A general copper-catalyzed radical C(sp3)?C(sp2) cross-coupling to access 1,1-diarylalkanes under ambient conditions

Article abstract of DOI:10.1016/j.tet.2021.132152

A general copper-catalyzed C(sp³)?C(sp²) cross-coupling of (hetero)benzyl bromides with the air- and moisture-stable aryl nucleophiles has been developed, providing a facile access to pharmaceutically useful 1,1-di(hetero)arylalkane and 1-aryl-1-heteroarylalkane scaffolds. Critical to the success is the utilization of a proline-based N,N,P-ligand to enhance the reducing capability of copper, thus easily converting benzyl bromides to the corresponding radical species via a single-electron transfer process under ambient conditions. The reaction features a broad substrate scope, covering (hetero)arylboronate esters, oxadiazoles, and benzo[d]oxazoles, as well as primary and secondary (hetero)benzyl bromides with excellent functional group tolerance.

Full text of DOI:10.1016/j.tet.2021.132152

Tetrahedron xxx (xxxx) xxx
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
A general copper-catalyzed radical C(sp3)¡C(sp2) cross-coupling to
access 1,1-diarylalkanes under ambient conditions
,
b
,
,
Xiao-Long Su a 1, Sheng-Peng Jiang b 1, Liu Ye c, Guo-Xing Xu d, Ji-Jun Chen b,
Qiang-Shuai Gu c, Zhong-Liang Li c **, Xin-Yuan Liu b
,
, *
a Shaanxi Key Laboratory of Phytochemistry, College of Chemistry and Chemical Engineering, Baoji University of Arts and Sciences, Baoji, Shaanxi, 721013,
China
b Shenzhen Grubbs Institute and Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and
Technology, Shenzhen, 518055, China
c Academy for Advanced Interdisciplinary Studies and Department of Chemistry Southern University of Science and Technology, Shenzhen, 518055, China
d College of Chemistry and Pharmaceutical Engineering, Jilin Institute of Chemical Technology, 132022, Jilin City, China
a r t i c l e i n f o
a b s t r a c t
A general copper-catalyzed C(sp3)ꢀC(sp2) cross-coupling of (hetero)benzyl bromides with the air- and
moisture-stable aryl nucleophiles has been developed, providing a facile access to pharmaceutically
useful 1,1-di(hetero)arylalkane and 1-aryl-1-heteroarylalkane scaffolds. Critical to the success is the
utilization of a proline-based N,N,P-ligand to enhance the reducing capability of copper, thus easily
converting benzyl bromides to the corresponding radical species via a single-electron transfer process
under ambient conditions. The reaction features a broad substrate scope, covering (hetero)arylboronate
esters, oxadiazoles, and benzo[d]oxazoles, as well as primary and secondary (hetero)benzyl bromides
with excellent functional group tolerance.
Article history:
Received 1 March 2021
Received in revised form
6 April 2021
Accepted 8 April 2021
Available online xxx
Keywords:
Copper
Cross-coupling
1,1-Diarylalkane
Proline-based N,N,P-ligand
Ambient conditions
© 2021 Elsevier Ltd. All rights reserved.
1. Introduction
process [4]. In the past two decades, great efforts have been made
to the first-row transition metal-catalyzed cross-coupling of alkyl
Transition metal-catalyzed CeC cross-coupling has emerged as
a powerful tool for the construction of complex molecular frame-
works from simple feedstocks in organic synthesis [1]. Despite the
noble progress in palladium-catalyzed C(sp2)eC(sp2) cross-
coupling of aryl/vinyl (pseudo)halides [2], the coupling of alkyl
(pseudo)halides to forge the C(sp3)eC(sp2) bonds has been less
developed due to the difficult oxidative addition process and the
halides with many organometallic reagents, such as organolithium
reagent, Grignard reagent, and organozinc reagent, etc (Scheme 1A)
[1c,4]. It should be noted that most of these organometallic re-
agents are sensitive to air or water, and are incompatible with many
polar functional groups, thus thwarting the general application of
the cross-coupling reactions [1c,4]. Therefore, the development of a
general C(sp3)eC(sp2) cross-coupling of alkyl halides with air- and
moisture-stable nucleophiles is highly urgent.
facile b-H elimination of the alkyl palladium complex [3]. In this
context, the first-row transition metals (Fe, Co, Ni, and Cu) engage
more easily in a single-electron transfer (SET) process owing to
their high-spin electronic configurations and thus provide a
pathway in the oxidative addition step of alkyl halides via a radical
Aryl boronate esters and heterocycles are reported to be a class
of air- and moisture-stable nucleophiles in the cross-coupling re-
actions [5,6]. Owing to the low cost and toxicity of copper [7], Hu,
Fu and others have disclosed the copper-catalyzed cross-coupling
of alkyl (pseudo)halides with heterocycles or arylboronates [8].
However, the reactions proceed at high temperature and it is
necessary to develop a general copper-catalyzed C(sp3)ꢀC(sp2)
cross-coupling under ambient conditions. As part of our continuous
interest in developing novel ligands to promote copper-catalyzed
radical reactions [9], we found that a cinchona alkaloid-based
multidentate N,N,P-ligand could greatly enhance the reducing
* Corresponding author.
** Corresponding author.
E-mail addresses: lizl@sustech.edu.cn (Z.-L. Li), liuxy3@sustech.edu.cn
(X.-Y. Liu).
1
Contribute equally to this work.
https://doi.org/10.1016/j.tet.2021.132152
0040-4020/© 2021 Elsevier Ltd. All rights reserved.
Please cite this article as: X.-L. Su, S.-P. Jiang, L. Ye et al., A general copper-catalyzed radical C(sp3)¡C(sp2) cross-coupling to access 1,1-
diarylalkanes under ambient conditions, Tetrahedron, https://doi.org/10.1016/j.tet.2021.132152

X.-L. Su, S.-P. Jiang, L. Ye et al.
Tetrahedron xxx (xxxx) xxx
Table 1
Screening of reaction conditionsa.
Scheme 1. The design of a general C(sp3)ꢀC(sp2) cross-coupling.
capability of copper, thus easily undergoing a SET process with
diverse alkyl halides under ambient conditions [9b]. Utilizing this
strategy, we further realized the enantioconvergent cross-coupling
of secondary alkyl halides with arylboronate esters or heterocycles
[10] to construct the synthetically important 1,1-di(hetero)ary-
lalkane scaffolds [11,12], which are important structural motifs in
natural products and pharmaceuticals [13]. It should be noted that
several drawbacks still existed in our developed approaches: (1) the
structurally congested cinchona alkaloid-based multidentate
N,N,P-ligands needed tedious synthesis; (2) due to the bulkiness of
the utilized ligands, the reaction efficiency was low and the sub-
strate scope was quite limited [10]. We surmise that the use of a less
bulky N,N,P-ligand might be crucial to address this issue. Herein,
we describe a general and efficient copper-catalyzed C(sp3)ꢀC(sp2)
cross-coupling of alkyl bromides with the air- and moisture-stable
arylboronate esters or heterocycles to provide an expeditious
synthesis of a library of 1,1-diarylalkanes under ambient conditions
(Scheme 1B). Notably, the reaction efficiency is high and the scope
is very broad, covering a number of (hetero)arylboronate esters and
heterocycles, as well as primary and secondary benzyl-, and het-
erobenzyl bromides with excellent functional group tolerance.
Entry
L
Solvent
Conversion (%)c
Yield(%)c
1
2
3
4
5
6
7
8
L1
L2
L3
L4
L5
L6
L7
L7
L7
L7
L7
DMA
DMA
DMA
DMA
DMA
DMA
DMA
PhCF3
88
57
75
76
46
30
100
48
76
90
100
0
0
0
0
0
0
39
23
67
81
91
9
DCM
DMA/DCM (1/2)
DMA/DCM (1/2)
10
11b
a
Reaction conditions: 1a (0.10 mmol), 2a (0.05 mmol), CuI (10 mol%), L (12 mol
%), LiOtBu (4.5 equiv) in solvent (0.60 mL) at room temperature for 36 h under argon.
b
H2O (2.0 equiv).
c
Conversion of 2a and yield of 3 were based on 1H NMR analysis of the crude
product using 1,3,5-trimethoxybenzene as an internal standard.
transmetalation step with azoles to form the CueC bond [14], we
added two equivalents of water to the reaction and both the con-
version and the yield were further improved (Table 1, entry 11). At
last, we identified the optimal conditions as follows: the reaction of
1a with 2a in the presence of 10 mol% of CuI, 12 mol% of L7, 4.5
equivalents of LiOtBu and 2.0 equivalents of H2O in DMA/DCM (v/
v ¼ 1:2) afforded 3 in 91% yield.
2. Results and discussion
The oxadiazoles are a class of pharmaceutically important het-
erocycles which have been used as nucleophiles in cross-coupling
reactions [5]. Based on the above assumption, we firstly investi-
gated the cross-coupling of (1-bromopropyl)benzene 1a with the
bench-stable 1,3,4-oxadiazole 2a under the catalysis of CuI in
presence of LiOtBu in N,N-dimethylacetamide (DMA) at room
temperature (Table 1). The initial trials with various types of
bidentate ligands, such as 1,2-bis(diphenylphosphino)ethane L1,
Xantphos L2, 2,20-bypyridine L3, and 1,10-phenanthroline ligands
(L4 and L5) failed to afford the desired C(sp3)ꢀC(sp2) coupling
product 3 and most of the azole substrate 2a was decomposed
(Table 1, entries 1e5). Further screening of a tridentate ligand L6
showed that it was not effective for the reaction (Table 1, entry 6).
When we used the proline-derived N,N,P-ligand L7 [9c], which was
utilized in our previous C(sp3)ꢀC(sp) coupling reaction, the desired
coupling product 3 was formed in 39% yield (Table 1, entry 7).
Inspired by this result, we next screened different solvents and
found that the reaction could afford 3 in 67% yield in dichloro-
methane (DCM), though the conversion was incomplete (Table 1,
entries 8 and 9). We then used a cosolvent of DMA/DCM to improve
both the reaction conversion and the yield of 3 (Table 1, entry 10).
