Copper-Mediated [3 + 2] Oxidative Cyclization Reaction of N-Tosylhydrazones and β-Ketoesters: Synthesis of 2,3,5-Trisubstituted Furans

Article abstract of DOI:10.1021/acs.joc.6b00568

The first attempt at utilizing N-tosylhydrazones as two-carbon synthons has been successfully achieved, which underwent a copper-mediated [3 + 2] oxidative cyclization reaction to afford 2,3,5-trisubstituted furans in moderate to good yields. The features of this method include inexpensive metal catalyst, readily available substrates, high regioselectivity, and convenient operation. The studies provide important approaches for further exploration of the powerful and diverse reaction abilities of N-tosylhydrazones.

Full text of DOI:10.1021/acs.joc.6b00568

Subscriber access provided by UOW Library
Article
Copper-Mediated [3 + 2] Oxidative Cyclization Reaction of N-Tosylhydrazones
and beta-Ketoesters: Synthesis of 2,3,5-Trisubstituted Furans
Yubing Huang, Xianwei Li, Yue Yu, Chuanle Zhu, Wanqing Wu, and Huanfeng Jiang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b00568 • Publication Date (Web): 26 May 2016
Downloaded from http://pubs.acs.org on May 28, 2016
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
The Journal of Organic Chemistry is published by the American Chemical Society.
1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 31
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Copper-Mediated [3 + 2] Oxidative Cyclization
Reaction of N-Tosylhydrazones and β-Ketoesters:
Synthesis of 2,3,5-Trisubstituted Furans
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
Yubing Huang, Xianwei Li, Yue Yu, Chuanle Zhu, Wanqing Wu*, Huanfeng Jiang*
Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of
Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640,
P. R. China
Fax: (+86) 20ꢀ87112906; Eꢀmail: cewuwq@scut.edu.cn, jianghf@scut.edu.cn
Abstract: The first attempt utilizing Nꢀtosylhydrazones as twoꢀcarbon synthons has
been successfully achieved, which underwent a copperꢀmediated [3 + 2] oxidative
cyclization reaction to afford 2,3,5ꢀtrisubstituted furans in moderate to good yields.
The features of this method include inexpensive metal catalyst, readily available
substrates, high regioselectivity and convenient operation. The studies provide
important approaches for further exploration of the powerful and diverse reaction
abilities of Nꢀtosylhydrazones.
INTRODUCTION
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 31
1
2
3
4
5
6
7
8
9
NꢀTosylhydrazones, derived easily from the corresponding ketones, have been long
applied in diverse organic transformations, including BamfordꢀStevens and Shapiro
reactions. It is wellꢀknown that, Nꢀtosylhydrazones can generate diazo compounds in
situ in the presence of base and further form metalꢀcarbene species, which have been
demonstrated exhibiting excellent synthetic utilities in crossꢀcoupling reactions.1
Recently, Nꢀtosylhydrazones have been widely explored in building various ring
products via cyclization reactions, such as [2 + 1], [3 + 2], [4 + 1] cycloaddition, in
which Nꢀtosylhydrazones are generally used as synthons by providing one or two
bonding sites. For example, Nꢀtosylhydrazones were utilized as singleꢀcarbon
synthons to construct cyclopropaneꢀcontaining products with electron deficient
alkenes2aꢀ2c (Scheme 1a, I). Valdés3aꢀ3b reported a [3 + 2] cycloaddition/[1,5]ꢀδ
rearrangement to prepare substituted pyrazoles from Nꢀtosylhydrazones and terminal
acetylenes (Scheme 1a, II), in which C2 and N2 were offered as bonding sites. Later,
Valdés group reported a [4 + 1] cyclization reaction to prepare spirofluorene and
spiroꢀacridine derivatives2d (Scheme 1a, III). It is noteworthy that Nꢀtosylhydrazone
was used C2 as single carbon synthons. Since 2013, several [4 + 1] cyclization
reactions4 between Nꢀtosylhydrazones and nucleophilic substrates, such as
isocyanides and anilines, to construct fiveꢀmembered heterocycles have been reported
successively (Scheme 1a, IV), among which nucleophilic reagents were applied to C1
and N2 positions. To the best of our knowledge, there are few reports3c on building
cyclized products by employing C1 and C2 as bonding sites. As part of our interest in
the synthetic applications of Nꢀtosylhydrazones, we are particularly interested in
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
ACS Paragon Plus Environment

Page 3 of 31
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
exploring novel methods to construct active structural motifs via unprecedented
utilization of Nꢀtosylhydrazones as C2 synthons in cyclization reactions, which still is
a great challenge.
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
Scheme 1. Cyclization Reactions of NꢀTosylhydrazones
a) Previous ways :
EWG
NNHTs
[2 + 1]
EWG
C2
(I)
+
+
Ar
Ar
C2
ref. 2a-2c
Ar
Ts
N2
N2
N1
N1
H
[3 + 2]
R
(II)
R
C2
ref. 3a-3b
C2
Ar
R2
Br
R1
NNHTs
[4 + 1]
ref. 2d
C2
(III)
+
R1
R2
C2
Br
Ts
N2
N2
N1
N1
C
N
or
R1
H
+
[4 + 1]
ref. 4
X
R
(IV)
Ar
H2N R2
C1
C2
C2
Ar
C1
( X-R = C-NHR1 or N-R2
)
b) Our strategy :
O
O
R1
R1
OR2
O
OR2
NNHTs
Ar
C2
C1
Ar
C2
O
C1
O
O
Cu
R1
OR2
[3 + 2]
[Cu], base
oxidation
Ar
C2
C1
cyclization
Polyꢀsubstituted furans, an important class of heterocyclic compounds, are
known to be ubiquitous structural motifs and building blocks in natural products,5
synthetic pharmaceuticals6 and agrochemicals. In the methods of transition metal
catalysis, including Pd7ꢀ, Cu8ꢀ, Ag9ꢀ, Au10ꢀ and Ru11ꢀcatalyzed organic
transformations, 1,3ꢀdicarbonyl compounds are generally used to construct
polyꢀsubstituted furans from functional olefins, electronꢀpoor alkynes or terminal
alkynes.12 Very recently, our group13 disclosed the transformations from
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 31
1
2
3
4
5
6
7
8
9
ketoneꢀderived Nꢀtosylhydrazones to alkynes and diynes via a copperꢀcatalyzed
selectively oxidative process. Unlike most of the transition metalꢀcatalyzed
crossꢀcouplings of Nꢀtosylhydrazones14, the oxidative crossꢀcoupling reactions
ultilized C1ꢀpositions as binding sites instead of C2ꢀpositions. Inspired by this study,
we herein disclose a novel approach for the construction of 2,3,5ꢀtrisubstituted furans
from Nꢀtosylhydrazones and βꢀketoesters via the copperꢀmediated [3 + 2] oxidative
cyclization reactions (Scheme 1b). We supposed that highly activated 1,3ꢀdicarbonyl
compounds would first connect to C1ꢀpositions of Nꢀtosylhydrazones, and then
undergo the cyclization process. To our knowledge, it is rarely application that
Nꢀtosylhydrazones as twoꢀcarbon synthons to build active cyclic compounds, which
would further broaden the synthetic applications of Nꢀtosylhydrazones and the
methods of constructing polyꢀsubstituted furans.
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
RESULTS AND DISCUSSION
Initially, Nꢀtosylhydrazone of 4ꢀfluoroacetophenone (1) and ethyl acetoacetate (2)
were chosen as model substrates, and the optimization results are shown in Table 1.
Based on the investigation to various copper catalysts and the corresponding equivalent
under simple conditions that Et3N (0.2 mmol) and Zn(OTf)2 (0.1 mmol) were added in
1.5 mL solvent (DMF: toluene = 3: 1) at 120 °C under air atmosphere for 10 h (entries
1ꢀ6), we found that when 1.0 equivalent of CuCl was added, the best reaction activity
was exhibited and the desired product (3) was obtained in 61% yield (entry 5).
According to our previous work on the oxidative crossꢀcouplings of Nꢀtosylhydrazones,
ACS Paragon Plus Environment

