Catalytic Cascade Access to Biaryl-2-Methyl Acetates from Pyruvate O-Arylmethyl Ketoximes via the Palladium-Catalyzed C(sp2)H Bond Arylation and C?O Bond Solvolysis

Article abstract of DOI:10.1002/adsc.201800216

A catalytic cascade has been developed for the synthesis of biaryl-2-methyl acetates via a palladium-catalyzed ortho-C(sp²)?H bond arylation of pyruvate O-arylmethyl ketoximes with aryl iodides followed by a solvolysis, in which the pyruvic ketoxime ester as a new auxiliary is employed to direct the C(sp²)?H bond activation. The straightforward treatment of O-arylmethyl hydroxylamines and ethyl pyruvate with aryl iodides also provides the target products in a one-pot fashion. Furthermore, the new palladacycle intermediate is unambiguously confirmed by single-crystal X-ray diffraction analysis. A plausible reaction pathway is proposed for the Pd-catalyzed arylation-acetolysis sequence. (Figure presented.).

Full text of DOI:10.1002/adsc.201800216

Title: Catalytic Cascade Access to Biaryl-2-Methyl Acetates from
Pyruvate O-Arylmethyl Ketoximes via the Palladium-Catalyzed
C(sp2)–H Bond Arylation and C–O Bond Solvolysis
Authors: Ya-Fei Ji, Ling-Yan Shao, Li-Hao Xing, Ying Guo, Kun-Lun
Yu, Wei Wang, Hong-Wei Liu, and Dao-Hua Liao
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Adv. Synth. Catal. 10.1002/adsc.201800216
Link to VoR: http://dx.doi.org/10.1002/adsc.201800216

Advanced Synthesis & Catalysis
10.1002/adsc.201800216
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Catalytic Cascade Access to Biaryl-2-Methyl Acetates from
Pyruvate O-Arylmethyl Ketoximes via the Palladium-Catalyzed
2
C(sp )–H Bond Arylation and C–O Bond Solvolysis
a,c
a,c
a
a
a,b
Ling-Yan Shao, Li-Hao Xing, Ying Guo, Kun-Kun Yu, Wei Wang, Hong-Wei
a
a
a
Liu, Dao-Hua Liao, and Ya-Fei Ji*
a
School of Pharmacy, East China University of Science & Technology, 130 Meilong Road, Shanghai 200237, P. R.
China.
Fax: +86-021-6425-3314; phone: +86-021-6425-3314; e-mail: jyf@ecust.edu.cn
Department of Chemistry & Chemical Biology, University of New Mexico, MSC03 2060, Albuquerque NM 87131-
b
c
0
001, USA
Fax: +1-505-277-2609; phone: +1-505 277 0756; e-mail: wwang@unm.edu
Ling-Yan Shao and Li-Hao Xing contributed equally as the first authors.
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.
Abstract. A catalytic cascade has been developed for the
synthesis of biaryl-2-methyl acetates via a palladium-
2
catalyzed ortho-C(sp )–H bond arylation of pyruvate O-
arylmethyl ketoximes with aryl iodides followed by a
solvolysis, in which the pyruvic ketoxime ester as a new
2
auxiliary is employed to direct the C(sp )–H bond
activation. The straightforward treatment of O-arylmethyl
hydroxylamines and ethyl pyruvate with aryl iodides also
provides the target products in a one-pot fashion.
Furthermore, the new palladacycle intermediate is
unambiguously confirmed by single-crystal X-ray
diffraction analysis. A plausible reaction pathway is
proposed for the Pd-catalyzed arylation-acetolysis
sequence.
2
Keywords: arylation; biaryl-2-methyl acetates; C(sp )–H
bond activation; pyruvate ketoximes; solvolysis
Introduction
Scheme 1. Previous related works and present work.
Biaryl motifs are broadly distributed in numerous
bioactive molecules, natural products, agrochemicals,
In addition to N-heterocyclic directing groups,
[1]
pharmaceuticals, and organic functional materials.
oxime functionality has been applied in C–H bond
activation enabling diversiform transformations such
as acetoxylation, acylation, olefination, amidation,
Over the past few decades, transition-metal-catalyzed
cross-couplings of arenes with aryl halides,
arylsilanes, arylboron reagents or other arylmetallic
reagents[ have been exploited to assemble myriads
of the molecular architectures. However, these
methods usually require prefunctionalized or
electronically biased substrates. For the sake of step-
economy, significant efforts have been devoted to
[6]
iodination and (hetero)arylation. These C–C as well
2]
as C–X (X = O, N, I) bonds were effectively built via
either endo- or exo-type cyclometalation (π-bond of
the directing group inside or outside the metallocycle).
In this context, with the aid of exogenous ligand,
II
0
Zhao’s group recently achieved a Pd /Pd -catalyzed
ortho-arylation with arylboronic esters as arylating
reagents, directed by simple acetoxime via an exo-
directing
inert
C–H
bond
activation/
[
3]
[3,4]
functionalization. In particular, heteroarenes
or
functionalities[
3,5]
directed arylations have been
[6g]
type activation (Scheme 1A). This work provides a
proved to be powerful strategies to furnish aromatic
concise two-step access to 2-aryl substituted
arylmethyl alcohols through arylation and Ni-
C–C bond formations.
1
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Advanced Synthesis & Catalysis
10.1002/adsc.201800216
catalyzed hydrogenation reduction. In fact, the biaryl-
Scheme 2. Screening of directing groups.[a,b]
2
-methyl alcohol scaffolds frequently appear in
various bioactive molecules, for example, HNF-4α
modulators, CaSR antagonists, VEGF receptor
inhibitors, etc.[ More recently, Ge’s group reported
7]
3
an exo-type directed site-selective C(sp )−H arylation
of primary aliphatic amines using glyoxylic acid as a
transient imine-carboxylic N,O-bidentate directing
group (Scheme 1B).[ Most recently, a powerful 2,2-
dimethyl aminooxyacetic acid auxiliary was disclosed
by Yu’s group to enable an endo-type Pd-catalyzed
8a]
3
[8b]
C(sp )−H (hetero)arylation,
demonstrating the
outstanding directing ability of oxime in concert with
another weak dentate.
Nevertheless, compared to developed pyridine-
[
3d,e]
based auxiliaries,
simple functionality-based
[
[
a]
b]
bidentates[
8,9]
Reaction conditions: 1 (0.3 mmol), 2a (84.2 mg, 0.36
deserve to pay more attention. Herein,
II
IV
2
mmol), Pd(OAc) (6.7 mg, 10 mol%), AgTFA (99.2 mg,
2
we report a new Pd /Pd -catalyzed ortho-C(sp )–H
arylation of masked arylmethyl alcohols followed by
a benzylic C–O bond solvolysis to straightforwardly
prepare biaryl-2-methyl acetates in a one-pot fashion.
The simple bidentate oxime-ester functions as a
directing group for the arylation, and a chelating
agent for the solvolysis. The activation mode of
pyruvic ketoxime ester directing group via oxime-
carbonylic N,O-bidentate chelation is revealed by
single-crystal X-ray diffraction analysis, and a
plausible reaction pathway is depicted based on a set
of rational mechanistic surveys.
o
0
.45 mmol), AcOH/H
2
O (9:1, v/v, 2.5 mL), 120 C, 20 h.
Isolated yields.
We turned our attention to investigating main
reaction parameters (Table 1). The desired product 3a
was obtained with up to 81% yield upon increasing
2
2
a to 3.0 equiv (entries 1−4). But, further increasing
a did not lead to a higher yield (entry 5). Based on
entry 4, we conducted an intensive survey of Pd
catalysts. Pd(PPh Cl was inefficient (entry 6) while
PdCl and Pd(CH CN) Cl resulted in inferior
efficiencies (entries 7 and 8). Albeit a similar
outcome with Pd(TFA) (entry 9), Pd(OAc) was
3
)
2
2
2
3
2
2
2
2
Results and Discussion
chosen as the suitable catalyst in light of its lower
cost. Moreover, AgTFA was identified as the best
additive among the tested silver salts (entries 10−12).
In addition, the yield of 3a dramatically diminished to
Our initial efforts aimed at evaluating the different
types of O-arylmethyl oxime bidentate directing
groups for the arylation without exogenous ligand
1
0% in the absence of water (entry 13). However,
(
Scheme 2). The reaction was carried out in the
presence of substrate 1 (0.3 mmol), Pd(OAc) (10
mol%), 1-iodo-4-methoxybenzene 2a (1.2 equiv),
AgTFA (1.5 equiv) in AcOH/H O (9:1, v/v, 2.5 mL)
increasing the amount of water in the mixed solvent
2
was detrimental (entries 14−16). Finally, it was
demonstrated that 120 C was an optimal temperature
o
2
for the process (entries 17−19). Thus, we established
entry 4 as the standard reaction conditions.
o
at 120 C. Unexpectedly, biaryl-2-methyl acetate 3a
was obtained at the end of all effective reactions.
Presumably, a nucleophilic C–O bond acetolysis
With the optimized reaction conditions, we then
explored the scope of aryl iodides. As shown in
Scheme 3, various electronically and sterically biased
2
proceeded following the directed C(sp )–H
arylation.[ Ge’s directing group of glyoxylic acid
10]
aryl iodides with OMe, Me, CH
2
OH, F, Cl, Br, I, CF
3
[8a]
aldoxime (DG
acetolysis product 3a in 37% yield. Furthermore,
ethyl glyoxylate aldoxime (DG ) delivered a better
yield of 42%. The outcomes were further increased to
1% and 67% by installing pyruvic ketoxime (DG
and pyruvic ketoxime ester (DG ), respectively.
However, bulkier ketoxime ester directing groups
DG and DG ) significantly reduced the yields. In
contrast, the alcohol-assisted ketoxime (DG ) and
monodentate acetoxime (DG ) failed to deliver any
1
)
firstly afforded the arylation-
or COOMe groups were suitable substrates (3a−n).
Generally, the partners with electron-donating groups
at para- and meta-positions gave higher yields of 75–
2
8
3% (3a, b and 3h−j). Interestingly, 3-iodobenzyl
6
3
)
alcohol underwent an additional esterification giving
a biarylmethyl diacetate compound 3j. As for the aryl
iodides containing electron-withdrawing groups at
para- and meta-positions, the relatively lower yields
of 62–69% were obtained (3c−f and 3k−m), but the
para-methoxycarbonyl substituted partner delivered a
4
(
5
6
7
8
anticipated product 3a, where only slight acetolysis
of starting ketoxime substrates were detected along
with a small amount of homocoupling of 2a. In the
[11]
better yield of 73% (3g). It should be noted that the
-
F, -Cl, -Br, -I, -CH OCOMe and -COOMe groups
2
add flexibility to further elaborate the biaryl-2-methyl
acetate products. It appears that steric effect
end, pyruvic ketoxime ester (DG
4
) was selected as
the optimal directing group for further investigations.
2
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Advanced Synthesis & Catalysis
10.1002/adsc.201800216
Table 1. Investigations of the reaction parameters.[a]
Scheme 3. Scope of aryl iodides.[a,b]
Mainly deviation from the “primary
conditions”
Entry
Yield[b]
1
2
3
4
5
6
7
8
9
None
67%
71%
77%
81%
80%
0%
23%
38%
79%
15%
33%
61%
10%
35%
41%
53%
63%
74%
79%
2a (2.0 equiv)
2a (2.5 equiv)
2a (3.0 equiv)
2a (3.5 equiv)
Pd(PPh
PdCl instead of Pd(OAc)
Pd(CH CN) Cl instead of Pd(OAc)
Pd(TFA) instead of Pd(OAc)
Ag PO instead of AgTFA
AgOAc instead of AgTFA
Ag CO instead of AgTFA
AcOH
3 2 2 2
) Cl instead of Pd(OAc)
2
2
3
2
2
2
2
2
1
1
0
1
3
4
1
1
1
1
1
1
1
1
2
3
4
5
6
7
8
9
2
3
AcOH/H
AcOH/H
AcOH/H
2
2
2
O (2:1)
O (4:1)
O (6:1)
o
90 C
o
110 C
o
130 C
[
a]
Reaction conditions: 1a (70.5 mg, 0.3 mmol), 2a (210.6
mg, 0.90 mmol, except otherwise specified), Pd(OAc)
2
(
6.7 mg, 10 mol%), AgTFA (99.2 mg, 0.45 mmol),
o
2
AcOH/H O (9:1, v/v, 2.5 mL), 120 C, 20 h.