The conversion can reach to 90% and the desired product can be
generated in 81% yield. Since the addition of water could not only
increase the solubility of LiOtBu but also enhance the
With the optimal reaction conditions in hand, we next investi-
gated the scope of the cross-coupling reaction (Table 2). The benzyl
bromides with electron-donating or -withdrawing groups at meta,
or para positions of phenyl rings were suitable for the reaction to
provide 4e7 in 69e92% yields. The linear benzyl bromides pos-
sessing different functional groups, such as terminal alkene, chlo-
ride, and silyl ether, at the alkyl branch proceeded smoothly to
deliver 8e13 in 58e91% yields under the standard conditions. More
importantly, the 1-bromo-1,2,3,4-tetrahydronaphthalene was also
a viable substrate to afford 14 in 50% yield. Furthermore, 3-(1-
bromopropyl)thiophene was applicable to the cross-coupling re-
action to furnish the 1,1-diheteroarylalkane product 15 in 71% yield.
The aryl-substituted azoles with the electron-neutral (16), -rich
(17e20) or -withdrawing (21e23) group, a naphthalene group (24)
and a pyridine group (25) were all compatible with the reaction
conditions. Moreover, the alkylated azole underwent the cross-
coupling reaction in high efficiency to generate 26 in 79% yield. In
addition to the 1,3,4-oxadiazole derivatives, the medicinally rele-
vant benzo[d]oxazole was also amenable to the cross-coupling,
affording 27, albeit with a moderate yield.
Aryl boronate esters have the unique feature of high stability,
ready availability, and low toxicity, and thus they have found wide
2

X.-L. Su, S.-P. Jiang, L. Ye et al.
Tetrahedron xxx (xxxx) xxx
Table 2
a
Substrate scope for the coupling with azoles
.
applications in the transition-metal catalyzed cross-coupling re-
actions [6]. As such, we switched our attention to the cross-
coupling of benzyl bromides with pinacol-derived aryl boronate
esters to provide straightforward access to a myriad of 1,1-
diarylalkanes. The optimal conditions for cross-coupling of benzyl
bromides with azoles were not suitable for the reaction of aryl-
boronate esters and the reaction conditions were screened
(Table S1 in the Supporting Information). Finally, we found that the
as the ester group, as can be seen in the formation of 43¡48. Next,
the scope of the arylboronate esters was also examined. Not only
the aryl- and naphthyl-substituted boronate esters, but also the
medicinally relevant thiophenyl- and pyridyl-substituted boronate
esters were easily coupled under the standard conditions to deliver
49e54 in moderate to good yields.
On the basis of our previous works [10], we proposed a plausible
mechanism as shown in Scheme 2. CuI first reacted with L7 to form
the CuI complex I in the presence of LiOtBu. This complex under-
went a transmetalation step with the nucleophile 2 to afford the
complex II, which reacted with benzyl bromides 1 via a single-
electron transfer process to generate the CuII complex III and the
benzyl radical IV. These two species underwent a coupling to
furnish the desired 1,1-diarylalkane scaffolds and regenerated the
complex I for the next catalytic cycle.
reaction
of
(1-bromoethyl)benzene
1b
with
4-
acetylphenylboronate ester 2b, in the presence of CuI (10 mol%),
the same ligand L7 (12 mol%), and LiOtBu (2.0 equiv) in DMSO
(2.4 mL) gave rise to 28 in 90% yield at room temperature under
argon (Table S1, entry 4). Under the optimal conditions, a wide
range of benzyl bromides with diverse substituents at the meta,
ortho, and para positions of the aryl rings reacted well to give the
desired 1,1-diarylalkanes 29e39 in up to 96% yield (Table 3). Many
functional groups were left untouched, such as methoxyl (29),
acetyl (30), bromide (34), methoxycarbonyl (36), carbonyl (37),
cyano (38), and nitro (39) group, etc. In addition, the naphthalene-
substituted alkyl bromides were also suitable for the reaction to
provide 40 and 41 in good yields. The reaction was not limited to
secondary benzyl bromides, and the primary benzyl bromide was a
viable substrate to afford 42, albeit with a lower yield. Notably, the
functional groups at the linear chain of the benzyl bromides were
also tolerated, such as the terminal alkene, bromide, nitrile as well
3. Conclusions
In sum, a general copper-catalyzed C(sp3)ꢀC(sp2) cross-coupling
of (hetero)benzyl bromides with the air- and moisture-stable nu-
cleophiles has been developed, providing a versatile tool to a
number of 1,1-diarylalkane scaffolds. It is crucial to use the proline-
based N,N,P-ligand to enhance the reducing capability of copper
catalyst, thus the reaction could proceed under ambient conditions.
The substrate scope is quite broad, covering primary and secondary
3

X.-L. Su, S.-P. Jiang, L. Ye et al.
Tetrahedron xxx (xxxx) xxx
Table 3
Substrate scope for the coupling with pinacol-derived (hetero)aryl boronate esters a
.
from Aladdin, which was redistilled with calcium hydride under
argon atmosphere. Anhydrous dichloromethane (DCM) was pur-
chased from JK and transferred under an argon atmosphere. LiOtBu
(98%) was purchased from JK. CuI was purchased from TCL.
Analytical thin layer chromatography (TLC) was performed on
precoated silica gel 60 GF254 plates. Flash column chromatography
was performed using Tsingdao silica gel (60, particle size
0.040e0.063 mm). Visualization on TLC was achieved by use of UV
light (254 nm) or iodine. NMR spectra were recorded on Bruker
DPX-400 spectrometer at 400 MHz for 1H NMR, 100 MHz for 13C
NMR, 376 MHz for 19F NMR, respectively, in CDCl3 with tetrame-
thylsilane (TMS) as internal standard. Mass spectrometric data
were obtained using Bruker Apex IV RTMS. The alkyl bromides [9c],
azoles, arylboronic-pinacol esters [8a] were synthesized according
to the reported procedures.
Scheme 2. A plausible reaction mechanism.
(hetero)benzyl bromides as well as aryl-, and heteroaryl boronate
esters, oxadiazoles, and benzo[d]oxazoles with excellent functional
group tolerance.
4.2. General procedures A for cross-coupling of racemic alkyl
bromides with azole C(sp2)eH bonds
To a flame-dried Schlenk tube equipped with a magnetic stir bar
were added CuI (1.9 mg, 0.010 mmol, 10 mol%), L7 (4.7 mg,
0.012 mmol, 12 mol%), LiOtBu (36 mg, 0.45 mmol, 4.5 equiv), and an
appropriate azole (0.10 mmol, 1.0 equiv). The tube was evacuated
and backfilled with argon for three times, and then, an appropriate
4. Experimental section
4.1. General experimental information
All reactions were carried out under argon atmosphere using
Schlenk techniques. Reagents were purchased at the highest com-
mercial quality and used without further purification, unless
otherwise stated. N,N-Dimethylacetamide (DMA) was purchased
alkyl bromide (0.20 mmol, 2.0 equiv), water (3.6 mL, 0.20 mmol, 2.0
equiv), and anhydrous N,N-dimethylacetamide (0.35 mL) and
dichloromethane (0.70 mL) were sequentially added. The reaction
mixture was stirred at room temperature for 36 h. The resulting
4

X.-L. Su, S.-P. Jiang, L. Ye et al.
Tetrahedron xxx (xxxx) xxx
reaction mixture was diluted with 10 mL ethyl acetate and washed
with brine (10 mL ꢁ 3). The organic layer was dried over anhydrous
Na2SO4 and filtered through a pad of celite. The organic solvent was
removed under vacuum and the residue was purified by column
chromatography on silica gel to afford the desired product.
4.2.6. 2-(4-methoxyphenyl)-5-(1-phenylethyl)-1,3,4-oxadiazole (8)
According to the general procedure A, the product 8 was ob-
tained in (17.1 mg, 61% yield). 1H NMR (400 MHz, CDCl3)
d
7.95e7.90 (m, 2H), 7.38e7.32 (m, 4H), 7.31e7.25 (m, 1H),
6.98e6.94 (m, 2H), 4.41 (q, J ¼ 7.3 Hz, 1H), 3.85 (s, 3H), 1.81 (d,
J ¼ 7.3 Hz, 3H).13C NMR (100 MHz, CDCl3)
d 168.2, 164.9, 162.2,
140.5, 128.9, 128.6, 127.5, 127.3, 116.5, 114.4, 55.4, 37.5, 19.7. HRMS
4.2.1. 2-(4-Methoxyphenyl)-5-(1-phenylpropyl)-1,3,4-oxadiazole
(3)
(ESI) m/z calcd. for C17H17N2O2 [M þ H]þ 281.1285, found 281.1282.
According to the general procedure A, the product 3 was ob-
tained in (25.5 mg, 87% yield). 1H NMR (400 MHz, CDCl3)
d
7.95 (d,
4.2.7. 2-(4-methoxyphenyl)-5-(2-methyl-1-phenylpropyl)-1,3,4-
oxadiazole (9)
J ¼ 8.9 Hz, 2H), 7.40e7.34 (m, 4H), 7.31e7.27 (m, 1H), 6.98 (d,
J ¼ 8.9 Hz, 2H), 4.16 (t, J ¼ 7.8 Hz, 1H), 3.86 (s, 3H), 2.42e2.31 (m,
1H), 2.20e2.09 (m, 1H), 1.00 (t, J ¼ 7.4 Hz, 3H). 13C NMR (100 MHz,
According to the general procedure A, the product 9 was ob-
tained in (27.4 mg, 89% yield). 1H NMR (400 MHz, CDCl3)
d 7.95 (d,
CDCl3)
d
167.6, 164.8, 162.2, 139.1, 128.8, 128.6, 127.9, 127.5, 116.6,
J ¼ 8.9 Hz, 2H), 7.42e7.40 (m, 2H), 7.35e7.32 (m, 2H), 7.28e7.24 (m,
1H), 7.02e6.94 (m, 2H), 3.91 (d, J ¼ 10.1 Hz, 1H), 3.86 (s, 3H),
2.62e2.53 (m, 1H), 1.04 (d, J ¼ 6.6 Hz, 3H), 0.88 (d, J ¼ 6.7 Hz, 3H).
114.4, 55.4, 45.1, 27.5, 12.2. HRMS (ESI) m/z calcd. for C18H19N2O2
[M þ H]þ 295.1441, found 295.1442.
