H), 7.45 – 7.41 (m, 2H), 7.39 (t, J = 8.0 Hz, 3H), 5.18 (s,
1H), 2.66 (d, J = 4.9 Hz, 3H). 13C NMR (151 MHz, CDCl3) δ 169.1, 141.0, 138.8, 135.9, 133.9,
130.4, 130.0, 128.7, 128.4, 128.3, 127.7, 26.7. HRMS (ESI) m/z calcd for C14H13ClNO [M+H]+:
246.0680; found: 246.0683.
5-bromo-N-methyl-[1,1'-biphenyl]-2-carboxamide (5c): Prepared according to GP H from
4ꢀbromo-Nꢀmethylbenzamide (42.6 mg, 0.2 mmol) and PhN2BF4 (115.2 mg, 0.6 mmol). The
resulting mixture was purified by flash chromatography (PE : EA = 2 : 1) to give the desired
product as a white solid (24.9 mg, 43% yield). Physical data were in accordance with literature
data.23 Mp 158–159 °C. 1H NMR (600 MHz, CDCl3) δ 7.57 (d, J = 8.7 Hz, 1H), 7.55 – 7.51 (m,
2H), 7.45 – 7.41 (m, 2H), 7.39 (t, J = 8.0 Hz, 3H), 5.18 (s, 1H), 2.66 (d, J = 4.9 Hz, 3H). 13C
NMR (151 MHz, CDCl3) δ 169.2, 141.2, 138.7, 134.3, 132.9, 130.6, 130.5, 128.7, 128.4, 128.3,
124.2, 26.6.
N,5-dimethyl-[1,1'-biphenyl]-2-carboxamide (5d): Prepared according to GP
H from
N,4ꢀdimethylbenzamide (29.8 mg, 0.2 mmol) and PhN2BF4 (115.2 mg, 0.6 mmol). The resulting
mixture was purified by flash chromatography (PE : EA = 2 : 1) to give the desired product as a
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white solid (35.1 mg, 78% yield). Physical data were in accordance with literature data.23 Mp
118–119 °C. 1H NMR (600 MHz, CDCl3) δ 7.60 (d, J = 7.8 Hz, 1H), 7.43 – 7.32 (m, 5H), 7.20 (d,
J = 7.9 Hz, 1H), 7.16 (s, 1H), 5.21 (s, 1H), 2.65 (d, J = 4.9 Hz, 3H), 2.40 (s, 3H). 13C NMR (151
MHz, CDCl3) δ 170.2, 140.2, 140.1, 139.3, 132.7, 130.7, 128.9, 128.5, 128.4, 128.2, 127.6, 26.5,
21.2.
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5-methoxy-N-methyl-[1,1'-biphenyl]-2-carboxamide (5e): Prepared according to GP H from
4ꢀmethoxy-Nꢀmethylbenzamide (33.0 mg, 0.2 mmol) and PhN2BF4 (115.2 mg, 0.6 mmol). The
resulting mixture was purified by flash chromatography (PE : EA = 2 : 1) to give the desired
product as a white solid (28.0 mg, 58% yield). Physical data were in accordance with literature
data.23 Mp 111–112 °C. 1H NMR (600 MHz, CDCl3) δ 7.70 (d, J = 8.6 Hz, 1H), 7.45 – 7.34 (m,
5H), 6.92 (dd, J = 8.6, 2.5 Hz, 1H), 6.84 (d, J = 2.4 Hz, 1H), 5.13 (s, 1H), 3.85 (s, 3H), 2.64 (d, J
= 4.9 Hz, 3H). 13C NMR (151 MHz, CDCl3) δ 169.7, 160.6, 141.2, 140.2, 130.9, 128.6, 127.9,
127.9, 115.4, 112.9, 55.4, 26.6.
