Palladium-catalyzed ortho-C-H arylation of acetophenone oxime ethers with aryl pinacol boronic esters

Article abstract of DOI:10.1021/acs.joc.7b01524

We report an efficient palladium-catalyzed ortho-C-H arylation of acetophenone oxime ethers with aryl pinacol boronic esters, leading to the synthesis of biaryl derivatives in good yields. Sequential process of iridiumcatalyzed C-H borylation and palladiu

Full text of DOI:10.1021/acs.joc.7b01524

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Article
Palladium-Catalyzed ortho-C-H Arylation of Acetophenone
Oxime Ethers with Aryl Pinacol Boronic Esters
Daggula Mallikarjuna Reddy, Shao-Chien Wang, Kai Du, and Chin-Fa Lee
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b01524 • Publication Date (Web): 31 Aug 2017
Downloaded from http://pubs.acs.org on August 31, 2017
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Palladium-Catalyzed ortho-C-H Arylation of Acetophenone Oxime
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Ethers with Aryl Pinacol Boronic Esters
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Daggula Mallikarjuna Reddy,† Shao-Chien Wang,† Kai Du, and Chin-Fa Lee*
Department of Chemistry, National Chung Hsing University, Taichung, Taiwan 402, R.O.C
E-mail: cfalee@dragon.nchu.edu.tw
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Abstract: We report an efficient palladium-catalyzed ortho-C-H arylation of acetophenone oxime
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ethers with aryl pinacol boronic esters, leading to the synthesis of biaryl derivatives in good yields.
Sequential process of iridium-catalyzed C-H borylation and palladium-catalyzed ortho C-H arylation
directed to access functionalized arenes.
Introduction
In recent years, direct C-H functionalization has emerged as an elegant pathway to construct
precise and complicated natural scaffolds, and synthetic structural entities.1 The sp2 and sp3 C-H bond
activation interface with subsequent C-C bond formation reactions catalyzed by ruthenium, rhodium,
palladium, iridium, and other metal complexes have been demonstrated.2 Owing to this, recently many
potential synthetic efforts have been made to pursue this goal.3,4 In particular, O-methyl oximyl group
has been applied in this field for ortho-acetoxylation and amination.5 Synthesis of biaryl compounds6
has consistently been of great interest in organic synthesis, due to their wide array of applications in
pharmaceuticals and agrochemicals.7 Various directing groups has been employed for
palladium-catalyzed arylation of ortho-aromatic C-H bonds to synthesize biaryl motifs.8 Direct C-H
arylation of O-methyl oximyl group has also been accomplished by using aryl iodides,9 aryldiazonium
salts,10 diaryliodonium salts,11 acylperoxides,12 and arenes as the coupling partners.13
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Indeed, aryl boronic acids14 are extensively used as versatile precursors in transition-metal
catalyzed cross-coupling reactions which include Suzuki-Miyaura cross-coupling reactions,15
Cu-catalyzed C-O, C-N, C-S and C-Se coupling reactions,16 Rh-catalyzed carbonyl conjugate addition
reactions,17 and very few examples of O-methyl oximyl group directed C-H arylation with aryl
boronic acids as coupling reagents.18
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The impact on stability of aryl pinacol boronates facilitate ease to handle and exhibits them to
use under a variety of reaction conditions. To the best of our knowledge, the synthetic approach to
biaryl products through Pd-catalyzed directed C-H arylation of O-methyl oximyl group with
arylboronic esters has not been developed. Herein, we report a palladium-catalyzed ortho-C-H
arylation of acetophenone oxime ethers with aryl pinacol boronic esters for the synthesis of biaryl
derivatives. To our delight, this protocol shows remarkable mono-arylation selectivity. We also have
achieved sequential cross-coupling with arenes via meta-C-H borylation followed by direct ortho-C-H
arylation of acetophenone oxime ethers to afford functionalized biaryl skeletons.
Results and Discussion
Initially, we have conducted reaction with the combination of 1-phenyl-ethanone-O-methyl-oxime
(1a), 3.0 equiv. of phenyl pinacol boronate (2a), 10 mol% of Pd(OAc)2 as catalyst, 20 mol% of
Ac-Gly-OH (N-acetyl glycine) as ligand, 2.0 equiv. of Ag2CO3 as oxidant and 3.0 equiv. of KF as base
in 1,1,1,3,3,3-hexafluoropropanol (HFIP) as solvent at 70 °C for 24 h. The desired product (3a) was
obtained in 39% yield (Table 1, entry 1). The reaction required excess amount of phenyl pinacol
boronate (2a), because it was observed the formation of biphenyl as by-product via homo-coupling of
phenyl pinacol boronate (2a) under these reaction conditions. Double transmetallation of active
Pd-catalyst with phenyl pinacol boronate leads to the formation of diphenylpalladium (II) species,
which underwent reductive elimination to give oxidative homo-coupling biphenyl by-product.
Encouraged by this result, we attempted to further optimize the reaction conditions. Different solvents
were tested first, and no desired product (3a) was obtained when DMSO, 1,2-dichloroethane (DCE)
and 2-propanol were used as solvents (Table 1, entries 2-4).
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Table 1. Screening of Reaction Conditionsa
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entry catalyst
base
KF
KF
KF
KF
KF
oxidant
solvent yield (%)b
1
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(TFA)2
Pd(dba)2
Ag2CO3 HFIP
Ag2CO3 DMSO
Ag2CO3 DCE
Ag2CO3 IPA
Ag2CO3 TFE
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0
2
3
0
4
0
5
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0
6
NaHCO3 Ag2CO3 HFIP
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CsOAc
Cs2CO3
Li2CO3
CsF
KF
Ag2CO3 HFIP
Ag2CO3 HFIP
Ag2CO3 HFIP
Ag2CO3 HFIP
0
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22
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0
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15c
16d
17e
18f
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22g
23h
24i
25j
26k
AgOAc
AgF
HFIP
HFIP
HFIP
HFIP
KF
trace
trace
trace
0
KF
AgSbF6
Ag2O
KF
KF
Ag2CO3 HFIP
Ag2CO3 HFIP
Ag2CO3 HFIP
Ag2CO3 HFIP
Ag2CO3 HFIP
Ag2CO3 HFIP
Ag2CO3 HFIP
Ag2CO3 HFIP
Ag2CO3 HFIP
Ag2CO3 HFIP
Ag2CO3 HFIP
Ag2CO3 HFIP
KF
0
KF
0
KF
29
43
47
68
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0
KF
KF
Pd2(dba)3 KF
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
KF
KF
KF
KF
KF
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35
0
aReaction conditions: 1a (0.2 mmol), 2a (3.0 equiv.), catalyst (10 mol%), Ligand (20 mol%), oxidant (2.0 equiv.), base (3.0
b
c
equiv.), and solvent (2.0 mL) in a sealed tube at 70 °C for 24 h. Isolated yield. 1,10-Phenanthroline was used as ligand.
dDPPE was used as ligand. eTMEDA was used as ligand. fPPh3 was used as ligand. g5 mol% Pd2(dba)3 was used as catalyst.
hPhB(OH)2 instead of PhB(pin). Phenyl hexylene glycol boronate instead of PhB(pin). Phenyl neopentylglycol boronate
i
j
instead of PhB(pin). kPhBF3K instead of PhB(pin).
