Cobalt-Catalyzed Cross-Dehydrogenative Coupling Reactions of (Benz)oxazoles with Ethers

Article abstract of DOI:10.1021/acs.joc.6b02211

The cobalt-catalyzed cross-dehydrogenative coupling of (benz)oxazoles and ethers is described. Access to some important bioactive heteroaryl ether derivatives was achieved using CoCO₃ as an inexpensive catalyst at levels as low as 1.0 mol %. In

Full text of DOI:10.1021/acs.joc.6b02211

Subscriber access provided by CORNELL UNIVERSITY LIBRARY
Article
Cobalt-Catalyzed Cross-Dehydrogenative
Coupling Reactions of (Benz)Oxazoles with Ethers
Yanrong Li, Mengshi Wang, Wei Fan, Fen Qian, Guigen Li, and Hongjian Lu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b02211 • Publication Date (Web): 27 Oct 2016
Downloaded from http://pubs.acs.org on October 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 22
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Cobalt-Catalyzed Cross-Dehydrogenative Coupling
Reactions of (Benz)Oxazoles with Ethers
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
†
†
†
†
†,‡,
Yanrong Li , Mengshi Wang , Wei Fan , Fen Qian , Guigen Li * and
†,
Hongjian Lu *
†
Institute of Chemistry and BioMedical Sciences, School of Chemistry and Chemical
Engineering, Nanjing University, Nanjing, 210093, China
‡
Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas
7
9409ꢀ1061, USA
ABSTRACT: The cobaltꢀcatalyzed crossꢀdehydrogenative coupling (CDC) of
benz)oxazoles and ethers is described. Access to some important bioactive heteroaryl
ether derivatives was achieved using CoCO as an inexpensive catalyst at levels as
(
3
low as 1.0 mole percent. Investigation of the mechanism indicates a catalytic cycle
involving a radical process.
Introduction
Direct transition metalꢀcatalyzed C−H functionalization has emerged in synthetic
1
organic and medicinal chemistry as an expedient means of introducing and expanding
molecular complexity. Cobalt as a catalyst has recently attracted much attention in the
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 22
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
development of applicable transformations due to its economy, low toxicity, and
2
ꢀ4
unique reaction modes. Crossꢀdehydrogenative coupling reactions are more
efficient and direct because they can avoid the introduction of oriented and activated
functional groups, shortening synthetic routes and making them more atom
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
5
economical. Cobaltꢀcatalyzed CDC reactions represent an interesting but challenging
6
,7
research area of C−H functionalization chemistry. Although C−C bonds are the
most common fundamental units in organic molecules, their formation by
3
e,7
cobaltꢀcatalyzed CDC reactions has not been explored fully. In 2006, Li et al. first
reported a CDC reaction of 1,3ꢀdicarbonyl compounds with allyl compounds
7a
catalyzed by cobalt/copper coꢀcatalysts. In 2015, Wu et al. reported CDC reactions
of tetrahydroisoquinolines and indoles using
a
cobalt complex as the
7b
photosensitizer. Recently, You et al. reported a CDC reaction between two
7c
heteroarenes catalyzed by Co(OAc)
2
,
and the Du group demonstrated
CoCl ꢀcatalyzed crossꢀcoupling reaction of coumarins and ethers under basic
2
7d
conditions. The catalyst loadings of these catalytic reactions utilized were relatively
high, in the range of 5ꢀ20 mol%. Development of different CDC reactions with cobalt
catalysts, especially those used with low loading could be of prime synthetic value.
2
ꢀSubtituted (benz)oxazoles are present in many medicinally active compounds
8
with a diverse array of biological activities. Earlier methods for the direct synthesis
of 2ꢀalkyloxazoles rely primarily on the direct Cꢀ2 alkylation of oxazoles, catalyzed
9
ꢀ12
9
10
by transition metals (Scheme 1A).
These reactions use alkyl halides, olefins,
11
12
carboxylic acids, and Nꢀtosylhydrazones as the alkylating reagents, and are mostly
performed under basic conditions. The successful direct catalytic C2ꢀalkylation of
(benz)oxazoles through CDC reactions has not been reported. Ethers are common
structural motifs in natural products and their construction in complex organic
13
molecules can be demanding, often requiring complicated synthetic routes.
14,15
Following our recent work on cobaltꢀcatalyzed C−H bond functionalization,
we
report in this paper the first example of a catalytic CDC reaction between oxazoles
and ethers (Scheme 1B), forming various oxazoles containing ether motifs, which
ACS Paragon Plus Environment

Page 3 of 22
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
16
may have special application in medicines. The reaction uses CoCO
3
as an
inexpensive catalyst with loadings as low as 0.3~1 mole percent.
Scheme 1. Metalꢀcatalyzed C−H Alkylation of (Benz)Oxazoles
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, we examined the CDC reactions of 5ꢀphenyloxazole (1a) and 1,4ꢀdioxane
2a) with oxidizing agents, such as Diꢀtertꢀbutyl peroxide (DTBP), tertꢀButyl
(
hydroperoxide (TBHP), K
2
S
2
O
8
or Dicumyl peroxide (DCP), in which TBHP
17
afforded the highest yield in the absence of any metal catalyst (Table 1, entries 1ꢀ4).