[
b]
Isolated yields.
plays a significant role. Low yield (3n) or no product
was observed for the ortho-substituted reactants.
Likely, the larger steric congestion around
palladacyclic intermediates would block oxidative
[
a]
Reaction conditions: 1a (70.6 mg, 0.3 mmol), 2 (0.90
mmol), Pd(OAc)
2
(6.7 mg, 10 mol%), AgTFA (99.2 mg,
o
[12]
0
.45 mmol), AcOH/H O (9:1, v/v, 2.5 mL), 120 C, 20 h.
2
addition or reductive elimination step.
The
[
[
b]
c]
Isolated yields.
The product of arylation-acetolysis and additional
disubstituted and fused O-heterocyclic aryl iodides,
as well as condensed arene 2-iodonaphthalene were
also effective to afford the arylmethyl acetates in
moderate yields (3o−r). Less strongly coordinating 2-
substituted pyridyl worked well to offer the N-
heteroarylated products in moderate yields (3s and t),
suggesting the ortho-steric effect against the
coordination of pyridine with Pd. Functional groups
such as ether, arylmethyl acetate, halogen,
methoxycarbonyl, 1,4-dioxane and pyridyl were well-
tolerated under the reaction conditions. Finally, the
NMR-based geometrical configuration of 3n was
esterification.
Next, different pyruvic O-arylmethyl ketoxime
esters were surveyed (Scheme 4). Similarly, wide
functional group tolerance was observed including
Me, OMe, i-Pr, Ph, F, Cl, Br, I, and CF groups (3a,
3
4c−f and h−p). The substrates bearing electron-
donating groups furnished the corresponding biaryl-
2-methyl acetates in good yields of 72–82% (3a, 4h, i,
l and m). Slightly lower yields were observed for the
substrates with electron-withdrawing groups (4d−f, j,
k, n and o). As for strongly coordinating -OMe and -
further confirmed by single-crystal X-ray diffraction
13]
(
Scheme 3, see ESI).[
[6d,k,l,8b]
NO
2
groups,
their ortho-substituted O-
arylmethyl ketoximes underwent a solvolysis to
exclusively offer the non-arylated arylmethyl acetates
’
’ [14]
(
4b and g ). It is likely that -OMe and -NO might
2
coordinate with the Pd center along with the
ketoxime ester directing group, bringing about a
larger molecular distortion and ring strain.
3
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Advanced Synthesis & Catalysis
10.1002/adsc.201800216
Consequently, the tri-dentate chelation would impede
potential arylation and impair the stability of benzylic
hydroxylamines and ethyl pyruvate as starting
materials (Scheme 5). Owing to the strong
coordinating ability and reactivity, free O-arylmethyl
hydroxylamines often interfere with the reactive
[14]
C–O bond, leading to the exclusive acetolysis.
Other ortho-systems were amenable to the approach
delivering desired products in moderate yields of 54–
[6m]
reagents and catalysts.
With the slightly modified
7
0% (4c−f). It should be pointed out that sterically
protocol (1.5 equiv ethyl pyruvate and other identical
conditions), these unsubstituted and para-substituted
free amines were subjected to the one-pot procedure
with various aryl iodides to generate the desired
products in moderate to good yields of 57–73%
(6a−l). Furthermore, it is noteworthy that only
monoarylated acetates were obtained without
diarylated products. We speculated that the excessive
ethyl pyruvate served as an exogenous ligand
coordinating with Pd to inhibit the potential
secondary activation/oxidative addition. With the
help of arylation-derived ortho-steric hindrance and
auxiliary chelation, such additional chelation further
impairs the stability of benzylic C–O bond.
crowded terphenyl 4c offered a relatively lower yield
of 54%, accompanying with 2-phenylbenzyl acetate
6a (see Scheme 5) as a by-product of direct acetolysis
therein.
With respect to the meta-substituted O-arylmethyl
ketoximes, the pivotal arylation appropriately took
[15]
place at less sterically hindered positions (4g−k).
As for para-substituted substrates (4l−n), the
corresponding diarylated acetates were also observed.
Besides, the method was applicable for disubstituted
masked arylmethyl alcohols in moderate yields (4o
and p). Furthermore, the condensed arene turned out
to be a feasible substrate for the arylation at less
hindered position (4q).
Scheme 5. One-pot synthesis of biaryl-2-methyl acetates
[a,b]
Scheme 4. Scope of pyruvic O-arylmethyl ketoxime
from O-arylmethyl hydroxylamines.
esters.[
a,b]
[
a]
Reaction conditions: 5 (0.3 mmol), 2 (0.90 mmol),
Pd(OAc) (6.7 mg, 10 mol%), AgTFA (99.2 mg, 0.45
mmol), ethyl pyruvate (52.2 mg, 0.45 mmol), AcOH/H
2
2
O
o
(
9:1, v/v, 2.5 mL), 120 C, 20 h.
[
b]
Isolated yields.
The strategy can be expediently adopted to prepare
synthetically valuable 2-aryl substituted arylmethyl
[
a]
Reaction conditions: 1 (0.3 mmol), 2a (210.6 mg, 0.90
mmol), Pd(OAc) (6.7 mg, 10 mol%), AgTFA (99.2 mg,
alcohols (Scheme 6A). Subjecting the acetate 3a and
2
NaOH to a mixed solvent of THF/MeOH/H O
2
o
0
.45 mmol), AcOH/H
Isolated yields.
The product of direct acetolysis observed in 91% yield,
2
O (9:1, v/v, 2.5 mL), 120 C, 20 h.
afforded biaryl alcohol 7 in 93% yield without the
need for a column-chromatographic purification (see
ESI). Thus, as an alternative to the laborious
[
[
b]
c]
see Ref.14a and ESI.
[6g]
hydrogenation,
this enabled a rapid access to
[
d]
The by-product of direct acetolysis observed in 21%
yield, see 6a in Scheme 5.
biaryl-2-methyl alcohols. In addition, the reaction on
gram scale has also been examined in good yield
[
e]
The product of direct acetolysis observed in 87% yield,
see Ref.14b and ESI.
(
Scheme 6B).
[
f]
Ratio of mono/di.
We demonstrated that the cascade of condensation,
arylation, and acetolysis could be accomplished in a
one-pot
fashion
by
using
O-arylmethyl
4
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Advanced Synthesis & Catalysis
10.1002/adsc.201800216
membered oxime-carbonylic N,O-bidentate chelation
with six-membered exo-carbopalladation (5,6-fused
[
13]
metallocycle mode, Scheme 8A, see ESI)
.
Accordingly, the palladacycle favorably converted
into the desired arylated benzyl acetate 6b in 74%
yield in the absence of Pd(OAc) (Scheme 8B).
2
Therefore, the cyclopalladated I was suggested as a
key intermediate engaged in the process. The present
work represents a new example of N,O-bidentate
activation.
Scheme 6. Convenient access to 2-aryl substituted
arylmethyl alcohol and a gram scale reaction.
To gain insight into the reaction mechanism of the
arylation, the intermolecular competition experiments
were firstly carried out to probe the electronic effect.
The treatment of a mixture of electronically biased
iodides 2a and 2c (1:1 equiv) with ketoxime ester 1a
generated the products 3a and 3c with the ratio of
2
.57/1.0 (Scheme 7A, see ESI). It was found that the
electron-rich 2a predominantly coupled with the
substrate 1a, suggesting that electron-donating group
substituted aryl iodides would facilitate the
transformation.[
12,16]
In addition, the competition
process of 1a and 1f gave a similar result that the
electron-rich ketoxime ester 1a was preferred to yield
Scheme 8. Preparation and arylation-solvolysis of the
palladacycle I.
3
a as a major product (Scheme 7B, see ESI). At last,
a deuterium labeling isotope experiment was carried
We implemented a set of control experiments to
detect the influences on acetolysis (Scheme 9). Firstly,
subjecting O-benzyl hydroxylamine 5a, iodide 2a,
and ethyl pyruvate to the one-pot protocol with
II
IV
out to probe the kinetics of Pd /Pd -catalyzed
2
C(sp )−H arylation (Scheme 7C). The intermolecular
competition reactions between 8 and 8´ (8-d ) with 2a
7
in one vessel clearly revealed a primary kinetic
isotopic effect (k /k = 4.0; see ESI). The result
indicates that bond
CD
deuterated acetate 6b’ was obtained as the desired
product (Scheme 9A). This suggests that
nucleophilic solvolysis of the benzylic C−O bond
3
2
COOD/D O (9:1, v/v) as a solvent, 2-arylbenzyl
H
D
2
the
C(sp )−H
a
cleavage/carbopalladation might be involved in the
rate-limiting step.
[10]
with acetic acid indeed occurs
after arylation.
Secondly, without the metal salt, the solvolysis of
biaryl pyruvate ketoxime 1c failed to provide any
deuterated acetate 6a’ (Scheme 9B), and the
stoichiometric AgTFA was proved to be completely
ineffective (Scheme 9C). However, introducing a
catalytic amount of Pd(OAc)
2
into the system
strikingly gave the deuterated 6a’ in 81% yield
(
(
Scheme 9D), or acetate product 6a in 92% yield
Scheme 9E). These facts undoubtedly revealed a
2
dual role of Pd catalyst, directing proximal C(sp )−H
bond activation and facilitating benzylic C−O bond
solvolysis.
On the other hand, the influence of ortho-aryl
hindrance on the acetolysis was further investigated.
Compared to biaryl pyruvate ketoxime 1c (Scheme
9
E), the solvolysis of O-benzyl ketoxime 8 was
considerably more sluggish to deliver only 33% yield
of acetate product (Scheme 9F). In this regard, it was
revealed that the arylation-derived ortho-hindrance
can result in a more accessible acetolysis. Meanwhile,
we considered that the use of 3 equiv of ArI greatly
enhances Pd-catalyzed arylation, accordingly
promoting the subsequent acetolysis. Finally, the
control experiment showed that the excessive ethyl
pyruvate can serve as an exogenetic ligand to
Scheme 7. Intermolecular kinetic competition experiments.
We successfully obtained
a
crystallizable
palladacycle I from PdCl and pyruvate O-benzyl
2
ketoxime 8.[ The structure of I was unambiguously
17]
confirmed by single-crystal X-ray diffraction analysis
to reveal an activation mode referring to five-
5
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Advanced Synthesis & Catalysis
10.1002/adsc.201800216
promote the solvolysis (Scheme 9G). These
synergistic effects of ethyl pyruvate coordination,
arylation-derived ortho-hindrance, and intrinsic
auxiliary chelation significantly accelerate the Pd-
catalyzed acetolysis with severely aggravated
molecular distortion.
Scheme 10. Plausible reaction pathway.
Conclusion
In summary, we have developed an efficient cascade
for synthesis of biaryl-2-methyl acetates via Pd-
2
catalyzed ortho-C(sp )–H arylation and acetolysis.
With the cost-effective ethyl pyruvate as a directing
group, structurally diverse masked arylmethyl
alcohols (1 and 5) can be arylated on the aromatic
ring and acetoxylated at the benzyl position in one-
pot fashion. The exo-six-membered palladacycle with
five-membered
N,O-bidentate
chelation
is
unambiguously confirmed by single-crystal X-ray
diffraction analysis. We have also conducted a series
of mechanistic studies depicting a plausible reaction
pathway. Further related studies are underway in our
laboratory.
Experimental Section
Scheme 9. Control experiments.
Unless otherwise indicated, all reagents were obtained
from commercial sources and used as received without
further purification. All reactions were carried out in an
oven-dried glass sealed tube and monitored by thin layer
chromatography (TLC, pre-coated silica gel plates
containing HF254). All solvents were only dried over 4 Å
molecular sieves. Reaction products were purified via
column chromatography on silica gel (300–400 mesh).
