Electrochemical oxidative decarboxylation and 1,2-aryl migration towards the synthesis of 1,2-diaryl ethers

Article abstract of DOI:10.1039/d0sc03708g

Carboxylic acid compounds are important chemicals and are widely present in various natural products. They are not only nucleophiles, but also radical precursors. Classic transition-metal-catalyzed and photochemical decarboxylation have shown their excellent site selectivity in radical chemistry. However, electrochemical decarboxylation with a long history hasn't got enough attention in recent years. In this work, the electrochemical oxidative decarboxylation and 1,2-aryl migration of 3,3-diarylpropionic acids have been introduced to construct C-O bonds with alcohols. Remarkably, this transformation can proceed smoothly without metal catalysts and external oxidants.

Full text of DOI:10.1039/d0sc03708g

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DOI: 10.1039/D0SC03708G
COMMUNICATION
Electrochemical Oxidative Decarboxylation and 1,2-Aryl Migration
towards the Synthesis of 1,2-Diaryl Ethers
Faxiang Bu†a, Lijun Lu†a, Xia Hua, Shengchun Wanga, Heng Zhang*a and Aiwen Lei*ab
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
Carboxylic acid compounds are important chemicals and widely existed in various natural products. They are not only
nucleophiles, but also radical precursors. Classic transition-metal-catalyzed and photochemical decarboxylation have showed
their excellent site selectivity in radical chemistry. However, electrochemical decarboxylation with a long history hasn’t got
enough attention in recent years. In this work, the electrochemical oxidative decarboxylation and 1,2-aryl migration of 3,3-
diarylpropionic acids have been introduced to construct C-O bonds with alcohols. Remarkably, this transformation can proceed
smoothly without metal catalysts and external oxidants.
academia and industry. For examples, Macmillan and co-workers
Introduction
made great contributions in photochemical decarboxylative
1,2-diaryl compounds are important structures in some
pharmaceuticals. For examples, Dextropropoxyphene is an
analgesic in the opioid category, Eslicarbazepine acetate is an
anticonvulsant medication.1 Directly using benzyl halides to
construct 1,2-diary compounds is a difficult process.2 In contrast,
1,2-aryl migration can afford 1,2-diaryl compounds easily.3 The 1,1-
diaryl ethyl radical is the key intermediate for achieving 1,2-aryl
migration. There are some types of producing 1,1-diaryl ethyl
radicals in previous reports (Scheme 1A). The first type is obtaining
radical species by dehalogenation or decarboxylation.4 The second
type is extra radicals adding to olefins to producing radical species.5
Intramolecular radical addition is similar to the second type.6 The
fourth type is the direct oxidation of C-H bond to give radical
species.7 The addition of radicals to olefins are the most common
types. But their products have the extra functional groups, which
influences its further modification. The intramolecular and C-H
oxidation types are usually limited on the substrate scope. Whereas,
the decarboxylation process of the first type is relatively simple and
efficient.
functionalization.11 On the other hand, many breakthroughs have
also
been
achieved
in
the
transition-metal-catalyzed
decarboxylative functionalization .12
Recently, electrochemical synthesis has become a hot topic again
for its mild reaction conditions, which meets with the requirement
of green and sustainable chemistry.13 Kolbe electrolysis is one of the
most famous electrochemical reactions, which involves the anodic
oxidation of alkyl carboxylates to afford alkyl radicals.14 Compared
A
Dehalogenation, deoxygenation or decarboxylation
R1
Ar1
R1
R1
Ar2
Ar1
Ar2
-X
Ar1
Ar2
X
X = Cl, Br, I, COOH
Intermolecular radical additon
R1
Ar1
Ar1
Ar2
Ar1
Ar2
R1
R1
R2
R2
R2
Ar2
Intramolecular radical additon
FG
Ar1
Ar1
Ar1
Ar2
-FG
Ar1
Ar2
Ar2
Ar2
Carboxylic acids are common precursors of pharmaceuticals,
agrochemicals and fine chemicals.8 They are commercially available
with low cost and more structural diversity. Meanwhile, they can be
prepared through many mature methods.9 Carboxylic acids with the
advantages of non-toxic, stable to air and water, easy to store and
operate, are the promising substitutes of organic halides due to the
good site selectivity.10 In the past decade, decarboxylative cross-
coupling reactions have undergone a rapid development in both
C-H oxidation
R2O2C
H
R2O2C
R1
R2O2C
CO2H
Ar2
-H, -e
R1
CO2H
CO2H
Ar2
R1
Ar1
Ar1
Ar2
Ar1
B
This work:
R3
Ar
R3
Ar
CO2
H
GF
1/2
2
COOH
R2
FG
R2
R1
R1
a. College of Chemistry and Molecular Sciences, The Institute for Advanced Studies
(IAS), Wuhan University, Wuhan 430072, Hubei, P. R. China. Email:
aiwenlei@whu.edu.cn; hengzhang@whu.edu.cn.