Subsequently, nine different types of simple cobalt salts were examined (entries 5ꢀ13)
and we found that the reaction could be improved by addition of different cobalt
compounds, including Co(acac)
CoBr and Co(OAc) ·4H O. Among the cobalt catalysts, CoCO
product (3a) in 68% yield, and was identified as the most effective catalyst. When the
CoCO catalyst loading was reduced from 20 to 1 mol%, the yield remained at 70%
entries 9, 14ꢀ16), distinguishing this reaction from the majority of cobaltꢀcatalyzed
2 2 3 3 2 4 2 2
, CoCl , CoCO , Co(acac) , CoF , Co(ClO ) ·6H O,
2
2
2
3
provided the desired
3
(
15e,18a
C−H activation reactions, which utilize relatively high catalyst loadings.
When
the CoCO loading was reduced to 0.3 mol%, the product was still formed in a
3
moderate yield (entry 18). Finally, we showed that the presence of K
2 3
CO blocked the
reaction (entries 19 and 20).
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 22
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Having optimized the reaction conditions, we investigated the scope of the
(
benz)oxazoles (1) in the direct alkylation with 1,4ꢀdioxane (2a) and obtained the
results shown in Table 2. The reaction of oxazoles with 1,4ꢀdioxane proceeds
smoothly to generate the anticipated product (3aꢀc) in moderate yields.
Electronꢀdonating groups (Me, tꢀBu and MeO) and electronꢀwithdrawing groups
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(
2 3
CO Me and CF ) on the phenyl ring are tolerated (3dꢀj), the latter giving generally a
higher yield. The benzoxazoles with halogen substituents in the phenyl ring (3kꢀo)
were also good coupling partners, and this could provide more options for further
potential transformations.
a
Table 1. Optimization of Reaction Conditions
entry
[Co] (mol %)
base
oxidant
DTBP
TBHP
3a(%)
15
1
2
3
4
5
6
7
8
9
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
19
<5
2 2 8
K S O
DCP
none
52
47
35
36
68
11
46
34
51
69
70
Co(acac)
CoCl (20)
Co(acac) (20)
CoF (20)
CoCO (20)
Co(NO ) ·6H O (20)
2
(20)
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
2
3
2
3
1
0
1
3 2
2
1
CoClO ·6H O (20)
4
2
12
CoBr
2
(20)
13
14
15
16
Co(OAc)
CoCO
CoCO
CoCO
2 2
·4H O (20)
3
(10)
(5)
3
b
3
(1)
70(69 )
17
CoCO
3
3
(0.5)
(0.3)
65
18
CoCO
57
ACS Paragon Plus Environment

Page 5 of 22
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
1
9
CoCO (1)
K CO3
TBHP
TBHP
8
3
2
20
ꢀ
K CO3
2
trace
a
Reaction conditions: 5ꢀphenyloxazole 1a (0.5 mmol), 1,4ꢀdioxane (5.0 mL), TBHP (4.0ꢀ5.0
equiv), [Co] (0.1~0.0015 mmol), TBHP (5.0ꢀ6.0 M in nꢀdecane, 0.42 mL, 2.0ꢀ2.4 mmol), sealed
o
1
tube, 120 C, air, 14 h. Yields are based on 1a, determined by crude HNMR using
b
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
1,3,5ꢀtrimethoxybenzene as the internal standard. Isolated yield.
a
Table 2. Scope of (Benz)oxazoles
CoCO3 (1 mol%)
TBHP (4.0 equiv)
120 o C, 14 h
O
N
O
O
N
O
R
H
+
H
R
O
O
1
2a
3
Cl
O
O
O
O
O
O
O
N
N
O
O
MeO C
N
O
2
3
3
a 69%
3b 67%
3c 64%
Me
O
O
O
O
O
N
O
O
Me
N
O
t-Bu
F3C
N
O
d 74%
3e 75%
3f 72%
O
N
O
O
O
O
O
O
N
O
N
Ph
MeO
Br
O
O
3g 83%
3j 91%
3h 65%
3i 87%
MeO2C
O
O
N
O
N
O
O
O
N
O
Br
3k 86%
3l 81%
O
N
O
Cl
Cl
O
O
F
O
O
Cl
O
N
O
Br
N
O
3m 83%
3n 71%
3o 57%
a
Reaction conditions: (benz)oxazole 1 (0.5 mmol), 1,4ꢀdioxane (5.0 mL), TBHP (4.0ꢀ5.0 equiv,
o
5.0ꢀ6.0 M in nꢀdecane, 0.42 mL, 2.0ꢀ2.4 mmol), Co
2
CO
3
(0.005 mmol), sealed tube, 120 C, air, 14
h, isolated yield.