Melting points were determined using open capillaries and
On the basis of experimental investigations and the
[
8,10,18]
well-documented reports,
a plausible reaction
catalytic cycle is
II
IV
pathway involving Pd /Pd
proposed for the cascade process (Scheme 10).
Pyruvate ketoxime 1 firstly coordinates with Pd to
form the palladated bicyclic intermediate II via a
five-membered chelation and an exo-type six-
membered concerted metallation–deprotonation
II
uncorrected. NMR spectra were determined on Bruker
1
AV400 in CDCl
3
with TMS as internal standard for H
13
NMR (400 MHz) and C NMR (100 MHz), respectively.
HRMS were measured on a QSTAR Pulsar I LC/TOF MS
mass spectrometer or Micromass GCTTM gas
chromatograph-mass spectrometer.
CMD).[
19,20]
Then, the key Pd species III is
IV
(
generated through the oxidative addition of
palladacycle II with aryl iodide. The highly active
IV
Procedure for the Synthesis of Biaryl-2-Methyl
Acetates (3, 4) from Pyruvate O-Arylmethyl Ketoximes
A mixture of substrate 1 (0.3 mmol), 2 (0.9 mmol),
hexa-coordinated Pd
adduct III undergoes a
II
following reductive elimination to furnish the Pd
pincer-type complex IV. Finally, the complex IV is
Pd(OAc)
2
(6.7 mg, 0.03 mmol), AgTFA (99.2 mg, 0.45
followed by a nucleophilic acetolysis and iodide
mmol), and AcOH/H O (9:1, v/v, 2.5 mL) was stirred in a
2
abstraction[
20]
glass sealed-tube at room temperature for 30 min, then the
mixture was heated to 120 °C for 20 h. Upon completion
of the reaction, the mixture was cooled to room
temperature and added dropwise into a saturated NaHCO
solution (25 mL). The solution was extracted with ethyl
acetate (25 mL×3), and then the combined organic layer
was dried over anhydrous MgSO4. Finally, the solution was
to release the arylated arylmethyl
II
acetate 3, 4 or 6, and regenerate the Pd catalyst. The
complex IV may be further chelated by excessive
ethyl pyruvate through ligand exchange, to drastically
accelerate the solvolysis (Scheme 5).
3
6
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Advanced Synthesis & Catalysis
10.1002/adsc.201800216
concentrated in vacuo to provide a crude product, which
was purified via a column chromatography on silica gel
(3'-methoxy-3-methyl-[1,1'-biphenyl]-2-yl)methyl
1
acetate (3h): yellow oil, 60.8 mg (75%); H NMR (400
(
eluents: petroleum ether/ethyl acetate 40:1) to supply the
3
MHz, CDCl , ppm): δ 7.22 (t, J = 7.6 Hz, 2H), 7.15 (d, J =
6.4 Hz, 1H), 7.09 (d, J = 7.6 Hz, 1H), 6.83−6.81 (m, 1H),
desired product 3 or 4.
6
.81−6.79 (m, 1H), 6.78 (t, J = 1.6 Hz, 1H), 4.94 (s, 2H),
13
3
.73 (s, 3H), 2.33 (s, 3H), 1.98 (s, 3H); C NMR (100
, ppm): δ 170.8, 159.3, 144.0, 142.4, 139.0,
30.9, 129.8, 129.2, 128.6, 128.0, 121.7, 114.9, 112.9, 62.3,
(
4'-methoxy-3-methyl-[1,1'-biphenyl]-2-yl)methyl
1
MHz, CDCl
3
acetate (3a): yellow oil, 65.7 mg (81%); H NMR (400
1
5
C
MHz, CDCl
3
, ppm): δ 7.30 (t, J = 7.6 Hz, 1H), 7.26−7.22
= 8.4 Hz, J
2.8 Hz, 2H), 5.03 (s, 2H), 3.85 (s, 3H), 2.42 (s, 3H), 2.08
+
5.2, 20.9, 19.4; HRMS (EI): m/z [M ] calcd. for
: 270.1256, found 270.1254.
(
m, 3H), 7.16 (d, J = 7.6 Hz, 1H), 6.94 (dt, J
1
2
17
H
18
O
3
=
1
3
(
s, 3H); C NMR (100 MHz, CDCl
3
, ppm): δ 170.9, 158.9,
1
1
43.8, 138.9, 133.4, 131.0, 130.3 (2C), 129.5, 128.5, 128.3, (3,3'-dimethyl-[1,1'-biphenyl]-2-yl)methyl acetate (3i):
13.6 (2C), 62.4, 55.3, 20.9, 19.6; HRMS (EI): m/z [M ]
: 270.1256, found 270.1254.
+
1
3
yellow oil, 61.0 mg (80%); H NMR (400 MHz, CDCl ,
calcd. for C17
H
18
O
3
ppm): δ 7.28 (q, J = 7.2 Hz, 2H), 7.22 (d, J = 7.2 Hz, 1H),
7
2
.16 (d, J = 7.6 Hz, 2H), 7.10 (d, J = 8.8 Hz, 2H), 5.01 (s,
13
H), 2.41 (s, 3H), 2.37 (s, 3H), 2.06 (s, 3H); C NMR
, ppm): δ 170.8, 144.3, 141.0, 138.9,
37.7, 130.9, 130.1, 129.6, 128.5, 128.1, 128.02, 127.96,
(
3,4'-dimethyl-[1,1'-biphenyl]-2-yl)methyl acetate (3b):
1
(100 MHz, CDCl
3
3
yellow oil, 57.2 mg (75%); H NMR (400 MHz, CDCl ,
1
1
ppm): δ 7.35 (t, J = 7.2 Hz, 1H), 7.30−7.28 (m, 1H),
+
26.3, 62.3, 21.5, 20.9, 19.6; HRMS (EI): m/z [M ] calcd.
: 254.1307, found 254.1306.
7
2
.29−7.26 (m, 4H), 7.22 (d, J = 7.6 Hz, 1H), 5.08 (s, 2H),
13
for C17
H
18
O
2
.48 (s, 3H), 2.45 (s, 3H), 2.12 (s, 3H); C NMR (100
, ppm): δ 170.8, 144.2, 138.9, 138.1, 136.9,
31.0, 129.5, 129.1 (2C), 128.9 (2C), 128.5, 128.2, 62.4,
MHz, CDCl
3
1
2
C
(3'-acetoxy-3-methyl-[1,1'-biphenyl]-2-yl)methyl
+
1
1.2, 20.9, 19.6; HRMS (EI): m/z [M ] calcd. for
: 254.1307, found 254.1308.
acetate (3j): yellow oil, 77.7 mg (83%); H NMR (400
17
H
18
O
2
MHz, CDCl
3
, ppm): δ 7.40 (t, J = 7.2 Hz, 1H), 7.36 (s, 1H),
7
2
.31 (s, 2H), 7.26 (s, 2H), 7.16 (d, J = 7.6 Hz, 1H), 5.13 (s,
H), 4.98 (s, 2H), 2.42 (s, 3H), 2.10 (s, 3H), 2.07 (s, 3H);
(
(
4'-fluoro-3-methyl-[1,1'-biphenyl]-2-yl)methyl acetate
1
3
1
3
C NMR (100 MHz, CDCl , ppm): δ 170.92, 170.86,
3c): yellow oil, 49.6 mg (64%); H NMR (400 MHz,
1
1
43.7, 141.4, 139.0, 136.6, 135.8, 130.9, 129.9, 129.1,
28.6, 128.4, 128.1, 127.2, 66.2, 62.2, 21.0, 20.9, 19.6;
CDCl
3
, ppm): δ 7.22 (s, 1H), 7.19 (d, J = 3.6 Hz, 1H),
7
8
.17−7.15 (m, 2H), 7.05 (d, J = 7.6 Hz, 1H), 7.00 (t, J =
+
13
HRMS (EI): m/z [M ] calcd. for C19
H
20
O
4
: 312.1263,
.8 Hz, 2H), 4.91 (s, 2H), 2.34 (s, 3H), 1.98 (s, 3H);
C
=
1
found 312.1262.
NMR (100 MHz, CDCl
3
, ppm): δ 170.8, 162.2 (d, JCF
4
2
44.8 Hz), 143.1, 139.0, 137.0 (d, JCF = 3.3 Hz), 131.1,
3
1
30.8 (d, JCF = 8.0 Hz, 2C), 129.9, 128.6, 128.2, 115.1 (d,
(3'-chloro-3-methyl-[1,1'-biphenyl]-2-yl)methyl acetate
2
1
J
CF = 21.3 Hz, 2C), 62.1, 20.9, 19.6; HRMS (EI): m/z
(3k): yellow oil, 51.1 mg (62%); H NMR (400 MHz,
+
[
M ] calcd. for C16
H
15
O
2
F:258.1056, found 258.1054.
3
CDCl , ppm): δ 7.33 (s, 1H), 7.32 (s, 1H), 7.32 (d, J = 1.2
Hz, 1H), 7.30 (d, J = 7.6 Hz, 1H), 7.25 (d, J = 6.8 Hz, 1H),
.20−7.17 (m, 1H), 7.13 (d, J = 7.6 Hz, 1H), 4.97 (s, 2H),
7
(
(
4'-chloro-3-methyl-[1,1'-biphenyl]-2-yl)methyl acetate
1
3
1
2.42 (s, 3H), 2.07 (s, 3H); C NMR (100 MHz, CDCl
3
,
3d): yellow oil, 60.2 mg (73%); H NMR (400 MHz,
ppm): δ 170.8, 142.8, 142.8, 139.1, 134.0, 130.9, 130.2,
3
CDCl , ppm): δ 7.29 (d, J = 8.4 Hz, 2H), 7.22 (t, J = 7.6
1
29.5, 129.4, 128.7, 127.9, 127.4, 127.4, 62.0, 20.9, 19.6;
+ 35
Hz, 1H), 7.17 (s, 2H), 7.15 (s, 1H), 7.04 (d, J = 7.6 Hz,
13
15 2
HRMS (EI): m/z [M ] calcd. for C16H O Cl: 274.0761,
1
H), 4.90 (s, 2H), 2.34 (s, 3H), 1.98 (s, 3H); C NMR
found 274. 0759.
(
3
100 MHz, CDCl , ppm): δ 170.7, 142.9, 139.5, 139.1,
1
6
C
33.4, 131.0, 130.6 (2C), 130.1, 128.7, 128.3 (2C), 128.0,
+
2.1, 20.9, 19.6; HRMS (EI): m/z [M ] calcd. for
(3'-bromo-3-methyl-[1,1'-biphenyl]-2-yl)methyl acetate
3
5
1
16
H
15
O
2
Cl: 274.0761, found 274.0762.
(3l): yellow oil, 62.2 mg (65%); H NMR (400 MHz,
3
CDCl , ppm): δ 7.42−7.39 (m, 2H), 7.23 (t, J = 8.0 Hz, 1H),
7
.18 (d, J = 2.0 Hz, 1H), 7.17−7.14 (m, 2H), 7.05 (d, J =
(
(
4'-bromo-3-methyl-[1,1'-biphenyl]-2-yl)methyl acetate
13
1
8.4 Hz, 1H), 4.89 (s, 2H), 2.34 (s, 3H), 2.00 (s, 3H);
C
3e): yellow oil, 59.4 mg (62%); H NMR (400 MHz,
NMR (100 MHz, CDCl
3
, ppm): δ 170.8, 143.1, 142.7,
3
CDCl , ppm): δ 7.45 (d, J = 8.4 Hz, 2H), 7.23 (t, J = 7.6
1
1
39.1, 132.4, 130.9, 130.3, 130.2, 129.7, 128.7, 127.9,
Hz, 1H), 7.17 (d, J = 6.0 Hz, 1H), 7.10 (d, J = 8.4 Hz, 2H),
+
27.8, 122.2, 62.0, 20.9, 19.6; HRMS (EI): m/z [M ] calcd.