Page 5 of 31
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
the judicious choice of the oxidant and base might be the key to the success of this
reaction. Through the examination of various oxidants, such as O2, BQ, DDQ,
PhI(OAc)2 and TBHP, O2 was considered to be the best choice (entries 7ꢀ9). To further
improve the yield, we replaced Et3N with different bases (entries 10ꢀ15). To our delight,
tertiary amines with olefins structure could effectively improve the yield of the desired
product (entries 12ꢀ15), and b6 displayed the best efficiency and the yield increased to
85% (entry 14). We suspected that triallylamine acted both as base and ligand to
facilitate this reaction. Thus, the optimal catalytic system for this copperꢀmediated [3 +
2] oxidative cyclization reaction was: 1 (0.1 mmol), 2 (0.15 mmol), CuCl (0.1 mmol),
triallylamine (0.2 mmol), Zn(OTf)2 (0.1 mmol), in 1.5 mL solvent (DMF: toluene = 3:
1) at 120 °C under O2 atmosphere for 10 h.
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
Table 1. Optimization of Reaction Conditions a
entry a
[Cu] (equiv)
CuCl (0.5)
CuI (0.5)
oxidant
air
base
b1
yield b(%)
1
2
3
4
37
19
16
30
air
b1
Cu (0.5)
air
b1
Cu(OAc)2 (0.5)
air
b1
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 31
1
2
3
4
5
6
7
8
9
5
CuCl (1)
CuCl (1.5)
CuCl (1)
CuCl (1)
CuCl (1)
CuCl (1)
CuCl (1)
CuCl (1)
CuCl (1)
CuCl (1)
CuCl (1)
air
b1
b1
b1
b1
b1
b2
b3
b4
b5
b6
b7
61
6
air
57
7
O2
71
8
BQ
74
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
9
PhI(OAc)2
36
10
11
12
13
14
15
O2
O2
O2
O2
O2
O2
46
42
72
77
85 (81) c
83
a Reaction conditions: All reactions were performed with 1 (0.1 mmol), 2 (0.15 mmol), base (0.2
mmol), Zn(OTf)2 (0.1 mmol) in 1.5 mL solvent (DMF: toluene = 3: 1) at 120 °C for 10 h unless
b
c
otherwise noted. Determined by GCꢀMS using nꢀdodecane as an internal standard. Isolated
yield.
With the optimal reaction conditions in hand, we began to explore the substrate
scope of Nꢀtosylhydrazones in this Cuꢀmediated [3 + 2] oxidative cyclization reaction
(Table 2). The results indicated that Nꢀtosylhydrazones containing
electronꢀwithdrawing or electronꢀdonating groups were well tolerated and the desired
polyꢀsubstituted furans could be afforded in moderate yields. In general,
Nꢀtosylhydrazones bearing electronꢀwithdrawing groups including paraꢀ (3aaꢀ3fa),
orthoꢀ (3na), metaꢀ (3oa and 3pa) and difluoroꢀsubstituted positions (3ra), gave
better results. Electronꢀdonating groups, such as 4ꢀmethyl, 4ꢀethyl, 4ꢀisopropyl,
2ꢀmethyl and dimethyl groups, were also well tolerated under the optimized
conditions. However, 4ꢀmethoxyꢀ and 4ꢀphenylꢀsubstituted substrates (3ka and 3la)
gave lower yields. Notably, heterocyclic and naophthone derived Nꢀtosylhydrazones
ACS Paragon Plus Environment

Page 7 of 31
The Journal of Organic Chemistry
1
2
3
4
5
6
are good substrates to deliver the correponding furans in moderate to good yield (3sa
and 3ta).
7
8
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
Table 2. Substrate Scope of NꢀTosylhydrazones a
CuCl, O2
O
O
O
NNHTs
+
triallylamine, Zn(OTf)2
OEt
Ar
OEt
Ar
DMF: toluene = 3: 1
4A MS, 120 oC
O
3
1
2a
O
O
O
OEt
OEt
OEt
F
Cl
Br
O
O
O
O
3ba, 80%
3aa, 81%
3ca, 80%
O
O
O
OEt
O2N
OEt
MeOOC
OEt
F3C
O
O
3ea, 84%
3da, 87%
3fa, 77%
O
O
O
OEt
Me
OEt
OEt
OEt
Et
O
O
O
O
3ga, 62%
3ha, 68%
3ia, 71%
O
O
O
OEt
MeO
OEt
iPr
Ph
O
O
3ja, 70%
3ka, 56%
3la, 58%
O
O
O
OEt
OEt
OEt
OEt
O
O
O
O
O
F
Me
3ma, 65%
F
3oa, 82%
3na, 87%
O
O
O
F
OEt
OEt
O
F
Cl
3pa, 85%
3ra, 90%
3qa, 70%
O
O
O
O
OEt
OEt
OEt
O
O
O
O
O
3sa, 43%
3ua, 62%
3ta, 61%
a Reaction conditions: All reactions were performed with 1 (0.3 mmol), 2a (0.45 mmol), CuCl (0.3
mmol), triallylamine (0.6 mmol), Zn(OTf)2 (0.3 mmol) and 2.0 mL solvent (DMF: toluene = 3: 1)
at 120 °C under O2 atmosphere for 10 h. Yields refer to the isolated yields.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 31
1
2
3
4
5
6
7
8
9
A series of βꢀketoesters were then examined in this transformation and the results
are shown in Table 3. Methyl, normꢀbutyl, tertꢀbutyl, allyl acetoacetates could be
tolerated and converted to the desired furans in good yields (3abꢀ3ae). Moreover,
when R1 were alkyl groups, including ethyl, isopropyl, cyclopropyl, normꢀpropyl and
tertꢀbutyl, good isolated yields were also obtained (3agꢀ3ak). Higher yield was
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
achieved
when
using
ethyl
benzoylacetate
and
ethyl
3ꢀoxoꢀ3ꢀ(thiophenꢀ2ꢀyl)propanoate as substrates, and the target furans was produced
in 90% (3af) and 86% (3al) yields, respectively.
Table 3. Substrate Scope of β-Ketoesters a
R1
NNHTs
+
CuCl, O2
triallylamine, Zn(OTf)2
O
O
O
OR2
1
R
OR2
F
DMF: toluene = 3: 1
4A MS, 120 oC
O
F
3
1a
2
O
O
O
OnBu
F
OtBu
OEt
OMe
F
F
O
O
O
O
3ac, 87%
3ad, 86%
3ab, 83%
Ph
Et
O
O
O
OAllyl
F
OEt
F
F
O
O
3ae, 85%
3af, 90%
3ag, 89%
nPr
iPr
Cy
O
O
O
OEt
OEt
OEt
F
F
F
F
O
O
O
3aj, 86%
3ai, 84%
3ah, 85%
S
tBu
O
O
OEt
F
OEt
O
O
3ak, 74%
3al, 86%
a Reaction conditions: All reactions were performed with 1 (0.3 mmol), 2a (0.45 mmol), CuCl (0.3
mmol), triallylamine (0.6 mmol), Zn(OTf)2 (0.3 mmol) and 2.0 mL solvent (DMF: toluene = 3: 1)
at 120 °C under O2 atmosphere for 10 h. Yields refer to the isolated yields.
To further verify the mechanism of the oxidative cyclization reaction, a series of
ACS Paragon Plus Environment

Page 9 of 31
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
control experiments were carried out, and the results are shown in Scheme 2. When
Nꢀtosylhydrazone 1a was used as the only substrate to react under the optimal
conditions (Scheme 2, Eqn. 1), no internal alkyne product was generated, which
indicated that the reactions might not proceed via copper acetylide intermediates13.
Moreover, when subjecting 4ꢀfluoroacetophenone and 4ꢀfluorostyrene and ethyl
acetoacetate under the standard conditions (Scheme 2, Eqn. 2), no desired furan
products were detected. This observation suggested that the oxidative cyclization
reactions would not occur via the formations of ketones or olefin intermediates.
Furthermore, only trace amount of desired product was detected when 1.5 equiv of
TEMPO was introduced into the standard reaction system (Scheme 2, Eqn. 3). When
1.5 equiv of radical trapping reagent BHT was added to the standard reaction system,
no desired product was detected. However, to our delight, ethyl acetoacetate radical
intermediates could be caught by BHT and 4aa was generated in 21% yield (Scheme
2, Eqn. 4), which strongly support that the reaction should proceed via radical
cyclization pathway.
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
Scheme 2. Mechanistic Studies
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 31
1
2
3
4
5
6
7
8
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
Interestingly, when the Nꢀtosylhydrazone of 4ꢀphenylacetophenone and
2ꢀacetonaphthone, with large conjugated structures, were utilized as substrates, the
olefin byproducts 4la and 4ta, which were supposed to be generated through the
protonation processes of vinyl copper intermediates, could be obtained in 20% and 26%
yields respectively, with the desired furans 3la and 3ta (Scheme 3).
Scheme 3. Formation of Olefins a
On the basis of the above experimental results, the plausible reaction mechanism
to rationalize this Cuꢀmediated [3 + 2] oxidative cyclization reaction of
ACS Paragon Plus Environment