Next, the scope of ethers (2) was examined. As shown in Table 3, cyclic aliphatic
ethers, such as 1,4ꢀdioxane, tetrahydrofuran and dioxolane produce the corresponding
crossꢀdehydrogenative coupling products in moderate to good yield (3pꢀt), and chain
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 22
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
aliphatic ethers are also good substrates in the coupling reaction (3uꢀx). With ethers
having two different reaction sites, the regioselectivity of the coupling reaction is
influenced by bond dissociation energy, steric and electric effects. For example, the
reaction of 1,3ꢀdioxolane shows a tendency to activate C−H bonds with weaker
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
a
Table 3. Scope of Ethers
OR1
R2
OR1
O
O
N
CoCO3 (1 mol %)
R
R
H
O
+
H
TBHP (4.0 equiv)
N
R2
o
1
20 C, 14 h
1
2
3
Ph
O
O
Ph
O
N
O
O
N
N
O
MeO C
2
3p 82%
3q 61%
3r 65%
Me
O
N
O
O
'
O
N
O
O
N
O
+
O
3t1
'
3t2
3s 85%
75% (3t1/ 3t2 = 2.6/1)
CꢀH)/ '(CꢀH) = 5.2/1
nPr
Me
O
'
'
O
N
O
+
O
MeOOC
O
N
O
'
n
nPr
Me
N
Pr
3
u1
3u2
6
9% (3u1/ 3u2 = 1.9/1)
CꢀH)/ '(CꢀH) = 1.9/1
3v 57%
CꢀH)/ '(CꢀH) > 20/1
CH OEt
CH OMe
2
2
'
'
O
N
O
O
O
O
N
O
+
'
CH OMe 3w1
3w2
N
Me
2
81% (3w1/ 3w2 = 1.9/1)
3x 78%
CꢀH)/ '(CꢀH) = 1.3/1
CꢀH)/ '(CꢀH) > 20/1
'
O
N
O
O
O
+
3y1
N
'
3y2
dr: 5.4/1
7
3% (3y1/ 3y2 = 2.1/1)
CꢀH)/ '(CꢀH) = 4.2/1
a
Reaction conditions: oxazole 1 (0.5 mmol), ether 2 (5.0 mL), TBHP (4.0ꢀ5.0 equiv, 5.0ꢀ6.0 M in
ACS Paragon Plus Environment

Page 7 of 22
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
o
nꢀdecane, 0.42 mL, 2.0ꢀ2.4 mmol), Co
2 3
CO (0.005 mmol), sealed tube, 120 C, air, 14 h, isolated
yield.
bond dissociation energy and so the yield of 3t1 is almost three times as high as that
of 3t2. When 1ꢀethoxybutane is used as the alkylating reagent, the less sterically
hindered C−H bond is activated preferentially and the products 3u1 and 3u2 are
produced in a ratio of 1.9:1. When both primary and secondary C−H bonds are
present, the secondary C−H bond is functionalized exclusively due to its weaker bond
dissociation energy, giving the product 3v. However, both primary and secondary
C−H bonds are activated when 1,2ꢀdimethoxyethane is used as the substrate (3w1 and
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
3
w2). This result indicates that the C−H bond with the higher electronꢀrich property is
preferred in the reaction. The contribution of an electronic effect is further evidenced
in the reactivity of 1,2ꢀdiethoxyethane. In this case, the regioselectivity is quite high
(>20/1) and just one product (3x) was isolated in good yield. When
2ꢀmethyltetrahydrofuran was used as the coupling component, the quaternary carbon
center product (3y1) is the main product. Unfortunately, no desired product was
detected when tetrahydropyran was used as a coupling component.
Scheme 2. Intermolecular Competition Experiment
Me
Me
O
N
O
O
N
H
O
1d
O
CoCO (1 mol%)
3
3d 8%
+
H
+
TBHP (4.0 equiv)
O
MeO C
o
2
O
120 C, 2 h
MeO C
2
O
N
O
H
N
O
1j
3j 20%
The intermolecular competition experiment between 1d and 1j was performed. In
this case, a simple electrophilicꢀtype C−H metalation could be ruled out, as the C−H
bond in the benzoxazole whose aromatic ring is substituted with an
1
8
electronꢀwithdrawing group is preferred in the reaction (Scheme 2).
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 22
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Figure 1. Monitoring the reactions with or without catalyst
1
7
In order to establish the role of the catalyst, reactions with or without catalyst
were monitored (Figure 1). The reaction with a cobalt catalyst is obviously faster than
3
that without the catalyst, showing that CoCO plays a critical role in the reaction.
Scheme 3. Mechanistic Studies
ACS Paragon Plus Environment

Page 9 of 22
The Journal of Organic Chemistry
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
To gain further insight into the mechanism of this catalytic CDC reaction, the
control experiments depicted in Scheme 3 were performed. The radical trapping
experiment outlined in Scheme 3A was conducted and it was found that the yield of
the product (3p) decreases when 2,2,6,6ꢀtetramethylpiperidine 1ꢀoxyl (TEMPO) is
added and 1ꢀ((1,4ꢀdioxanꢀ2ꢀyl)oxy)ꢀ2,2,6,6ꢀtetramethylpiperidine (4) is formed in
21% yield when a large amount of TEMPO (6 equiv) is added, suggesting that the
reaction may perform through a radical mechanism. We monitored the reactions of
TBHP with 1,4ꢀdioxane with or without Co
reagent (Scheme 3B), and found that in the presence of Co
trapping product (4) was formed. This suggests that Co CO plays an important role
2 3
CO using TEMPO as a radical trapping
2
3
CO , the alkyl radical
2
3
18
in the decomposition of tertꢀbutylhydroperoxide to generate an alkyl radical.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 22
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
14b
Coordination between cobalt and oxazole is not ruled out by this result. Primary
kinetic isotope effects were observed in parallel deuterium labeling experiments
(
Scheme 3C). Meanwhile, some intermolecular H/D exchange (91% D retained) was
observed when the reaction was performed with an isotopically labeled substrate
(Scheme 3D), and the H/D exchange in the absence of the Co catalyst is very little
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(
97% D retained), suggesting a metalꢀmediated C−H cleavage is involved in the
mechanism.