79
7
.04 (d, J = 7.2 Hz, 1H), 4.90 (s, 2H), 2.34 (s, 3H), 1.98 (s,
13
for C16
H
15
O
2
Br: 318.0255, found 318.0253.
3
3
H); C NMR (100 MHz, CDCl , ppm): δ 170.7, 142.9,
1
40.0, 139.1, 131.3 (2C), 130.9 (2C), 130.1, 128.8, 128.7,
+
1
27.9, 121.6, 62.1, 20.9, 19.6; HRMS (EI): m/z [M ] calcd.
(3-methyl-3'-(trifluoromethyl)-[1,1'-biphenyl]-2-o
8
1
for C16
H
15
O
2
Br: 320.0235, found 320.0238.
yl)methyl acetate (3m): yellow solid, m.p. 48–50 C, 58.3
1
mg (63%); H NMR (400 MHz, CDCl
3
, ppm): δ 7.62 (s,
2
H), 7.56−7.51 (m, 2H), 7.34 (t, J = 7.6 Hz, 1H), 7.29 (d, J
= 6.8 Hz, 1H), 7.16 (d, J = 8.4 Hz, 1H), 4.94 (s, 2H), 2.45
(
(
4'-iodo-3-methyl-[1,1'-biphenyl]-2-yl)methyl
acetate
1
o
3f): yellow solid, m.p. 78–80 C, 75.8 mg (69%); H
1
3
(
1
1
s, 3H), 2.08 (s, 3H); C NMR (100 MHz, CDCl
3
, ppm): δ
NMR (400 MHz, CDCl
3
, ppm): δ 7.65 (d, J = 8.4 Hz, 2H),
70.7, 142.7, 141.8, 139.2, 132.4, 131.0, 130.6, 130.3,
7
.22 (t, J = 7.6 Hz, 1H), 7.17 (d, J = 6.4 Hz, 1H), 7.03 (d, J
3
2
28.8, 128.7, 128.0, 126.2 (q, JCF = 3.8 Hz), 124.1 (q, JCF
=
7.6 Hz, 1H), 6.97 (d, J = 8.0 Hz, 2H), 4.90 (s, 2H), 2.33
13
1
= 3.7 Hz), 124.1 (q, JCF = 270.8 Hz), 62.0, 20.7, 19.6;
(
s, 3H), 1.98 (s, 3H); C NMR (100 MHz, CDCl
3
, ppm): δ
70.7, 142.9, 140.6, 139.1, 137.3 (2C), 131.2 (2C), 130.8,
30.1, 128.7, 127.9, 93.2, 62.1, 20.9, 19.6; HRMS (EI):
+
15 2 3
HRMS (EI): m/z [M ] calcd. for C17H O F : 308.1024,
1
1
found 308.1023.
+
127
m/z [M ] calcd. for C16
H
15
O
2
I: 366.0117, found
3
66.0115.
(2'-methoxy-3-methyl-[1,1'-biphenyl]-2-yl)methyl
o
acetate (3n): yellow solid, m.p. 82–84 C, 22.7 mg (28%);
1
3
H NMR (400 MHz, CDCl , ppm): δ 7.25 (t, J = 7.6 Hz,
Methyl 2'-(acetoxymethyl)-3'-methyl-[1,1'-biphenyl]-4-
1
1H), 7.21 (t, J = 7.6 Hz, 1H), 7.14 (d, J = 7.2 Hz, 1H), 7.07
(
6
carboxylate (3g): yellow oil, 65.3 mg (73%); H NMR
dd, J
1
= 7.2 Hz, J
2
= 1.6 Hz, 1H), 7.01 (d, J = 7.6 Hz, 1H),
(
(
3
400 MHz, CDCl , ppm): δ 7.99 (d, J = 8.4 Hz, 2H), 7.30
.90 (t, J = 7.2 Hz, 1H), 6.85 (d, J = 8.4 Hz, 1H), 4.99 (d, J
d, J = 8.4 Hz, 2H), 7.23 (t, J = 7.6 Hz, 1H), 7.18 (d, J =
=
12.0 Hz, 1H), 4.75 (d, J = 12.0 Hz, 1H), 3.64 (s, 3H),
6
3
.4 Hz, 1H), 7.06 (d, J = 7.6 Hz, 1H), 4.89 (s, 2H), 3.85 (s,
13
13
2.33 (s, 3H), 1.88 (s, 3H); C NMR (100 MHz, CDCl
3
,
H), 2.34 (s, 3H), 1.97 (s, 3H); C NMR (100 MHz,
, ppm): δ 170.7, 166.9, 145.8, 143.1, 139.1, 130.9,
30.3, 129.4 (2C), 129.3 (2C), 129.0, 128.7, 127.8, 62.0,
ppm): δ 170.9, 156.4, 140.0, 138.3, 132.1, 131.3, 129.9,
CDCl
3
1
29.7, 129.0, 128.5, 128.4, 120.4, 110.6, 62.6, 55.4, 20.8,
1
5
+
+
19.7; HRMS (EI): m/z [M ] calcd. for C17
H
18
O
3
: 270.1256,
2.2, 20.8, 19.6; HRMS (EI): m/z [M ] calcd. for
: 298.1205, found 298.1204.
found 270.1254.
C
18
H
18
O
4
7
This article is protected by copyright. All rights reserved.

Advanced Synthesis & Catalysis
10.1002/adsc.201800216
(
(
3,3',5'-trimethyl-[1,1'-biphenyl]-2-yl)methyl
acetate
6.85 (d, J = 8.8 Hz, 2H), 4.73 (s, 2H), 3.75 (s, 3H), 1.82 (s,
1
13
3o): yellow oil, 49.1 mg (61%); H NMR (400 MHz,
3H); C NMR (100 MHz, CDCl
3
, ppm): δ 170.2, 159.0,
1
CDCl
3
, ppm): δ H NMR (400 MHz, CDCl
3
, ppm): δ 7.21
144.6, 144.3, 141.1, 133.3, 130.5, 130.4 (2C), 129.8, 129.3,
(
7
3
t, J = 7.6 Hz, 1H), 7.14 (d, J = 7.2 Hz, 1H), 7.08 (d, J =
129.2 (2C), 128.4, 128.1 (2C), 127.4, 113.6 (2C), 62.7,
+
.6 Hz, 1H), 6.91 (s, 1H), 6.84 (s, 2H), 4.93 (s, 2H), 2.34 (s,
55.3, 20.8; HRMS (EI): m/z [M ] calcd. for C22
H
20
O
3
:
1
3
H), 2.26 (s, 6H), 1.99 (s, 3H); C NMR (100 MHz,
, ppm): δ 170.8, 144.4, 140.9, 138.8, 137.5 (2C),
30.9, 129.5, 128.8, 128.5, 128.0, 127.1 (2C), 62.4, 21.4
332.1412, found 332.1411.
CDCl
3
1
(
(
3-fluoro-4'-methoxy-[1,1'-biphenyl]-2-yl)methyl
1
+
2C), 20.9, 19.6; HRMS (EI): m/z [M ] calcd. for
: 268.1463, found 268.1462.
acetate (4d): yellow oil, 57.6 mg (70%); H NMR (400
MHz, CDCl , ppm): δ 7.27 (dd, J = 80 Hz, J = 2.0 Hz,
18 20 2
C H O
3
1
2
1
H), 7.17 (d, J = 8.8 Hz, 2H), 7.02 (d, J = 7.6 Hz, 1H),
(
3',5'-dichloro-3-methyl-[1,1'-biphenyl]-2-yl)methyl
6.98 (d, J = 8.4 Hz, 1H), 7.86 (d, J = 8.8 Hz, 2H), 4.97 (s,
1
13
acetate (3p): yellow oil, 58.4 mg (63%); H NMR (400
2H), 3.76 (s, 3H), 1.97 (s, 3H); C NMR (100 MHz,
1
MHz, CDCl
3
, ppm): δ 7.29 (t, J = 2.0 Hz, 1H), 7.24 (t, J =
.6 Hz, 1H), 7.20 (d, J = 8.0 Hz, 1H), 7.15 (t, J = 1.6 Hz,
H), 7.03 (d, J = 6.8 Hz, 1H), 4.87 (s, 2H), 2.35 (s, 3H),
CDCl
3
, ppm): δ 170.6, 162.3 (d, JCF = 247.8 Hz), 159.3,
3
4
7
2
2
1
145.3 (d, JCF = 3.2 Hz), 132.6 (d, JCF = 2.6 Hz), 130.3
3
4
(2C), 130.0 (d, JCF = 9.4 Hz), 125.9 (d, JCF = 3.1 Hz),
1
3
2
2
.02 (s, 3H); C NMR (100 MHz, CDCl
3
, ppm): δ 169.7,
120.6 (d, JCF = 14.4 Hz), 114.1 (d, JCF = 22.2 Hz), 113.8
3
42.9, 140.5, 138.2, 133.6 (2C), 129.9, 129.6, 127.7, 126.8
(2C), 58.4 (d, JCF = 4.8 Hz), 55.3, 20.9; HRMS (EI): m/z
+
+
(
2C), 126.6, 126.4, 60.7, 19.8, 18.5; HRMS (EI): m/z [M ]
[M ] calcd. for C16
H
15
O
3
F: 274.1005, found 274.1006.
3
5
calcd. for C16
H
14
O
2
Cl: 308.0371, found 308.0373.
(
3-iodo-4'-methoxy-[1,1'-biphenyl]-2-yl)methyl acetate
1
2
-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-6-methylbenzyl
(4e): yellow oil, 66.5 mg (58%); H NMR (400 MHz,
1
acetate (3q): yellow oil, 62.6 mg (70%); H NMR (400
MHz, CDCl , ppm): δ 7.19 (t, J = 7.6 Hz, 1H), 7.12 (d, J =
.2 Hz, 1H), 7.06 (d, J = 7.6 Hz, 1H), 6.79 (d, J = 8.0 Hz,
H), 6.75 (d, J = 2.0 Hz, 1H), 6.69 (dd, J = 8.4 Hz, J
.0 Hz, 1H), 4.95 (s, 2H), 4.20 (s, 4H), 2.32 (s, 3H), 2.00 (s,
3 1 2
CDCl , ppm): δ 7.86 (t, J = 7.6 Hz, J = 0.8 Hz, 1H),
3
7.29 (s, 1H), 7.21 (d, J = 8.4 Hz, 1H), 7.06 (t, J = 7.6 Hz,
1H), 6.93 (d, J = 8.8 Hz, 2H), 5.05 (s, 2H), 3.85 (s, 3H),
7
1
2
3
1
1
13
1
2
=
3
2.10 (s, 3H); C NMR (100 MHz, CDCl , ppm): δ 170.8,
159.0, 142.1, 139.0, 133.3, 132.8, 130.2 (2C), 129.6, 128.3,
1
3
+
H); C NMR (100 MHz, CDCl
3
, ppm): δ 171.0, 143.7,
127.3, 113.7 (2C), 64.5, 55.3, 21.0; HRMS (EI): m/z [M ]
127
43.1, 143.0, 138.9, 134.4, 131.0, 129.5, 128.5, 128.1,
22.4, 118.2, 116.9, 64.4 (2C), 62.4, 20.9, 19.6; HRMS
3
calcd. for C16H15 IO : 382.0066, found 382.0067.
+
(
EI): m/z [M ] calcd. for C18
H
18
O
4
: 298.1205, found
(
4'-methoxy-3-(trifluoromethyl)-[1,1'-biphenyl]-2-
2
98.1204.