Page 11 of 31
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Nꢀtosylhydrazones and βꢀketoesters is illustrated in Scheme 4. Initially, the diazo
compound A is generated in situ from Nꢀtosylhydrazone 1 in the presence of base,13
which further react with copper(І) catalyst to form the copper(І) carbene species B.
Then, the oxidation of B gives the vinyl copper(II) complex C.15 Meanwhile,
singleꢀelectron oxidation of βꢀketoesters yields free radical intermediate D,16
Zn(OTf)2 as a Lewis acid might increase the activity of radical D,17 which could
subsequently attack the C1 positon of C to generate the radical intermediate E. After
further oxidation and electronic rearrangement, E can convert into the vinyl copper(II)
intermediate F (path a), and the intermediate G is subsequently formed through the
departure of Lewis acid. Finally, the reductive elimination of G18 releases the desired
product 3 and copper(0) under reaction condition. Alternatively, radical intermediate
E may also convert into heterocyclic intermediates H via intramolecular addition19
(path b), and after further oxidation, H converts into the final product 3.
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
Scheme 4. Proposed Mechanism
In summary, a copperꢀmediated [3 + 2] oxidative cyclization reaction to afford
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 31
1
2
3
4
5
6
7
8
9
2,3,5ꢀtrisubstituted furans from Nꢀtosylhydrazones and βꢀketoesters has been
developed, which is the first implementation of utilizing Nꢀtosylhydrazones as
twoꢀcarbon synthons. The formations of vinyl copper complex and βꢀketoester free
radical intermediates are supposed to be the key steps of this oxidative cyclization
process. This transformation provides a novel protocol in cyclization reactions and
crossꢀcouplings of hydrazone compounds, and presents potential applications in
hydrazine chemistry. Furthermore, the uses of inexpensive metal catalyst, readily
available substrates, high regioselectivity, as well as convenient operation make this
innovative and practical method particularly attractive.
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
EXPERIMENTAL SECTION
General Information. Melting points were measured with a melting point instrument
1
and were uncorrected. H and 13C NMR spectra were recorded using a 400 MHz
NMR spectrometer. The chemical shifts are referenced to signals at 7.26 and 77.0
ppm, respectively, and chloroform is solvent with TMS as the internal standard. IR
spectra were obtained either as potassium bromide pellets or as liquid films between
two potassium bromide pellets with a spectrometer. GCꢀMS was obtained using
electron ionization. HRMS was obtained with a LCMSꢀITꢀTOF mass spectrometer.
TLC was performed by using commercially prepared 100ꢀ400 mesh silica gel plates
and visualization was effected at 254 nm. Unless otherwise noted, all reagents and
solvents were obtained from commercial suppliers and used without further
purification.
ACS Paragon Plus Environment

Page 13 of 31
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
General Procedure for N-Tosylhydrazones: A mixture of ketone compounds (5.0
mmol) and pꢀtoluenesulfonhydrazide (5.0 mmol) in 7.5 mL MeOH was stirred at 70
oC for 0.5ꢀ3 h to afford the corresponding Nꢀtosylhydrazone 1 as white precipitate.
After that, the precipitate was washed and filtered with petroleum ether twice and
dried under vacuum to provide the pure compounds.
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
General Procedure for 2,3,5-Trisubstituted Furans
:
A
mixture of
Nꢀtosylhydrazone (0.3 mmol), ethyl acetoacetate (0.45 mmol), CuCl (0.3 mmol),
triallylamine (0.6 mmol), and Zn(OTf)2 (0.3 mmol) in 2.0 mL solvent (DMF: toluene
= 3: 1) was successively added to a Schlenk tube. The mixture was stirred under O2
atmosphere at 120 oC for 10 h. After that, water was added to quench the reaciton and
extracted with ethyl acetate twice. The combined organic phase was dried over
Na2SO4 and concentrated. The residue was purified by flash column chromatography
on silica gel with petroleum ether/ethyl acetate (PE/EA = 30: 1–50: 1) as the eluent to
afford the corresponding furans.
Ethyl 5-(4-Fluorophenyl)-2-methylfuran-3-carboxylate (3aa)12a: Yield: 60 m
1
(81%), pale white solid, M.p.: 60ꢀ62 ºC. H NMR (400 MHz, CDCl3, ppm): δ = 7.60
(t, J = 6.0 Hz, 2H), 7.07 (t, J = 8.4 Hz, 2H), 6.81 (s, 1H), 4.31 (q, J = 7.0 Hz, 2H),
2.63 (s, 3H), 1.37 (t, J = 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3, ppm): δ = 164.0,
162.3 (d, J = 247.5 Hz), 158.6, 150.9, 126.5 (d, J = 3.3 Hz), 125.4 (d, J = 8.1 Hz),
115.8 (d, J = 22.0 Hz), 115.5, 105.2, 60.2, 14.4, 13.9; IR (KBr, cmꢀ1): ν = 1714, 1600,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 31
1
2
3
4
5
6
1500, 1428, 1233, 1096, 1042; HRMS (ESI) calc. C14H13FNaO3 [M+Na]+: 271.0741,
found: 271.0745.
7
8
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
Ethyl 5-(4-Chlorophenyl)-2-methylfuran-3-carboxylate (3ba)12a: Yield: 64 mg
1
(80%), pale white solid, M.p.: 77ꢀ79 ºC. H NMR (400 MHz, CDCl3, ppm): δ = 7.56
(d, J = 8.5 Hz, 2H), 7.34 (d, J = 8.5 Hz, 2H), 6.87 (s, 1H), 4.31 (q, J = 7.1 Hz, 2H),
2.64 (s, 3H), 1.37 (t, J = 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3, ppm): δ = 163.9,
158.9, 150.7, 133.3, 128.9, 128.6, 124.9, 115.6, 106.0, 60.3, 14.4, 13.9; IR (KBr,
cmꢀ1): ν = 1691, 1480, 1430, 1390, 1235, 1089, 1040; HRMS (ESI) calc.
C14H13ClNaO3 [M+Na]+: 287.0445, found: 287.0447.
Ethyl 5-(4-Bromophenyl)-2-methylfuran-3-carboxylate (3ca)12a: Yield: 73 mg
1
(80%), pale white solid, M.p.: 72ꢀ74 ºC. H NMR (400 MHz, CDCl3, ppm): δ = 7.48
(s, 4H), 6.87 (s, 1H), 4.31 (q, J = 7.1 Hz, 2H), 2.63 (s, 3H), 1.36 (t, J = 7.1 Hz, 3H);
13C NMR (101 MHz, CDCl3, ppm): δ = 163.8, 158.9, 150.6, 131.8, 129.0, 125.1,
121.4, 115.6, 106.1, 60.3, 14.4, 13.9; IR (KBr, cmꢀ1): ν = 1698, 1604, 1477, 1425,
1386, 1232, 1094, 1038, 1005; HRMS (ESI) calc. C14H13BrNaO3 [M+Na]+: 330.9940,
found: 330.9939.
Ethyl 2-Methyl-5-(4-(trifluoromethyl)phenyl)furan-3-carboxylate (3da): Yield: 78
mg (87%), yellow solid, M.p.: 60ꢀ63 ºC. 1H NMR (400 MHz, CDCl3): δ = 7.62 (d, J =
7.8 Hz, 2H), 7.53 (d, J = 7.8 Hz, 2H), 6.91 (s, 1H), 4.24 (q, J = 6.6 Hz, 2H), 2.57 (s,
ACS Paragon Plus Environment