13C NMR (100 MHz, CDCl3)
d 167.3, 164.6, 162.2, 138.3, 128.7, 128.6,
4.2.2. 2-(4-Methoxyphenyl)-5-(1-(m-tolyl)propyl)-1,3,4-oxadiazole
(4)
128.5, 127.5, 116.6, 114.4, 55.5, 51.3, 32.6, 21.4, 20.8. HRMS (ESI) m/z
calcd. for C19H21N2O2 [M þ H]þ 309.1598, found 309.1599.
According to the general procedure A, the product 4 was ob-
tained in (27.4 mg, 89% yield). 1H NMR (400 MHz, CDCl3)
4.2.8. 2-(cyclopentyl(phenyl)methyl)-5-(4-methoxyphenyl)-1,3,4-
oxadiazole (10)
d
7.95e7.91 (m, 2H), 7.26e7.20 (m, 1H), 7.16e7.14 (m, 2H), 7.08 (d,
J ¼ 7.8 Hz, 1H), 6.98e6.94 (m, 2H), 4.09 (t, J ¼ 7.8 Hz, 1H), 3.85 (s,
According to the general procedure A, the product 10 was ob-
3H), 2.38e2.28 (m, 1H), 2.34 (s, 3H), 2.17e2.06 (m, 1H), 0.98 (t,
tained in (30.4 mg, 91% yield). 1H NMR (400 MHz, CDCl3)
J ¼ 7.3 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d
167.7, 164.8, 162.2,
d 7.96e7.92 (m, 2H), 7.43e7.40 (m, 2H), 7.35e7.31 (m, 2H),
139.0, 138.5, 128.7, 128.6(2), 128.6(0), 128.3, 124.9, 116.6, 114.4, 55.4,
45.1, 27.5, 21.5, 12.2. HRMS (ESI) m/z calcd. for C19H21N2O2 [M þ H]þ
309.1598, found 309.1597.
7.28e7.23 (m, 1H), 6.99e6.95 (m, 2H), 3.99 (d, J ¼ 11.0 Hz, 1H), 3.85
(s, 3H), 2.85e2.74 (m, 1H), 1.92e1.83 (m, 1H), 1.72e1.51 (m, 5H),
1.37e1.27 (m, 1H), 1.22e1.16 (m, 1H). 13C NMR (100 MHz, CDCl3)
d
167.6, 164.6, 162.2, 139.1, 128.7, 128.6, 128.3, 127.4, 116.6, 114.4,
4.2.3. 2-(1-(4-(tert-Butyl)phenyl)propyl)-5-(4-methoxyphenyl)-
1,3,4-oxadiazole (5)
55.4, 49.2, 44.0, 31.6, 31.4, 25.1, 25.0. HRMS (ESI) m/z calcd. for
C
21H23N2O2 [M þ H]þ 335.1754, found 335.1755.
According to the general procedure A, the product 5 was ob-
tained in (24.2 mg, 69% yield). 1H NMR (400 MHz, CDCl3)
4.2.9. 2-(4-Methoxyphenyl)-5-(1-phenylbut-3-en-1-yl)-1,3,4-
oxadiazole (11)
d
7.96e7.92 (m, 2H), 7.37e7.34 (m, 2H), 7.30e7.27 (m, 2H),
6.98e6.95 (m, 2H), 4.12 (t, J ¼ 7.8 Hz,1H), 3.85 (s, 3H), 2.38e2.27 (m,
According to the general procedure A, the product 11 was ob-
1H), 2.15e2.08 (m, 1H), 1.30 (s, 9H), 0.98 (t, J ¼ 7.4 Hz, 3H). 13C NMR
tained in (23.6 mg, 77% yield). 1H NMR (400 MHz, CDCl3)
(100 MHz, CDCl3)
d
167.7, 164.7, 162.1, 150.3, 136.0, 128.6, 127.5,
d 7.95e7.91 (m, 2H), 7.39e7.32 (m, 4H), 7.30e7.26 (m, 1H),
125.7, 116.6, 114.4, 55.4, 44.6, 34.5, 31.3, 27.6, 12.3. HRMS (ESI) m/z
6.98e6.95 (m, 2H), 5.83e5.73 (m, 1H), 5.11 (dq, J ¼ 17.1, 1.5 Hz, 1H),
calcd. for C22H27N2O2 [M þ H]þ 351.2067, found 351.2067.
5.04e5.00 (m, 1H), 4.33 (t, J ¼ 7.8 Hz,1H), 3.85 (s, 3H), 3.10e7.91 (m,
1H), 2.89e2.81 (m, 1H). 13C NMR (100 MHz, CDCl3)
d 167.1, 164.9,
4.2.4. 2-(1-(4-Fluorophenyl)propyl)-5-(4-Methoxyphenyl)-1,3,4-
oxadiazole (6)
162.2, 138.6, 134.6, 128.9, 128.6, 127.9, 127.6, 117.9, 116.5, 114.4, 55.5,
43.4, 38.4. HRMS (ESI) m/z calcd. for C19H19N2O2 [M þ H]þ 307.1441,
found 307.1442.
According to the general procedure A, the product 6 was ob-
tained in (25.3 mg, 81% yield). 1H NMR (400 MHz, CDCl3)
d
7.95e7.91 (m, 2H), 7.36e7.31 (m, 2H), 7.06e7.00 (m, 2H),
4.2.10. 2-(4-Chloro-1-phenylbutyl)-5-(4-methoxyphenyl)-1,3,4-
oxadiazole (12)
6.99e6.95 (m, 2H), 4.13 (t, J ¼ 7.8 Hz,1H), 3.86 (s, 3H), 2.38e2.27 (m,
1H), 2.15e2.04 (m, 1H), 0.98 (t, J ¼ 7.4 Hz, 3H). 13C NMR (100 MHz,
According to the general procedure A, the product 12 was ob-
CDCl3)
d
166.1 (d, J ¼ 257.3 Hz), 163.3, 162.2, 160.9, 134.7 (d,
tained in (19.8 mg, 58% yield). 1H NMR (400 MHz, CDCl3)
J ¼ 3.3 Hz), 129.5 (d, J ¼ 8.1 Hz), 128.6, 116.4, 115.7 (d, J ¼ 21.5 Hz),
d
7.95e7.90 (m, 2H), 7.36 (d, J ¼ 4.4 Hz, 4H), 7.32e7.28 (m, 1H),
114.4, 55.5, 44.3, 27.6, 12.1. 19F NMR (376 MHz, CDCl3):
d
ꢀ115.1.
6.98e6.95 (m, 2H), 4.25 (t, J ¼ 7.8 Hz, 1H), 3.85 (s, 3H), 3.56 (td,
J ¼ 6.4, 2.1 Hz, 2H), 2.50e2.42 (m, 1H), 2.33e2.22 (m, 1H), 1.93e1.78
HRMS (ESI) m/z calcd. for C18H18FN2O3 [M þ H]þ 313.1347, found
313.1347.
(m, 2H). 13C NMR (100 MHz, CDCl3)
d 167.1,165.0,162.3,138.6,129.0,
128.6, 127.8(2), 127.7(8), 116.4, 114.4, 55.5, 44.4, 42.8, 31.5, 30.3.
35
4.2.5. 2-(4-Methoxyphenyl)-5-(1-(3-(thiophen-3-yl)phenyl)
propyl)-1,3,4-oxadiazole (7)
HRMS (ESI) m/z calcd. for C
H
19 20
ClN2O2 [M þ H]þ 343.1208, found
37
343.1210; for C H
19 20
ClN2O2 [M þ H]þ 345.1178, found 345.1181.
According to the general procedure A, the product 7 was ob-
tained in (34.6 mg, 92% yield). 1H NMR (400 MHz, CDCl3)
4.2.11. 2-(4-((tert-Butyldiphenylsilyl)oxy)-1-phenylbutyl)-5-(4-
methoxyphenyl)-1,3,4-oxadiazole (13)
d
7.95e7.92 (m, 2H), 7.58 (t, J ¼ 1.8 Hz, 1H), 7.51 (dt, J ¼ 7.7, 1.4 Hz,
1H), 7.45 (t, J ¼ 2.1 Hz,1H), 7.39e7.35 (m, 3H), 7.29 (dt, J ¼ 7.7, 1.5 Hz,
1H), 6.99e6.93 (m, 2H), 4.18 (t, J ¼ 7.8 Hz, 1H), 3.84 (s, 3H),
2.44e2.33 (m, 1H), 2.22e2.10 (m, 1H), 1.01 (t, J ¼ 7.4 Hz, 3H). 13C
According to the general procedure A, the product 13 was ob-
tained in 34.8 mg, 62% yield). 1H NMR (400 MHz, CDCl3)
d 7.96e7.89
(m, 2H), 7.65e7.61 (m, 4H), 7.42e7.30 (m, 10H), 7.29e7.25 (m, 1H),
6.98e6.94 (m, 2H), 4.24 (t, J ¼ 7.9 Hz, 1H), 3.85 (s, 3H), 3.69 (t,
J ¼ 6.2 Hz, 2H), 2.45e2.35 (m, 1H), 2.26e2.16 (m, 1H), 1.62e1.56 (m,
NMR (100 MHz, CDCl3)
d 167.5, 164.9, 162.2, 141.9, 139.7, 136.4,
129.3, 128.6, 126.6, 126.4, 126.3, 126.1, 125.7, 120.7, 116.5, 114.4, 55.4,
45.2, 27.5, 12.3. HRMS (ESI) m/z calcd. for C22H21N2O2S [M þ H]þ
377.1318, found 377.1319.
2H), 1.03 (s, 9H). 13C NMR (100 MHz, CDCl3)
d 167.6, 164.8, 162.2,
139.1, 135.6, 133.8, 129.6, 128.9,128.6, 127.9, 127.7, 127.5, 116.6, 114.4,
5

X.-L. Su, S.-P. Jiang, L. Ye et al.
Tetrahedron xxx (xxxx) xxx
63.3, 55.5, 43.0, 30.6, 30.2, 26.9, 19.2. HRMS (ESI) m/z calcd. for
C
279.1492, found 279.1494.
35H39N2O3Si [M þ H]þ 563.2724, found 563.2730.