1
yl)methyl acetate (4f): yellow oil, 63.2 mg (65%); H
3
NMR (400 MHz, CDCl , ppm): δ 7.72 (t, J = 4.4 Hz, 1H),
2
-methyl-6-(naphthalen-2-yl)benzyl acetate (3r): yellow
7.50 (d, J = 4.4 Hz, 2H), 7.23 (d, J = 8.8 Hz, 2H), 6.95 (d,
J = 8.4 Hz, 2H), 5.07 (s, 2H), 3.86 (s, 3H) , 2.01 (s, 3H);
1
oil, 54.9 mg (63%); H NMR (400 MHz, CDCl
3
, ppm): δ
.76 (d, J = 8.4 Hz, 2H), 7.72 (t, J = 5.2 Hz, 1H), 7.68 (s,
H), 7.40 (t, J = 4.4 Hz, 2H), 7.35 (dd, J = 8.4 Hz, J = 1.2
13
7
1
3
C NMR (100 MHz, CDCl , ppm): δ 170.2, 159.3, 146.0,
1
2
134.3, 131.8, 131.1, 130.8, 130.3 (2C), 128.6, 125.4, 124.2
1
Hz, 1H), 7.24 (t, J = 7.6 Hz, 1H), 7.16 (t, J = 7.2 Hz, 2H),
(q, JCF = 272.7 Hz), 113.7 (2C), 60.7, 55.3, 20.8; HRMS
1
3
+
4
.96 (s, 2H), 2.35 (s, 3H), 1.96 (s, 3H); C NMR (100
, ppm): δ 170.8, 144.2, 139.1, 138.6, 133.2,
32.5, 131.2, 129.9, 128.7, 128.4, 128.2, 128.1, 127.8,
27.7, 127.6, 126.4, 126.1, 62.4, 20.9, 19.7; HRMS (EI):
(EI): m/z [M ] calcd. for C17
H
15
O
3 3
F : 324.0973, found
MHz, CDCl
3
324.0975.
1
1
2-nitrobenzyl acetate (4g'): yellow oil, 50.9 mg (87%);
1
+
m/z [M ] calcd. for C20
H
18
O
2
: 290.1307, found 290.1304.
H NMR (400 MHz, CDCl
= 1.2 Hz, 1H), 7.67 (t, J = 8.0 Hz, 1H), 7.60 (d, J = 7.2
Hz, 1H), 7.50 (t, J = 7.2 Hz, 1H), 5.52 (s, 2H), 2.17 (s,
3 1
, ppm): δ 8.11 (dd, J = 8.4 Hz,
J
2
2
-methyl-6-(6-(trifluoromethyl)pyridin-2-yl)benzyl
o
13
acetate (3s): yellow solid, m.p. 75–77 C, 60.3 mg (65%);
3
3H); C NMR (100 MHz, CDCl , ppm): δ 170.4, 147.5,
1
H NMR (400 MHz, CDCl
3
, ppm): δ 7.86 (t, J = 8.0 Hz,
133.8, 132.1, 129.0, 128.8, 125.1, 63.0, 20.8; HRMS (EI):
+
1
7
H), 7.56 (t, J = 8.8 Hz, 2H), 7.27 (t, J = 7.2 Hz, 1H),
.24−7.20 (m, 2H), 5.03 (s, 2H), 2.37 (s, 3H), 1.93 (s, 3H);
m/z [M-NO
149.0599.
2
]
9 9 2
calcd. for C H O : 149.0603, found
13
3
C NMR (100 MHz, CDCl , ppm): δ 170.9, 160.1, 147.6
2
(
q, JCF = 34.4 Hz), 140.8, 139.7, 137.9, 131.7, 131.4,
1
(
(
4,4'-dimethoxy-[1,1'-biphenyl]-2-yl)methyl
acetate
4h): yellow oil, 63.6 mg (74%); H NMR (400 MHz,
, ppm): δ 7.23 (d, J = 4.0 Hz, 1H), 7.21 (d, J = 5.6
1
28.8, 128.0, 126.8, 121.5 (q, JCF = 272.7 Hz), 118.6 (q,
1
3
+
J
CF = 2.7 Hz), 61.6, 20.7, 19.5; HRMS (EI): m/z [M ]
CDCl
3
calcd. for C16 : 309.0977, found 309.0979.
H
2 3
14NO F
Hz, 2H), 7.20 (d, J = 2.4 Hz, 1H), 6.93 (d, J = 8.4 Hz, 2H),
.90 (d, J = 2.8 Hz, 1H), 5.01 (s, 2H), 3.85 (s, 3H) , 3.84 (s,
6
13
2
-(6-chloropyridin-3-yl)-6-methylbenzyl acetate (3t):
3
3H), 2.07 (s, 3H); C NMR (100 MHz, CDCl , ppm): δ
1
yellow oil, 48.8 mg (59%); H NMR (400 MHz, CDCl
ppm): δ 8.29 (d, J = 2.4 Hz, 1H), 7.55 (dd, J = 8.4 Hz, J
2.4 Hz, 1H), 7.30 (t, J = 8.0 Hz, 2H), 7.24 (t, J = 7.6 Hz,
H), 7.04 (d, J = 7.6 Hz, 1H), 4.88 (s, 2H), 2.36 (s, 3H),
3
,
170.8, 158.8 (2C), 134.51, 134.49, 132.5, 131.4, 130.4
1
2
(2C), 114.7, 113.73, 113.67 (2C), 64.6, 55.4, 55.3, 21.1;
+
=
HRMS (EI): m/z [M ] calcd. for C17
H
18
O
4
: 286.1205,
1
1
1
1
found 286.1204.
13
3
.99 (s, 3H); C NMR (100 MHz, CDCl , ppm): δ 170.6,
50.5, 149.6, 139.5, 139.3, 139.0, 135.6, 131.3, 130.9,
(
4'-methoxy-4-methyl-[1,1'-biphenyl]-2-yl)methyl
1
29.0, 128.1, 123.7, 61.7, 20.8, 19.6; HRMS (EI): m/z
acetate (4i): yellow oil, 58.4 mg (72%); H NMR (400
MHz, CDCl , ppm): δ 7.20 (s, 1H), 7.16 (d, J = 8.4 Hz,
H), 7.10 (s, 2H), 6.85 (d, J = 8.4 Hz, 2H), 4.93 (s, 2H),
+
35
[
2
M ] calcd. for C15H14NO Cl: 275.0713, found 275.0712.
3
2
13
2
-methoxybenzyl acetate (4b'): yellow oil, 49.2 mg
3.75 (s, 3H), 2.31 (s, 3H), 1.98 (s, 3H); C NMR (100
MHz, CDCl , ppm): δ 170.8, 158.9, 139.3, 137.1, 133.0,
1
(
91%); H NMR (400 MHz, CDCl
3
, ppm): δ 7.32 (t, J =
3
8
.0 Hz, 2H), 6.96 (td, J = 7.6 Hz, J = 0.8 Hz, 1H), 6.90 (d, 132.7, 130.4, 130.32 (2C), 130.30, 129.2, 113.7 (2C), 64.2,
1 2
+
J = 8.0 Hz, 1H), 5.17 (s, 2H), 3.85 (s, 3H), 2.11 (s, 3H);
18 3
55.3, 21.1 (2C); HRMS (EI): m/z [M ] calcd. for C17H O :
13
C NMR (100 MHz, CDCl
3
, ppm): δ 171.1, 157.5, 129.8,
270.1256, found 270.1257.
1
29.6, 124.2, 120.4, 110.5, 61.8, 55.4, 21.1; HRMS (EI):
+
m/z [M ] calcd. for C10H O : 180.0786, found 180.0785.
12 3
(
4-chloro-4'-methoxy-[1,1'-biphenyl]-2-yl)methyl
1
acetate (4j): yellow oil, 54.9 mg (63%); H NMR (400
MHz, CDCl , ppm): δ 7.38 (d, J = 2.0 Hz, 1H), 7.24 (dd, J
= 8.4 Hz, J = 2.4 Hz, 1H), 7.14 (d, J = 3.6 Hz, 1H), 7.11
(d, J = 2.8 Hz, 2H), 6.86 (d, J = 8.4 Hz, 2H), 4.91 (s, 2H),
(
(
4-methoxy-[1,1',3',1''-terphenyl]-2'-yl)methyl acetate
3
1
o
1
4c): yellow solid, m.p. 56–58 C, 53.8 mg (54%); H
, ppm): δ 7.35 (d, J = 7.6 Hz, 1H),
.31 (d, J = 4.0 Hz, 1H), 7.29 (s, 3H), 7.28 (d, J = 1.2 Hz,
H), 7.23 (s, 1H), 7.22 (s, 1H), 7.21 (s, 1H), 7.20 (s, 1H),
2
NMR (400 MHz, CDCl
3
13
7
1
3
3.76 (s, 3H), 2.00 (s, 3H); C NMR (100 MHz, CDCl ,
ppm): δ 170.6, 159.2, 140.2, 135.2, 133.1, 131.6, 131.5,
8
This article is protected by copyright. All rights reserved.

Advanced Synthesis & Catalysis
10.1002/adsc.201800216
3
1
30.2 (2C), 129.0, 128.2, 113.9 (2C), 63.8, 55.3, 20.9;
Hz), 159.3 (2C), 146.7 (d, JCF = 8.5 Hz, 2C), 132.4 (d,
+
35
4
4
HRMS (EI): m/z [M ] calcd. for C16
H
15
O
3
Cl: 290.0710,
J
CF = 1.8 Hz, 2C), 130.2 (4C), 126.8 (d, JCF = 3.1 Hz),
2
found 290.0714.
116.1 (d, JCF = 20.8 Hz, 2C), 113.6 (4C), 62.3, 55.3 (2C),
+
2
3
21 4
0.9; HRMS (EI): m/z [M ] calcd. for C23H O F:
80.1424, found 380.1429.
(
4-bromo-4'-methoxy-[1,1'-biphenyl]-2-yl)methyl
1
acetate (4k): yellow oil, 66.4 mg (66%); H NMR (400
MHz, CDCl , ppm): δ 7.62 (d, J = 2.0 Hz, 1H), 7.48 (dd, J
= 2.4 Hz, 1H), 7.22 (d, J = 8.4 Hz, 2H), 7.15
3
1
(3,5-dichloro-4'-methoxy-[1,1'-biphenyl]-2-yl)methyl
1
=
(
8.4 Hz, J
2
acetate (4o): yellow oil, 56.6 mg (58%); H NMR (400
MHz, CDCl , ppm): δ 7.43 (d, J = 2.0 Hz, 1H), 7.23 (s,
1H), 7.22 (d, J = 8.4 Hz, 2H), 6.94 (d, J = 8.4 Hz, 2H),
d, J = 8.4 Hz, 1H), 6.95 (d, J = 8.8 Hz, 2H), 5.00 (s, 2H),
3
1
3
3
3
.85 (s, 3H), 2.09 (s, 3H); C NMR (100 MHz, CDCl ,
13
ppm): δ 170.6, 159.2, 140.7, 135.5, 131.95, 131.86, 131.5,
5.03 (s, 2H), 3.85 (s, 3H), 2.08 (s, 3H); C NMR (100
MHz, CDCl , ppm): δ 170.5, 159.6, 146.6, 137.2, 134.7,
1
31.2, 130.1 (2C), 121.2, 113.9 (2C), 63.7, 55.3, 21.0;
3
+
79
HRMS (EI): m/z [M ] calcd. for C16
H
15
O
3
Br: 324.0205,
131.0, 130.1 (2C), 129.6, 129.1, 128.3, 113.9 (2C), 61.6,
+
35
found 324.0204.
55.4, 20.8; HRMS (EI): m/z [M ] calcd. for C16
24.0320, found 324.0321.
H
14
O
3
Cl :
2
3
(
4'-methoxy-5-methyl-[1,1'-biphenyl]-2-yl)methyl
1
acetate (4l): yellow oil, 47.8 mg (59%); H NMR (400
MHz, CDCl , ppm): δ 7.28 (d, J = 8.0 Hz, 1H), 7.17 (d, J =
.4 Hz, 2H), 7.07 (d, J = 8.8 Hz, 1H), 7.03 (s, 1H), 6.85 (d,
(5-chloro-4'-methoxy-3-methyl-[1,1'-biphenyl]-2-
1
3
yl)methyl acetate (4p): yellow oil, 62.2 mg (68%); H
8
3
NMR (400 MHz, CDCl , ppm): δ 7.22−1.19 (m, 3H),7.15
J = 8.8 Hz, 2H), 4.91 (s, 2H), 3.75 (s, 3H), 2.28 (s, 3H),
(d, J = 2.4 Hz, 1H), 6.93 (d, J = 8.4 Hz, 2H), 4.97 (s, 2H),
1
3
13
1
1
1
.95 (s, 3H); C NMR (100 MHz, CDCl
3
, ppm): δ 170.9,
3.85 (s, 3H), 2.39 (s, 3H), 2.07 (s, 3H); C NMR (100
58.9, 142.1, 138.2, 132.9, 131.1, 130.3, 130.2 (2C), 129.9,
3
MHz, CDCl , ppm): δ 170.8, 159.2, 145.4, 140.9, 134.0,
28.0, 113.6 (2C), 64.5, 55.3, 21.2, 21.1; HRMS (EI): m/z
132.1, 130.2 (2C), 129.7, 129.2, 128.0, 113.7 (2C), 61.7,
+
+
[
M ] calcd. for C17
H
18
O
3
: 270.1256, found 270.1258.