Page 15 of 31
The Journal of Organic Chemistry
1
2
3
4
13
3H), 1.29 (t, J = 6.7 Hz, 3H); C NMR (101 MHz, CDCl3): δ = 163.7, 159.6, 150.2,
5
6
7
8
9
133.2, 129.2 (q, J = 32.7 Hz), 125.7 (q, J = 3.8 Hz), 124.1 (q, J = 272.0 Hz), 123.6,
115.8, 107.6, 60.4, 14.3, 13.9; IR (KBr, cmꢀ1): ν = 1713, 1616, 1435, 1327, 1245,
1160, 1107, 1067; HRMS (ESI) calc. C15H14F3O3 [M+H]+: 299.0890, found:
299.0887.
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
Ethyl 2-Methyl-5-(4-nitrophenyl)furan-3-carboxylate (3ea): Yield: 69 mg (84%),
yellow solid, M.p.: 129ꢀ131 ºC. 1H NMR (400 MHz, CDCl3): δ = 8.24 (d, J = 8.4 Hz,
2H), 7.75 (d, J = 8.2 Hz, 2H), 7.11 (s, 1H), 4.34 (q, J = 6.7 Hz, 2H), 2.68 (s, 3H), 1.39
(t, J = 6.9 Hz, 3H).; 13C NMR (101 MHz, CDCl3): δ =163.4, 160.6, 149.4, 146.6,
135.7, 124.3, 123.8, 116.3, 109.6, 60.5, 14.3, 14.0; IR (KBr, cmꢀ1): ν = 1702, 1602,
1509, 1436, 1332, 1243, 1101, 846; HRMS (ESI) calc. C14H13NNaO5 [M+Na]+:
298.0686, found: 298.0685.
Ethyl 5-(4-(Methoxycarbonyl)phenyl)-2-methylfuran-3-carboxylate (3fa)20: Yield:
67 mg (77%), yellow solid, M.p.: 89ꢀ91 ºC. 1H NMR (400 MHz, CDCl3): δ = 7.96 (d,
J = 6.8 Hz, 2H), 7.59 (d, J = 7.0 Hz, 2H), 6.93 (s, 1H), 4.27 (d, J = 6.0 Hz, 2H), 3.86
(s, 3H), 2.59 (s, 3H), 1.34 (d, J = 6.2 Hz, 3H); 13C NMR (101 MHz, CDCl3): δ =
166.5, 163.6, 159.5, 150.5, 133.8, 130.0, 128.7, 123.1, 115.7, 107.7, 60.2, 52.0, 14.3,
13.8; IR (KBr, cmꢀ1): ν = 1707, 1610, 1434, 1275, 1245, 1100, 1040; HRMS (ESI)
calc. C16H16NaO5 [M+Na]+: 311.0890, found: 311.0898.
Ethyl 2-Methyl-5-phenylfuran-3-carboxylate (3ga)12a: Yield: 44 mg (62%), yellow
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 31
1
2
3
4
5
6
7
8
9
1
oil. H NMR (400 MHz, CDCl3, ppm): δ = 7.67 (d, J = 7.7 Hz, 2H), 7.41 (t, J = 7.5
Hz, 2H), 7.29 (t, J = 3.2 Hz, 1H), 6.91 (s, 1H), 4.35 (q, J = 7.1 Hz, 2H), 2.68 (s, 3H),
1.40 (t, J = 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3, ppm): δ = 164.1, 158.6, 151.7,
130.1, 128.7, 127.6, 123.7, 115.4, 105.5, 60.2, 14.4, 13.9; IR (KBr, cmꢀ1): ν = 1715,
1602, 1444, 1296, 1235, 1094, 1040; HRMS (ESI) calc. C14H14NaO3 [M+Na]+:
253.0835, found: 253.0838.
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
Ethyl 2-Methyl-5-(p-tolyl)furan-3-carboxylate (3ha)12a: Yield: 49 mg (68%), pale
white solid, M.p.: 59ꢀ61 ºC. 1H NMR (400 MHz, CDCl3, ppm): δ = 7.53 (d, J = 7.9
Hz, 2H), 7.18 (d, J = 7.8 Hz, 2H), 6.82 (s, 1H), 4.31 (q, J = 7.1 Hz, 2H), 2.64 (s, 3H),
2.36 (s, 3H), 1.37 (t, J = 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3, ppm): δ = 164.2,
158.3, 151.9, 137.5, 129.4, 127.4, 123.6, 115.3, 104.7, 60.2, 21.3, 14.4, 13.9; IR (KBr,
cmꢀ1): ν = 1703, 1429, 1388, 1236, 1099, 1039; HRMS (ESI) calc. C15H16NaO3
[M+Na]+: 267.0992, found: 267.0986.
Ethyl 5-(4-Ethylphenyl)-2-methylfuran-3-carboxylate (3ia)12a: Yield: 54 mg (71%),
yellow oil. 1H NMR (400 MHz, CDCl3, ppm): δ = 7.56 (d, J = 8.0 Hz, 2H), 7.22 (d, J
= 7.9 Hz, 2H), 6.83 (s, 1H), 4.32 (q, J = 7.1 Hz, 2H), 2.64ꢀ2.69 (m, 5H), 1.38 (t, J =
13
7.1 Hz, 3H), 1.25 (t, J = 7.5 Hz, 3H); C NMR (101 MHz, CDCl3, ppm): δ = 164.2,
158.3, 152.0, 143.9, 128.2, 127.7, 123.7, 115.3, 104.8, 60.2, 28.7, 15.5, 14.4, 13.9; IR
(KBr, cmꢀ1): ν = 1716, 1606, 1426, 1234, 1095, 1043; HRMS (ESI) calc. C16H18NaO3
[M+Na]+: 281.1148, found: 281.1151.
ACS Paragon Plus Environment

Page 17 of 31
The Journal of Organic Chemistry
1
2
3
4
5
6
7
Ethyl 5-(4-Isopropylphenyl)-2-methylfuran-3-carboxylate (3ja): Yield: 58 mg
8
9
1
(70%), yellow oil. H NMR (400 MHz, CDCl3, ppm): δ = 7.55 (d, J = 7.8 Hz, 2H),
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
7.23 (d, J = 8.0 Hz, 2H), 6.82 (s, 1H), 4.30 (q, J = 6.5 Hz, 2H), 2.87ꢀ2.94 (m, 1H),
2.63 (s, 3H), 1.36 (t, J = 7.0 Hz, 3H), 1.25 (d, J = 6.6 Hz, 6H); 13C NMR (101 MHz,
CDCl3, ppm): δ = 164.2, 158.3, 152.0, 148.5, 127.8, 126.8, 123.8, 115.3, 104.8, 60.2,
33.9, 23.9, 14.4, 13.9; IR (KBr, cmꢀ1): ν = 1716, 1607, 1422, 1235, 1096, 1050;
HRMS (ESI) calc. C17H20NaO3 [M+Na]+: 295.1305, found: 295.1305.
Ethyl 5-(4-Methoxyphenyl)-2-methylfuran-3-carboxylate (3ka)12a: Yield: 43 mg
1
(56%), yellow oil. H NMR (400 MHz, CDCl3, ppm): δ = 7.56 (d, J = 8.6 Hz, 2H),
6.91 (d, J = 8.6 Hz, 2H), 6.73 (s, 1H), 4.30 (q, J = 7.1 Hz, 2H), 3.82 (s, 3H), 2.63 (s,
3H), 1.36 (t, J = 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3, ppm): δ = 164.2, 159.2,
158.0, 151.8, 125.1, 123.2, 115.3, 114.2, 103.8, 60.1, 55.3, 14.4, 13.9; IR (KBr, cmꢀ1):
ν = 1714, 1604, 1502, 1427, 1246, 1176, 1096, 1033; HRMS (ESI) calc. C15H16NaO4
[M+Na]+: 283.0941, found: 283.0947.
Ethyl 5-([1,1'-Biphenyl]-4-yl)-2-methylfuran-3- carboxylate (3la)21: Yield: 53 mg
(58%), white solid, M.p.: 83ꢀ86 ºC. 1H NMR (400 MHz, CDCl3, ppm): δ = 7.74 (d, J
= 6.3 Hz, 2H), 7.65 (d, J = 6.7 Hz, 4H), 7.48 (s, 2H), 7.39 (s, 1H), 6.97 (s, 1H), 4.41–
4.31 (m, 2H), 2.71 (s, 3H), 1.43 (s, 3H); 13C NMR (101 MHz, CDCl3, ppm): δ = 164.0,
158.7, 151.5, 140.5, 140.3, 129.1, 128.8, 127.4, 127.4, 126.9, 124.1, 115.6, 105.7,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 18 of 31
1
2
3
4
60.2, 14.4, 13.9; IR (KBr, cmꢀ1): ν = 1715, 1606, 1418, 1235, 1097, 1045; HRMS
5
6
7
(ESI) calc. C20H18NaO3 [M+Na]+: 329.1148, found: 329.1153.
8
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
Ethyl 2-Methyl-5-(o-tolyl)furan-3-carboxylate (3ma)22: Yield: 48 mg (65%),
yellow oil. 1H NMR (400 MHz, CDCl3, ppm): δ = 7.66 (d, J = 6.2 Hz, 1H), 7.21ꢀ7.24
(m, 3H), 6.76 (s, 1H), 4.32 (d, J = 6.3 Hz, 2H), 2.64 (s, 3H), 2.48 (s, 3H), 1.37 (t, J =
5.8 Hz, 3H); 13C NMR (101 MHz, CDCl3, ppm): δ = 164.2, 158.2, 151.2, 134.6, 131.2,
129.4, 127.7, 126.8, 126.0, 115.2, 109.1, 60.2, 21.9, 14.4, 13.9; IR (KBr, cmꢀ1): ν =
1716, 1609, 1418, 1234, 1092, 1033; HRMS (ESI) calc. C15H16NaO3 [M+Na]+:
267.0992, found: 267.0994.
Ethyl 5-(2-Fluorophenyl)-2-methylfuran-3-carboxylate (3na): Yield: 65 mg (87%),
yellow oil. 1H NMR (400 MHz, CDCl3, ppm): δ = 7.76 (t, J = 7.5 Hz, 1H), 7.21 (t, J =
6.2 Hz, 1H), 7.17 (t, J = 7.4 Hz, 1H), 7.10 (t, J = 5.6 Hz, 1H), 7.05 (s, 1H), 4.31 (q, J
= 7.0 Hz, 2H), 2.65 (s, 3H), 1.37 (t, J = 7.0 Hz, 3H); 13C NMR (101 MHz, CDCl3,
ppm): δ = 164.0, 158.6, 158.5 (d, J = 251.1 Hz), 145.8 (d, J = 2.7 Hz), 128.6 (d, J =
8.3 Hz), 125.7 (d, J = 2.9 Hz), 124.2 (d, J = 3.5 Hz), 118.4 (d, J = 12.0 Hz), 116.1,
115.8 (d, J = 13.8 Hz), 115.7 (d, J = 1.4 Hz), 110.6 (d, J = 11.9 Hz), 60.2, 14.4, 13.8;
IR (KBr, cmꢀ1): ν = 1717, 1607, 1489, 1421, 1237, 1092, 1039; HRMS (ESI) calc.
C14H13FNaO3 [M+Na]+: 271.0741, found: 271.0741.
ACS Paragon Plus Environment