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When the reaction was performed in CF3CH2OH (TFE), the product was obtained in lower yield
as we compared with HFIP (Table 1, entry 5). These above results clearly demonstrate that fluorinated
solvent plays a key role in this transformation.
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We next examined the reaction using different bases and the result shows that no product was
formed when NaHCO3 and CsOAc were used. However, other bases such as Cs2CO3 and Li2CO3
could afford the product in lower yields (Table 1, entries 6-9). Replacing KF with CsF could not
improve the yield of the product (Table 1, entry 10). No desired product or trace amount of product
was observed, when AgOAc, AgF, AgSbF6 and Ag2O were used as oxidants (Table 1, entries 11-14).
The choice of ligand was crucial in this transformation. The use of bidentate ligands such as
1,10-phenanthroline, 1,2-bis(diphenylphosphino)ethane (dppe) and TMEDA instead of Ac-Gly-OH
failed to give the product (Table 1, entries 15-17). When PPh3 was used as ligand, the product was
obtained in 29% yield (Table 1, entry 18). Next, we tested the reaction with other Pd-catalysts such as
Pd(TFA)2, Pd(dba)2, Pd2(dba)3 (Table 1, entries 19-21). Interestingly, Pd2(dba)3 gave a better result
(68% yield) when compared with other Pd-catalysts (Table 1, entry 21). When the catalyst loading
was reduced to 5 mol%, lower yield of the product was observed (Table 1, entry 22). The reactivity of
various phenyl boronic sources [phenylboronic acid (4), phenyl hexylene glycol boronate (5a), phenyl
neopentylglycol boronate (5b) and potassium phenyltrifluoroborate (6)] was also investigated (Table 1,
entries 23-26). The output of these results revealed that phenyl pinacol boronate (2a) was best for this
transformation.
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With these optimized conditions in hand, we examined the various scopes of the substrate (Table
2). In addition to the phenyl pinacol boronate (2a), other substituted phenyl pinacol boronates were
also tested to couple with 1-phenyl-ethanone-O-methyl-oxime (1a). 4-Trifluoromethylphenyl (2b),
3-nitrophenyl (2c), 3-(methoxycarbonyl)phenyl (2d), and 4-nitrophenyl (2e) pinacol boronates were
coupled well with 1-phenyl-ethanone-O-methyl-oxime (1a), and it provided the corresponding biaryl
derivatives (3b-3e) in good yields.
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Table 2. Substrate Scope with O-methyl oximes and Arylboronic estersa,b
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aReaction conditions: 1 (0.2 mmol), 2 (3.0 equiv.), Pd2(dba)3 (10 mol%), Ac-Gly-OH (20 mol%), Ag2CO3 (2.0
equiv.), KF (3.0 equiv.), and HFIP (2.0 mL) in a sealed tube at 70 °C for 24 h. bIsolated yield.
It is worthy to mention here that aryl pinacol boronates with electron-rich substituents such as
4-methyl and 4-methoxy groups failed to give the desired coupling products with 1-phenyl-ethanone-
O-methyl-oxime (1a) as like phenylboronic acid and potassium phenyl trifluoroborate, whereas aryl
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pinacol boronates with electron with-drawing substituents such as CF3, NO2 and CO2Me gave better
results in this transformation. Increasing the electron density in the aryl system of boronic esters,
preferentially underwent homo-coupling over cross-coupling (coupling with other substrate). It was
already clearly observed in case of phenylboronic acid and potassium phenyltrifluoroborate (Table 1)
which are more electron-rich when compared with corresponding aryl boronic esters. 4-Methyl and
4-methoxy aryl boronic esters are also more electron rich substrates as like phenylboronic acid and
potassium phenyltrifluoroborate when compared with other aryl boronic esters which contain electron
with-drawing groups.
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Table 3. Cross-Coupling of Acetophenone Oxime Ethers with 1,3-Disubstituted Arenesa,b
aReaction conditions: step 1: 4 (1.0 mmol), Ir-catalyst (1.0 mol%) and dtbpy (2.0 mol%) in THF (2.0 mL) at 80 °C for 24 h;
step 2: 1 (0.2 mmol), crude borylated arene as such, Pd2(dba)3 (10 mol%), Ac-Gly-OH (20 mol%), Ag2CO3 (2.0 equiv.),
KF (3.0 equiv.), and HFIP (2.0 mL) in a sealed tube at 70 °C for 24 h. bIsolated yield.
The generality of this coupling reaction was further demonstrated by using aryl boronic esters
with various ketoxime ethers, such as 1-(3-methylphenyl)-ethanone-O-methyl-oxime (1b),
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3,4-dihydro-2H-naphthalen-1-one-O-methyl-oxime (1c) and 1-phenyl-propan-1-one-O-methyl-oxime
(1d) which afforded the corresponding biaryl derivatives (3f-3p) in moderate to good yields.
Interestingly, we observed only mono-arylated products selectively at less steric hindrance site, and no
double C-H arylation products were detected. The formation of mono-arylated products can be
explained on the basis of availability of less steric hindrance sites in the substrate. Moreover, this
protocol showed good functional group tolerance with trifluoromethyl, nitro and ester moieties.