55.3, 20.9, 19.6; HRMS (EI): m/z [M ] calcd. for
3
5
17 17 3
C H O Cl: 304.0866, found 304.0862.
(
4,4''-dimethoxy-5'-methyl-[1,1':3',1''-terphenyl]-2'-
o
yl)methyl acetate (4l'): yellow solid, m.p. 68–70 C, 26.0
(3-(4-methoxyphenyl)naphthalen-2-yl)methyl
acetate
1
1
mg (23%); H NMR (400 MHz, CDCl
3
, ppm): δ 7.30 (d, J
(4q): yellow oil, 57.0 mg (62%); H NMR (400 MHz,
=
8.4 Hz, 4H), 7.12 (s, 2H), 6.92 (d, J = 8.4 Hz, 4H), 4.77
3
CDCl , ppm): δ 7.96 (s, 1H), 7.89 (d, J = 4.8 Hz, 1H), 7.83
13
(
(
s, 2H), 3.84 (s, 6H), 2.40 (s, 3H), 1.95 (s, 3H); C NMR
100 MHz, CDCl , ppm): δ 170.3, 158.9 (2C), 144.3 (2C),
38.2, 133.5 (2C), 130.30 (4C), 130.25 (2C), 127.7, 113.5
(d, J = 4.8 Hz, 1H), 7.75 (s, 1H), 7.51 (d, J = 4.0 Hz, 2H),
7.36 (d, J = 8.0 Hz, 2H), 6.99 (d, J = 8.0 Hz, 2H), 5.19 (s,
3
13
1
2H), 3.88 (s, 3H), 2.08 (s, 3H); C NMR (100 MHz,
+
(
4C), 62.7, 55.3 (2C), 29.7, 20.9; HRMS (EI): m/z [M ]
CDCl
3
, ppm): δ 169.7, 158.0, 138.7, 132.0, 131.7, 131.3,
calcd. for C24 : 376.1675, found 376.1672.
24 4
H O
130.8, 129.3 (2C), 128.1, 127.7, 126.7, 126.6, 125.6, 125.1,
+
1
12.6 (2C), 63.8, 54.3, 20.0; HRMS (EI): m/z [M ] calcd.
: 306.1256, found 306.1255.
18 3
for C20H O
(
5-isopropyl-4'-methoxy-[1,1'-biphenyl]-2-yl)methyl
1
acetate (4m): yellow oil, 53.7 mg (60%); H NMR (400
MHz, CDCl , ppm): δ 7.41 (d, J = 8.0 Hz, 1H), 7.28 (d, J =
.4 Hz, 2H), 7.23 (dd, J = 8.0 Hz, J = 2.0 Hz, 1H), 7.16
d, J = 2.0 Hz, 1H), 6.95 (d, J = 8.4 Hz, 2H), 5.01 (s, 2H),
3
Procedure for the One-pot Synthesis of Biaryl-2-methyl
Acetates (6) from O-Arylmethyl Hydroxylamines
A mixture of O-arylmethyl hydroxylamines 5 (0.3 mmol),
8
1
2
(
3
6
1
1
.86 (s, 3H), 2.98−2.90 (m, 1H), 2.06 (s, 3H), 1.27 (d, J =
2
2 (0.9 mmol), Pd(OAc) (6.7 mg , 0.03 mmol), AgTFA
1
3
.8 Hz, 6H); C NMR (100 MHz, CDCl
3
, ppm): δ 170.9,
(99.2 mg, 0.45 mmol), ethyl pyruvate (52.3 mg, 0.45
58.9, 149.2, 142.2, 133.1, 130.6, 130.3 (2C), 129.9, 128.5,
2
mmol), and AcOH/H O (9:1, v/v, 2.5 mL) was stirred in a
25.4, 113.6 (2C), 64.5, 55.3, 33.9, 24.0 (2C), 21.1; HRMS
glass sealed-tube at room temperature for 30 min, then the
mixture was heated to 120 °C for 20 h. Upon completion
of the reaction, the mixture was cooled to room
+
(
EI): m/z [M ] calcd. for C19
H
22
O
3
: 298.1569, found
2
98.1570.
temperature and added dropwise into a saturated NaHCO
3
solution (25 mL). The solution was extracted with ethyl
acetate (25 mL×3), and then the combined organic layer
was dried over anhydrous MgSO4. Finally, the solution was
concentrated in vacuo to provide a crude product, which
was purified via a column chromatography on silica gel
(
5'-isopropyl-4,4''-dimethoxy-[1,1':3',1''-terphenyl]-2'-
1
yl)methyl acetate (4m'): yellow oil, 20.6 mg (17 %); H
NMR (400 MHz, CDCl , ppm): δ 7.40 (d, J = 8.0 Hz, 2H),
.29 (s, 2H), 7.23 (dd, J = 8.0 Hz, J = 2.0 Hz, 2H), 7.16
d, J = 1.6 Hz, 2H), 6.95 (d, J = 8.4 Hz, 2H), 5.01 (s, 2H),
3
7
1
2
(
(
eluents: petroleum ether/ethyl acetate 40:1) to supply the
3
1
1
.86 (s, 6H), 2.98−2.90 (m, 1H), 2.06 (s, 3H), 1.28 (s, 3H),
13
desired product 6.
.26 (s, 3H); C NMR (100 MHz, CDCl
3
, ppm): δ 170.6,
59.1, 144.5, 133.9 (2C), 130.6 (4C), 127.9 (2C), 116.2
(
(
2C), 115.0 (2C), 113.7 (4C), 63.1, 55.5 (2C), 34.2, 24.1
[1,1'-biphenyl]-2-ylmethyl acetate (6a): yellow oil, 44.1
+
1
2C), 21.1; HRMS (EI): m/z [M ] calcd. for C26
H
28
O
4
:
mg (65%); H NMR (400 MHz, CDCl
3
, ppm): δ 7.51 (dd,
4
04.1988, found 404.1989.
J
1
= 6.0 Hz, J
0−7. 38 (m, 2H), 7.38−7.35 (m, 2H), 7.34 (d, J = 1.6 Hz,
H), 7.32 (dd, J = 4.0 Hz, J = 1.6 Hz, 1H), 5.05 (s, 2H),
, ppm): δ 170.7,
42.4, 140.4, 133.2, 130.2, 129.6, 129.1, 128.6, 128.32,
28.29, 128.2, 127.6, 127.4, 64.4, 21.0; HRMS (EI): m/z
2
= 2.0 Hz, 1H), 7.42 (d, J = 7.2 Hz, 2H), 7.
4
1
1
2
(
5-fluoro-4'-methoxy-[1,1'-biphenyl]-2-yl)methyl
1
13
2.06 (s, 3H); C NMR (100 MHz, CDCl
3
acetate (4n): yellow oil, 46.1 mg (56%); H NMR (400
1
1
[
MHz, CDCl
3
, ppm): δ 7.37 (dd, J
1
= 8.4 Hz, J
= 8.4 Hz, J
= 2.4 Hz, 1H), 6.87
2
= 5.6 Hz,
1
2
H), 7.18 (d, J = 8.8 Hz, 2H), 6.97 (dd, J
1
2
=
+
14 2
M ] calcd. for C15H O : 226.0994, found 226.0993.
.8 Hz, 1H), 6.92 (dd, J
1
= 9.6 Hz, J
2
(
d, J = 8.8 Hz, 2H), 4.91 (s, 2H), 3.77 (s, 3H), 1.98 (s, 3H);
1
3
1
C NMR (100 MHz, CDCl
3
, ppm): δ 170.8, 162.3 (d, JCF
(4'-methoxy-[1,1'-biphenyl]-2-yl)methyl acetate (6b):
1
3
3
=
246.3 Hz), 159.3, 144.4 (d, JCF = 8.0 Hz), 131.8 (d, JCF
3
yellow oil, 56.1 mg (73%); H NMR (400 MHz, CDCl ,
4
=
8.6 Hz), 131.7 (d, JCF = 1.7 Hz), 130.1 (2C), 129.3 (d,
ppm): δ 7.49−7.46 (m, 1H), 7.36 (t, J = 3.6 Hz, 2H), 7.30
(d, J = 2.4 Hz, 1H), 7.26 (d, J = 8.4 Hz, 2H), 6.95 (d, J =
4
2
2
J
CF = 3.1 Hz), 117.0 (d, JCF = 21.3 Hz), 114.1 (d, JCF =
1
3
2
[
1.0 Hz), 113.8 (2C), 63.9, 55.3, 21.0; HRMS (EI): m/z
8.8 Hz, 2H), 5.04 (s, 2H), 3.85 (s, 3H), 2.06 (s, 3H);
C
+
M ] calcd. for C16
H
15
O
3
F: 274.1005, found 274.1004.
NMR (100 MHz, CDCl
3
, ppm): δ 170.8, 159.0, 142.1,
1
(
33.3, 132.8, 130.4, 130.3 (2C), 129.6, 128.3, 127.3, 113.7
+
2C), 64.6, 55.3, 21.1; HRMS (EI): m/z [M ] calcd. for
(
5'-fluoro-4,4''-dimethoxy-[1,1':3',1''-terphenyl]-2'-
o
C H O : 256.1099, found 256.1100.
16 18 3
yl)methyl acetate (4n'): yellow solid, m.p. 60–62 C, 16.0
1
mg (14%); H NMR (400 MHz, CDCl
3
, ppm): δ 7.30 (d, J
=
8.8 Hz, 4H), 7.01 (d, J = 9.2 Hz, 2H), 6.94 (d, J = 8.8 Hz, Methyl
2´-(acetoxylmethyl)-[1,1´-biphenyl]-4-
1
13
4
H), 4.74 (s, 2H), 3.85 (s, 6H), 1.98 (s, 3H); C NMR
carboxylate (6c): yellow oil, 52.0 mg (61%); H NMR
1
(
100 MHz, CDCl
3
, ppm): δ 170.2, 161.7 (d, JCF = 247.6
(400 MHz, CDCl
3
, ppm): δ 8.10 (d, J = 8.4 Hz, 2H),
9
This article is protected by copyright. All rights reserved.

Advanced Synthesis & Catalysis
10.1002/adsc.201800216
7
2
.51(dd, J
1
= 5.6 Hz, J
2
= 3.6 Hz, 1H), 7.43 (d, J = 2.4 Hz,
= 5.6 Hz, J = 3.6
MHz, CDCl
= 8.4 Hz, J
(dt, J = 8.4 Hz, J
2.8 Hz, 2H), 4.99 (s, 2H), 3.85 (s, 3H), 2.06 (s, 3H);
NMR (100 MHz, CDCl
3
, ppm): δ 7.41 (d, J = 8.4 Hz, 1H), 7.32 (dd, J
1
H), 7.41 (t, J = 2.0 Hz, 2H), 7.30 (dd, J
1
2
2
= 2.4 Hz, 1H), 7.29 (d, J = 2.4 Hz, 1H), 7.24
13
Hz, 1H), 5.01 (s, 2H), 3.95 (s, 3H), 2.04 (s, 3H); C NMR
1
2
= 2.8 Hz, 2H), 6.95(dt, J
1
= 8.4 Hz, J
2
=
1
3
(
1
1
100 MHz, CDCl
3
, ppm): δ 170.5, 166.8, 145.1, 141.3,
37.8, 133.0, 129.9, 129.8, 129.4 (2C), 129.1 (2C), 128.4,
C
3
, ppm): δ 170.7, 159.3, 143.7,
+
28.1, 64.1, 52.1, 20.8; HRMS (EI): m/z [M ] calcd. for
: 284.1049, found 284.1046.