Page 19 of 31
The Journal of Organic Chemistry
1
2
3
4
Ethyl 5-(3-Fluorophenyl)-2-methylfuran-3-carboxylate (3oa): Yield: 61 mg (82%),
5
6
7
1
pale white solid, M.p.: 53ꢀ55 ºC. H NMR (400 MHz, CDCl3, ppm): δ = 7.39 (d, J =
8
9
7.6 Hz, 1H), 7.30ꢀ7.34 (m, 2H), 6.94 (t, J = 8.3 Hz, 1H), 6.90 (s, 1H), 4.31 (q, J = 7.1
Hz, 2H), 2.64 (s, 3H), 1.37 (t, J = 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3, ppm): δ
= 163.8, 163.1 (d, J = 244 Hz), 159.0, 150.5 (d, J = 2.9 Hz), 132.1 (d, J = 8.5 Hz),
130.3 (d, J = 8.5 Hz), 119.2 (d, J = 2.9 Hz), 115.6, 114.4 (d, J = 21.4 Hz), 110.5 (d, J
= 23.7 Hz), 106.6, 60.3, 14.4, 13.9; IR (KBr, cmꢀ1): ν = 1701, 1611, 1428, 1233, 1185,
1094, 1040; HRMS (ESI) calc. C14H13FNaO3 [M+Na]+: 271.0741, found: 271.0744.
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
Ethyl 5-(3-Chlorophenyl)-2-methylfuran-3-carboxylate (3pa): Yield: 67 mg (85%),
pale yellow solid, M.p.: 57ꢀ60 ºC. 1H NMR (400 MHz, CDCl3, ppm): δ = 7.62 (s, 1H),
7.49 (d, J = 7.7 Hz, 1H), 7.29 (t, J = 7.9 Hz, 1H), 7.22 (d, J = 7.9 Hz, 1H), 6.91 (s,
1H), 4.31 (q, J = 7.1 Hz, 2H), 2.64 (s, 3H), 1.37 (t, J = 7.1 Hz, 3H); 13C NMR (101
MHz, CDCl3, ppm): δ = 163.8, 159.1, 150.2, 134.8, 131.7, 130.0, 127.5, 123.6, 121.7,
115.6, 106.7, 60.3, 14.4, 13.9; IR (KBr, cmꢀ1): ν = 1715, 1608, 1556, 1424, 1236,
1098, 1047; HRMS (ESI) calc. C14H13ClNaO3 [M+Na]+: 287.0445, found: 287.0444.
Ethyl 5-(3,4-Dimethylphenyl)-2-methylfuran-3-carboxylate (3qa): Yield: 54 mg
(70%), yellow solid, M.p.: 102ꢀ105 ºC. 1H NMR (400 MHz, CDCl3, ppm): δ = 7.41 (s,
1H), 7.36 (d, J = 7.5 Hz, 1H), 7.13 (d, J = 7.5 Hz, 1H), 6.81 (s, 1H), 4.31 (q, J = 6.1
Hz, 2H), 2.63 (s, 3H), 2.27 (d, J = 9.0 Hz, 6H), 1.36 (t, J = 6.5 Hz, 3H); 13C NMR
(101 MHz, CDCl3, ppm): δ = 164.2, 158.2, 152.1, 136.9, 136.2, 130.0, 127.8, 124.9,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 20 of 31
1
2
3
4
5
6
7
8
9
121.2, 115.3, 104.6, 60.1, 19.8, 19.6, 14.4, 13.9; IR (KBr, cmꢀ1): ν = 1699, 1599, 1427,
1224, 1094, 1020; HRMS (ESI) calc. C16H18NaO3 [M+Na]+: 281.1148, found:
281.1149.
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
Ethyl 5-(2,5-Difluorophenyl)-2-methylfuran-3-carboxylate (3ra): Yield: 72 mg
1
(90%), yellow solid, M.p.: 78ꢀ79 ºC. H NMR (400 MHz, CDCl3, ppm): δ = 7.43 (s,
1H), 7.12–7.00 (m, 2H), 6.89 (s, 1H), 4.32 (q, J = 7.0 Hz, 2H), 2.65 (s, 3H), 1.37 (t, J
= 7.0 Hz, 3H); 13C NMR (101 MHz, CDCl3, ppm): δ = 163.7, 159.0, 158.8 (dd, J =
241.8, 2.1 Hz), 154.4 (dd, J = 247.0, 2.1 Hz), 144.8, 119.5 (dd, J = 14.7, 8.7 Hz),
117.0 (dd, J = 24.3, 8.9 Hz), 115.9 (d, J = 1.2 Hz), 114.7 (dd, J = 24.4, 8.7 Hz), 111.9
(dd, J = 26.5, 3.6 Hz), 111.6 (d, J = 12.5 Hz), 60.3, 14.3, 13.8; IR (KBr, cmꢀ1): ν =
1713, 1614, 1496, 1232, 1103, 1041; HRMS (ESI) calc. C14H12F2NaO3 [M+Na]+:
289.0647, found: 289.0647.
Ethyl 5-Methyl-[2,2'-bifuran]-4-carboxylate (3sa): Yield: 28 mg (43%), yellow oil.
1H NMR (400 MHz, CDCl3, ppm): δ = 7.44 (s, 1H), 6.79 (s, 1H), 6.56 (s, 1H), 6.47 (d,
J = 1.3 Hz, 1H), 4.33 (q, J = 7.1 Hz, 2H), 2.65 (s, 3H), 1.39 (t, J = 7.1 Hz, 3H); 13C
NMR (101 MHz, CDCl3, ppm): δ = 163.8, 158.4, 145.7, 144.3, 142.1, 115.1, 111.3,
105.5, 60.3, 14.3, 13.8; IR (KBr, cmꢀ1): ν = 1719, 1598, 1463, 1251, 1095; HRMS
(ESI) calc. C12H12NaO4 [M+Na]+: 243.0628, found: 243.0623.
ACS Paragon Plus Environment