5-(tert-butyl)-N-methyl-[1,1'-biphenyl]-2-carboxamide (5f): Prepared according to GP H from
4ꢀ(tertꢀbutyl)ꢀNꢀmethylbenzamide (38.2 mg, 0.2 mmol) and PhN2BF4 (115.2 mg, 0.6 mmol). The
resulting mixture was purified by flash chromatography (PE : EA = 2 : 1) to give the desired
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product as a white solid (37.9 mg, 71% yield). Mp 220–221 °C. H NMR (600 MHz, CDCl3) δ
7.64 (d, J = 8.1 Hz, 1H), 7.46 – 7.40 (m, 5H), 7.39 – 7.33 (m, 2H), 5.20 (s, 1H), 2.66 (d, J = 4.8
Hz, 3H), 1.35 (d, J = 8.5 Hz, 9H). 13C NMR (151 MHz, CDCl3) δ 170.2, 153.3, 140.7, 139.0,
132.7, 128.7, 128.6, 128.5, 127.6, 127.1, 124.6, 34.8, 31.1, 26.5. HRMS (ESI) m/z calcd for
C18H22NO [M+H]+: 268.1696; found: 268.1699.
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The Journal of Organic Chemistry
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N,3-dimethyl-[1,1'-biphenyl]-2-carboxamide (5g): Prepared according to GP
H from
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N,2ꢀdimethylbenzamide (29.8 mg, 0.2 mmol) and PhN2BF4 (115.2 mg, 0.6 mmol). The resulting
mixture was purified by flash chromatography (PE : EA = 2 : 1) to give the desired product as a
white solid (34.7 mg, 77% yield). Mp 148–149 °C. 1H NMR (600 MHz, CDCl3) δ 7.44 (d, J = 7.5
Hz, 2H), 7.39 (t, J = 7.4 Hz, 2H), 7.32 (t, J = 8.0 Hz, 2H), 7.21 (d, J = 7.6 Hz, 2H), 5.22 (s, 1H),
2.64 (d, J = 4.8 Hz, 3H), 2.42 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 170.6, 140.4, 139.0, 136.3,
135.7, 129.3, 128.9, 128.3, 128.3, 127.3, 127.2, 26.4, 19.5. HRMS (ESI) m/z calcd for C15H16NO
[M+H]+: 226.1226; found: 226.1229.
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N,4-dimethyl-[1,1'-biphenyl]-2-carboxamide (5h): Prepared according to GP
H from
N,3ꢀdimethylbenzamide (29.8 mg, 0.2 mmol) and PhN2BF4 (115.2 mg, 0.6 mmol). The resulting
mixture was purified by flash chromatography (PE : EA = 2 : 1) to give the desired product as a
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white solid (26.1 mg, 58% yield). Mp 145–146 °C. H NMR (600 MHz, CDCl3) δ 7.50 (s, 1H),
7.43 – 7.37 (m, 4H), 7.34 (t, J = 6.5 Hz, 1H), 7.28 (d, J = 8.3 Hz, 1H), 7.27 – 7.25 (m, 1H), 5.19 (s,
1H), 2.66 (d, J = 5.0 Hz, 3H), 2.40 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 170.4, 140.0, 137.5,
136.4, 135.4, 130.8, 130.0, 129.3, 128.5, 128.5, 127.5, 26.6, 20.9. HRMS (ESI) m/z calcd for
C15H16NO [M+H]+: 226.1226; found: 226.1228.
N-(tert-butyl)-[1,1'-biphenyl]-2-carboxamide (5i): Prepared according to GP
H from
Nꢀ(tertꢀbutyl)benzamide (35.4 mg, 0.2 mmol) and PhN2BF4 (115.2 mg, 0.6 mmol). The resulting
mixture was purified by flash chromatography (PE : EA = 2 : 1) to give the desired product as a
white solid (31.9 mg, 63% yield). Mp 108–109 °C. 1H NMR (600 MHz, CDCl3) δ 7.73 (d, J = 7.5
Hz, 1H), 7.49 – 7.36 (m, 7H), 7.33 (d, J = 7.6 Hz, 1H), 4.99 (s, 1H), 1.10 (s, 9H). 13C NMR (151
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