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Iridium-catalyzed C-H borylation is a powerful method to form aryl pinacol boronic esters with
exclusive meta-selectivity. Stretching this strategy, iridium-catalyzed C-H borylation has been utilized
as an intermediate for one-pot chemical transformations.19,20 Inspired by this method, we next turned
our attention towards the cross-coupling of acetophenone oxime ethers (1) with 1,3-disubstituted
arenes (7) via sequential meta-C-H borylation followed by direct ortho-C-H arylation of acetophenone
oxime ethers (Table 3). In this regard, 1,3-bis(trifluoromethyl)benzene (7a) was selected as a model
substrate for iridium-catalyzed borylation, and it was executed under optimal reaction condition. After
the reaction, the resultant reaction mixture was subjected to filtration, and the filtrate was concentrated
under vacuum to remove the volatile components. Then, the existing crude borylated product (8a) was
directly used as coupling partner for ortho-C-H arylation of acetophenone oxime ethers to attain the
desired product (9a) in 88% yield. In addition to 1,3-bis(trifluoromethyl)benzene (7a), other arenes
such as meta-xylene (7b), 3-chlorotoluene (7c) and 1,3-dichlorobenzene (7d) have also been applied
for the iridium-catalyzed borylation followed by ortho-arylation with 1-phenyl-ethanone
-O-methyl-oxime (1a), 1-(3-methylphenyl)-ethanone-O-methyl-oxime (1b) and 3,4-dihydro-2H-
naphthalen-1-one-O-methyl-oxime (1c) to give the functionalized biaryls (9a-9g) in moderate to high
yields. Trifluoromethyl and chloro functional group patterns were well tolerated in this sequential
process.
The removal of directing group from resulting biaryl oxime (3k) was also performed using
simple acid hydrolysis to give the corresponding ketone (10)13 in 59% yield. To gain insight into
mechanistic study of this C-H activation process, kinetic isotope effects (KIE) experiments were
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performed by using deuterated substrate [D5]-1a. Intermolecular H/D competition between [D5]-1a
and 1a with 2a had a primary KIE value of 1.28, which indicated that the cleavage of C-H bond may
not have considerable importance in the rate-determined step, although the initial step of
oximyl-directing group assisted C-H(D) bond activation (Scheme 1a). To further probe the relevancy
of C-H activation, a separate experiment was carried out between [D5]-1a and 2a under identical
reaction conditions, and product [D4]-3a was isolated in 62% yield (Scheme 1b).
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Scheme 1. Kinetic Isotope Effects (KIE) Experiments
Although the mechanism of this transformation was not clear at this stage, based on
experimental and literature18,21 results we proposed a plausible mechanism for this work (Scheme 2).
Initially, the active catalytic species A is formed from Pd-catalyst and the ligand Ac-Gly-OH in the
presence of Ag2CO3, which then react with O-methyl ketoxime ether (1a) via ortho palladation to
generate aryl Pd(II) species B. The species B further underwent transmetallation with arylpinacol
boronate 2a to produce diaryl Pd(IV) species C. Reductive elimination of C produced the desired
ortho-arylated product 3a and Pd(II) species to regenerate the catalytic cycle.
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Scheme 2. Mechanistic proposal for Pd-Catalyzed Arylation
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Conclusion
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In summary, we have developed a palladium-catalyzed ortho-C-H arylation of acetophenone
oxime ethers with aryl pinacol boronic esters leading to the formation of biaryl derivatives in
moderate to good yields. Functionalized arenes can be prepared through sequential iridium-catalyzed
C-H borylation followed by palladium-catalyzed ortho-C-H arylation.
Experimental Section
General Remarks
Experiments were performed under a dinitrogen atmosphere using standard Schlenk techniques unless
otherwise stated. Flash chromatography was performed on Merck silica gel 60 (230–400 mesh). NMR
spectra were recorded on a Varian Unity Inova-600 or a Varian Mercury-400 instrument using CDCl3
as a solvent. Chemical shifts are reported in parts per million (ppm) and referenced to the residual
solvent resonance. Coupling constant (J) are reported in hertz (Hz). Standard abbreviations indicating
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multiplicity were used as follows: s = singlet, d = doublet, t = triplet, dd = double of doublet, q =
quartet, m = multiplet, b = broad. Melting points (M.P.) were determined using a Büchi 535 apparatus
and are reported uncorrected. GC-MS analyses were performed on a GC-MS analysis on Agilent
Technologies 5977A GC equipped with Agilent 7890B MS. High-resolution mass spectra were carried
out on a Jeol JMS-HX 110 spectrometer by the services at the National Chung Hsing University. All
commercial chemicals were used as received except where noted. Aryl pinacol boronates22 and
ketoxime ethers23 were all prepared through literature procedures.
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Analysis: NMR spectra were recorded using CDCl3 as solvent. Chemical shifts are reported in parts
per million (ppm) and referenced to the residual solvent resonance. Coupling constant (J) are reported
in Hertz (Hz). 13C NMR spectra were recorded on 100 MHz spectrometer using broadband proton
decoupling. Standard abbreviations indicating multiplicity were used as follows: brs (broad singlet), s
(singlet), d (doublet), t (triplet), dd (double doublet), q (quartet), m (multiplet). Melting points (m.p.)
were determined using an apparatus and are reported uncorrected. High-resolution mass spectra
(HRMS) were performed on an electron ionization time-of-flight (EI-TOF) mass spectrometer.
General Procedure for the preparation of compounds 3.
To a mixture of O-methylacetophenoneoximes (0.2 mmol), Pd2(dba)3 (0.02 mmol, 10 mol%),
arylboronic ester (0.6 mmol, 3.0 equiv), Ac-Gly-OH (0.04 mmol, 20 mol%), Ag2CO3 (0.4 mmol, 2
equiv) and KF (0.6 mmol, 3 equiv) was added HFIP (2 mL), and the resulting suspension was heated
in a sealed tube at 70 °C for 24 h. After 24 h, the reaction mixture was cooled down to room
temperature, and was filtered through a pad of silica gel and the filtrate was concentrated under
vacuum. The crude product was purified by flash column chromatography (ether/hexane=1/99).
1-(Biphenyl-2-yl)ethanone O-methyloxime (3a):24 Pale yellow oil; (0.031g, 68% yield); Rf = 0.75
1
(Et2O/Hexanes, 1:99 v/v); H NMR (400 MHz, CDCl3): δ 1.62 (s, 3H), 3.96 (s, 3H), 7.32-7.45 (m,
9H); 13C NMR (100 MHz, CDCl3): δ 16.5, 61.7, 127.2, 127.4, 128.4, 128.9, 129.0, 129.2, 130.3, 136.8,
140.4, 141.0, 158.3.
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1-(4'-Trifluoromethylbiphenyl-2-yl)ethanone O-methyloxime (3b): Pale yellow oil; (0.044g, 75%
yield); Rf = 0.71 (Et2O/Hexanes, 1:99 v/v); 1H NMR (400 MHz, CDCl3): δ 1.66 (s, 3H), 3.93 (s, 3H),
7.35-7.48 (m, 4H), 7.51 (d, J = 8.0 Hz, 2H), 7.66 (d, J = 8.0 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ
16.6, 61.8, 124.2 (q, J = 270.5 Hz), 125.3 (q, J = 3.8 Hz), 128.2, 129.0, 129.3, 129.37, 129.41 (q, J =
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23.5 Hz), 129.5, 130.2, 136.9, 138.9, 144.8, 157.4; F NMR (376 MHz, CDCl3): δ = -62.46 (CF3);
HRMS (EI) calcd for C16H14NOF3 [M]+ 293.1027, found 293.1033.