4.2.18. 2-(1-Phenylpropyl)-5-(o-tolyl)-1,3,4-oxadiazole (20)
According to the general procedure A, the product 20 (25.9 mg,
4.2.12. 2-(4-methoxyphenyl)-5-(1,2,3,4-tetrahydronaphthalen-1-
yl)-1,3,4-oxadiazole (14)
93% yield). 1H NMR (400 MHz, CDCl3)
d
7.86 (dd, J ¼ 7.8, 1.4 Hz, 1H),
According to the general procedure A, the product 14 was ob-
7.39e7.34 (m, 4H), 7.30e7.25 (m, 4H), 4.18 (t, J ¼ 7.8 Hz, 1H), 2.65 (s,
tained in (15.3 mg, 50% yield). 1H NMR (400 MHz, CDCl3)
3H), 2.41e2.30 (m, 1H), 2.22e2.10 (m, 1H), 0.99 (t, J ¼ 7.4 Hz, 3H).
d
7.97e7.93 (m, 2H), 7.23e7.17 (m, 2H), 7.16e7.14 (m, 2H), 7.02e6.97
13C NMR (100 MHz, CDCl3)
d 167.7, 165.1, 139.0, 138.3, 131.7, 131.1,
(m, 2H), 4.61 (t, J ¼ 6.6 Hz, 1H), 3.88 (s, 3H), 3.02e2.86 (m, 2H),
128.9(3), 128.9(5), 127.9, 127.6, 126.1, 123.1, 45.1, 27.5, 22.0, 12.2.
HRMS (ESI) m/z calcd. for C18H19N2O [M þ H]þ 279.1492, found
279.1494.
2.35e2.22 (m, 2H), 2.19e2.10 (m, 1H), 1.97e1.88 (m, 1H). 13C NMR
(100 MHz, CDCl3)
d 168.6, 164.9, 162.2, 137.1, 133.0, 129.7, 129.1,
128.6, 127.2, 126.2, 116.6, 114.4, 55.5, 36.6, 29.2, 27.9, 21.0. HRMS
(ESI) m/z calcd. for C19H19N2O2 [M þ H]þ 307.1441, found 307.1443.
4.2.19. 2-(4-Bromophenyl)-5-(1-phenylpropyl)-1,3,4-oxadiazole
(21)
4.2.13. 2-(4-Methoxyphenyl)-5-(1-(thiophen-3-yl)propyl)-1,3,4-
oxadiazole (15)
According to the general procedure A, the product 21 (28.9 mg,
84% yield). 1H NMR (400 MHz, CDCl3)
d 7.88e7.85 (m, 2H),
According to the general procedure A, the product 15 was ob-
7.62e7.59 (m, 2H), 7.35 (d, J ¼ 4.3 Hz, 4H), 7.31e7.27 (m, 1H), 4.15 (t,
tained in (21.3 mg, 71% yield). 1H NMR (400 MHz, CDCl3)
d
J ¼ 7.8 Hz, 1H), 2.41e2.30 (m, 1H), 2.19e2.08 (m, 1H), 0.99 (t,
7.99e7.95 (m, 2H), 7.32 (dd, J ¼ 5.0, 3.0 Hz, 1H), 7.23 (dd, J ¼ 3.1,
J ¼ 7.4 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d 168.3, 164.2, 138.8,
132.3, 128.9, 128.3, 127.9, 127.6, 126.2, 122.9, 45.1, 27.5, 12.2. HRMS
1.3 Hz, 1H), 7.12 (dd, J ¼ 5.0, 1.4 Hz, 1H), 7.03e6.97 (m, 2H), 4.34 (t,
79
J ¼ 7.7 Hz, 1H), 3.88 (s, 3H), 2.35e2.24 (m, 1H), 2.22e2.10 (m, 1H),
(ESI) m/z calcd. for C
H
BrN2O [M þ H]þ 343.0441, found
17 16
81
1.01 (t, J ¼ 7.4 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d
167.3, 164.8,
343.0443, C
H
BrN2O [M þ H]þ 345.0420 found 345.0422.
17 16
162.2, 139.3, 128.6, 127.0, 126.2, 122.2, 116.5, 114.4, 55.5, 40.3, 27.5,
12.1. HRMS (ESI) m/z calcd. for C16H17N2O2S [M þ H]þ 301.1005,
found 301.1006.
4.2.20. 2-(1-Phenylpropyl)-5-(4-(trifluoromethyl)phenyl)-1,3,4-
oxadiazole (22)
According to the general procedure A, the product 22 was ob-
4.2.14. 2-Phenyl-5-(1-phenylpropyl)-1,3,4-oxadiazole (16)
tained in (15.7 mg, 63% yield). 1H NMR (400 MHz, CDCl3)
d 8.13 (d,
According to the general procedure A, the product 16 was ob-
J ¼ 7.9 Hz, 2H), 7.74 (d, J ¼ 8.9 Hz, 2H), 7.38e7.33 (m, 4H), 7.31e7.27
tained in (23.8 mg, 90% yield). 1H NMR (400 MHz, CDCl3)
d
(m, 1H), 4.18 (t, J ¼ 7.8 Hz, 1H), 2.43e2.32 (m, 1H), 2.24e2.10 (m,
8.01e7.99 (m, 2H), 7.52e7.44 (m, 3H), 7.38e7.32 (m, 4H),
1H),1.00 (t, J ¼ 7.4 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d 168.8,163.7,
7.30e7.25 (m, 1H), 4.16 (t, J ¼ 7.8 Hz, 1H), 2.41e2.30 (m, 1H),
138.6, 133.2 (q, J ¼ 32.9 Hz), 128.9, 127.9, 127.7, 127.2, 126.0 (q,
2.20e2.09 (m, 1H), 0.99 (t, J ¼ 7.4 Hz, 3H). 13C NMR (100 MHz,
J ¼ 3.9 Hz), 123.6 (q, J ¼ 272.5 Hz), 45.2, 27.5, 12.2. 19F NMR
CDCl3)
d
168.1, 164.9, 138.9, 131.6, 129.0, 128.9, 127.9, 127.6, 126.9,
(376 MHz, CDCl3)
d
ꢀ63.11. HRMS (ESI) m/z calcd. for C18H16F3N2O
124.0, 45.1, 27.5, 12.2. HRMS (ESI) m/z calcd. for C17H17N2O [M þ H]þ
[M þ H]þ 333.1209, found 333.1210.
265.1335, found 265.1336.
4.2.21. 2-(3-Chlorophenyl)-5-(1-phenylpropyl)-1,3,4-oxadiazole
(23)
4.2.15. 2-(4-(tert-Butyl) phenyl)-5-(1-phenylpropyl)-1,3,4-
oxadiazole (17)
According to the general procedure A, the product 23 was ob-
According to the general procedure A, the product 17 was ob-
tained in (22.7 mg,76% yield) isolated. 1H NMR (400 MHz, CDCl3)
tained in (30.1 mg, 94% yield). 1H NMR (400 MHz, CDCl3)
d
7.93 (d,
d
7.97 (t, J ¼ 1.8 Hz, 1H), 7.90 (dt, J ¼ 7.7, 1.4 Hz, 1H), 7.49e7.46 (m,
J ¼ 8.6 Hz, 2H), 7.48 (d, J ¼ 8.6 Hz, 2H), 7.38e7.32 (m, 4H), 7.29e7.25
(m, 1H), 4.16 (t, J ¼ 7.8 Hz, 1H), 2.40e2.29 (m, 1H), 2.19e2.08 (m,
1H), 1.33 (s, 9H), 0.98 (t, J ¼ 7.4 Hz, 3H). 13C NMR (100 MHz, CDCl3)
1H), 7.41 (t, J ¼ 7.8 Hz, 1H), 7.37e7.31 (m, 4H), 7.30e7.27 (m, 1H),
4.16 (t, J ¼ 7.8 Hz, 1H), 2.41e2.30 (m, 1H), 2.20e2.09 (m, 1H), 0.99 (t,
J ¼ 7.3 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d 168.5, 163.8, 138.7,
d
167.8, 165.0, 155.2, 139.0, 128.8, 127.9, 127.5, 126.7, 125.9, 121.2,
135.1, 131.6, 130.4, 128.9, 127.9, 127.7, 126.8, 125.6, 125.0, 45.1, 27.5,
35
45.1, 35.0, 31.1, 27.6, 12.2. HRMS (ESI) m/z calcd. for C21H25N2O [M þ
12.2. HRMS (ESI) m/z calcd. for C
found 299.0947; for C
301.0917.
H
17 16
ClN2O [M þ H]þ 299.0946,
37
H]þ 321.1961, found 321.1962.
H
ClN2O [M þ H]þ 301.0916 found
17 15
4.2.16. 2-(1-Phenylpropyl)-5-(p-tolyl)-1,3,4-oxadiazole (18)
According to the general procedure A, the product 18 was ob-
4.2.22. 2-(Naphthalen-1-yl)-5-(1-phenylpropyl)-1,3,4-oxadiazole
(24)
tained in (22.5 mg, 81% yield). 1H NMR (400 MHz, CDCl3)
d 7.88 (d,
J ¼ 8.3 Hz, 2H), 7.38e7.32 (m, 4H), 7.29e7.25 (m, 3H), 4.15 (t,
According to the general procedure A, the product 24 was ob-
J ¼ 7.8 Hz, 1H), 2.40 (s, 3H), 2.37e2.29 (m, 1H), 2.17e7.25 (m, 1H),
tained in (22.3 mg, 71% yield). 1H NMR (400 MHz, CDCl3)
d 9.16 (d,
0.98 (t, J ¼ 7.4 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d
167.8, 165.0,
J ¼ 8.4 Hz, 1H), 8.08 (d, J ¼ 7.3 Hz, 1H), 7.99 (d, J ¼ 8.4 Hz, 1H),
7.91e7.88 (m, 1H), 7.66e7.62 (m, 1H), 7.58e7.51 (m, 2H), 7.43e7.35
(m, 4H), 7.31e7.27 (m, 1H), 4.23 (t, J ¼ 7.8 Hz, 1H), 2.46e2.35 (m,
1H), 2.45e2.15 (m, 1H), 1.03 (t, J ¼ 7.4 Hz, 3H). 13C NMR (100 MHz,
142.1, 139.0, 129.7, 128.8, 127.9, 126.8, 121.2, 45.1, 27.6, 21.6, 12.2.