Scheme 4. Proposed Catalytic Cycle
t-BuOOH
Co(II)X
SET
Co(III)X2OH
A
OR1
3
H
2
1
R2
t-BuO
t-BuOH
H O
2
OR1
R2
B
X2
CoIV
O
X2
CoIII
O
N
N
OR1
R2
D
C
X2 = CO32-or t-BuO-
3c,14b,18
On the basis of these results and previous reports,
the Co(III/IV/II) catalytic
II
cycle in Scheme 4 is proposed. First, the Co catalyst is oxidized by TBHP giving the
III
Co species A, and alkoxy radical tꢀBuO· which abstracts hydrogen atoms from the
III
ether (2) producing the alkyl radical B. The Co species (A) reacts with the oxazole
III
(1) generating the Co intermediate C. This is followed by oxidative addition of the
IV
3e,19
radical (B) formed in situ, to give the Co species (D).
Finally, the catalytic cycle
ACS Paragon Plus Environment

Page 11 of 22
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
IV
is completed by reductive elimination of the Co species (D), leading to the desired
II
product (3) and regeneration of the Co catalyst.
In summary, an efficient cobalt catalysis for crossꢀdehydrogenative coupling (CDC)
reactions of (benz)oxazoles and ethers has been developed. This transformation is the
first example of direct C2ꢀalkylation of (benz)oxazoles through a catalytic CDC
strategy, and provides an efficient means of construction of bioactive heteroaryl ether
derivatives. In particular, the reaction could be performed efficiently with low loading
of an inexpensive cobalt catalyst.
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. All solvents and commercially available reagents were purchased from commercial
20aꢀc
sources and used directly. (Benz)oxazoles were prepared by known methods.
Thin layer
chromatography (TLC) was performed on EMD precoated plates (silica gel 60). Visualization of
TLC plates was achieved with UV light (254 nm). Column chromatography was performed on
1
silica gel (300ꢀ400 mesh) using a forced flow of 0.5ꢀ1.0 bar.Chemical shifts of H NMR are
reported in parts per million (ppm) referenced to the appropriate solvent peak or 0.0 ppm for
tetramethylsilane.High resolution mass spectra were obtained with the QꢀTOF.
General procedure for the synthesis of (benz)oxazoles. Azoles (1a, 1d, 1e, 1i, 1j) and ethers
were purchased from commercial sources and used directly. Azoles (1f, 1g, 1h, 1k, 1l, 1m, 1n
20a
and 1o) were prepared according to published procedures. The corresponding 2ꢀaminophenol
derivative (1.0 equiv) was dissolved in triethyl orthoformate (12.0 equiv) , then the reaction
mixture was carefully heated to 140 °C or 160 °C and stirred for 4ꢀ8 h. After cooling to room
temperature, the excess orthoformate and EtOH were removed under reduced pressure, the crude
product was then purified by silica gel chromatography to give the desired product. The azole (1b)
was prepared from methyl 2ꢀisocyanoacetate and benzoic anhydride in THF according to reported
20b
procedures.
Azole (1c) was prepared from pꢀtoluenesulfonylmethylisocyanide and
20c
20e
20b,e
4ꢀchlorobenzaldehyde in MeOH according to the reported procedure. Compounds 1a , 1b
,
20c, e
20e
20d,e
20d
20d
20d
20f
20f
20e
20e
20d
1
c
, 1d , 1e , 1f , 1g , 1h ,1i , 1j , 1k , 1l , 1m are known compounds.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 22
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1
5
,6-Dichlorobenzo[d]oxazole (1n). White solid, m.p.: 104ꢀ106 °C, 319 mg, 85%. H NMR (400
13
MHz, CDCl
3
) δ 8.16 (s, 1H), 7.69 (d, J = 1.8 Hz, 1H), 7.40 (d, J = 1.7 Hz, 1H). C NMR (101
MHz, CDCl
3
) δ 153.8, 145.6, 141.9, 130.6, 126.2, 119.3, 117.0. IR (neat) ν 3069, 2947, 2856,
ꢀ1
1610, 1589, 1453, 1394, 1296, 1246, 1065, 911, 861, 758, 624 cm . HRMS (ESI, m/z): calcd. for
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
+
C
7
H Cl
3 2
NONa (M+Na) : 209.9490, found: 209.9486. The residue was purified by silica gel
chromatography (10% ethyl acetate in hexane, v/v) to give the desired product.