1-(3'-Nitrobiphenyl-2-yl)ethanone O-methyloxime (3c): Pale yellow oil; (0.041g, 76% yield); Rf =
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0.50 (Et2O/Hexanes, 1:99 v/v); H NMR (400 MHz, CDCl3): δ 1.72 (s, 3H), 3.91 (s, 3H), 7.38-7.41
(m, 1H), 7.42-7.50 (m, 3H), 7.55-7.60 (m, 1H), 7.72 (dd, J = 7.8 Hz & 0.8 Hz, 1H), 8.19-8.23 (m, 1H),
8.29-8.31 (m, 1H); 13C NMR (100 MHz, CDCl3): δ 16.6, 61.8, 122.0, 123.8, 128.5, 129.1, 129.2,
129.4, 130.1, 135.1, 136.8, 137.8, 142.8, 148.1, 156.6; HRMS (EI) calcd for C15H14N2O3 [M]+
270.1004, found 270.1011.
1-(3'-Methoxycarbonylbiphenyl-2-yl)ethanone O-methyloxime (3d):25 Pale yellow oil; (0.035g,
62% yield); Rf = 0.50 (Et2O/Hexanes, 1:99 v/v); 1H NMR (400 MHz, CDCl3): δ 1.64 (s, 3H), 3.93 (s,
3H), 3.94 (s, 3H), 7.37-7.41 (m, 2H), 7.43-7.49 (m, 3H), 7.57-7.60 (m, 1H), 8.01-8.04 (m, 1H),
8.11-8.12 (m, 1H); 13C NMR (100 MHz, CDCl3): δ 16.6, 52.2, 61.8, 127.8, 128.38, 128.41, 129.0,
129.2, 130.0, 130.2, 130.3, 133.5, 136.8, 139.3, 141.4, 157.6, 166.9; HRMS (EI) calcd for C17H17NO3
[M]+ 283.1208, found 283.1212.
1-(4'-Nitrobiphenyl-2-yl)ethanone O-methyloxime (3e): Pale yellow solid; m.p. 100-102 °C;
(0.040g, 74% yield); Rf = 0.50 (Et2O/Hexanes, 1:99 v/v); 1H NMR (400 MHz, CDCl3): δ 1.71 (s, 3H),
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3.91 (s, 3H), 7.36-7.39 (m, 1H), 7.43-7.50 (m, 3H), 7.54-7.58 (m, 2H), 8.25-8.29 (m, 2H); C NMR
(100 MHz, CDCl3): δ 16.7, 61.9, 123.6, 128.7, 129.1, 129.5, 129.8, 130.1, 136.8, 138.1, 146.9, 148.0,
156.7; HRMS (EI) calcd for C15H14N2O3 [M]+ 270.1004, found 270.0994.
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1-(4-Methylbiphenyl-2-yl)ethanone O-methyloxime (3f):26 Pale yellow oil; (0.038g, 80% yield); Rf
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= 0.78 (Et2O/Hexanes, 1:99 v/v); H NMR (400 MHz, CDCl3): δ 1.61 (s, 3H), 2.40 (s, 3H), 3.97 (s,
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61.7, 127.0, 128.3, 128.9, 129.6, 129.8, 130.2, 136.5, 137.2, 137.6, 141.0, 158.6.
1-(4'-Trifluoromethyl-4-methylbiphenyl-2-yl)ethanone O-methyl oxime (3g): Pale yellow oil;
(0.040g, 65% yield); Rf = 0.71 (Et2O/Hexanes, 1:99 v/v); 1H NMR (400 MHz, CDCl3): δ 1.64 (s, 3H),
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2.42 (s, 3H), 3.95 (s, 3H), 7.26 (s, 3H), 7.50 (d, J = 8.4 Hz, 2H), 7.65 (d, J = 8.0 Hz, 2H); C NMR
(100 MHz, CDCl3): δ 16.8, 21.0, 61.8, 124.2 (q, J = 270.5 Hz), 125.2 (q, J = 3.4 Hz), 129.1 (q, J =
32.3 Hz), 129.2, 129.8, 130.0, 130.1, 136.1, 136.7, 138.1, 144.8, 157.7; 19F NMR (376 MHz, CDCl3):
δ = -62.45 (CF3); HRMS (EI) calcd for C17H16ONF3 [M]+ 307.1184, found 307.1182.
1-(4-Methyl-3'-nitrobiphenyl-2-yl)ethanone O-methyloxime (3h): Pale yellow oil. (0.040g, 70%
yield); Rf = 0.53 (Et2O/Hexanes, 1:99 v/v); 1H NMR (400 MHz, CDCl3): δ 1.70 (s, 3H), 2.43 (s, 3H),
3.93 (s, 3H), 7.28 (s, 3H), 7.53-7.58 (m, 1H), 7.68-7.72 (m, 1H), 8.17-8.21 (m, 1H), 8.28-8.29 (m, 1H);
13C NMR (100 MHz, CDCl3): δ 16.7, 21.0, 61.8, 121.9, 123.8, 129.2, 129.9, 130.0, 130.1, 135.0,
135.1, 136.7, 138.6, 142.8, 148.2, 157.0; HRMS (EI) calcd for C16H16N2O3 [M]+ 284.1161, found
284.1164.
1-(3'-Methoxycarbonyl-4-methylbiphenyl-2-yl)ethanone O-methyloxime (3i): Pale yellow solid;
m.p. 77-80 °C; Rf = 0.44 (Et2O/Hexanes, 1:99 v/v); (0.026g, 43% yield); 1H NMR (400 MHz, CDCl3):
δ 1.62 (s, 3H), 2.41 (s, 3H), 3.93 (s, 3H), 3.96 (s, 3H), 7.22-7.32 (m, 3H), 7.43-7.47 (m, 1H),
7.55-7.60 (m, 1H), 7.98-8.03 (m, 1H), 8.09-8.11 (m, 1H); 13C NMR (100 MHz, CDCl3): δ 16.6, 21.0,
52.2, 61.8, 128.2, 128.4, 129.7, 129.8, 130.0, 130.2, 130.3, 133.5, 136.5, 136.6, 137.7, 141.3, 158.0,
167.0; HRMS (EI) calcd for C18H19NO3 [M]+ 297.1365, found 297.1361.