HRMS (ESI) m/z calcd. for C18H19N2O [M þ H]þ 279.1492, found
279.1494.
CDCl3)
d 167.7, 164.9, 139.0, 133.8, 132.4, 130.1, 128.9, 128.6, 128.3,
4.2.17. 2-(1-Phenylpropyl)-5-(m-tolyl)-1,3,4-oxadiazole (19)
According to the general procedure A, the product 19 was ob-
128.1, 128.0, 127.6, 126.7, 126.2, 124.8, 120.6, 45.1, 27.6, 12.2. HRMS
(ESI) m/z calcd. for C21H19N2O [M þ H]þ 315.1492, found 315.1493.
tained (23.9 mg, 86% yield). 1H NMR (400 MHz, CDCl3)
d 7.82 (br s,
1H), 7.79 (d, J ¼ 7.5 Hz, 1H), 7.38e7.34 (m, 4H), 7.33e7.24 (m, 3H),
4.2.23. 2-(1-Phenylpropyl)-5-(pyridin-3-yl)-1,3,4-oxadiazole (25)
According to the general procedure A, the product 25 was ob-
4.16 (t, J ¼ 7.8 Hz, 1H), 2.40 (s, 3H), 2.37e2.30 (m, 1H), 2.19e2.08 (m,
1H), 0.99 (t, J ¼ 7.3 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d
168.0,
tained in (19.1 mg, 72% yield). 1H NMR (400 MHz, CDCl3)
d 9.21 (s,
165.0, 139.0, 138.8, 132.4, 128.9, 127.9, 127.5, 127.4, 124.0, 123.9, 45.1,
1H), 8.75 (br s, 1H), 8.31 (dt, J ¼ 8.0, 1.9 Hz, 1H), 7.43 (dd, J ¼ 8.0,
27.5, 21.3, 12.2. HRMS (ESI) m/z calcd. for C18H19N2O [M þ H]þ
4.8 Hz, 1H), 7.38e7.34 (m, 4H), 7.31e7.27 (m, 1H), 4.18 (t, J ¼ 7.8 Hz,
6

X.-L. Su, S.-P. Jiang, L. Ye et al.
Tetrahedron xxx (xxxx) xxx
1H), 2.43e2.28 (m, 1H), 2.24e2.08 (m, 1H), 1.00 (t, J ¼ 7.4 Hz, 3H).
J ¼ 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d 197.8, 169.4, 151.3,
13C NMR (100 MHz, CDCl3)
d
168.7, 162.8, 152.3, 147.8, 138.6, 134.2,
150.8, 147.0, 135.3, 129.4, 128.6, 127.8, 125.1, 120.7, 119.6, 44.5, 26.6,
21.4, 21.1. HRMS (ESI) m/z calcd. for C18H19O3 [M þ H]þ 283.1329,
found 283.1329.
129.0, 127.9, 127.7, 123.8, 120.6, 45.1, 27.5, 12.2. HRMS (ESI) m/z
calcd. for C16H16N3O [M þ H]þ 266.1288, found 266.1288.
4.2.24. 2-Phenethyl-5-(1-phenylpropyl)-1,3,4-oxadiazole (26)
According to the general procedure A, the product 26 was ob-
tained in (23.1 mg, 79% yield). 1H NMR (400 MHz, CDCl3)
4.3.4. 1-(4-(1-(m-tolyl)ethyl)phenyl)ethan-1-one (31)
According to the general procedure B, the product 31 was ob-
tained in (40.5 mg, 85% yield). 1H NMR (400 MHz, CDCl3)
d 7.85 (d,
d
7.35e7.31 (m, 2H), 7.30e7.17 (m, 6H), 7.14e7.11 (m, 2H), 4.03 (t,
J ¼ 8.0 Hz, 2H), 7.33e7.07 (m, 6H), 4.36 (q, J ¼ 7.2 Hz, 1H), 2.55 (s,
J ¼ 7.8 Hz, 1H), 3.12e3.02 (m, 4H), 2.30e2.19 (m, 1H), 2.10e2.00 (m,
3H), 2.20 (s, 3H), 1.62 (d, J ¼ 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3)
1H), 0.92 (t, J ¼ 7.4 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d
168.2,
d 197.8, 152.2, 142.3,135.9, 135.1, 129.2,128.5,127.7,127.4, 44.4, 26.5,
21.5, 20.9.
166.4, 139.5, 139.0, 128.8, 128.6, 128.3, 127.9, 127.5, 126.6, 45.0, 32.6,
27.2 (9), 27.2 (7), 12.13. HRMS (ESI) m/z calcd. for C19H21N2O [M þ
H]þ 293.1648, found 293.1648.
4.3.5. 1-(4-(1-(o-tolyl)ethyl)phenyl)ethan-1-one (32)
According to the general procedure B, the product 32 was ob-
4.2.25. 5-Phenyl-2-(1-phenylpropyl)benzo[d]oxazole (27)
tained in (30.0 mg, 63% yield). 1H NMR (400 MHz, CDCl3)
d 7.85 (d,
According to the general procedure A, the product 27 was ob-
J ¼ 8.0 Hz, 2H), 7.33e7.07 (m, 6H), 4.36 (q, J ¼ 7.2 Hz, 1H), 2.55 (s,
tained in (11.0 mg, 35% yield). 1H NMR (400 MHz, CDCl3)
d 7.90 (t,
3H), 2.20 (s, 3H), 1.62 (d, J ¼ 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3)
J ¼ 1.2 Hz, 1H), 7.63e7.58 (m, 2H), 7.53e7.49 (m, 2H), 7.47e7.28 (m,
d 197.7, 152.0, 142.9, 136.0, 135.0, 130.5, 128.5, 127.8, 126.6, 126.4,
8H), 4.15 (t, J ¼ 7.8 Hz, 1H), 2.49e2.38 (m, 1H), 2.24e2.11 (m, 1H),
126.1, 41.1, 26.5, 21.8, 19.7. HRMS (ESI) m/z calcd. for C17H19O [M þ
1.00 (t, J ¼ 7.3 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d
168.8, 150.4,
H]þ 239.1430, found 239.1431.
141.9, 141.2, 139.8,138.1, 128.9,128.8,128.0,127.5,127.4, 127.2, 124.2,
118.4, 110.5, 48.0, 27.6, 12.3. HRMS (ESI) m/z calcd. for C22H20NO
[M þ H]þ 313.1539, found 313.1539.
4.3.6. 1-(4-(1-(p-tolyl)ethyl)phenyl)ethan-1-one (33)
According to the general procedure B, the product 33 was ob-
tained in (45.8 mg, 96% yield). 1H NMR (400 MHz, CDCl3)
d 7.85 (d,
4.3. General procedures B for cross-coupling of racemic alkyl
bromides with organoboronate esters
J ¼ 8.0 Hz, 2H), 7.33e7.07 (m, 6H), 4.36 (q, J ¼ 7.2 Hz, 1H), 2.55 (s,
3H), 2.20 (s, 3H), 1.62 (d, J ¼ 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d
197.8, 152.1, 145.2, 138.0, 135.1, 128.5, 128.4, 128.3, 127.8, 127.1,
To a flame-dried Schlenk tube equipped with a magnetic stir bar
were added CuI (3.8 mg, 0.020 mmol, 10 mol%), L7 (9.4 mg,
0.024 mmol, 12 mol%), LiOtBu (32 mg, 0.40 mmol, 2.0 equiv), and an
appropriate organoboronate esters (0.20 mmol, 1.0 equiv). The tube
was evacuated and backfilled with argon for three times, and then,
an appropriate alkyl bromide (0.30 mmol, 1.5 equiv), and anhy-
drous DMSO (2.4 mL) were sequentially added. The reaction
mixture was stirred at room temperature for 3 h. The resulting
reaction mixture was diluted with 10 mL ethyl acetate and washed
with brine (10 mL ꢁ 3). The organic layer was dried over anhydrous
Na2SO4 and filtered through a pad of celite. The organic solvent was
removed under vacuum and the residue was purified by column
chromatography on silica gel to afford the desired product.
124.5, 44.7, 26.5, 21.5, 21.4.
4.3.7. 1-(4-(1-(4-bromophenyl)ethyl)phenyl)ethan-1-one (34)
According to the general procedure B, the product 34 was ob-
tained in (42.4 mg, 70% yield). 1H NMR (400 MHz, CDCl3)
d 7.88 (d,
J ¼ 8.4 Hz, 2H), 7.40 (d, J ¼ 8.4 Hz, 2H), 7.27 (d, J ¼ 8.4 Hz, 2H), 7.07
(d, J ¼ 8.4 Hz, 2H), 4.16 (q, J ¼ 7.2 Hz, 1H), 2.56 (s, 3H), 1.63 (d,
J ¼ 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d 197.7,151.2,144.3,135.3,
131.5, 129.3, 128.6, 127.7, 120.1, 44.2, 26.5, 21.4. HRMS (ESI) m/z
calcd. for C16H16BrO [M þ H]þ 303.0379, found 303.0381.
4.3.8. 1-(4-(1-([1,10-biphenyl]-4-yl)ethyl)phenyl)ethan-1-one (35)
According to the general procedure B, the product 35 was ob-
tained in (39.2 mg, 65% yield). 1H NMR (400 MHz, CDCl3)
4.3.1. 1-(4-(1-phenylethyl)phenyl)ethan-1-one (28)
d
7.92e7.85 (m, 2H), 7.59e7.53 (m, 2H), 7.51 (d, J ¼ 8.4 Hz, 2H),
According to the general procedure B, the product 28 was ob-
7.44e7.38 (m, 2H), 7.36e7.23 (m, 5H), 4.23 (q, J ¼ 7.2 Hz,1H), 2.55 (s,
tained in (40.4 mg, 90% yield). 1H NMR (400 MHz, CDCl3)
d
7.88 (d,
3H),1.68 (d, J ¼ 6.8 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d 197.7,151.8,
J ¼ 8.0 Hz, 2H), 7.36e7.25 (m, 4H), 7.23e7.16 (m, 3H), 4.20 (q,
144.4,140.7,139.2,135.2,128.7,128.6,127.9,127.8,127.2,127.1,126.9,
44.5, 26.5, 21.5. HRMS (ESI) m/z calcd. for C22H21O [M þ H]þ
301.1587, found 301.1589.