1
5
-Bromo-6-fluorobenzo[d]oxazole (1o). Light yellow liquid, 350 mg, 81%. H NMR (400 MHz,
13
CDCl
MHz, CDCl
d, J = 4.6 Hz), 116.8 (d, J = 7.2 Hz), 116.2 (d, J = 19.5 Hz). IR (neat) ν 3015, 2969, 2878, 1653,
3
) δ 8.13 (s, 1H), 7.76 (d, J = 1.1 Hz, 1H), 7.34 (dd, J = 9.2, 1.5 Hz, 1H). C NMR (101
3
) δ 153.6, 146.8 (d, J = 257.9 Hz), 144.3 (d, J = 2.2 Hz), 136.7 (d, J = 11.2 Hz), 119.7
(
ꢀ1
1
7 3
576, 1437, 1365, 1228, 1091, 912, 747, 527 cm . HRMS (ESI, m/z): calcd. for C H BrFNONa
+
(M+Na) : 237.9298, found: 237.9291. The residue was purified by silica gel chromatography
(10% ethyl acetate in hexane, v/v) to give the desired product.
General procedure for the direct alkylation of (benz)oxazole with ethers. A 35 mL ovenꢀdried
pressure tube was charged with 5ꢀphenyloxazole (73 mg, 0.50 mmol), CoCO
mmol), tertꢀbutyl hydroperoxide (TBHP, 5.0~6.0 M in nꢀdecane, 0.4 mL, 2.0~2.4 mmol) and ether
5.0 mL). The tube was then sealed and stirred vigorously at 120 ˚C. After stirring the mixture at
3
(0.6 mg, 0.005
(
this temperature for 14 h, it was cooled to room temperature, diluted with EtOAc, filtered through
a celite pad and concentrated under reduced pressure. The residue was purified by silica gel
chromatography (10%ꢀ20% ethyl acetate in hexane, v/v) to give the desired product. (Note the
safety of the reaction for overꢀpressurization associated with heating the tertꢀbutyl hydroperoxide
o
solution with a metal catalyst at 120 C in a sealed vessel.)
1
2
-(1,4-Dioxan-2-yl)-5-phenyloxazole (3a). White solid, m.p.: 65ꢀ67 °C, 79 mg, yield: 69%. H
NMR (400 MHz, CDCl
3
) δ 7.69ꢀ7.62 (m, 2H), 7.43 (t, J = 7.5 Hz, 2H), 7.38ꢀ7.30 (m, 2H), 4.86
(
dd, J = 9.3, 2.9 Hz, 1H), 4.12 (dd, J = 11.7, 2.9 Hz, 1H), 4.02ꢀ3.89 (m, 3H), 3.85ꢀ3.79 (m, 2H).
13
C NMR (101 MHz, CDCl ) δ 159.3, 152.1, 128.9, 128.8, 127.6, 124.4, 122.0, 70.7, 68.4, 66.5,
3
ꢀ1
6
6.4. IR (neat) ν 2965, 2914, 2857, 1590, 1487, 1449, 1258, 1120, 1079, 914, 763 cm . HRMS
+
(ESI, m/z): calcd. for C13
H13NO
3
Na (M+Na) : 254.0793, found: 254.0788.
ACS Paragon Plus Environment

Page 13 of 22
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Methyl-2-(1,4-dioxan-2-yl)-5-phenyloxazole-4-carboxylate (3b). White solid, m.p.: 83ꢀ85 °C, 97
1
mg, yield: 67%. H NMR (400 MHz, CDCl
3
) δ 8.08 (dd, J = 6.6, 3.1 Hz, 2H), 7.62ꢀ7.39 (m, 3H),
4
.90 (dd, J = 9.5, 2.9 Hz, 1H), 4.15 (dd, J = 11.6, 2.9 Hz, 1H), 4.03ꢀ3.97 (m, 2H), 3.95 (s, 3H),
1
3
3.94ꢀ3.88 (m, 1H), 3.86ꢀ3.78 (m, 2H). C NMR (101 MHz, CDCl
3
) δ 162.3, 158.2, 156.1, 130.6,
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
128.5, 128.4, 126.7, 126.5, 70.6, 68.3, 66.6, 66.3, 52.3. IR (neat) ν 2971, 2925, 2861, 1735, 1586,
ꢀ1
1
5
484, 1450, 1259, 1119, 1081, 881, 692 cm . HRMS (ESI, m/z): calcd. for C15H15NO Na
+
(
M+Na) : 312.0848, found: 312.0844.
5-(4-Chlorophenyl)-2-(1,4-dioxan-2-yl)oxazole (3c). White solid, m.p.: 75ꢀ77 °C, 85 mg, yield:
1
6
4%. H NMR (400 MHz, CDCl
3
) δ 7.63ꢀ7.58 (m, 2H), 7.45ꢀ7.39 (m, 2H), 7.33 (s, 1H), 4.86 (dd,
13
J = 9.3, 2.8 Hz,1H), 4.13 (dd, J = 11.7, 2.8 Hz, 1H), 4.02ꢀ3.89 (m, 3H), 3.88ꢀ3.78 (m, 2H). C
NMR (101 MHz, CDCl ) δ 159.6, 151.1, 134.6, 129.2, 126.1, 125.7, 122.4, 70.7, 68.4, 66.5, 66.4.