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1-(4'-Chloro-4-methylbiphenyl-2-yl)ethanone O-methyloxime (3j): Pale yellow oil; (0.023g, 42%
yield); Rf = 0.72 (Et2O/Hexanes, 1:99 v/v); 1H NMR (400 MHz, CDCl3): δ 1.64 (s, 3H), 2.40 (s, 3H),
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MHz, CDCl3): δ 16.6, 21.0, 61.8, 128.5, 129.7, 129.9, 130.1, 130.2, 133.2, 136.3, 136.5, 137.6, 139.5,
158.1; HRMS (EI) calcd for C16H16ClNO [M]+ 273.0920, found 273.0923.
8-Phenyl-3,4-dihydronaphthalen-1(2H)-one-O-methyl oxime (3k):27 Pale yellow oil; (0.035g, 70%
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yield); Rf = 0.71 (Et2O/Hexanes, 1:99 v/v); H NMR (400 MHz, CDCl3): δ 1.81-1.87 (m, 2H),
2.68-2.72 (m, 4H), 3.40 (s, 3H), 7.13-7.15 (m, 1H), 7.17-7.19 (m, 1H), 7.24-7.28 (m, 4H), 7.31-7.35
(m, 2H); 13C NMR (100 MHz, CDCl3): δ 21.3, 25.0, 30.8, 61.4, 125.8, 127.0, 127.6, 128.0, 129.0,
129.3, 129.5, 141.3, 142.2, 143.7, 153.1.
8-(3-Nitrophenyl)-3,4-dihydronaphthalen-1(2H)-one-O-methyl oxime (3l): Pale yellow solid; m.p
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87-89 °C; (0.047g, 80% yield); Rf = 0.56 (Et2O/Hexanes, 1:99 v/v); H NMR (400 MHz, CDCl3): δ
1.82-1.89 (m, 2H), 2.70 (t, J = 7.2 Hz, 2H), 2.74 (t, J = 6.0 Hz, 2H), 3.36 (s, 3H), 7.13-7.15 (m, 1H),
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7.21-7.26 (m, 1H), 7.29-7.33 (m, 1H), 7.46-7.50 (m, 1H), 7.57-7.59 (m, 1H), 8.13-8.15 (m, 2H); C
NMR (100 MHz, CDCl3): δ 21.1, 25.0, 61.5, 120.8, 124.1, 128.2, 128.3, 129.1, 129.3, 135.4, 138.6,
142.3, 145.7, 147.8, 152.9; HRMS (EI) calcd for C17H16N2O3 [M]+ 296.1161, found 296.1162.
8-(3-Methoxycarbonylphenyl)-3,4-dihydronaphthalen-1(2H)-one-O-methyl oxime (3m): Pale
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yellow oil; (0.046g, 74% yield); Rf = 0.50 (Et2O/Hexanes, 1:99 v/v); H NMR (400 MHz, CDCl3): δ
1.82-1.88 (m, 2H), 2.68-2.73 (m, 4H), 3.36 (s, 3H), 3.91 (s, 3H), 7.15-7.18 (m, 2H), 7.26-7.29 (m, 1H),
7.36-7.42 (m, 1H), 7.43-7.46 (m, 1H), 7.95-7.97 (m, 2H); 13C NMR (100 MHz, CDCl3): δ 21.2, 25.0,
30.8, 52.0, 61.4, 127.1, 127.48, 127.53, 128.1, 129.2, 129.5, 130.1, 133.8, 140.2, 142.1, 144.2, 153.0,
167.3; HRMS (EI) calcd for C19H19NO3 [M]+ 309.1365, found 309.1360.
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8-(4-Chlorophenyl)-3,4-dihydronaphthalen-1(2H)-one-O-methyl oxime (3n): Pale yellow oil;
(0.041g, 71% yield); Rf = 0.72 (Et2O/Hexanes, 1:99 v/v); 1H NMR (400 MHz, CDCl3): δ 1.82-1.87 (m,
2H), 2.68-2.71 (m, 4H), 3.45 (s, 3H), 7.11-7.20 (m, 4H), 7.22-7.30 (m, 3H); 13C NMR (100 MHz,
CDCl3): δ 21.3, 25.0, 30.8, 61.5, 127.4, 127.7, 127.8, 128.1, 129.2, 129.4, 130.3, 130.8, 131.8, 140.0,
142.3, 142.3, 153.0; HRMS (EI) calcd for C17H16ClNO [M]+ 285.0920, found 285.0922.
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1-(4'-Trifluoromethylbiphenyl-2-yl)propanone O-methyl oxime (3o): Pale yellow oil; (0.031g,
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50% yield); Rf = 0.66 (Et2O/Hexanes, 1:99 v/v); H NMR (400 MHz, CDCl3): δ 0.76 (t, J =7.6 Hz,
3H), 2.10 (q, J = 7.6 Hz, 2H), 3.92 (s, 3H), 7.35-7.46 (m, 4H), 7.54 (d, J = 8.0 Hz, 2H), 7.66 (d, J =
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8.0 Hz, 1H); C NMR (100 MHz, CDCl3): δ 10.1, 22.9, 61.8, 124.2 (q, J = 270.6 Hz), 125.2 (q, J =
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3.8 Hz), 128.1, 128.3, 128.97 (q, J = 32.2 Hz), 129.0, 129.8, 130.0, 135.5, 139.0, 144.7, 162.6. F
NMR (376 MHz, CDCl3): δ = -62.45 (CF3); HRMS (EI) calcd for C17H16ONF3 [M]+ 307.1184, found
307.1187.
1-(3'-Methoxycarbonylbiphenyl-2-yl)propanone O-methyl oxime (3p): Pale yellow oil; (0.032g,
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54% yield); Rf = 0.44 (Et2O/Hexanes, 1:99 v/v); H NMR (400 MHz, CDCl3): δ 0.75 (t, J = 7.6 Hz,
3H), 2.09 (q, J = 7.6 Hz, 2H), 3.93 (s, 6H), 7.36-7.42 (m, 3H), 7.44-7.49 (m, 2H), 7.61-7.63 (m, 1H),
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8.00-8.03 (m, 1H), 8.14-8.15 (m, 1H); C NMR (100 MHz, CDCl3): δ 10.1, 22.9, 52.2, 61.7, 127.7,
128.3, 128.4, 128.9, 129.9, 130.1, 130.2, 130.2, 133.6, 135.5, 139.3, 141.2, 162.9, 166.9; HRMS (EI)
calcd for C18H19NO3 [M]+ 297.1365, found 297.1373.
General Procedure for Sequential meta-C-H borylation28 and ortho-C-H arylation 9.