H+
CO2
R3
FG
R3
e
b. 2National Research Center for Carbohydrate Synthesis, Jiangxi Normal University,
Nanchang 330022, Jiangxi, P. R. China.
1,2-Aryl Migration
Ar
Ar
† These authors contributed equally to this work.
R2
R2
R1
R1
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
Scheme 1. A. The 1,2-aryl migration of different substrates. B.
Electrochemical oxidative decarboxyla-tion and 1,2-aryl migration reaction.
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Table 1. Optimization of the reaction conditionsa
the only byproducts.15 Due to the above merits, elVeiecwtrAorctihcleemOnilcinael
Cl
decarboxylation is an ideal method to obtain radical species from
DOI: 10.1039/D0SC03708G
O
C Cloth(+) | Pt(-)
nBu4NOAc, HFIP
carboxylic acids. Herein, we report an electrochemical oxidative
decarboxylation and 1,2-aryl migration of 3,3-diarylpropionic acids
to synthesize a series of 1,2-diaryl ethers (Scheme 1B).
COOH
MeOH
CO2
H2
Cl
Cl
Cl
1a
2a
3aa
Entry Variation from the standard conditions
Yield (%)b
80 (75)
21
57
37
57
70
80
1
2
None
Results and Discussion
nBu4NBF4 instead of nBu4NOAc
nBu4NBF4 and KOMe instead of nBu4NOAc
3,3-di(2-chlorophenyl)-propionic acid (1a) and MeOH (2a) were
selected as model substrates (Table 1). With the combination of
carbon cloth as anode, platinum plate as cathode, nBu4NOAc as
electrolyte and base in the mixed solvent of MeOH and HFIP
(hexafluoroisopropanol), 80% GC yield of the desired product (3aa)
was obtained at 15 mA current and room temperature in 3.5 hours
(entry 1). Base was important for this transformation. The yield
sharply decreased to 21% with nBu4NBF4 as the electrolyte (entry 2).
Replacing nBu4NOAc with other bases, such as KOMe, Li2CO3 or
nBu4NOH, gave lower yields (entry 3-5). Using MeOH and DCE (1,2-
dichloroethane) as co-solvent, the yield decreased to 70% (entries
6). Reducing the current to 10 mA didn’t influence the reaction
(entry 7). Notably, only trace amount of product was detected by
utilizing platinum plate as anode (entry 8). When nickel plate was
used as cathode, the reaction also proceeded smoothly (entry 9). In
addition, when the reaction was operated under air (entry 10) or at
0 oC (entry 11), the yields decreased slightly.
3c
4c
5
nBu4NBF4 and Li2CO3 instead of nBu4NOAc
nBu4NOH instead of nBu4NOAc
MeOH/DCE as solvent
I = 10 mA, 5.25 h
6d
7
8
9
10
11
Platinum plate as anode
Nickel plate as cathode
In air
trace
74
68
0 oC
72
aStandard conditions: Carbon cloth anode (15 mm x 15 mm x 0.36 mm ), Pt
plate cathode (15 mm x 15 mm x 0.3 mm), 1a (0.4 mmol), 2a (12.0 mL),
nBu4NOAc (0.6 mmol), HFIP (0.7 mL), constant current, I = 15 mA, 3.5 h,
room temperature, N2 atmosphere.