3
ꢀ1
IR (neat) ν 2969, 2946, 2850, 1587, 1475, 1489, 1255, 1092, 905, 806, 768 cm . HRMS (ESI,
+
m/z): calcd. For C13
H
12ClNO
3
Na (M+Na) : 288.0404, found: 288.0401.
2-(1,4-Dioxan-2-yl)-6-methylbenzo[d]oxazole (3d). White solid, m.p.: 89ꢀ91 °C, 81 mg, yield:
1
7
4%. H NMR (400 MHz, CDCl
3
) δ 7.61 (d, J = 8.1 Hz, 1H), 7.36 (s, 1H), 7.17 (d, J = 8.0 Hz,
1H), 4.96 (dd, J = 9.1, 2.6 Hz, 1H), 4.20 (dd, J = 11.7, 2.8 Hz, 1H), 3.98 (dtd, J = 15.3, 11.8, 2.8
13
Hz, 3H), 3.88ꢀ3.74 (m, 2H), 2.50 (s, 3H). C NMR (101 MHz, CDCl
3
) δ 161.1, 150.9, 138.4,
1
1
2
36.0, 125.9, 119.7, 111.0, 71.1, 68.5, 66.6, 66.4, 21.8. IR (neat) ν 3028, 2915, 2866, 1613, 1577,
ꢀ1
+
487, 1363, 1270, 1130, 820, 602 cm . HRMS (ESI, m/z): calcd. for C12
3
H13NO Na (M+Na) :
42.0793, found: 242.0791.
2-(1,4-Dioxan-2-yl)-5-methylbenzo[d]oxazole (3e).White solid, m.p.: 80ꢀ82 °C, 82 mg, yield:
1
75%. H NMR (400 MHz, CDCl
3
) δ 7.52 (s, 1H), 7.42 (d, J = 8.3 Hz, 1H), 7.17 (d, J = 8.3 Hz,
1H), 4.95 (dd, J = 9.2, 2.8 Hz, 1H), 4.19 (dd, J = 11.7, 2.8 Hz, 1H), 3.99ꢀ3.92 (m, 3H), 3.87ꢀ3.77
13
(
m, 2H), 2.47 (s, 3H). C NMR (101 MHz, CDCl
3
) δ 161.7, 148.8, 140.8, 134.5, 126.7, 120.2,
1
8
5
7
10.2, 71.2, 68.5, 66.6, 66.4, 21.4. IR (neat) ν 2969, 2921, 2856, 1576, 1365, 1228, 1118, 915,
ꢀ1
+
83, 598 cm . HRMS (ESI, m/z): calcd. for C12
H
3
13NO Na (M+Na) : 242.0793, found: 242.0790.
-(tert-Butyl)-2-(1,4-dioxan-2-yl)benzo[d]oxazole (3f). White solid, m.p.: 83ꢀ85 °C, 93 mg, yield:
1
2%. H NMR (400 MHz, CDCl ) δ 7.76 (d, J = 1.6 Hz, 1H), 7.44 (dt, J = 8.7, 5.2 Hz, 2H), 4.96
3
(dd, J = 9.1, 3.0 Hz, 1H), 4.19 (dd, J = 11.7, 3.0 Hz, 1H), 4.04ꢀ3.91 (m, 3H), 3.86ꢀ3.79 (m, 2H),
13
3
1.38 (s, 9H). C NMR (101 MHz, CDCl ) δ 161.8, 148.6, 148.2, 140.5, 123.3, 116.8, 110.0, 71.1,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 22
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
6
8.5, 66.5, 66.4, 34.9, 31.7. IR (neat) ν 2961, 2918, 2857, 1573, 1557, 1481, 1395, 1119, 915, 800
ꢀ1
+
3
cm . HRMS (ESI, m/z): calcd. for C15H19NO Na (M+Na) : 284.1263, found: 284.1261.
2-(1,4-Dioxan-2-yl)-5-phenylbenzo[d]oxazole (3g). White solid, m.p.: 97ꢀ99 °C, 117 mg, yield:
1
83%. H NMR (400 MHz, CDCl
3
) δ 7.95 (s, 1H), 7.63 (d, J = 6.3 Hz, 4H), 7.49 (t, J = 7.6 Hz, 2H),
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
7.39 (t, J = 7.3 Hz, 1H), 5.02 (dd, J = 9.1, 2.9 Hz, 1H), 4.24 (dd, J = 11.7, 2.9 Hz, 1H), 4.02 (tdd, J
13
=
11.8, 10.2, 4.2 Hz, 3H), 3.91ꢀ3.81 (m, 2H). C NMR (101 MHz, CDCl
3
) δ 162.4, 150.1, 141.2,
1
2
40.8, 138.7, 128.9, 127.5, 127.4, 125.2, 118.9, 110.9, 71.1, 68.5, 66.6, 66.4. IR (neat) ν 3061,
ꢀ1
964, 2913, 2856, 1574, 1469, 1452, 1263, 1118, 915, 762 cm . HRMS (ESI, m/z): calcd. for
+
C
17
H
15NO
3
Na (M+Na) : 304.0950, found: 304.0952.