133.9, 131.9, 131.4, 131.0, 130.2, 130.1 (2C), 127.3, 113.8
+
C
17
H
16
O
4
(2C), 63.8, 55.3, 21.0; HRMS (EI): m/z [M ] C16
90.0710, found 290.0708.
3
H15ClO :
2
Ethyl 2´-(acetoxylmethyl)-[1,1´-biphenyl]-4-carboxylate
1
(
6d): yellow oil, 55.5 mg (62%); H NMR (400 MHz,
CDCl , ppm): δ 8.10 (d, J = 8.4 Hz, 2H), 7.51 (dd, J = 5.2
Hz, J = 3.6 Hz, 1H), 7.43 (d, J = 1.6 Hz, 2H), 7.41 (t, J =
.2 Hz, 2H), 7.30 (dd, J = 5.6 Hz, J = 3.6 Hz, 1H), 5.01
s, 2H), 4.41 (q, J = 7.2 Hz, 2H), 2.04 (s, 3H), 1.42 (t, J =
(5-Bromo-4´-methoxy-[1,1´-biphenyl]-2-yl)methyl
1
3
1
acetate (6k): yellow oil, 61.3 mg (61%); H NMR (400
MHz, CDCl , ppm): δ 7.40 (s, 1H), 7.37 (s, 1H), 7.27 (d, J
= 8.4 Hz, 1H), 7.15 (d, J = 8.4 Hz, 2H), 6.87 (d, J = 8.4 Hz,
2
3
3
1
2
13
(
2H), 4.89 (s, 2H), 3.77 (s, 3H), 1.98 (s, 3H); C NMR
13
7
1
.2 Hz, 3H); C NMR (100 MHz, CDCl
66.4, 145.0, 141.4, 133.1, 130.0, 129.9, 129.52, 129.50
3
, ppm): δ 170.6,
3
(100 MHz, CDCl , ppm): δ 170.6, 159.3, 144.0, 133.1,
132.4, 131.3, 131.1, 130.3, 130.1 (2C), 122.1, 113.8 (2C),
+
(
2C), 129.2 (2C), 128.5, 128.2, 64.2, 61.1, 20.9, 14.4;
63.8, 55.3, 21.0; HRMS (EI): m/z [M ] calcd. for
+
81
HRMS (EI): m/z [M ] calcd. for C18
H
18
O
4
: 298.1205,
C
16
H
15 BrO
3
: 336.0184, found 336.0190.
found 298.1204.
Methyl 2'-(acetoxymethyl)-5'-bromo-[1,1'-biphenyl]-4-
1
(
3´-Methoxy-[1,1´-biphenyl]-2-yl)methyl acetate (6e):
carboxylate (6l): yellow oil, 68.6 mg (63%); H NMR
1
yellow oil, 53.1 mg (69%); H NMR (400 MHz, CDCl
ppm): δ 7.49 (dd, J = 5.6 Hz, J = 2.8 Hz, 1H), 7.40−7.37
m, 2H), 7.34 (d, J = 6.0 Hz, 1H), 7.32 (d, J = 7.2 Hz, 1H),
3
,
3
(400 MHz, CDCl , ppm): δ 8.10 (d, J = 8.4 Hz, 2H), 7.54
1
2
(dd, J
1 2
= 8.4 Hz, J = 2.0 Hz, 1H), 7.46 (d, J = 2.0 Hz, 1H),
(
7.40 (d, J = 8.0 Hz , 2H), 7.37 (s, 1H), 4.94 (s, 2H), 3.95 (s,
13
6
2
.93 (d, J = 2.0 Hz, 1H), 6.90 (dd, J
1
= 4.0 Hz, J
2
= 2.0 Hz,
3
3H), 2.04 (s, 3H); C NMR (100 MHz, CDCl , ppm): δ
1
3
H), 5.05 (s, 2H), 3.83 (s, 3H), 2.06 (s, 3H); C NMR
170.5, 166.7, 143.6, 143.2, 132.7, 132.3, 131.4, 131.2,
129.7 (2C), 129.1 (2C), 122.4, 63.5, 52.3, 20.9; HRMS
(
3
100 MHz, CDCl , ppm): δ 170.6, 159.3, 142.2, 141.6,
+
81
1
1
33.1, 130.0, 129.5, 129.1, 128.2, 127.5, 121.5, 114.7,
(EI): m/z [M ] calcd. for C17
H
15
O
4
Br: 364.0133, found
+
12.9, 64.3, 55.1, 20.9; HRMS (EI): m/z [M ] calcd. for
364.0132.
C
16
H
16
O
3
: 256.1099, found 256.1098.
Supporting Information Available: Experimental details for
1
13
Methyl
2´-(acetoxylmethyl)-[1,1´-biphenyl]-3-
Scheme 6−9; copies of H NMR, C NMR spectral,
HRMS and crystallographic data for 3n and I.
1
carboxylate (6f): yellow oil, 48.6 mg (57%); H NMR
(
(
400 MHz, CDCl
3
, ppm): δ 8.06 (d, J = 1.6 Hz, 1H), 8.04
d, J = 1.2 Hz, 1H), 7.55 (d, J = 7.6 Hz, 1H), 7.50 (dd, J
1
=
8
2
2
1
1
.0 Hz, J
2 1 2
= 7.2 Hz, 2H), 7.41 (dd, J = 4.8 Hz, J = 4.0 Hz,
Acknowledgments
H), 7.31 (t, J = 3.6 Hz, 1H), 4.98 (s, 2H), 3.92 (s, 3H),
13
3
.07 (s, 3H); C NMR (100 MHz, CDCl , ppm): δ 170.7,
We gratefully thank the National Natural Science Foundation of
China (Project Nos. 21476074 and 21676088) for financial
support.
66.9, 141.5, 140.6, 133.5, 133.2, 130.4, 130.20, 130.15,
30.1, 128.60, 128.58, 128.4, 128.0, 64.4, 52.2, 20.9;
+
HRMS (EI): m/z [M ] calcd. for C17
H
16
O
4
: 284.1049,
found 284.1048.
2
-(2,3-2H-benzo[b][1,4]dioxin-6-yl)benzyl acetate (6g): References
3
1
yellow oil, 52.9 mg (62%); H NMR (400 MHz, CDCl ,
ppm): δ 7.47 (t, J = 4.4 Hz, 1H), 7.36 (t, J = 4.4 Hz, 2H),
[
1] a) J. S. Carey, D. Laffan, C. Thomson, M. T. Williams,
Org. Biomol. Chem. 2006, 4, 2337−2347; b) A. R.
Murphy, J. M. J. Fre´chet, Chem. Rev. 2007, 107,
7
1
1
.28 (dd, J
H), 6.86 (d, J = 1.6 Hz, 1H), 6.80 (dd, J
.6 Hz, 1H), 5.05 (s, 2H), 4.30 (s, 4H), 2.08 (s, 3H);
1
= 7.2 Hz, J
2
= 3.6 Hz, 1H), 6.90 (d, J = 8.4 Hz,
1
= 8.0 Hz, J
2
=
13
C
NMR (100 MHz, CDCl
3
, ppm): δ 170.8, 143.15, 143.05,
1
066−1096; c) R. A. Hughes, C. J. Moody, Angew.
1
1
41.9, 133.7, 133,2, 130.2, 129.6, 128.3, 127.4, 122.3,
18.1, 117.0, 64.5, 64.423, 64.418, 21,1; HRMS (EI): m/z
Chem. Int. Ed. 2007, 46, 7930−7954; d) D. S. Surry, S.
L. Buchwald, Angew. Chem. 2008, 120, 6438−6461; e)
R. E. Dolle, B. L. Bourdonnec, K. Worm, G. A.
Morales, C. J. Thomas, W. Zhang, J. Comb. Chem.
+
[
16 4
M ] calcd. for C17H O : 284.1049, found 284.1050.
(
5-Methyl-3´-methoxy-[1,1´-biphenyl]-2-yl)methyl
1
acetate (6h): yellow oil, 52.7 mg (65%); H NMR (400
2
010, 12, 765−806; f) G. Bringmann, T. Gulder, T. M.
MHz, CDCl
3
, ppm): δ 7.38 (d, J = 7.6 Hz, 1H), 7.32 (t, J =
.0 Hz, 1H), 7.20 (d, J = 7.6 Hz, 1H), 7.15 (s, 1H), 6.92 (s,
H), 6.91−6.89 (m, 2H), 5.01 (s, 2H), 3.83 (s, 3H), 2.39 (s,
Gulder, M. Breuning, Chem. Rev. 2011, 111, 563−639;
g) Z. Ding, W. G. Osminski, H. Ren, W. Wulff, Org.
Process Res. Dev. 2011, 15, 1089−1107; h) S.
Sengupta, G. Mehta, Tetrahedron Letters 2017, 58,
1357−1372.
8
1
3
1
1
1
3
3
H), 2.04 (s, 3H); C NMR (100 MHz, CDCl , ppm): δ
70.8, 159.3, 142.3, 141.9, 138.2, 130.8, 130.2, 129.9,
29.2, 128.4, 121.6, 114.8, 112.9, 64.4, 55.2, 21.2, 21.1;
+
HRMS (EI): m/z [M ] calcd. for C17
H
18
O
3
: 270.1256,
found 270.1255.
[2] a) J. A. Ashenhurst, Chem. Soc. Rev. 2010, 39,
5
2
40−548; b) D. Zhao, J. You, C. Hu, Chem. Eur. J.
011, 17, 5466−5492; c) V. P. Mehta, B. Punji, RSC.
Methyl 5´-methyl-2´-(acetoxylmethyl)-[1,1´-biphenyl]-
1
4
-carboxylate (6i): yellow oil, 60.9 mg (68%); H NMR
400 MHz, CDCl , ppm): δ 8.08 (d, J = 8.4 Hz, 2H), 7.41
d, J = 8.4 Hz, 2H), 7.39 (d, J = 8.4 Hz, 1H), 7.22 (d, J =
Adv. 2013, 3, 11957−11986; d) T. L. Chan, Y. Wu, P.
Y. Choy, F. Y. Kwong, Chem. Eur. J. 2013, 19,
1
J. Org. Chem. 2013, 19−30; f) B. Li, H. Dixneuf,
Chem. Soc. Rev. 2013, 42, 5744−5767; g) M.
Grzybowski, K. Skonieczny, H. Butenschon, D. T.
Gryko, Angew. Chem. Int. Ed. 2013, 52, 9900−9930; h)
H. Aldemir, R. Richarz, T. A. M. Gulder, Angew. Chem.
Int. Ed. 2014, 53, 8286−8293; i) J. Antonio, G. Lo’pez,
(
(
8
3
1
1
2
3
.4 Hz, 1H), 7.12 (s, 1H), 4.97 (s, 2H), 3.95 (s, 3H), 2.40 (s,
5802−15814; e) J. Yamaguchi, K. Muto, K. Itami, Eur.
13
3
H), 2.02 (s, 3H); C NMR (100 MHz, CDCl , ppm): δ
70.7, 167.0, 145.3, 141.4, 138.5, 130.7, 130.2, 130.1,
29.5 (2C), 129.2 (2C), 129.0, 128.9, 64.2, 52.2, 21.2,
+
1.0; HRMS (EI): m/z [M ] calcd. for C18
H
18
O
4
: 298.1205,
found 298.1204.
(
5-Chloro-4´-methoxy-[1,1´-biphenyl]-2-yl)methyl
1
acetate (6j): yellow oil, 51.5 mg (59%); H NMR (400
1
0
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Advanced Synthesis & Catalysis
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M. F. Greaney, Chem. Soc. Rev. 2016, 45, 6766−6798;
j) F. R. Leroux, A. Panossian, D. Augros, C. R. Chimie.
017, 20, 682−692; k) K. Zhao, L. Shen, Z. L. Shen, T.