Q =
189 C, 4.9 F. bYields were
determined by gas chromatography analysis and calibrated with
naphthalene as the internalstandard (isolated yield in parentheses).
cnBu4NBF4 (0.4 mmol) and base (0.6 mmol) were used. dMeOH/DCE = 8.0/4.0
mL, no HFIP.
With the optimized conditions in hand, we investigated the
substrate scope of this transformation. Firstly, a variety of alcohols
were tested (Scheme 2). Primary, secondary and tertiary alcohols all
could be tolerated (3aa-3aj, 3ba-3bf). The example of 3ac and 3bc
with transition-metal-catalyzed and photochemical decarboxylation,
electrochemical decarboxylative functionalization can proceed
smoothly without transition-metal catalysts, photocatalysts,
external oxidants or high temperature. In addition, CO2 and H2 are
C Cloth(+)|Pt(-)
OR3
R2
R1
15 mA
R3OH
COOH
R2
CO2
H2
nBu4NOAc
R1
HFIP
1
2
O
R
3
O
R
F3C
O
R
O
R
R
R
R
R
3aa, R = Cl, 75%
3ba, R = H, 65%a
3ab, R = Cl, 69%
3bb, R = H, 58%a
3ac, R = Cl, 52%b
3bc, R = H, 52%c
3ad, R = Cl, 52%b
3bd, R = H, 55%a
3ag, R = (CH2)2CH3 64%b
3ah, R = CH2CH(CH3)2 54%
3ai, R = CH2C(CH3)3 38%f
3aj, R = (CH2)6CH3 31%f
OR
O
O
Cl
Cl
R
R
R
R
3ae, R = Cl, 28%f
3be, R = H, 41%e
3af, R = Cl, 43%d
3bf, R = H, 36%e
O
O
O
O
Cl
F
F
3da, 63%
Br
Br
3ea, 74%
Cl
3ca, 78%b
3fa, 48%a
3ga, R = CH3, 52%c
3ha, R = F, 63%
3ia, R = Cl, 63%
3ja, R = Br, 61%
3ka, R = tBu, 48%b
3la, R = CF3, 48%a
3na, R1 = Br, R2 = Me, 65%, C1:C2 = 3.5:1
3oa, R1 = Cl, R2 = Me, 65%, C1:C2 = 2.6:1
3pa, R1 = H, R2 = Me, 56%, C1:C2 = 2:1
3qa, R1 = H, R2 = Cl, 62%, C1:C2 = 1.5:1
3ra, R1 = H, R2 = Br, 61%a, C1:C2 = 1.5:1
3sa, R1 = H, R2 = CF3, 58%a, C1:C2 = 1.3:1
3ta, R1 = H, R2 = CN, 39%a, C1:C2 = 1:1.2
R2
R
O
1
O
2
R1
R
3ma, R = OCF3, 48%
Scheme 2. Substrate scope of 3,3-diarylpropionic acids and alcohols. Reaction conditions: 1 (0.4 mmol), 2 (12.0 mL), nBu4NOAc (1.5 equiv. based on 1), HFIP
(0.7 mL), room temperature, carbon cloth anode, Pt cathode, constant current, I = 15 mA, 3.5 h. Isolated yields are shown. a2 (8.0 mL), DCE (4.0 mL), no HFIP.
bT = 55 oC. c2 (8.0 mL), DCE (4.0 mL), T = 70 oC. dT = 55 oC, I = 5 mA, 10.5 h. e2 (8.0 mL), DCE (4.0 mL), T = 70 oC, I = 5 mA, 10.5 h. f1 (0.2 mmol), 2 (2.0 mL), HFIP
(120 μL), T = 55 oC, I = 3.3 mA, 8 h.