Page 21 of 31
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Ethyl 2-Methyl-5-(naphthalen-2-yl)furan-3-carboxylate (3ta)22: Yield: 51 mg
(61%), white solid, M.p.: 76ꢀ79 ºC. 1H NMR (400 MHz, CDCl3, ppm): δ = 8.08 (s,
1H), 7.81 (dd, J = 17.7, 8.2 Hz, 3H), 7.69 (d, J = 8.4 Hz, 1H), 7.41ꢀ7.47 (m, 2H), 6.98
(s, 1H), 4.32 (q, J = 6.5 Hz, 2H), 2.67 (s, 3H), 1.37 (t, J = 6.8 Hz, 3H); 13C NMR (101
MHz, CDCl3, ppm): δ = 164.1, 158.9, 151.8, 133.5, 132.8, 128.5, 128.2, 127.8, 127.4,
126.6, 126.1, 122.1, 122.0, 115.6, 106.1, 60.3, 14.4, 14.0; IR (KBr, cmꢀ1): ν = 1713,
1606, 1422, 1232, 1094, 1045; HRMS (ESI) calc. C18H16NaO3 [M+Na]+: 303.0992,
found: 303.0985.
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
Ethyl 5-(Benzo[d][1,3]dioxol-5-yl)-2-methylfuran-3-carboxylate (3ua): Yield: 51
mg (62%), white solid, M.p.: 122ꢀ124 ºC. 1H NMR (400 MHz, CDCl3): δ = 7.14 (d, J
= 7.6 Hz, 1H), 7.09 (s, 1H), 6.82 (d, J = 7.8 Hz, 1H), 6.72 (s, 1H), 5.97 (s, 2H), 4.30
(q, J = 6.3 Hz, 2H), 2.62 (s, 3H), 1.36 (t, J = 6.5 Hz, 3H); 13C NMR (101 MHz,
CDCl3): δ = 164.10, 158.08, 151.53, 148.04, 147.24, 124.52, 117.59, 115.32, 108.61,
104.46, 104.31, 101.20, 60.18, 14.38, 13.86; IR (KBr, cmꢀ1): ν = 1712, 495, 1450,
1270, 1232, 1094, 932; HRMS (ESI) calc. C15H14NaO5 [M+Na]+: 297.0733, found:
297.0731.
Methyl 5-(4-Fluorophenyl)-2-methylfuran-3-carboxylate (3ab)23: Yield: 59 mg
(83%), brown solid, M.p.: 92ꢀ95 ºC. 1H NMR (400 MHz, CDCl3, ppm): δ = 7.59 (t, J
= 6.2 Hz, 2H), 7.07 (t, J = 8.3 Hz, 2H), 6.80 (s, 1H), 3.84 (s, 3H), 2.63 (s, 3H); 13C
NMR (101 MHz, CDCl3, ppm): δ = 164.4, 162.3 (d, J = 247.5 Hz), 158.7, 151.0,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 22 of 31
1
2
3
4
5
6
7
8
9
126.4 (d, J = 3.3 Hz), 125.4 (d, J = 8.1 Hz), 115.8 (d, J = 22.0 Hz), 115.2, 105.1, 51.4,
13.8; IR (KBr, cmꢀ1): ν = 1702, 1594, 1498, 1443, 1230, 1096, 1039; HRMS (ESI)
calc. C13H11FNaO3 [M+Na]+: 257.0584, found: 257.0584.
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
Butyl 5-(4-Fluorophenyl)-2-methylfuran-3-carboxylate (3ac): Yield: 72 mg (87%),
yellow solid, M.p.: 49ꢀ51 ºC. 1H NMR (400 MHz, CDCl3): δ = 7.59 (t, J = 6.6 Hz,
2H), 7.06 (t, J = 8.4 Hz, 2H), 6.80 (s, 1H), 4.26 (t, J = 6.4 Hz, 2H), 2.63 (s, 3H), 1.72
(m, J = 7.0 Hz, 2H), 1.47 (m, J = 3.0 Hz, 2H), 0.98 (t, J = 7.0 Hz, 3H); 13C NMR (101
MHz, CDCl3): δ = 164.1, 162.3 (d, J = 247.4 Hz), 158.5, 150.9, 126.5 (d, J = 3.3 Hz),
125.4 (d, J = 8.1 Hz), 115.7 (d, J = 22.0 Hz), 115.5, 105.2 (d, J = 1.3 Hz), 64.1, 30.8,
19.3, 13.9, 13.7; IR (KBr, cmꢀ1): ν = 1710, 1565, 1440, 1245, 1161, 1108, 1042;
HRMS (ESI) calc. C16H17FNaO3 [M+Na]+: 299.1054, found: 299.1059.
tert-Butyl 5-(4-Fluorophenyl)-2-methylfuran-3-carboxylate (3ad): Yield: 72 mg
1
(86%), brown oil. H NMR (400 MHz, CDCl3, ppm): δ = 7.52 (t, J = 5.4 Hz, 2H),
6.99 (t, J = 7.7 Hz, 2H), 6.68 (s, 1H), 2.53 (s, 3H), 1.50 (s, 9H); 13C NMR (101 MHz,
CDCl3, ppm): δ = 163.4, 162.2 (d, J = 247.3 Hz), 157.9, 150.6, 126.6 (d, J = 2.8 Hz),
125.4 (d, J = 8.1 Hz), 116.9, 115.7 (d, J = 21.9 Hz), 105.5, 80.7, 28.3, 13.9; IR (KBr,
cmꢀ1): ν = 1709, 1599, 1499, 1401, 1235, 1166, 1096, 1034; HRMS (ESI) calc.
C16H17FNaO3 [M+Na]+: 299.1054, found: 299.1057.
ACS Paragon Plus Environment

Page 23 of 31
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Allyl 5-(4-Fluorophenyl)-2-methylfuran-3-carboxylate (3ae): Yield: 66 mg (85%),
yellow oil. 1H NMR (400 MHz, CDCl3, ppm): δ = 7.60 (t, J = 5.8 Hz, 2H), 7.07 (t, J =
8.0 Hz, 2H), 6.83 (s, 1H), 6.02 (dq, J = 10.0, 5.3 Hz, 1H), 5.39 (d, J = 17.1 Hz, 1H),
5.28 (d, J = 10.4 Hz, 1H), 4.77 (d, J = 4.8 Hz, 2H), 2.65 (s, 3H); 13C NMR (101 MHz,
CDCl3, ppm): δ = 163.6, 162.3 (d, J = 247.7 Hz), 158.9, 151.0, 132.4, 126.4 (d, J =
3.4 Hz), 125.5 (d, J = 8.1 Hz), 118.1, 115.8 (d, J = 22.0 Hz), 115.2, 105.1, 64.9, 13.9;
IR (KBr, cmꢀ1): ν = 1716, 1599, 1499, 1404, 1229, 1091, 1038; HRMS (ESI) calc.
C15H13FNaO3 [M+Na]+: 283.0741, found: 283.0739.
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
Ethyl 5-(4-Fluorophenyl)-2-phenylfuran-3-carboxylate (3af): Yield: 83 mg (90%),
1
white solid, M.p.: 93ꢀ95 ºC. H NMR (400 MHz, CDCl3, ppm): δ = 8.06 (d, J = 7.0
Hz, 2H), 7.70 (s, 2H), 7.45 (t, J = 9.8 Hz, 3H), 7.11 (t, J = 7.7 Hz, 2H), 7.03 (s, 1H),
4.34 (q, J = 6.3 Hz, 2H), 1.37 (t, J = 6.3 Hz, 3H); 13C NMR (101 MHz, CDCl3): δ =
163.5, 162.6 (d, J = 248.0 Hz), 156.5, 151.5, 129.7, 129.4, 128.4, 128.2, 126.2 (d, J =
2.9 Hz), 125.8 (d, J = 8.2 Hz), 115.9 (d, J = 22.0 Hz), 115.8, 107.6, 60.7, 14.3; IR
(KBr, cmꢀ1): ν = 1717, 1593, 1495, 1227, 1094; HRMS (ESI) calc. C19H15FNaO3
[M+Na]+: 333.0897, found: 333.0893.
Ethyl 2-Ethyl-5-(4-fluorophenyl)furan-3-carboxylate (3ag): Yield: 70 mg (89%),
1
yellow oil. H NMR (400 MHz, CDCl3, ppm): δ = 7.60 (s, 2H), 7.06 (t, J = 8.0 Hz,
2H), 6.81 (s, 1H), 4.31 (q, J = 6.4 Hz, 2H), 3.06 (q, J = 6.6 Hz, 2H), 1.36 (t, J = 6.6
Hz, 3H), 1.31 (t, J = 7.4 Hz, 3H); 13C NMR (101 MHz, CDCl3): δ = 163.9, 163.4,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 24 of 31
1
2
3
4
5
6
7
8
9
162.3 (d, J = 247.3 Hz), 150.8, 126.5 (d, J = 3.1 Hz), 125.4 (d, J = 8.1 Hz), 115.7 (d, J
= 22.0 Hz), 114.6, 105.2, 60.2, 21.3, 14.3, 12.3; IR (KBr, cmꢀ1): ν = 1715, 1598, 1500,
1231, 1101, 1050; HRMS (ESI) calc. C15H15FNaO3 [M+Na]+: 285.0897, found:
285.0899.
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
Ethyl 5-(4-Fluorophenyl)-2-isopropylfuran-3-carboxylate (3ah): Yield: 72 mg
1
(85%), yellow oil. H NMR (400 MHz, CDCl3, ppm): δ = 7.61 (t, J = 6.0 Hz, 2H),
7.08 (t, J = 8.0 Hz, 2H), 6.81 (s, 1H), 4.31 (q, J = 6.6 Hz, 2H), 3.80 (m, J = 6.6 Hz,
1H), 1.33ꢀ1.38 (m, 9H) ; 13C NMR (101 MHz, CDCl3, ppm): δ = 166.6, 163.9, 162.3
(d, J = 247.0 Hz), 150.5, 126.6 (d, J = 3.4 Hz), 125.4 (d, J = 8.1 Hz), 115.7 (d, J =
22.0 Hz), 113.6, 105.2, 60.2, 27.4, 20.8, 14.4; IR (KBr, cmꢀ1): ν = 1715, 1596, 1500,
1382, 1229, 1060; HRMS (ESI) calc. C16H17FNaO3 [M+Na]+: 299.1054, found:
299.1051.
Ethyl 2-Cyclopropyl-5-(4-fluorophenyl)furan-3-carboxylate (3ai): Yield: 68 mg
(84%), pale yellow oil. 1H NMR (400 MHz, CDCl3, ppm): δ = 7.50 (t, J = 5.8 Hz, 2H),
7.04 (t, J = 7.8 Hz, 2H), 6.78 (s, 1H), 4.32 (q, J = 6.5 Hz, 2H), 2.82 (m, J = 6.6
Hz,1H), 1.37 (t, J = 6.5 Hz, 3H), 1.07ꢀ1.13 (m, 4H); 13C NMR (101 MHz, CDCl3,
ppm): δ = 164.2, 162.6, 162.2 (d, J = 247.3 Hz), 149.5, 126.4 (d, J = 3.3 Hz), 125.2 (d,
J = 8.0 Hz), 115.7 (d, J = 22.0 Hz), 115.0, 105.5, 60.2, 14.4, 9.3, 8.9; IR (KBr, cmꢀ1):
ν = 1713, 1596, 1501, 1426, 1229, 1065; HRMS (ESI) calc. C16H15FNaO3 [M+Na]+:
297.0897, found: 297.0896.
ACS Paragon Plus Environment