A mixture of arenes (1.0 mmol), [Ir(OMe)(cod)]2 (1 mol%), B2pin2 (0.75 mmol, 1.5 equiv.) and
4,4′-Di-tert-butyl-2,2′-dipyridine (2 mol%), combined in THF (2 mL) was in schlenk tubes with
nitrogen. The tubes were heated at 80C for 24 h. Then the reaction mixture was filtered through a pad
of silica gel and the filtrate was concentrated under vacuum. Then the resulting crude boronate was
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transferred to a sealed tube which contains Pd2(dba)3 (0.02 mmol, 10 mol%), Ac-Gly-OH (0.04 mmol,
20 mol%), Ag2CO3 (0.4 mmole, 2 equiv) and KF (0.6 mmole, 3 equiv). To this mixture was added
HFIP (2 mL) and heated at 70 °C for 24 h. After cooling down to room temperature, the reaction
mixture was filtered through a pad of silica gel and the filtrate was concentrated under vacuum. The
crude product was purified by flash column chromatography (ether/hexane=1/99).
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1-[3', 5'-Bis(trifluoromethyl)biphenyl-2-yl]ethanone O-methyl oxime (9a): Pale yellow oil;
(0.064g, 88% yield); Rf = 0.71 (Et2O/Hexanes, 1:99 v/v); 1H NMR (400 MHz, CDCl3): δ 1.76 (s, 3H),
3.87 (s, 3H), 7.38-7.40 (m, 1H), 7.46-7.49 (m, 3H), 7.87-7.89 (m, 3H); 13C NMR (100 MHz, CDCl3):
δ 16.6, 61.8, 120.8 (q, J = 3.4 Hz), 123.3 (q, J = 271.4 Hz), 128.9, 129.2, 129.3 (q, J = 3.4 Hz), 130.1,
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131.5 (q, J = 33.4 Hz), 137.0, 137.3, 143.2, 156.1; F NMR (376 MHz, CDCl3): δ = -62.93 (CF3);
HRMS (EI) calcd for C17H13NOF6 [M]+ 361.0901, found 361.0899.
1-(3',5'-Dimethylbiphenyl-2-yl)ethanone O-methyl oxime (9b): Light yellow oil; (0.035g, 69%
yield); Rf = 0.66 (Et2O/Hexanes, 1:99 v/v); 1H NMR (400 MHz, CDCl3): δ 1.63 (s, 3H), 2.33 (s, 6H),
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3.98 (s, 3H), 6.98 (s, 1H), 7.01 (s, 2H), 7.31-7.36 (m, 2H), 7.39-7.43 (m, 2H). C NMR (100 MHz,
CDCl3): δ 16.5, 21.3, 61.7, 126.9, 127.1, 128.8, 128.8, 129.1, 130.2, 136.6, 137.7, 140.6, 140.9, 158.6.
HRMS (EI) calcd for C17H19NO [M]+ 253.1467, found 253.1469.
1-(3'-Chloro-5'-methylbiphenyl-2-yl)ethanone O-methyl oxime (9c): Pale yellow oil; (0.038g, 70%
yield); Rf = 0.72 (Et2O/Hexanes, 1:99 v/v); 1H NMR (400 MHz, CDCl3): δ 1.68 (s, 3H), 2.36 (s, 3H),
3.96 (s, 3H), 7.08 (s, 1H), 7.15 (s, 1H), 7.20 (s, 1H), 7.34-7.43 (m, 4H); 13C NMR (100 MHz, CDCl3):
δ 16.6, 21.2, 61.8, 126.1, 127.8, 127.9, 128.1, 128.9, 129.2, 130.1, 133.8, 136.7, 139.1, 139.7, 142.6,
157.8; HRMS (EI) calcd for C16H16NOCl [M]+ 273.0920, found 273.0918.
1-[3',5'-Bis(trifluoromethyl)-4-methylbiphenyl-2-yl]ethanone O-methyl oxime (9d): Pale yellow
oil; (0.026g, 34% yield); Rf = 0.71 (Et2O/Hexanes, 1:99 v/v); 1H NMR (400 MHz, CDCl3): δ 1.73 (s,
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3H), 2.43 (s, 3H), 3.89 (s, 3H), 7.26-7.28 (m, 3H), 7.83-7.85 (m, 3H). 13C NMR (100 MHz, CDCl3): δ
16.6, 21.1, 61.8, 120.6 (q, J = 3.8 Hz), 123.3 (q, J = 271.0 Hz), 129.2, 129.9, 129.98, 130.0, 131.4 (q,
J = 33.0 Hz), 134.4, 136.8, 139.0, 143.1, 156.5; 19F NMR (376 MHz, CDCl3): δ = -62.94 (CF3);
HRMS (EI) calcd for C18H15NOF6 [M]+ 375.1058, found 375.1055.
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8-[3,5-Bis(trifluoromethyl)phenyl]-3,4-dihydronaphthalen-1(2H)-one-O-methyl oxime (9e): Pale
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yellow oil; (0.049g, 63% yield); Rf = 0.81 (Et2O/Hexanes, 1:99 v/v); H NMR (400 MHz, CDCl3): δ
1.82-1.89 (m, 2H), 2.69 (t, J = 7.2 Hz, 2H), 2.75 (t, J = 6.0 Hz, 2H), 3.36 (s, 3H), 7.12 (dd, J = 7.6 &
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1.2 Hz, 1H), 7.23-7.25 (m, 1H), 7.29-7.33 (m, 1H), 7.72 (s, 2H), 7.79 (s, 1H); C NMR (100 MHz,
CDCl3): δ 21.1, 24.9, 30.8, 61.4, 119.6 (q, J = 3.8 Hz), 123.6 (q, J = 271.3 Hz), 128.3, 128.7, 129.0,
129.3, 130.1, 130.5, 130.8, 131.1, 138.0, 142.3, 146.1, 152.7; 19F NMR (376 MHz, CDCl3): δ = -62.78
(CF3); HRMS (EI) calcd for C19H15NOF6 [M]+ 387.1058, found 387.1055.
8-(3-Chloro-5-methylphenyl)-3,4-dihydronaphthalen-1(2H)-one-O-methyl oxime (9f): Pale
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yellow oil; (0.053g, 89% yield); Rf = 0.81 (Et2O/Hexanes, 1:99 v/v); H NMR (400 MHz, CDCl3): δ
1.80-1.86 (m, 2H), 2.34 (s, 3H), 2.70 (t, J = 6.8 Hz, 4H), 3.47 (s, 3H), 6.96 (s, 1H), 7.06-7.15 (m, 4H),
7.23-7.27 (m, 1H); 13C NMR (100 MHz, CDCl3): δ 21.16, 21.21, 25.0, 30.8, 61.5, 126.3, 126.4, 127.5,
128.02, 128.04, 129.1, 129.4, 132.8, 138.8, 139.9, 142.1, 145.3, 152.9; HRMS (EI) calcd for
C18H18NOCl [M]+ 299.1077, found 299.1070.