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
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were noteworthy due to the widespread existence of
trifluoroethoxy group in drug molecules. Then, we focused our
attentions on the diarylpropionic acids. Diarylpropionic acids with
ortho-substituted functional groups, such as methyl, fluorine and
bromine, afforded satisfactory yields (3ca-3ea). Substrates with
para-substituted electron-donating functional groups, such as
methyl (3ga), tert-butyl (3ka) and trifluoromethoxy (3ma), and
electron-withdrawing functional groups, such as fluorine (3ha),
chlorine (3ia), bromine (3ja) and trifluoromethyl (3la), were all well
compatible in this system. Diarylpropionic acid containing meta-
substitution was also transformed to the desired product (3fa). It is
worth mentioning that, ortho-substituted diarylpropionic acids
usually gave higher yields than para or meta substituted ones. As
they could inhibit the formation of side-products (Supplementary
Scheme S1-S5). Subsequently, we turned to study the 1,1-
diarylpropionic acids with different substituted aryl groups.
However, the migration selectivity between different aryl groups
was unsatisfactory (3na-3ta, Supplementary scheme S6-S8).
Moreover, we explored the applicability of the carboxylic acids
with additional α- and β-site substituted groups (Scheme 3). The
diarylpropionic acids with α- or β- methyl group could afford the
corresponding products (3ua-3wa). Triphenylpropionic acid gave 76%
yield (3xa). Remarkably, this transformation could still proceed
when one of the two aryl groups was replaced with methoxyl or
benzyl group (3ya, 3za). The wide substrate compatibility made this
protocol promising application in organic synthesis.
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A
DOI: 10.1039/D0SC03708G
Experiment
Simulation
O
N
Ph
Ph
3460
3480
3500
3520
3540
Field (G)
△
G/kcalmol-1
E/kcalmol-1)
B
△
(
Cl
H
31.6
(34.2)
Cl
CH2
Cl
Cl
Cl
CH
Cl
2-ts
13.8
(13.3)
6-ts
4-ts
8.5
(8.2)
6.5
(5.4)
Cl
0.0
(0.0)
Cl
Cl
Cl
Cl
Cl
-10.4
(-11.0)
Cl
CH2
-12.6
(-13.0)
5
Cl
CH2
7
3
To gain futher insight into the reaction mechanism, some related
experiments were conducted. Firstly, the oxidation potentials of the
substrates were measured by using cyclic voltammetry
(Supplementary Figure S1). There was no obvious oxidation peak for
3,3-diphenylpropionic acid (1b) alone. However, the oxidation peak
could be observed by adding base into the solution of 3,3-
diphenylpropionic acid (1b), which suggested that 3,3-
diphenylpropionic carboxylate could be oxidized easily. In addition,
3,3-diphenylpropionic carboxylate and nBu4NOAc have similar
oxidation potentials, which might indicate they could be oxidized
simultaneously during the reaction (Supplementary Scheme S14).
Furthermore, EPR experiments were performed to investigate
the radical intermediate produced by the oxidation of 3,3-
1
C
AcO
AcOH
COO
COOH
AcOH
I
1b
e
e
CO2
COO
1,2-Aryl
Migration
AcO
1/2 H2
II
R3
III
C Cloth(+) | Pt(-)
R1
R2
O
R1
IV
V
COOH
R2
15 mA
CO2
H2
MeOH
nBu4NOAc
HFIP
e
OMe
3ba
R3
AcOH
AcO, MeOH
1
2
3
Substrates
Products
Substrates
Products
O
Cathode
Anode
Figure 1. A. EPR spectrum. B. Free energy barriers for the 1,2-Aryl migration
vs. 1,2-H transfer of radical intermediate. C. Proposed mechanism.