J ¼ 7.2 Hz, 1H), 2.56 (s, 3H), 1.65 (d, J ¼ 7.2 Hz, 3H). 13C NMR
(100 MHz, CDCl3)
d 197.8, 152.0, 145.3, 135.1, 128.5(4), 128.4(9),
127.8, 127.5, 126.3, 44.8, 26.5, 21.5.
4.3.9. methyl 4-(1-(4-acetylphenyl)ethyl)benzoate (36)
4.3.2. 1-(4-(1-(3-methoxyphenyl)ethyl)phenyl)ethan-1-one (29)
According to the general procedure B, the product 29 was ob-
According to the general procedure B, the product 36 was ob-
tained in (33.9 mg, 60% yield). 1H NMR (400 MHz, CDCl3)
d 7.96 (d,
tained in (28.0 mg, 55% yield). 1H NMR (400 MHz, CDCl3)
d
7.87 (d,
J ¼ 8.4 Hz, 2H), 7.89 (d, J ¼ 8.4 Hz, 2H), 7.33e7.23 (m, 4H), 4.25 (q,
J ¼ 8.4 Hz, 2H), 7.31 (d, J ¼ 8.4 Hz, 2H), 7.27e7.16 (m, 1H), 6.87e6.69
J ¼ 7.2 Hz, 1H), 3.89 (s, 3H), 2.57 (s, 3H), 1.67 (d, J ¼ 7.2 Hz, 3H). 13C
(m, 3H), 4.17 (q, J ¼ 7.2 Hz, 1H), 3.76 (s, 3H), 2.56 (s, 3H), 1.64 (d,
NMR (100 MHz, CDCl3)
d 197.6, 166.8, 150.9, 150.5, 135.4, 129.8,
J ¼ 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d
197.7,159.7,151.8, 146.9,
128.6,128.3,127.8,127.6, 52.0, 44.7, 26.5, 21.2. HRMS (ESI) m/z calcd.
135.1, 129.4, 128.5, 127.7, 120.0, 113.8, 111.1, 55.1, 44.7, 26.5, 21.4.
HRMS (ESI) m/z calcd. for C17H19O2 [M þ H]þ 255.1380, found
255.1379.
for C18H19O3 [M þ H]þ 283.1329, found 283.1330.
4.3.10. 1-(3-(1-(4-acetylphenyl)ethyl)phenyl)ethan-1-one (37)
According to the general procedure B, the product 37 was ob-
4.3.3. 3-(1-(4-acetylphenyl)ethyl)phenyl acetate (30)
tained in (36.7 mg, 69% yield). 1H NMR (400 MHz, CDCl3)
d 7.89 (d,
According to the general procedure B, the product 30 was ob-
J ¼ 8.4 Hz, 2H), 7.85 (s, 1H), 7.82e7.77 (m, 1H), 7.42e7.37 (m, 2H),
tained in (29.2 mg, 52% yield). 1H NMR (400 MHz, CDCl3)
d 7.89 (d,
7.31 (d, J ¼ 8.4 Hz, 2H), 4.27 (q, J ¼ 7.2 Hz, 1H), 2.58 (s, 3H), 2.57 (s,
J ¼ 6.4 Hz, 2H), 7.38e7.27 (m, 3H), 7.07 (d, J ¼ 7.6 Hz, 1H), 6.99e6.86
3H),1.69 (d, J ¼ 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d 198.1,197.6,
(m, 2H), 4.21 (q, J ¼ 7.2 Hz, 1H), 2.57 (s, 3H), 2.27 (s, 3H), 1.65 (d,
151.1, 145.9, 137.3, 135.3, 132.3, 128.7, 128.6, 127.7, 127.0, 126.6, 44.6,
7

X.-L. Su, S.-P. Jiang, L. Ye et al.
Tetrahedron xxx (xxxx) xxx
26.6, 26.5, 21.4. HRMS (ESI) m/z calcd. for C18H19O2 [M þ H]þ
4.3.18. 1-(4-(1-phenylbut-3-en-1-yl)phenyl)ethan-1-one (45)
According to the general procedure B, the product 45 was ob-
tained in (31.5 mg, 63% yield). 1H NMR (400 MHz, CDCl3)
7.87 (d,
267.1380, found 267.1380.
d
4.3.11. 3-(1-(4-acetylphenyl)ethyl)benzonitrile (38)
J ¼ 6.4 Hz, 2H), 7.36e7.25 (m, 4H), 7.24e7.16 (m, 3H), 5.79e5.61 (m,
According to the general procedure B, the product 38 was ob-
1H), 5.08e4.91 (m, 2H), 4.07 (t, J ¼ 8.0 Hz, 1H), 2.89e2.77 (m, 2H),
tained in (30.7 mg, 55% yield). 1H NMR (400 MHz, CDCl3)
d
7.91 (d,
2.55 (s, 3H). 13C NMR (100 MHz, CDCl3)
d 197.7, 150.0, 143.5, 136.1,
J ¼ 8.4 Hz, 2H), 7.53e7.48 (m, 2H), 7.47e7.37 (m, 2H), 7.28 (d,
135.2, 128.6, 128.5, 128.1, 127.8, 126.5, 116.7, 51.1, 39.5, 26.5. HRMS
J ¼ 8.4 Hz, 2H), 4.24 (q, J ¼ 7.2 Hz,1H), 2.59 (s, 3H),1.67 (d, J ¼ 6.8 Hz,
(ESI) m/z calcd. for C18H19O [M þ H]þ 251.1430, found 251.1431.
3H). 13C NMR (100 MHz, CDCl3)
d 197.6, 150.1, 146.8, 135.6, 132.2,
131.1, 130.1, 129.3, 128.8, 127.7, 118.8, 112.6, 44.4, 26.6, 21.2. HRMS
4.3.19. 1-(4-(3-bromo-1-phenylpropyl)phenyl)ethan-1-one (46)
According to the general procedure B, the product 46 was ob-
(ESI) m/z calcd. for C17H16NO [M þ H]þ 250.1226, found 250.1227.
tained in (33.6 mg, 53% yield). 1H NMR (400 MHz, CDCl3)
d 7.89 (d,
4.3.12. 1-(4-(1-(4-nitrophenyl)ethyl)phenyl)ethan-1-one (39)
According to the general procedure B, the product 39 was ob-
J ¼ 8.0 Hz, 2H), 7.38e7.27 (m, 4H), 7.27e7.18 (m, 3H), 4.28 (t,
J ¼ 8.0 Hz, 1H), 3.31 (t, J ¼ 6.8 Hz, 2H), 2.63e2.53 (m, 5H). 13C NMR
tained in (20.5 mg, 38% yield). 1H NMR (400 MHz, CDCl3)
d
8.15 (d,
(100 MHz, CDCl3) d 197.6, 149.0, 142.3, 135.6, 128.8, 128.7, 128.1,
J ¼ 8.4 Hz, 2H), 7.91 (d, J ¼ 8.4 Hz, 2H), 7.37 (d, J ¼ 8.8 Hz, 2H), 7.30
127.8, 126.9, 49.0, 37.8, 31.6, 26.5. HRMS (ESI) m/z calcd. for
C
(d, J ¼ 8.0 Hz, 2H), 4.32 (q, J ¼ 7.2 Hz, 1H), 2.58 (s, 3H), 1.70 (d,
17H18BrO [M þ H]þ 317.0536, found 317.0538.
J ¼ 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d 197.6, 152.8, 149.9,
146.5,135.7,128.8,128.4,127.8,123.8, 44.7, 26.5, 21.2. HRMS (ESI) m/
4.3.20. 5-(4-acetylphenyl)-5-phenylpentanenitrile (47)
z calcd. for C16H16NO3 [M þ H]þ 270.1125, found 270.1125.
According to the general procedure B, the product 47 was ob-
tained in (30 mg, 54% yield). 1H NMR (400 MHz, CDCl3)
d 7.89 (d,
4.3.13. 1-(4-(1-(naphthalen-1-yl)ethyl)phenyl)ethan-1-one (40)
According to the general procedure B, the product 40 was ob-
J ¼ 8.0 Hz, 2H), 7.39e7.27 (m, 4H), 7.25e7.18 (m, 3H), 3.98 (t,
J ¼ 8.0 Hz, 1H), 2.56 (s, 3H), 2.35 (t, J ¼ 7.2 Hz, 2H), 2.28e2.15 (m,
tained in (34 mg, 62% yield). 1H NMR (400 MHz, CDCl3)
d
7.94 (d,
2H), 1.67e1.54 (m, 2H). 13C NMR (100 MHz, CDCl3)
d 197.6, 149.5,
J ¼ 7.2 Hz, 1H), 7.83 (d, J ¼ 8.0 Hz, 3H), 7.76 (d, J ¼ 8.0 Hz, 1H),
7.51e7.36 (m, 4H), 7.29 (d, J ¼ 8.0 Hz, 2H), 4.94 (q, J ¼ 7.2 Hz, 1H),
2.51 (s, 3H), 1.76 (d, J ¼ 7.6 Hz, 3H). 13C NMR (100 MHz, CDCl3)
142.9, 135.5, 128.8, 128.7, 128.6, 127.9, 127.8, 127.6, 126.8, 119.3, 50.6,
34.1, 26.5, 23.8, 17.1. HRMS (ESI) m/z calcd. for C19H20NO [M þ H]þ
278.1539, found 278.1541.
d
197.7, 152.4, 140.4, 135.1, 134.0, 131.5, 128.8, 128.6, 127.7, 127.3,
126.0, 125.4, 124.3, 123.7, 40.6, 26.5, 22.2.