2-(1,4-Dioxan-2-yl)-5-methoxybenzo[d]oxazole (3h). White solid, m.p.: 99ꢀ101 °C, 76 mg, yield:
1
65%. H NMR (400 MHz, CDCl ) δ 7.42 (d, J = 8.9 Hz, 1H), 7.21 (d, J = 2.4 Hz, 1H), 6.96 (dd, J
3
=
8.9, 2.4 Hz, 1H), 4.94 (dd, J = 9.1, 2.9 Hz, 1H), 4.18 (dd, J = 11.7, 2.9 Hz, 1H), 4.05ꢀ3.91 (m,
13
3H), 3.84 (s, 3H), 3.83ꢀ3.78 (m, 2H). C NMR (101 MHz, CDCl
3
) δ 162.4, 157.4, 145.2, 141.4,
114.3, 111.0, 103.2, 71.1, 68.5, 66.5, 66.4, 55.9. IR (neat) ν 3010, 2969, 2857, 1575, 1483, 1365,
ꢀ1
+
1279, 1119, 916, 838, 754 cm . HRMS (ESI, m/z): calcd. for C12
4
H13NO Na (M+Na) : 258.0743,
found: 258.0740.
2-(1,4-Dioxan-2-yl)-6-(trifluoromethyl)benzo[d]oxazole (3i). White solid, m.p.: 107ꢀ108 °C, 118
1
mg, yield: 87%. H NMR (400 MHz, CDCl ) δ 8.04 (s, 1H), 7.67 (s, 2H), 5.02 (dd, J = 8.9, 2.8
3
13
Hz, 1H), 4.23 (dd, J = 11.7, 2.9 Hz, 1H), 4.09ꢀ3.95 (m, 3H), 3.85 (dt, J = 10.2, 7.0 Hz, 2H).
NMR (101 MHz, CDCl
122.9 (q, J = 3.6 Hz), 118.2 (q, J = 4.0 Hz), 111.4, 70.9, 68.4, 66.5, 66.4. IR (neat) ν 3041, 2919,
C
3
) δ 163.6, 152.3 (s), 140.8, 127.6 (q, J = 33.1 Hz), 124.0 (q, J = 271 Hz),
ꢀ1
2865, 1629, 1451, 1352, 1339, 1119, 914, 888, 673 cm . HRMS (ESI, m/z): calcd. for
+
C
H
12 11
3
F NO
3
(M+H) : 274.0691, found: 274.0690.
Methyl-2-(1,4-dioxan-2-yl)benzo[d]oxazole-6-carboxylate (3j). White solid, m.p.: 117ꢀ118 °C,
1
119 mg, yield: 91%. H NMR (400 MHz, CDCl
3
) δ 8.25 (d, J = 1.0 Hz, 1H), 8.10 (dd, J = 8.4, 1.5
Hz, 1H), 7.78 (d, J = 8.4 Hz, 1H), 5.01 (dd, J = 8.9, 3.0 Hz, 1H), 4.22 (dd, J = 11.7, 3.0 Hz, 1H),
13
4
.10ꢀ3.99 (m, 2H), 3.97 (s, 3H), 3.96ꢀ3.91 (m, 1H), 3.89ꢀ3.80 (m, 2H). C NMR (101 MHz,
CDCl ) δ 166.4, 164.4, 150.2, 144.4, 127.7, 126.4, 120.1, 112.6, 71.0, 68.4, 66.5, 66.4, 52.4. IR
3
ꢀ1
(
neat) ν 3014, 2969, 2875, 1737, 1607, 1365, 1228, 1118, 882, 772, 605 cm . HRMS (ESI, m/z):
+
calcd. for C13
H14NO
5
(M+H) : 264.0866, found: 264.0868.
ACS Paragon Plus Environment

Page 15 of 22
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
6
-Bromo-2-(1,4-dioxan-2-yl)benzo[d]oxazole (3k). White solid, m.p.: 131ꢀ132 °C, 121 mg, yield:
1
86%. H NMR (400 MHz, CDCl
3
) δ 7.75 (s, 1H), 7.62 (d, J = 8.5 Hz, 1H), 7.50 (dd, J = 8.5, 1.7
Hz, 1H), 4.97 (dd, J = 9.0, 2.7 Hz, 1H), 4.21 (dd, J = 11.7, 2.9 Hz, 1H), 4.00 (ddd, J = 14.3, 12.1,
13
7.3 Hz, 3H), 3.90ꢀ3.80 (m, 2H). C NMR (101 MHz, CDCl
3
) δ 162.3, 151.1, 139.8, 128.2, 121.4,
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
118.6, 114.4, 70.9, 68.4, 66.5, 66.4. IR (neat) ν 3045, 2930, 2869, 1685, 1568, 1482, 1256, 1125,
ꢀ1
+
9
17, 841, 689, 590 cm . HRMS (ESI, m/z): calcd. for C11
3
H10BrNO Na (M+Na) : 305.9742,
found: 305.9737.