O
O
O
OH
OH
diphenylpropionic carboxylate. With the addition of radical spin
1u
3ua, 60%
1x
3xa, 76%
trapping reagent DMPO (5,5-dimethyl-1-pyrroline N-oxide),
mixture signal of DMPO trapping carbon radicals (g = 2.0068, AN
14.30 G, AH = 21.00 G) and hydrogenated DMPO (g = 2.0068, AN
a
=
=
CF3
CF3
O
O
O
O
1
2
O
O
OH
OH
OH
14.65 G, AH1 = 19.54 G, AH2 = 19.54 G) was identified (Figure 1A,
Supplementary Figure S3C). Meanwhile, the reaction system of EPR
trapping experiment was also tested by high resolution electrospray
ionization mass spectrometry (Supplementary Figure S3D). The
results demonstrated the possible existence of carbon radical
intermediate (Figure 1C III or IV) according to the coincidence of the
molecular weight of DMPO trapping products. Moreover, BrCCl3
and O2 were used as radical trapping reagents, respectively. 22%
yield of 1,1-diphenyl-2-bromoethane and 16% yield of
benzophenone were obtained in the respective experiments, which
1v
3va, 61%, C1:C2 = 1.8:1
1y
3ya, 56%
O
O
O
O
OH
1w
3wa, 32%
1z
3za, 42%
Scheme 3. Substrate scope of carboxylic acids. Reaction conditions: 1 (0.4
mmol), 2a (12.0 mL), nBu4NOAc (1.5 equiv. based on 1), HFIP (700 μL), room
temperature, constant current, I = 15 mA, 3.5 h. All yields are isolated yields.
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indicated the possibility of the involvement of 1,1-diphenylethyl smoothly on gram scale. 1.17 g 3ba was obtained by using 50 mA
View Article Online
radical (Figure 1C III) in the transformation (Supplementary Scheme current without changing the size of the electrodes (Scheme 4C).
DOI: 10.1039/D0SC03708G
S15 and Scheme S16).
In order to understand the process of the aryl migration, DFT
calculations were conducted (Figure 1B). According to the
Conclusions
calculated free energy barriers, 1,2-aryl migration (13.8 kcal/mol) of
In Summary, the strategy of decarboxylation and 1,2-aryl
1,1-diarylethyl carbon radical 1 was much easier than that of 1,2-H
migration have been integrated to achieve the electrochemical
transfer (31.6 kcal/mol), which met with the experimental results.
oxidative cross-coupling between 3,3-diarylpropionic acids and
Another possibility was that 1,1-diarylethyl carbon radical 1 was
alcohols to yield 1,2-diaryl ethers under mild conditions in one
oxidized to form 1,1-diarylethyl carbocation firstly, which further
step. The good substrate compatibility and the diversified
underwent 1,2-aryl migration to give the desired product. However,
further functionalization of the target 1,2-diaryl ethers
DFT calculation results indicated that the 1,2-H transfer is more
demonstrate the potential application of this protocol.
favourable than 1,2-aryl migration for this carbocation intermediate
(Supplementary Figure S4).
Based on the above mechanistic experiments and previous
reports, a plausible mechanism was proposed (Figure 1C). Firstly,
3,3-diphenylpropionic acid (1b) is deprotonated in the presence of
Conflicts of interest
There are no conflicts to declare.
acetate to produce carboxylate I, which was oxidized at the anode
to generate carboxyl radical II. The following decarboxylation can
afford the primary carbon radical III. Subsequently, benzyl
carbocation V was formed through successive 1,2-aryl migration
and anodic oxidation. At last, the reaction between benzyl
carbocation V and methanol can yield the desired product 3ba with
the help of acetate. The acetate can be regenerated at the cathode
with the liberation of dihydrogen concomitantly.
The product 1-methoxy-1,2-diphenyl ethane (3ba) could be
Acknowledgements
This work was supported by the National Natural Science
Foundation of China (21520102003) and the Hubei Province Natural
Science Foundation of China (2017CFA010). The Program of
Introducing Talents of Discipline to Universities of China (111
Program) is also appreciated. The numerical calculations in this
paper have been done on the supercomputing system in the
Supercomputing Center of Wuhan University. Dedicated to P.H.
further modified to get useful chemicals. For example, 3ba reacted
with azidotrimethylsilane or allyltrimethylsilane to contruct C-N or
Dixneuf for his outstanding (or meaningful) contribution to
organometallic chemistry and catalysis.