8-(3,5-Dichlorophenyl)-3,4-dihydronaphthalen-1(2H)-one-O-methyl oxime (9g): Pale yellow oil;
(0.055g, 86% yield); Rf = 0.84 (Et2O/Hexanes, 1:99 v/v); 1H NMR (400 MHz, CDCl3): δ 1.80-1.87 (m,
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2H), 2.68-2.73 (m, 4H), 3.50 (s, 3H), 7.08-7.10 (m, 1H), 7.14-7.20 (m, 3H), 7.25-7.28 (m, 2H); C
NMR (100 MHz, CDCl3): δ 21.1, 24.9, 30.8, 61.6, 125.7, 127.6, 128.11, 128.15, 129.0, 129.2, 133.7,
138.4, 142.2, 146.9, 152.7; HRMS (EI) calcd for C17H15NOCl2[M]+ 319.0531, found 319.0533.
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Synthesis of [D4]-3a.
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Compound [D5]-1a was synthesized according to the literature procedure.29 To a mixture of [D5]-1a
(0.2 mmol), Pd2(dba)3 (0.02 mmol, 10 mol%), phenylboronic ester 2a (0.6 mmol, 3.0 equiv),
Ac-Gly-OH (0.04 mmol, 20 mol%), Ag2CO3 (0.4 mmol, 2 equiv) and KF (0.6 mmol, 3 equiv) was
added HFIP (2 mL), and the resulting suspension was heated in a sealed tube at 70 °C for 24 h. After
24 h, the reaction mixture was cooled down to room temperature, and was filtered through a pad of
silica gel and the filtrate was concentrated under vacuum. The crude product was purified by flash
column chromatography to afford compound [D4]-3a as pale yellow oil in 62% yield (0.046g)
(ether/hexane=1/99). Rf = 0.63 (Et2O/Hexanes, 1:99 v/v); 1H NMR (400 MHz, CDCl3): δ 1.62 (s, 3H),
3.97 (s, 3H), 7.30-7.41 (m, 5H); 13C NMR (100 MHz, CDCl3): δ 16.5, 61.8, 127.2, 128.4, 128.9,
136.6, 140.3, 141.0, 158.3; HRMS (EI) calcd for C15H11D4NO [M]+ 229.1405, found 229.1401.
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Synthesis of 8-phenyl-3,4-dihydronaphthalen-1(2H)-one (10).
The compound was readily obtained by hydrolysis of biphenyl O-methyl oxime 3k following the
literature procedure29 with slight modification in 59% isolated yield. O-Methyl oxime 3k (0.1 mmol),
12N HCl (0.5 mL) were added to a sealed tube. Then the mixture was stirred at 100 °C for 24 h. After
completion of reaction, the reaction mixture was extracted with CH2Cl2 and the combined organic
layers were washed successively with saturated sodium bicarbonate and brine, dried over anhydrous
MgSO4 and concentrated in vacuum. Then, the resulting residue was purified by silica gel flash
chromatography to afford the desired product as a colorless solid (0.0131 mg, 59%). The spectral data
were in accordance with the literature.30
ASSOCIATED CONTENT
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Supporting information: H and
NMR copies of compounds are available in supporting
information file. This material is available free of charge via the Internet at http://pubs.acs.org.
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AUTHOR INFORMATION
Corresponding Author
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*E-mail: cfalee@dragon.nchu.edu.tw.
Author Contributions
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†D.M.R. and S.-C.W. contributed equally to this work.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
The Ministry of Science and Technology, Taiwan (NSC 106-2113-M-005-001-) and National Chung
Hsing University are gratefully acknowledged for financial support.
References
(1) (a) Beccalli, E. M.; Broggini, G.; Martinelli, M.; Sottocornola, S. Chem. Rev. 2007, 107, 5318.
(b) Alberico, D.; Scott, M. E.; Lautens, M. Chem. Rev. 2007, 107, 174. (c) Lyons, T. W.;
Sanford, M. S. Chem. Rev. 2010, 110, 1147.
(2) (a) Kakiuchi, F.; Kan, S.; Igi, K.; Chatani, N.; Murai, S. J. Am. Chem. Soc. 2003, 125, 1698. (b)
Lim, S.-G.; Ahn, J.-A.; Jun, C.-H. Org. Lett. 2004, 6, 4687. (c) Kalyani, D.; Deprez, N. R.; Desai,
L. V.; Sanford, M. S. J. Am. Chem. Soc. 2005, 127, 7330. (d) Giri, R.; Chen, X.; Yu, J.-Q. Angew.
Chem. Int. Ed. 2005, 44, 2112. (e) He, H.; Liu, W.-B.; Dai, L.-X.; You, S. L. J. Am. Chem. Soc.
2009, 131, 8346. (f) Yanagisawa, S.; Sudo, T.; Noyori, R.; Itami, K. J. Am. Chem. Soc. 2006,
128, 11748.
(3) (a) Godula, K.; Sames, D. Science 2006, 312, 67. (b) Kakiuchi, F.; Chatani, N. Adv. Synth.
Catal. 2003, 345, 1077. (c) Ritleng, V.; Sirlin, C.; Pfeffer, M. Chem. Rev. 2002, 102, 1731. (d)
Dyker, G. Angew. Chem., Int. Ed. 1999, 38, 1699. (e) Guo, K.; Chen, X.; Zhang, J.; Zhao, Y.
Chem. Eur. J. 2015, 21, 17474.
18
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Page 19 of 20
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
(4) (a) Giri, R.; Yu, J.-Q. J. Am. Chem. Soc. 2008, 130, 14082. (b) Wang, C.; Piel, I.; Glorius, F. J.
Am. Chem. Soc. 2009, 131, 4194. (c) Tredwell, M. J.; Gulias, M.; Bremeyer, N. G.; Johansson, C.
C. C.; Collins, B. S. L.; Gaunt, M. J. Angew. Chem., Int. Ed. 2011, 50, 1076. (d) Meng, G.;
Szostak, M. Org. Lett. 2016, 18, 796.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(5) (a) Desai, L. V.; Hull, K. L.; Sanford, M. S. J. Am. Chem. Soc. 2004, 126, 9542. (b) Thu, H.;
Yu, W.; Che, C. J. Am. Chem. Soc. 2006, 128, 9048.