4.3.21. methyl 5-(4-acetylphenyl)-5-phenylpentanoate (48)
According to the general procedure B, the product 48 was ob-
4.3.14. 1-(4-(1-(naphthalen-2-yl)ethyl)phenyl)ethan-1-one (41)
According to the general procedure B, the product 41 was ob-
tained in (38.3 mg, 59% yield). 1H NMR (400 MHz, CDCl3)
d 7.87 (d,
J ¼ 8.4 Hz, 2H), 7.33 (d, J ¼ 8.0 Hz, 2H), 7.31e7.25 (m, 2H), 7.25e7.15
(m, 3H), 4.10 (q, J ¼ 7.2 Hz, 2H), 3.97 (t, J ¼ 7.6 Hz, 1H), 2.55 (s, 3H),
2.32 (t, J ¼ 7.2 Hz, 2H), 2.17e2.05 (m, 2H), 1.70e1.52 (m, 2H), 1.23 (t,
tained in (31.8 mg, 58% yield). 1H NMR (400 MHz, CDCl3)
d 7.87 (d,
J ¼ 6.4 Hz, 2H), 7.82e7.76 (m, 2H), 7.74 (d, J ¼ 8.4 Hz, 1H), 7.68 (s,
1H), 7.49e7.39 (m, 2H), 7.33 (d, J ¼ 8.4 Hz, 2H), 7.26 (dd, J1 ¼ 8.8 Hz,
J1 ¼ 2.0 Hz, 1H), 4.35 (q, J ¼ 7.2 Hz, 1H), 2.55 (s, 3H), 1.74 (d,
J ¼ 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d 197.7,173.3,150.3,143.7,
135.2, 128.6(1), 128.5(8), 128.0, 127.7, 126.5, 60.2, 51.1, 34.7, 34.0,
26.5, 23.3, 14.2. HRMS (ESI) m/z calcd. for C21H25O3 [M þ H]þ
325.1798, found 325.1800.
J ¼ 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d 197.8,151.8,142.7,135.2,
133.4, 132.1, 128.6, 128.1, 127.9, 127.7, 127.6, 126.5, 126.1, 125.6, 125.4,
44.8, 26.5, 21.4. HRMS (ESI) m/z calcd. for C20H19O [M þ H]þ
275.1430, found 275.1430.
4.3.22. 4-(1-phenylethyl)-1,10-biphenyl (49)
According to the general procedure B, the product 49 was ob-
4.3.15. 1-(4-benzylphenyl)ethan-1-one (42)
tained in (29.5 mg, 57% yield). 1H NMR (400 MHz, CDCl3)
According to the general procedure B, the product 42 was ob-
d 7.59e7.54 (m, 2H), 7.53e7.48 (m, 2H), 7.44e7.37 (m, 2H),
tained in (10.1 mg, 30% yield). 1H NMR (400 MHz, CDCl3)
d
7.88 (d,
7.34e7.23 (m, 7H), 7.22e7.16 (m, 1H), 4.19 (t, J ¼ 7.2 Hz, 1H), 1.67 (d,
J ¼ 8.3 Hz, 2H), 7.32e7.27 (m, 4H), 7.24e7.16 (m, 3H), 4.04 (s, 2H),
J ¼ 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d 146.2, 145.5, 141.0,
138.9, 128.7, 128.4, 128.0, 127.6, 127.1, 127.0(2), 126.9(9), 126.1, 44.4,
21.8.
2.58 (s, 3H). 13C NMR (100 MHz, CDCl3)
d
197.8, 146.8, 140.1 135.3,
129.1, 129.0, 128.7, 126.4, 41.9, 26.6.
4.3.16. 1-(4-(1-phenylpropyl)phenyl)ethan-1-one (43)
4.3.23. 1-(1-phenylethyl)naphthalene (50)
According to the general procedure B, the product 43 was ob-
According to the general procedure B, the product 50 was ob-
tained in (28.6 mg, 60% yield). 1H NMR (400 MHz, CDCl3)
d 7.87 (d,
tained in (24.2 mg, 52% yield). 1H NMR (400 MHz, CDCl3)
J ¼ 8.4 Hz, 2H), 7.39e7.13 (m, 7H), 3.85 (t, J ¼ 8.0 Hz, 1H), 2.55 (s,
d
8.09e7.98 (m, 1H), 7.89e7.80 (m, 1H), 7.73 (d, J ¼ 6.8 Hz, 1H),
3H), 2.09 (dt, J ¼ 14.8 Hz, J ¼ 7.6 Hz, 2H), 0.90 (d, J ¼ 7.6 Hz, 3H). 13C
7.49e7.36 (m, 4H), 7.30e7.20 (m, 4H), 7.20e7.11 (m, 1H), 4.91 (t,
NMR (100 MHz, CDCl3)
d 197.8, 150.8, 144.1, 135.2, 128.6, 128.5,
J ¼ 7.2 Hz, 1H), 1.75 (d, J ¼ 6.8 Hz, 3H). 13C NMR (100 MHz, CDCl3)
128.1, 127.8, 126.3, 53.2, 28.3, 26.5, 12.6. HRMS (ESI) m/z calcd. for
d 146.6, 141.5, 134.0, 131.7, 128.7, 128.4, 127.6, 127.0, 125.9, 125.8,
C
17H19O [M þ H]þ 239.1430, found 239.1432.
125.4, 125.3, 124.3, 123.9, 40.5, 22.5.
4.3.17. 1-(4-(1-phenylbutyl)phenyl)ethan-1-one (44)
4.3.24. 2-(1-phenylethyl)naphthalene (51)
According to the general procedure B, the product 44 was ob-
According to the general procedure B, the product 51 was ob-
tained in (37.8 mg, 75% yield). 1H NMR (400 MHz, CDCl3)
d 7.86 (d,
tained in (31.6 mg, 68% yield). 1H NMR (400 MHz, CDCl3)
J ¼ 8.0 Hz, 2H), 7.39e7.11 (m, 7H), 3.96 (t, J ¼ 8.0 Hz, 1H), 2.54 (s,
d
7.82e7.75 (m, 2H), 7.72 (d, J ¼ 8.8 Hz, 1H), 7.69 (s, 1H), 7.47e7.37
3H), 2.09e1.96 (m, 2H), 1.35e1.21 (m, 2H), 0.92 (t, J ¼ 7.2 Hz, 3H).
(m, 2H), 7.34e7.22 (m, 5H), 7.21e7.15 (m, 1H), 4.30 (t, J ¼ 7.2 Hz,1H),
13C NMR (100 MHz, CDCl3)
d
197.7, 151.0, 144.2, 135.1, 128.5(3),
1.72 (d, J ¼ 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d 146.2, 143.7,
128.4(7), 128.0, 127.8, 126.3, 51.0, 37.5, 26.5, 21.0, 14.0. HRMS (ESI)
133.5, 132.1, 128.4, 127.9, 127.7(3), 127.7(0), 127.5, 126.8, 126.1, 125.9,
125.3(4), 125.3(2), 44.8, 21.7.
m/z calcd. for C18H21O [M þ H]þ 253.1587, found 253.1587.
8

X.-L. Su, S.-P. Jiang, L. Ye et al.
Tetrahedron xxx (xxxx) xxx
(c) M.R. Netherton, C. Dai, K. Neuschütz, G.C. Fu, J. Am. Chem. Soc. 123 (2001)
4.3.25. 3-(1-phenylethyl)thiophene (52)
10099e10100.
According to the general procedure B, the product 52 was ob-
ꢁ
[4] (For selected reviews, see:). (a) S.H. Kyne, G. Lefevre, C. Ollivier, M. Petit, V.-
tained in (29.7 mg, 79% yield). 1H NMR (400 MHz, CDCl3)
A.R. Cladera, L. Fensterbank, Chem. Soc. Rev. 49 (2020) 8501e8542;
ꢀ
(b) A. Guerinot, J. Cossy, Acc. Chem. Res. 53 (2020) 1351e1363;
d
7.31e7.25 (m, 2H), 7.24e7.17 (m, 4H), 6.98e6.94 (m, 1H), 6.87 (dd,
(c) R. Trammell, K. Rajabimoghadam, I. Garcia-Bosch, Chem. Rev. 119 (2019)
2954e3031;
(d) J. Choi, G.C. Fu, Science 356 (2017) eaaf7230;
(e) A.C. Frisch, M. Beller, Angew. Chem. Int. Ed. 44 (2005) 674e688 (for
selected examples, see:);
J1 ¼ 5.2 Hz, J1 ¼1.2 Hz, 1H), 4.15 (q, J ¼ 7.2 Hz, 1H), 1.62 (d, J ¼ 7.2 Hz,
3H). 13C NMR (100 MHz, CDCl3)
d 147.2, 146.2, 128.4, 127.8, 127.4,
126.1, 125.3, 119.8, 40.8, 22.2.
(f) C.-T. Yang, Z.-Q. Zhang, J. Liang, J.-H. Liu, X.-Y. Lu, H.-H. Chen, L. Liu, J. Am.
Chem. Soc. 134 (2012) 11124e11127;
4.3.26. 3-(1-phenylethyl)pyridine (53)
(g) M. Nakamura, K. Matsuo, S. Ito, E. Nakamura, J. Am. Chem. Soc. 126 (2004)
3686e3687;
(h) K. Wakabayashi, H. Yorimitsu, K. Oshima, J. Am. Chem. Soc. 123 (2001)
5374e5375;
(i) A. Devasagayaraj, T. Stüdemann, P. Knochel, Angew Chem. Int. Ed. Engl. 34
(1995) 2723e2725.
According to the general procedure B, the product 53 was ob-
tained in (21.3 mg, 58% yield). 1H NMR (400 MHz, CDCl3)
d 8.48 (d,
J ¼ 7.6 Hz, 2H), 7.48 (d, J ¼ 7.6 Hz, 1H), 7.35e7.26 (m, 2H), 7.25e7.14
(m, 4H), 4.17 (q, J ¼ 7.2 Hz, 1H), 1.66 (d, J ¼ 7.2 Hz, 3H). 13C NMR
(100 MHz, CDCl3)
d 149.3, 147.5, 144.9, 141.5, 134.9, 128.5, 127.5,
[5] For selected reviews on coupling with heteroarene C(sp2)eH bonds, see:. (a)
Y. Xia, D. Qiu, J. Wang, Chem. Rev. 117 (2017) 13810e13889;
(b) L. Ackermann, Chem. Commun. 46 (2010) 4866e4877 (for selected ex-
amples, see:);
126.4, 123.3, 42.4, 21.5.