C-C bond (Scheme 4A, 6a, 6b) by Fe-catalysis.16 In addition, the
elimination reaction of 3ba afforded C-C double bond by leaving
methoxy group (6c).17 Notably, the methoxy group could be acted
as the directing group to achieve ortho-C-H olefination of 3ba
Notes and references
(6d).18 When 3-phenyl-3-(2-bromophenyl)propionic acid was used
as substrate, two isomers were obtained (Scheme 4B, 5aa,
Supplementary Scheme S13). When the mixture was employed as
starting material directly in the palladium-catalyzed intramolecular
cyclization, the sole product 9,10-dihydro-9-methoxy-phenanthrene
was obtained (6f).19 Remarkably, this reaction could proceed
1
(a) W. M. O’Neill, G. W. Hanks, L. White, P. Simpson and K.
Wesnes, Eur. J. Clin. Pharmacol. 1995, 48, 447; (b) C. Elger, P.
Hala´sz, J. Maia, L. Almeida and P. Soares-da-Silva, Epilepsia
2009, 50, 454.
(a) A. H. Stoll, A. Krasovskiy and P. Knochel, Angew. Chem. Int.
Ed. 2006, 45, 606; (b) M. P.ꢀDrapeau, I. Fabre, L. Grimaud, I.
Ciofini, T. Ollevier and M. Taillefer, Angew. Chem. Int. Ed.
2015, 54, 10587; (c) G. Fumagalli and S. Boyd, M. F. Org. Lett.
2013, 15, 4398.
2
A
N3
l 3
10%
TMS
FeC
FeC
10%
3
4
Z. M. Chen, X. M. Zhang and Y. Q. Tu, Chem. Soc. Rev. 2015,
44, 5220.
(a) L. Li, P. Cai, Q. Guo, and S. Xue, J. Org. Chem. 2008, 73,
3516; (b) N. Tsuji, Y. Kobayashi and Y. Takemoto, Chem.
Commun. 2014, 50, 13691; (c) W. A. Bonner and F. D. Mango,
J. Org. Chem. 1963, 29, 430.
(a) W. Kong, M. Casimiro, E. Merino and C. Nevado, J. Am.
Chem. Soc. 2013, 135, 14480; (b) Z. M. Chen, W. Bai, S. Wang,
B Yang, Y. Tu and F. Zhang, Angew. Chem. Int. Ed. 2013, 52,
9781; (c) X. Liu, F. Xiong, X. Huang, L. Xu, P. Li and X. Wu,
Angew. Chem. Int. Ed. 2013, 52, 6962; (d) A. Bunescu, Q.
Wang, and J. Zhu, Angew. Chem. Int. Ed. 2015, 54, 3132; (e) S.
Wang, C. Chuang, J. Lee and S. Liu, Tetrahedron 1999, 55,
2273.
l
3
6b, 59%
N
TMS
6a, 70%
3
O
5%
Pd(OAc)
O
Zn
25%
Ac
2
10%
Ag
Ac
2CO3
l
C
-
G
l
y-OH
6d, 40%
CO2Et
6c
, 50%
Br
5
O
5% Pd(OAc)2
10% ligand
B
C
C Cloth(+) | Pt(-)
15 mA
nNBu4NOAc
O
1
COOH
2
K2CO3
DMA, 130oC
Br
MeOH/HFIP
5aa, 56%, C1:C2 = 2:1
6f, 71%
4a
C Cloth(+) | Pt(-), 50 mA
O
6
7
8
9
W. R. Bowman and J. M. D. Storey, Chem. Soc. Rev. 2007, 36,
1803.
Z. Cong, T. Miki, O. Urakawa and H. Nishino, J. Org. Chem.
2009, 74, 3978.
K. P. C. Vollhardt and N. E. Schore, Organische Chemie, 3.
Aufl., Wiley-VCH, Weinheim, S. 2000, 893.
L. S. Hegedus and L. Wade, In Compendium of Organic
Synthetic Methods, Vol. 3, John Wiley & Sons: Hoboken, NJ,
1997, 8.
COOH
MeOH
nBu4NBF4, nBu4NOAc
36.0 mL DCE, r.t., 23 h
2a
3ba
1b
72.0 mL
63%, 1.17 g
8.8 mmol, 1.99 g
Scheme 4. A. Further functionalization of 1-methoxy-1,2-diphenyl
ethane. B. Derivatization of 5aa. C. Gram scale electrochemical
synthesis of 3ba.