Page 25 of 31
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Ethyl 5-(4-Fluorophenyl)-2-propylfuran-3-carboxylate (3aj): Yield: 71 mg (86%),
yellow oil. 1H NMR (400 MHz, CDCl3): δ = 7.60 (dd, J = 8.2, 5.5 Hz, 2H), 7.07 (t, J
= 8.5 Hz, 2H), 6.82 (s, 1H), 4.31 (q, J = 7.1 Hz, 2H), 3.02 (t, J = 7.5 Hz, 2H), 1.77 (m,
J = 7.2 Hz, 2H), 1.37 (t, J = 7.1 Hz, 3H), 1.00 (t, J = 7.4 Hz, 3H); 13C NMR (101 MHz,
CDCl3): δ = 163.9, 162.5, 162.3 (d, J = 247.5 Hz), 150.8, 126.6 (d, J = 3.2 Hz), 125.5
(d, J = 8.1 Hz), 115.8 (d, J = 22.0 Hz), 115.2, 105.2, 60.2, 29.6, 21.6, 14.4, 13.8; IR
(KBr, cmꢀ1): ν = 1716, 1598, 1501, 1428, 1229, 1106, 1054; HRMS (ESI) calc.
C16H17FNaO3 [M+Na]+: 299.1054, found: 299.1060.
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
Ethyl 2-(tert-Butyl)-5-(4-fluorophenyl)furan-3-carboxylate (3ak): Yield: 64 mg
1
(74%), yellow oil. H NMR (400 MHz, CDCl3, ppm): δ = 7.60 (t, J = 6.6 Hz, 2H),
7.07 (t, J = 8.0 Hz, 2H), 6.87 (s, 1H), 4.31 (q, J = 6.5 Hz, 2H), 1.49 (s, 9H), 1.38 (t, J
= 6.5 Hz, 3H); 13C NMR (101 MHz, CDCl3, ppm): δ = 167.6, 163.6, 162.2 (d, J =
247.5 Hz), 148.8, 126.6 (d, J = 3.5 Hz), 125.4 (d, J = 8.1 Hz), 115.8 (d, J = 22.0 Hz),
114.2, 107.2, 60.3, 34.8, 28.2, 14.3; IR (KBr, cmꢀ1): ν = 1722, 1594, 1498, 1377, 1239,
1158, 1067; HRMS (ESI) calc. C17H19FNaO3 [M+Na]+: 313.1210, found: 313.1210.
Ethyl 5-(4-Fluorophenyl)-2-(thiophen-2-yl)furan-3-carboxylate (3al): Yield: 82
1
mg (86%), white solid. M.p.: 83ꢀ85 ºC. H NMR (400 MHz, CDCl3): δ = 8.10 (d, J =
3.7 Hz, 1H), 7.65 (dd, J = 8.3, 5.5 Hz, 2H), 7.43 (d, J = 5.0 Hz, 1H), 7.06ꢀ7.13 (m,
3H), 6.94 (s, 1H), 4.36 (q, J = 7.1 Hz, 2H), 1.40 (t, J = 7.1 Hz, 3H); 13C NMR (101
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 26 of 31
1
2
3
4
5
6
7
8
9
MHz, CDCl3): δ = 163.2, 162.6 (d, J = 248.4 Hz), 152.0, 150.8, 131.6, 128.8, 128.0,
127.5, 125.9 (d, J = 3.4 Hz), 125.8 (d, J = 8.2 Hz), 115.9 (d, J = 22.1 Hz), 114.2,
107.2, 60.7, 14.4; IR (KBr, cmꢀ1): ν = 1712, 1538, 1562, 1497, 1383, 1242, 1096;
HRMS (ESI) calc. C17H13FNaO3S [M+Na]+: 339.0462, found: 339.0465.
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
Acknowledgements
The authors thank the National Natural Science Foundation of China (21420102003,
21472051), the Fundamental Research Funds for the Central Universities
(2015ZY001), the China Postdoctoral Science Foundation Funded Project
(2015M580717), and the Guangdong Natural Science Foundation (2016A030310460)
for financial support.
Supporting Information
Spectral data for all new compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
Reference
(1)
For selected reviews, see: (a) Barluenga, J.; Valdés, C. Angew. Chem. Int. Ed.
2011, 50, 7486. (b) Shao, Z.ꢀH.; Zhang, H.ꢀB. Chem. Soc. Rev. 2012, 41, 560ꢀ572. (c)
Fulton, J. R.; Aggarwal, V. K.; de Vicente, J. Eur. J. Org. Chem. 2005, 1479ꢀ1492.
(2)
(a) Jiang, H.; Fu, W.; Chen, H. Chem. Eur. J. 2012, 18, 11884ꢀ11888. (b)
Barluenga, J.; Quiñones, N.; TomásꢀGamasa, M.; Cabal, M. P. Eur. J. Org. Chem.
2012, 2312ꢀ2317. (c) Chen, S.ꢀF.; Ma, J.; Wang, J.ꢀB. Tetrahedron Lett. 2008, 49,
ACS Paragon Plus Environment