P. Loh, Chem. Soc. Rev. 2017, 46, 586−602; l) Y. Yang,
J. Lan, J. You, Chem. Rev. 2017, 117, 8787−8863; m)
G. J. P. Perry, I. Larrosa, Eur. J. Org. Chem. 2017,
7405−7409; i) D. K. Qin, J. Wang, X. R. Qin, C. X.
Wang, G. Gao, J. S. You, Chem. Commun. 2015, 51,
6190−6193; j) K. Guo, X. L. Chen, M. Y. Guan, Y. S.
Zhao, Org. Lett. 2015, 17, 1802−1805; k) Z. Ren, J. E.
Schulz, G. B. Dong, Org. Lett. 2015, 17, 2696−2699; l)
L. Y. Shao, C. Li, Y. Guo, K. K. Yu, F. Y. Zhao, W. L.
Qiao, H. W. Liu, D. H. Liao, Y. F. Ji, RSC Adv. 2016, 6,
78875−78880; m) R. Y. Zhu, L. Y. Liu, J. Q. Yu, J. Am.
Chem. Soc. 2017, 139, 12394−12397.
2
3
517−3527.
[
3] For selected reviews: a) B. J. Li, S. D. Yang, Z. J. Shi,
Synlett 2008, 7, 949−957; b) K. M. Engle, T. S. Mei, M.
Wasa, J. Q. Yu, Acc. Chem. Res. 2012, 45, 788−802; c)
S. R. Neufeldt, M. S. Sanford, Acc. Chem. Res. 2012,
[7] a) J. H. Chen, D. Karanewsky, C. Mapes, P. Michellys,
D. Ruppar, A. Thompson, WO 2005/009104; b) J.
Fensholdt, B. Noerremark, J. Thorhauge, WO
2005/054179; c) Y. Shinagawa, T. Inoue, T.
Katsushima, T. Kiguchi, T. Ikenogami, N. Ogawa, K.
Fukuda, K. Hirata, K. Harada, M. Takagi, T. Nakagawa,
S. Kimura, Y. Matsuo, M. Maekawa, M. Hayashi, Y.
Soejima, M. Takahashi, M. Shindo, H. Hashimoto, ACS
Med. Chem. Lett. 2011, 2, 238−242.
4
5, 936−946; d) G. Rouquet, N. Chatani, Angew. Chem.
Int. Ed. 2013, 52, 11726−11743; e) Z. K. Chen, B. J.
Wang, J. T. Zhang, W. L. Yu, Z. X. Liu, Y. H. Zhang,
Org. Chem. Front. 2015, 2, 1107−1295; f) J. J.
Topczewski, M. S. Sanford, Chem. Sci. 2015, 6, 70−76;
g) P. Nareddy, F. Jordan, M. Szostak, ACS. Catal. 2017,
7
, 5721−5745.
[
4] For selected heteroarene directed arylation: a) L.
Ackermann, Org. Lett. 2005, 7, 3123−3125; b) V. G.
Zaitsev, D. Shabashov, O. Daugulis, J. Am. Chem. Soc.
[8] a) Y. B. Liu, H. B. Ge, Nat. Chem. 2017, 9, 26−32; b)
R. Y. Zhu, L. Y. Liu, H. S. Park, K. Hong, Y. Wu, C. H.
Senanayake, J. Q. Yu, J. Am. Chem. Soc. 2017, 139,
16080−16083.
2
005, 127, 13154−13155; c) Q. P. Ding, H. F. Ji, D.
Wang, Y. Q. Lin, W. H. Yu, Y. Y. Peng, J.
Organometal. Chem. 2012, 711, 62−67; d) D. E.
Stephens, J. Lakey-Beitia, A. C. Atesin, T. A. Atesin, G.
Chavez, H. D. Arman, O. V. Larionov, ACS Catal.
[9] a) W. Gong, G. Zhang, T. Liu, R. Giri, J. Q. Yu, J. Am.
Chem. Soc. 2014, 136, 16940−16946; b) L. C. Misal, N.
Chatani, Chem. Eur. J. 2014, 20, 4548−4553; c) C.
Wang, C. Chen, J. Zhang, J. Han, Q. Wang, K. Guo, P.
Liu, M. Guan, Y. Yao, Y. Zhao, Angew. Chem. Int. Ed.
2014, 53, 9884−9888; d) J. Kim, M. Sim, N. Kim, S.
Hong, Chem. Sci. 2015, 6, 3611−3616; e) M. Guan, Y.
Pang, J. Zhang, Y. Zhao, Chem. Commun. 2016, 52,
7043−7046; f) X. Chen, J. Han, Y. Zhu, C. Yuan, J.
Zhang, Y. Zhao, Chem. Commun. 2016, 52,
10241−10244; g) K. Hong, H. Park, J. Q, Yu, ACS
Catal. 2017, 7, 6938−6941; h) R. Y. Zhu, Z. Q. Li, H.
S. Park, C. H. Senanayake, J. Q. Yu, J. Am. Chem. Soc.
2018, 140, 3564−3568.
[10] a) Y. Endo, Y. Taoda, Tetrahedron Lett. 2001, 42,
6327−6331; b) Z. S. Jia, H. Ottosson, X. Zeng, A.
Thibblin, J. Org. Chem. 2002, 67, 182−187; c) G.
Hughes, P. O´shea, J. Goll, D. Gauvreau, J. Steele,
Tetrahedron 2009, 65, 3189–3196; d) P. Wang, L.
Zhou, X. Zhang, X. Liang, Chem. Commun. 2010, 46,
1514–1516; e) J. Xiao, J. Yang, T. Chen, L. B. Han,
Adv. Synth. Catal. 2016, 358, 816−819.
2
015, 5, 167−175; e) G. F. Zha, H. L. Qin, E. A. B.
Kantchev, RSC Adv. 2016, 6, 30875−30885.
[
5] For selected functional groups directed arylation: a) F.
Kakiuchi, S. Kan, K. Igi, N. Chatani, S. Murai, J. Am.
Chem. Soc. 2003, 125, 1698−1699; b) D. H. Wang, M.
Wasa, R. Giri, J. Q. Yu, J. Am. Chem. Soc. 2008, 130,
7
190−7191; c) D. Shabashov, O. Daugulis, J. Am.
Chem. Soc. 2010, 132, 3965−3972; d) H. X. Dai, A. F.
Stepan, M. S. Plummer, Y. H. Zhang, J. Q. Yu, J. Am.
Chem. Soc. 2011, 133, 7222−7228; e) W. Li, Z. P. Xu,
P. P. Sun, X. Q. Jiang, M. Fang, Org. Lett. 2011, 13,
1
286−1289; f) J. Z. Yao, M. Yu, Y. H. Zhang, Adv.
Synth. Catal. 2012, 354, 3205−3210; g) N.
Senthilkumar, K. Parthasarathy, P. Gandeepan, C. H.
Cheng, Chem. Asian J. 2013, 8, 2175−2181; h) J. C.
Zhang, J. L. Shi, B. Q. Wang, P. Hu, K. Q. Zhao, Z. J.
Shi, Chem. Asian J. 2015, 10, 840−843; i) S. Zhao, B.
Liu, B. B. Zhan, W. D. Zhang, B. F. Shi, Org. Lett.
2
016, 18, 4586−4589; j) T. T. Nguyen, O. Daugulis,
[11] A. Yokota, Y. Aihara, N. Chatani, J. Org. Chem.
2014, 79, 11922−11932.
Chem. Commun. 2017, 53, 4609−4611; k) B. P.
Zavesky, S. L. Bartlett, J. S. Johnson, Org. Lett. 2017,
1
[12] a) R. Shang, L. Ilies, A. Matsumoto, E. Nakamura, J.
Am. Chem. Soc. 2013, 135, 6030−6032; b) Y. Aihara,
N. Chatani, J. Am. Chem. Soc. 2014, 136, 898–901; c)
M. Iyanaga, Y. Aihara, N. Chatani, J. Org. Chem. 2014,
79, 11933−11939.
9, 2126−2129.
[
6] a) L. V. Desai, K. L. Hull, M. S. Sanford, J. Am. Chem.
Soc. 2004, 126, 9542−9543; b) C. W. Chan, Z. Y. Zhou,
A. S. C. Chan, W. Y. Yu, Org. Lett. 2010, 12,
3
926−3929; c) Y. X. Yang, B. Zhou, Y. C. Li, Adv.
[13] The X-ray crystal structures of compound 3n and I
are also available from CCDC 1815998 and CCDC
1554822, respectively, which can be obtained free of
charge via www.ccdc.cam.ac.uk
Synth. Catal. 2012, 354, 2916−2920; d) Z. Ren, F. Y.
Mo, G. B. Dong, J. Am. Chem. Soc. 2012, 134,
1
6991−16994; e) S. Han, S. Sharma, J. Park, M. Kim,
Y. M. Shin, N. K. Mishra, J. J. Bae, J. H. Kwak, Y. H.
Jung, I. S. Kim, J. Org. Chem. 2014, 79, 275−284; f) T.
Kang, Y. Kim, D. Lee, Z. Wang, S. Chang, J. Am.
Chem. Soc. 2014, 136, 4141−4144; g) K. Guo, X. L.
Chen, J. Y. Zhang, Y. S. Zhao, Chem. Eur. J. 2015, 21,
[14] a) Herein, the product of direct acetolysis 4b’ was
only detected in 91% yield without arylation, see ESI;
1
7474−17478; h) F. Xie, Z. P. Zhang, X. Z. Yu, G. D.
Tang, X. W. Li, Angew. Chem. Int. Ed. 2015, 54,
1
1
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b) Herein, the product of direct acetolysis 4g’ was
only detected in 87% yield without arylation, see ESI.
[17] a) Y. Xu, M. C. Young, C. Wang, D. M. Magness, G.
Dong, Angew. Chem. Int. Ed. 2016, 55, 9084–9087; b)
Z. Ren, G. Dong, Organometallics 2016, 35, 1057–
1
059.
[
18] a) P. Gandeepan, K. Parthasarathy, C. H. Cheng, J.
Am. Chem. Soc. 2010, 132, 8569−8571; b) F. L. Zhang,
K. Hong, T. J. Li, H. Park, J. Q. Yu, Science 2016, 351,
[
15] a) Y. Zhao, G. He, W. A. Nack, G. Chen, Org. Lett.
2
2
52−256.
19] D. Lapointe, K. Fagnou, Chem. Lett. 2010, 39,
118−1126.
20] a) J. M. Weibel, A. Blanc, P. Pale, Chem. Rev. 2008,
08, 3149-3173; b) C. Arroniz, J. G. Denis, A.
Ironmonger, G. Rassias, I. Larrosa, Chem. Sci. 2014, 5,
509−3514.
012, 14, 2948–2951; b) M. Nishino, K. Hirano, T.
Satoh, M. Miura, Angew. Chem. Int. Ed. 2013, 52,
457−4461; c) Q. Gu, H. A. Mamari, K. Graczyk, E.
Diers, L. Ackermann, Angew.Chem. Int. Ed. 2014, 53,
868–3871.
16] a) Y. Aihara, N. Chatani, Chem. Sci. 2013, 4,
64−670; b) M. Shang, S. Z. Sun, H. X. Dai, J. Q. Yu,
[
[
1
4
1
3
[
3
6
Org. Lett. 2014, 16, 5666–5669; c) J. Liu, Y. Xie, W.
Zeng, D. Lin, Y. Deng, X. Lu, J. Org. Chem. 2015, 80,
4
618−4626.
1
2
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FULL PAPER
Catalytic Cascade Access to Biaryl-2-Methyl
Acetates from Pyruvate O-Arylmethyl Ketoximes
2
via the Palladium-Catalyzed C(sp )–H Bond
Arylation and C–O Bond Solvolysis
Adv. Synth. Catal. Year, Volume, Page – Page
Ling-Yan Shao, Li-Hao Xing, Ying Guo, Kun-Kun
Yu, Wei Wang, Hong-Wei Liu, Dao-Hua Liao, and
Ya-Fei Ji*
1
3
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