4.3.27. 4-(1-phenylethyl)pyridine (54)
(c) C. Liu, C.L. Ji, T. Zhou, X. Hong, M. Szostak, Angew. Chem. Int. Ed. (2021),
https://doi.org/10.1002/anie.202100949;
(d) X. Zhao, G. Wu, Y. Zhang, J. Wang, J. Am. Chem. Soc. 133 (2011)
3296e3299;
(e) O. Vechorkin, V. Proust, X. Hu, Angew. Chem. Int. Ed. 49 (2010)
3061e3064;
(f) T. Kawano, K. Hirano, T. Satoh, M. Miura, J. Am. Chem. Soc. 132 (2010)
6900e6901.
According to the general procedure B, the product 54 was ob-
tained in (19.1 mg, 52% yield). 1H NMR (400 MHz, CDCl3)
d
8.50 (s,
2H), 7.34e7.27 (m, 2H), 7.25e7.16 (m, 3H), 7.13 (d, J ¼ 5.2 Hz, 2H),
4.11 (q, J ¼ 7.2 Hz, 1H), 1.63 (d, J ¼ 7.2 Hz, 3H). 13C NMR (100 MHz,
CDCl3)
d 155.0, 149.8, 144.4, 128.6, 127.6, 126.6, 122.9, 44.2, 21.0.
[6] (For selected reviews on coupling with aryl boron reagents, see:). (a)
D.V. Partyka, Chem. Rev. 111 (2011) 1529e1595;
(b) D.G. Hall (Ed.), Boronic Acids: Preparation and Applications in Organic
Synthesis, Medicine and Materials, Wiley-VCH, Weinheim, 2011.
[7] F. Wang, P. Chen, G. Liu, Acc. Chem. Res. 51 (2018) 2036e2046.
Declaration of competing interest
The authors declare that they have no known competing finical
interests or personal relationships that could have appeared to
influence the work reported in this paper.
[8] (a) K. Nakamura, R. Hara, Y. Sunada, T. Nishikata, ACS Catal.
8 (2018)
6791e6795;
(b) Y.-Y. Sun, J. Yi, X. Lu, Z.-Q. Zhang, B. Xiao, Y. Fu, Chem. Commun. 50 (2014)
11060e11062;
(c) P. Ren, I. Salihu, R. Scopelliti, X. Hu, Org. Lett. 14 (2012) 1748e1751;
(d) C.-T. Yang, Z.-Q. Zhang, Y.-C. Liu, L. Liu, Angew. Chem. Int. Ed. 50 (2011)
3904e3907.
Acknowledgement
Financial support from the National Natural Science Foundation
of China (Nos. 21831002, 22025103, and 21801116), Guangdong
Provincial Key Laboratory of Catalysis (No. 2020B121201002),
Guangdong Innovative Program (No. 2019BT02Y335), SUSTech
Special Fund for the Construction of High-Level Universities (No.
G02216303), the Shaanxi Provincial Key Laboratory Project (No.
19JS007), the Project of Science and Technology Department of
Shaanxi Province (No. 2020JQ-894), Baoji University of Arts And
Sciences (No. 209040030) is appreciated. The authors acknowledge
the assistance of the SUSTech Core Research Facilities for technical
support.
[9] (For a review on radical reactions from our group, see:). (a) Q.-S. Gu, Z.-L. Li,
X.-Y. Liu, Acc. Chem. Res. 53 (2020) 170e181, for selected examples, see:);
(b) X.-Y. Dong, Y.-F. Zhang, C.-L. Ma, Q.-S. Gu, F.-L. Wang, Z.-L. Li, S.-P. Jiang, X.-
Y. Liu, Nat. Chem. 11 (2019) 1158e1166;
(c) Y.-X. Cao, X.-Y. Dong, J. Yang, S.-P. Jiang, S. Zhou, Z.-L. Li, G.-Q. Chen, X.-
Y. Liu, Adv. Synth. Catal. 362 (2020) 2280e2284;
(d) X.-Y. Dong, J.-T. Cheng, Y.-F. Zhang, Z.-L. Li, T.-Y. Zhan, J.-J. Chen, F.-
L. Wang, N.-Y. Yang, L. Ye, Q.-S. Gu, X.-Y. Liu, J. Am. Chem. Soc. 142 (2020)
9501e9509;
(e) H.-D. Xia, Z.-L. Li, Q.-S. Gu, X.-Y. Dong, J.-H. Fang, X.-Y. Du, L.-L. Wang, X.-
Y. Liu, Angew. Chem. Int. Ed. 59 (2020) 16926e16932;
(f) C.-J. Yang, C. Zhang, Q.-S. Gu, J.-H. Fang, X.-L. Su, L. Ye, Y. Sun, Y. Tian, Z.-
L. Li, X.-Y. Liu, Nat. Catal. 3 (2020) 539e546;
(g) Z. Chai, Chin. J. Org. Chem. 40 (2020) 3001e3003.
[10] (a) S.-P. Jiang, X.-Y. Dong, Q.-S. Gu, L. Ye, Z.-L. Li, X.-Y. Liu, J. Am. Chem. Soc.
142 (2020) 19652e19659;
Appendix A. Supplementary data
(b) X.-L. Su, L. Ye, J.-J. Chen, X.-D. Liu, S.-P. Jiang, F.-L. Wang, L. Liu, C.-J. Yang,
X.-Y. Chang, Z.-L. Li, Q.-S. Gu, X.-Y. Liu, Angew. Chem. Int. Ed. 60 (2021)
380e384.
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.tet.2021.132152.
[11] For selected examples of cross-coupling reactions to provide 1,1-
diarylalkanes, see:. (a) K.J. Jiao, D. Liu, H.X. Ma, H. Qiu, P. Fang, T.S. Mei,
Angew. Chem. Int. Ed. 59 (2020) 6520e6524;
References
(b) W. Zhang, P. Chen, G. Liu, J. Am. Chem. Soc. 139 (2017) 7709e7712;
(c) A. Vasilopoulos, S.L. Zultanski, S.S. Stahl, J. Am. Chem. Soc. 139 (2017)
7705e7708;
(d) K.E. Poremba, N.T. Kadunce, N. Suzuki, A.H. Cherney, S.E. Reisman, J. Am.
Chem. Soc. 139 (2017) 5684e5687;
[1] (For selected recent reviews on cross-coupling reaction, see:). (a) L. Zani,
A. Dessì, D. Franchi, M. Calamante, G. Reginato, A. Mordini, Coord. Chem. Rev.
392 (2019) 177e236;
(e) H.-Q. Do, E.R.R. Chandrashekar, G.C. Fu, J. Am. Chem. Soc. 135 (2013)
16288e16291.
(b) Y.-F. Zhang, Z.-J. Shi, Acc. Chem. Res. 52 (2019) 161e169;
(c) A.H. Cherney, N.T. Kadunce, S.E. Reisman, Chem. Rev. 115 (2015)
9587e9652;
[12] For other selected methods to generate the 1,1-diarylalkanes, see:. (a) Z. Li,
D. Wu, C. Ding, G. Yin, CCS Chem 2 (2020) 576e582;
(b) Y. Yin, Y. Dai, H. Jia, J. Li, L. Bu, B. Qiao, X. Zhao, Z. Jiang, J. Am. Chem. Soc.
140 (2018) 6083e6087;
(d) J. Magano, J.R.L. Dunetz, Chem. Rev. 111 (2011) 2177e2250.
[2] For selected reviews on Pd-catalyzed of cross-coupling of aryl/vinyl (pseudo)
halides, see:. (a) A. Biffis, P. Centomo, A. Del Zotto, M. Zecca, Chem. Rev. 118
(2018) 2249e2295;
(c) S.D. Friis, M.T. Pirnot, S.L. Buchwald, J. Am. Chem. Soc. 138 (2016)
8372e8375;
(d) Z. Wang, F. Ai, Z. Wang, W. Zhao, G. Zhu, Z. Lin, J. Sun, J. Am. Chem. Soc. 137
(2015) 383e389;
(e) J.F. Paquin, C. Defieber, C.R.J. Stephenson, E.M. Carreira, J. Am. Chem. Soc.
127 (2005) 10850e10851.
(b) C.C.C. Johansson Seechurn, M.O. Kitching, T.J. Colacot, V. Snieckus, Angew.
Chem. Int. Ed. 51 (2012) 5062e5085;
(c) G.C. Fu, Acc. Chem. Res. 41 (2008) 1555e1564;
(d) U. Christmann, R. Vilar, Angew. Chem. Int. Ed. 44 (2005) 366e374;
ꢀ
(e) J. Hassan, M. Sevignon, C. Gozzi, E. Schulz, M. Lemaire, Chem. Rev. 102
[13] (a) A.V. Cheltsov, M. Aoyagi, A. Aleshin, E.C.-W. Yu, T. Gilliland, D. Zhai,
A.A. Bobkov, J.C. Reed, R.C. Liddington, R. Abagyan, J. Med. Chem. 53 (2010)
3899e3906;
(2002) 1359e1469.
[3] (For one selected review, see:). (a) N. Kambe, T. Iwasaki, J. Terao, Chem. Soc.
Rev. 40 (2011) 4937e4947 (for selected leading examples, see:);
(b) T. Ishiyama, S. Abe, N. Miyaura, A. Suzuki, Chem. Lett. 21 (1992) 691e694;
(b) W.J. Moree, B.-F. Li, F. Jovic, T. Coon, J. Yu, R.S. Gross, F. Tucci, D. Marinkovic,
9

X.-L. Su, S.-P. Jiang, L. Ye et al.
Tetrahedron xxx (xxxx) xxx
S. Zamani-Kord, S. Malany, M.J. Bradbury, L.M. Hermandez, Z. O ’ Brien, J. Wen,
H. Wang, S.R.J. Hoare, R.E. Petroski, A. Sacaan, A. Madan, P.D. Crowe,
G.J. Beaton, Med. Chem. 52 (2009) 5307e5310;
(c) D.H.S. Silva, S.C. Davino, S.B. deMoraes Barros, M. Yoshida, J. Nat. Prod. 62
(1999) 1475e1478.
[14] (a) T. Xiong, Y. Li, X. Bi, Y. Lv, Q. Zhang, Angew. Chem. Int. Ed. 50 (2011)
7140e7143;
(b) B.G. Hashiguchi, K.J.H. Young, M. Yousufuddin, W.A. Goddard, R.A. Periana,
J. Am. Chem. Soc. 132 (2010) 12542e12545.
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