4 | J. Name., 2012, 00, 1-3
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10 (a) Y. Wei, P. Hu, M. Zhang and W. Su, Chem. Rev. 2017, 117,
8864; (b) B. Song, T. Knauber and L. J. Goossen, Angew.
Chem. Int. Ed. 2013, 52, 2954; (c) Z. Zuo and D. W. C.
MacMillan, J. Am. Chem. Soc. 2014, 136, 5257.
View Article Online
DOI: 10.1039/D0SC03708G
11 (a) Y. Liang, X. Zhang and D. W. C. MacMillan, Nature 2018,
559, 83; (b) N. A. Till, R. T. Smith and D. W. C. MacMillan, J.
Am. Chem. Soc. 2018, 140, 5701; (c) L. Chu, J. M. Lipshultz,
and D. W. MacMillan, Angew. Chem. Int. Ed. 2015, 54, 7929.
12 (a) J. Zhang, J. R. Shrestha, J. F. Hartwig and P. Zhao, Nat.
Chem. 2016, 8, 1144; (b) K. Takamatsu, K. Hirano, and M.
Miura, Angew. Chem. Int. Ed. 2017, 56, 5353; (c) Q. Q. Zhou,
W. Guo, W. Ding, X. Wu, X. Chen, L. Q. Lu and W. J. Xiao,
Angew. Chem. Int. Ed. 2015, 54, 11196; (d) P. J. Moon, S. Yin
and R. J. Lundgren, J. Am. Chem. Soc. 2016, 138, 13826.
13 (a) J. Xiang et al. Nature 2019, 573, 398; (b) Y. Jiang, K. Xu
and C. Zeng, Chem. Rev. 2018, 118, 4485; (c) N. Fu, G. S.
Sauer, A. Saha, A. Loo and S. Lin, Science 2017, 357, 575; (d)
R. Hayashi, A. Shimizu and J. Yoshida, J. Am. Chem. Soc. 2016,
138, 8400; (e) P. Xiong, H. H. Xu and H. C. Xu, J. Am. Chem.
Soc. 2017, 139, 2956; (f) Y. Qiu, W. Kong, J. Struwe, N.
Sauermann, T. Rogge, A. Scheremetjew and L. Ackermann,
Angew. Chem. Int. Ed. 2018, 57, 5828; (g) X. Gao, P. Wang, L.
Zeng, S. Tang and A. Lei, J. Am. Chem. Soc. 2018, 140, 4195.
14 (a) H. J. Schaefer, Topics in Current Chemistry. 1990, 152, 91;
(b) G. N. Wanyoik, O. Onomura, T. Maki and Y. Matsumura,
Org. Lett. 2002, 4, 1875; (c) L. B. Rodewald and M. C. Lewis,
Tetrahedron 1971, 27, 5273; (d) R. F. Garwood, Naser-ud-Din,
and B. C. L. Weedon, J. Chem. Soc., Perkin Trans. 1, 1973,
2714.
15 (a) B. A. Frontana-Uribe, R. D. Little, J. G. Ibanez, A. Palmad
and R. Vasquez-Medrano, Green Chem. 2010, 12, 2099; (b) A.
Wiebe, T. Gieshoff, S. Möhle, E. Rodrigo, M. Zirbes and S. R.
Waldvogel, Angew. Chem. Int. Ed. 2018, 57, 5594; (c) H.
Kurihara, T. Fuchigami, and T. Tajima, J. Org. Chem. 2008, 73,
6888.
16 Y. Sawama, R. Goto, S. Nagata, Y. Shishido, Y. Monguchi and
H. Sajiki, Chem. Eur. J. 2014, 20, 2631.
17 S. Bhar and B. Ranu, J. Org. Chem. 1995, 60, 745.
18 G. Li, D. Leow, L. Wan and J. Yu, Angew. Chem. Int. Ed. 2013,
52, 1245.
19 L. Campeau, M. Parisien, M. Leblanc and K. Fagnou, J. Am.
Chem. Soc. 2004, 126, 9186.
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