(6) (a) McGlacken, G. P.; Bateman, L. M. Chem. Soc. Rev. 2009, 38, 2447. (b) Alberico, D.; Scott,
M. E.; Lautens, M. Chem. Rev. 2007, 107, 174. (c) Hassan, J.; Sꢀvignon, M.; Gozzi, C.; Schulz,
E.; Lemaire, M. Chem. Rev. 2002, 102, 1359.
(7) Bringmann, G.; Gulder, T.; Gulder, T. A. M.; Breuning, M. Chem. Rev. 2011, 111, 563.
(8) (a) Li, D.-D.; Yuan, T.-T.; Wang, G.-W. J. Org. Chem. 2012, 77, 3341. (b) Shabashov, D.;
Maldonado, J. R. M.; Daugulis, O. J. Org. Chem. 2008, 73, 7818. (c) Du, Z.-J.; Guan, J.; Wu,
G.-J.; Xu, P.; Gao, L.-X.; Han, F.-S. J. Am. Chem. Soc. 2015, 137, 632. (d) Xu, Z.; Xiang, B.;
Sun, P. Eur. J. Org. Chem. 2012, 3069.
(9) Thirunavukkarasu, V. S.; Parthasarathy, K.; Cheng, C. Angew. Chem., Int. Ed. 2008, 47, 9462.
(10) Kalyani, D.; McMurtrey, K. B.; Neufeldt, S. R.; Sanford, M. S. J. Am. Chem. Soc. 2011, 133,
18566.
(11) Neufeldt, S. R.; Sanford, M. S. Adv. Synth. Catal. 2012, 354, 3517.
(12) Yu, W.-Y.; Sit, W. N.; Zhou, Z.; Chan, A. S.-C. Org. Lett. 2009, 11, 3174.
(13) Lou, S.-J.; Mao, Y.-J.; Xu, D.-Q.; He, J.-Q.; Chen, Q.; Xu, Z.-Y. ACS Catal. 2016, 6, 3890.
(14) (a) Brown, H. C.; Kramer, G. W.; Levy, A. B.; Midland, M. M. Organic Syntheses via
Boranes; Wiley-Interscience: New York, 1975. (b) Brown, H. C.; Singaram, B. Acc. Chem. Res.
1988, 21, 287. (c) Crudden, C. M.; Edwards, D. Eur. J. Org. Chem. 2003, 4695.
(15) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
(16) (a) Chan, D. M. T.; Monaco, K. L.; Li, R.; Bonne, D.; Clark, C. G.; Lam, P. Y. S. Tetrahedron
Lett. 2003, 44, 3863. (b) Tzschucke, C. C.; Murphy, J. M.; Hartwig, J. F. Org. Lett. 2007, 9, 761.
19
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The Journal of Organic Chemistry
Page 20 of 20
1
2
3
4
5
6
7
8
(c) Cheng, J.-H.; Yi, C.-L.; Liu, T.-J.; Lee, C.-F. Chem. Commun. 2012, 48, 8440. (d) Yi, C.-L.;
Liu, T.-J.; Cheng, J.-H.; Lee, C.-F. Eur. J. Org. Chem. 2013, 2013, 3910.
(17) (a) Sibi, M. P.; Tatamidani, H.; Patil, K. Org. Lett. 2005, 7, 2571. (b) Chen, G.; Tokunaga, N.;
Hayashi, T. Org. Lett. 2005, 7, 2881.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
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39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(18) Sun, C.-L.; Liu, N.; Li, B.-J.; Yu, D.-G.; Wang, Y.; Shi, Z.-J. Org. Lett. 2010, 12, 184.
(19) Mkhalid, I. A. I.; Barnard, J. H.; Marder, T. B.; Murphy, J. M.; Hartwig, J. F. Chem. Rev. 2010,
110, 890.
(20) (a) Chen, H. Y.; Schlecht, S.; Semple, T. C.; Hartwig, J. F. Science 2000, 287, 1995. (b)
Ishiyama, T.; Takagi, J.; Ishida, K.; Miyaura, N.; Anastasi, N. R.; Hartwig, J. F. J. Am. Chem.
Soc. 2002, 124, 390. (c) Boller, T. M.; Murphy, J. M.; Hapke, M.; Ishiyama, T.; Miyaura, N.;
Hartwig, J. F. J. Am. Chem. Soc. 2005, 127, 14263. (d) Cho, J. Y.; Iverson, C. N.; Smith, M. R.
J. Am. Chem. Soc. 2000, 122, 12868. (e) Cho, J. Y.; Tse, M. K.; Holmes, D.; Maleczka, R. E.;
Smith, M. R. Science 2002, 295, 305.
(21) (a) Wolfe, J. P.; Buchwald, S. L. J. Org. Chem. 2000, 65, 1144. (b) Cheng, G.-J.; Yang, Y.-F.;
Liu, P.; Chen, P.; Sun, T.-Y.; Li, G.; Zhang, X.; Houk, K. N.; Yu, J.-Q.; Wu, Y.-D. J. Am. Chem.
Soc. 2014, 136, 894. (c) Fan, Z.; Shu, S.; Ni, J.; Yao, Q.; Zhang, A. ACS Catal. 2016, 6, 769.
(22) Ratniyom, J.; Dechnarong, N.; Yotphan, S.; Kiatisevi, S. Eur. J. Org. Chem. 2014, 1381.
(23) Liu, Y.-K.; Lou, S.-J.; Xu, D.-Q.; Xu, Z.-Y. Chem. Eur. J. 2010, 16, 13590.
(24) Xie, F.; Zhang, Z.; Yu, X.; Tang, G.; Li, X. Angew. Chem. Int. Ed. 2015, 54, 7405.
(25) Lou, S.-J.; Mao, Y.-J.; Xu, D.-Q.; He, J.-Q.; Chen, Q.; Xu, Z.-Y. ACS Catal. 2016, 6, 3890.
(26) Yu, W.-Y.; Sit, W. N.; Zhou, Z.; Chan, A. S.-C. Org. Lett. 2009, 11, 3174.
(27) Kalyani, D.; McMurtrey, K. B.; Neufeldt, S. R.; Sanford, M. S. J. Am. Chem. Soc. 2011, 133,
18566.
(28) Partridge, B. M.; Hartwig, J. F. Org. Lett. 2013, 15, 140.
(29) Zhang, W.; Lou, S.; Liu, Y.; Xu, Z. J. Org. Chem. 2013, 78, 5932.
(30) Kakiuchi, F.; Matsuura, Y.; Kan, S.; Chatani, N. J. Am. Chem. Soc. 2005, 127, 5936.
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