Page 27 of 31
The Journal of Organic Chemistry
1
2
3
4
5
6
6781ꢀ6783. (d) Barroso, R.; Cabal, M. P.; BadíaꢀLaiño, R.; Valdés, C. Chem. Eur. J.
2015, 21, 16463ꢀ16473.
7
8
9
(3)
(a) PérezꢀAguilar, M. C.; Valdés, C. Angew. Chem. Int. Ed. 2013, 52,
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
7219ꢀ7223. (b) PérezꢀAguilar, M. C.; Valdés, C. Angew. Chem. Int. Ed. 2015, 54,
13729ꢀ13733. (c) Tan, W.; Yoshikai, N. Chem. Sci., 2015, 6, 6448ꢀ6455.
(4)
(a) Chen, Z.; Yan, Q.; Liu, Z.; Xu, Y.; Zhang, Y. Angew. Chem. Int. Ed. 2013,
52, 13324ꢀ13328. (b) Cai, Z.ꢀJ.; Lu, X.ꢀM.; Zi, Y.; Yang, C.; Shen, L.ꢀJ.; Li, J.; Wang,
S.ꢀY.; Ji, S.ꢀJ. Org. Lett. 2014, 16, 5108ꢀ5111. (c) Senadi, G. C.; Hu, W.ꢀP.; Lu, T.ꢀY.;
Garkhedkar, A. M.; Vandavasi, J. K.; Wang, J.ꢀJ. Org. Lett. 2015, 17, 1521ꢀ1524. (d)
Bai, H.ꢀW.; Cai, Z.ꢀJ.; Wang, S.ꢀY.; Ji, S.ꢀJ.; Org. Lett. 2015, 17, 2898ꢀ2901. (e) van
Berkel, S. S.; Brauch, S.; Gabriel, L.; Henze, M.; Stark, S.; Vasilev, D.; Wessjohann, L.
A.; Abbas, M.; Westermann, B. Angew. Chem., Int. Ed. 2012, 51, 5343ꢀ5346. (f) Bai,
H.ꢀW.; Cai, Z.ꢀJ.; Wang, S.ꢀY.; Ji, S.ꢀJ. Org. Lett. 2015, 17, 2898ꢀ2901. (g) Wan, J.ꢀP.;
H, D.ꢀQ.; Liu, Y.ꢀY.; Sheng, S.ꢀY. ChemCatChem 2015, 7, 901ꢀ903. (h) Zhu, T.ꢀH.;
Wei, T.ꢀQ.; Wang, S.ꢀY.; Ji, S.ꢀJ. Org. Chem. Front., 2015, 2, 259ꢀ264. (i) Chen, J.ꢀF.;
Jiang, Y.; Yu, J.ꢀT.; Cheng, J. J. Org. Chem. 2016, 81, 271ꢀ275.
(5)
(a) Lipshutz, B. H. Chem. Rev. 1986, 86, 795ꢀ819. (b) Marshall, J. A.; DuBay,
W. J. J. Org. Chem. 1994, 59, 1703ꢀ1708. (c) Marshall, J. A.; McNulty, L. M.; Zou, D.
J. Org. Chem. 1999, 64, 5193ꢀ5200.
(6)
(a) Brown, R. C. D. Angew. Chem. Int. Ed. 2005, 44, 850ꢀ852. (b) Kirsch, S. F.
Org. Biomol. Chem. 2006, 4, 2076ꢀ2080. (c) Cacchi, S. J. Organomet. Chem. 1999,
576, 42ꢀ64. (d) Giza, C. A.; Hinman, R. L. J. Org. Chem. 1964, 29, 1453ꢀ1461.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 28 of 31
1
2
3
4
(7)
(a) Gu, Z.; Wang, X.; Shu, W.; Ma, S. J. Am. Chem. Soc. 2007, 129,
5
6
7
8
9
10948ꢀ10956. (b) Zheng, M.; Huang, L.; Wu, W.; Jiang, H. Org. Lett. 2013, 15,
1838ꢀ1841.(c) Chen, Z.; Huang, G.; Jiang, H.; Huang, H.; Pan, X. J. Org. Chem. 2011,
76, 1134ꢀ1139. (d) Ma, S.; Gu, Z. J. Am. Chem. Soc. 2005, 127, 6182ꢀ6183. (e) Murai,
M.; Miki, K.; Ohe, K. Chem. Commun. 2009, 3466ꢀ3468.
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
(8)
(a) Yu, H.; Zhong, W.; He, T.; Gu, W.; Yin, B. Tetrahedron Lett. 2013, 54,
1256ꢀ1260. (b) Cao, H.; Zhan, H.; Cen, J.; Lin, J.; Lin, Y.; Zhu, Q.; Fu, M.; Jiang, H.
Org. Lett. 2013, 15, 1080ꢀ1083. (c) Cao, H.; Jiang, H.ꢀF.; Zhou, X.ꢀS.; Qi, C.ꢀR.; Lin,
Y.ꢀG.; Wu, J.ꢀY.; Liang, Q.ꢀM. Green Chem. 2012, 14, 2710ꢀ2714. (d) Liu, W.; Jiang,
H.; Zhang, M.; Qi, C. J. Org. Chem. 2010, 75, 966ꢀ968. (e) Pan, Y.ꢀM.; Zhao, S.ꢀY.; Ji,
W.ꢀH.; Zhan, Z.ꢀP. J. Comb. Chem. 2009, 11, 103ꢀ109. (f) Hossain, M. L.; Ye, F.;
Zhang, Y.; Wang, J.ꢀB. Tetrahedron 2014, 70, 6957ꢀ6962. (g) Schmidt, D.; Malakar, C.
C.; Beifuss, U. Org. Lett. 2014, 16, 4862ꢀ4865.
(9)
143ꢀ152. (b) Liu, W.ꢀB.; Chen, C.; Zhang, Q. Synth. Commun. 2013, 43, 951ꢀ960.
(10) For some recent Auꢀcatalyzed methods to furans, see: (a) Ma, J.; Jiang, H.;
(a) Cao, H.; Jiang, H.; Mai, R.; Zhu, S.; Qi, C. Adv. Synth. Catal. 2010, 352,
Zhu, S. Org. Lett. 2014, 16, 4472ꢀ4475. (b) Li, J.; Liu, L.; Ding, D.; Sun, J.; Ji, Y.;
Dong, J. Org. Lett. 2013, 15, 2884ꢀ2887. (c) Hoffmann, M.; Miaskiewicz, S.; Weibel,
J. M.; Pale, P.; Blanc, A. Beilstein J. Org. Chem. 2013, 9, 1774ꢀ1780. (d) Hashmi, A.
S. K.; Yang, W.; Rominger, F. Angew. Chem. Int. Ed. 2011, 50, 5762ꢀ5765. (e) Huang,
X.; Peng, B.; Luparia, M. A.; Gomes, L. F. R.; Veiros, L. F.; Maulide, N. Angew.
Chem. Int. Ed. 2012, 51, 8886ꢀ8890.
ACS Paragon Plus Environment

Page 29 of 31
The Journal of Organic Chemistry
1
2
3
4
(11)
(a) Xia, L. K.; Lee, Y. R. Eur. J. Org. Chem. 2014, 3430ꢀ3442. (b) Pridmore, S.
5
6
7
8
9
J.; Slatford, P. A.; Taylor, J. E.; Whittlesey, M. K.; Williams, J. M. J. Tetrahedron.
2009, 65, 8981ꢀ8986. (c) Donohoe, T. J.; Fishlock, L. P.; Lacy, A. R.; Procopiou, P. A.
Org. Lett. 2007, 9, 953ꢀ956. (d) Nishibayashi, Y.; Yoshikawa, M.; Inada, Y.; Milton,
M. D.; Hidai, M.; Uemura, S. Angew. Chem. Int. Ed. 2003, 42, 2681ꢀ2684.
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
(12)
(a) He, C.; Guo, S.; Ke, J.; Hao, J.; Xu, H.; Chen, H.; Lei, A. J. Am. Chem.
Soc. 2012, 134, 5766ꢀ5769. (b) Ma, Y.; Zhang, S.; Yang, S.; Song, F.; You, J. Angew.
Chem. Int. Ed. 2014, 53, 7870ꢀ7874. (c) Arcadi, A.; Cerichelli, G.; Chiarini, M.;
Giuseppe, S. D.; Marinelli, F. Tetrahedron Lett. 2000, 41, 9195ꢀ9198.
(13)
Li, X.; Liu, X.; Chen, H.; Wu, W.; Qi, C.; Jiang, H. Angew. Chem. Int . Ed.
2014, 53, 14485ꢀ14489.
(14)
(a) Xiao, Q.; Zhang, Y.; Wang, J. Acc. Chem. Res. 2013, 46, 236ꢀ247. (b) Xia,
Y.; Zhang, Y.; Wang, J. ACS. Catal. 2013, 3, 2586ꢀ2598.
(15)
(a) Mao, S.; Gao, Y.ꢀR.; Zhu, X.ꢀQ.; Guo, D.ꢀD.; Wang, Y.ꢀQ. Org. Lett. 2015,
17, 1692ꢀ1695. (b) Gagnon, N.; Tolman, W. B. Acc. Chem. Res. 2015, 48, 2126ꢀ2131.
(c) Donoghue, P. J.; Tehranchi, J.; Cramer, C. J.; Sarangi, R.; Solomon, E. I.; Tolman,
W. B. J. Am. Chem. Soc. 2011, 133, 17602ꢀ17605. (d) Reinaud, O.; Patrice C.; Maumy,
M. J. Chem. Soc., Chem. Commun. 1990, 566ꢀ568.
(16)
Liu, P.; Liu, J.ꢀL.; Wang, H.ꢀS.; Pan, Y.ꢀM.; Liang, H.; Chen, Z.ꢀF. Chem.
Commun. 2014, 50, 4795ꢀ4798.
(17) Huang, Z.ꢀL.; Jin, L.ꢀQ.; Feng, Y.; Peng, P.; Yi, H.; Lei, A.ꢀW. Angew. Chem. Int.
Ed. 2013, 52, 7151ꢀ7155.
ACS Paragon Plus Environment