5-Bromo-2-(1,4-dioxan-2-yl)benzo[d]oxazole (3l). White solid, m.p.: 78ꢀ79 °C, 114 mg, yield:
1
8
1%. H NMR (400 MHz, CDCl
3
) δ 7.89 (d, J = 1.6 Hz, 1H), 7.49 (dd, J = 8.6, 1.8 Hz, 1H), 7.44
(d, J = 8.6 Hz, 1H), 4.97 (dd, J = 9.0, 2.9 Hz, 1H), 4.20 (dd, J = 11.7, 2.9 Hz, 1H), 4.06ꢀ3.93 (m,
1
3
3
H), 3.89ꢀ3.76 (m, 2H). C NMR (101 MHz, CDCl ) δ 163.0, 149.6, 142.2, 128.7, 123.4, 117.4,
3
112.1, 70.9, 68.4, 66.5, 66.4. IR (neat) ν 3051, 2923, 2854, 1685, 1566, 1480, 1258, 1120, 916,
ꢀ1
+
837, 681, 591 cm . HRMS (ESI, m/z): calcd. for C11
3
H10BrNO Na (M+Na) : 305.9742, found:
305.9739.
5-Chloro-2-(1,4-dioxan-2-yl)benzo[d]oxazole (3m). White solid, m.p.: 129ꢀ130 °C, 99 mg, yield:
1
8
3%. H NMR (400 MHz, CDCl
3
) δ 7.67 (d, J = 8.5 Hz, 1H), 7.58 (s, 1H), 7.36 (dd, J = 8.4, 1.2
Hz, 1H), 4.97 (dd, J = 9.0, 2.7 Hz, 1H), 4.21 (dd, J = 11.7, 2.7 Hz, 1H), 4.10ꢀ3.91 (m, 3H), 3.84
13
(
dt, J = 9.5, 7.1 Hz, 2H). C NMR (101 MHz, CDCl ) δ 162.4, 150.8, 139.4, 131.3, 125.5, 121.0,
3
111.5, 70.9, 68.4, 66.5, 66.4. IR (neat) ν 3015, 2969, 2942, 1563, 1488, 1365, 1228, 1092, 880,
ꢀ1
+
6
3
68 cm . HRMS (ESI, m/z): calcd. for C11H10ClNO Na (M+Na) : 262.0247, found: 262.0244.
5,6-Dichloro-2-(1,4-dioxan-2-yl)benzo[d]oxazole (3n). White solid, m.p.: 119ꢀ120 °C, 97 mg,
1
yield: 71%. H NMR (400 MHz, CDCl
3
) δ 7.64 (d, J = 1.6 Hz, 1H), 7.41 (d, J = 1.7 Hz, 1H), 5.00
(dd, J = 8.7, 2.8 Hz, 1H), 4.21 (dd, J = 11.6, 2.5 Hz, 1H), 4.11ꢀ3.90 (m, 3H), 3.89ꢀ3.80 (m, 2H).
13
3
C NMR (101 MHz, CDCl ) δ 163.6, 146.1, 142.4, 130.6, 126.1, 119.1, 116.8, 70.8, 68.3, 66.5,
ꢀ1
6
6.4. IR (neat) ν 2989, 2947, 2865, 1610, 1591, 1454, 1387, 1279, 1235, 1120, 881, 769, 628 cm .
+
HRMS (ESI, m/z): calcd. for C11
H
9
Cl
2
NO
3
Na (M+Na) : 295.9857, found: 295.9853.
5-Bromo-2-(1,4-dioxan-2-yl)-6-fluorobenzo[d]oxazole (3o). Light yellow liquid, 85 mg, yield:
1
5
7%. H NMR (400 MHz, CDCl ) δ 7.70 (d, J = 1.2 Hz, 1H), 7.32 (dd, J = 9.2, 1.6 Hz, 1H), 4.99
3
(dd, J = 8.8, 3.0 Hz, 1H), 4.20 (dd, J = 11.7, 3.0 Hz, 1H), 4.09ꢀ3.87 (m, 3H), 3.87ꢀ3.65 (m, 2H).
13
3
C NMR (101 MHz, CDCl ) δ 163.5, 146.6 (d, J = 258.0 Hz), 144.8 (d, J = 2.2 Hz), 137.1 (d, J =
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 22
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1
1.0 Hz), 119.5 (d, J = 4.5 Hz), 116.8 (d, J = 7.1 Hz), 116.2 (d, J = 19.5 Hz), 70.7, 68.3, 66.5, 66.4.
ꢀ1
IR (neat) ν 3015, 2999, 2867, 1611, 1450, 1365, 1228, 1121, 921, 750, 529 cm . HRMS (ESI,
+
m/z): calcd. for C11
H
9
BrFNO
3
Na (M+Na) : 323.9648, found: 323.9645.
2-(1,4-Dioxan-2-yl)benzo[d]oxazole (3p). White solid, m.p.: 61ꢀ62 °C, 84 mg, yield: 82%. (known
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
17
1
compound ). H NMR (400 MHz, CDCl
3
) δ 7.76 (dd, J = 5.6, 3.4 Hz, 1H), 7.58 (d, J = 6.1 Hz,
1H), 7.44ꢀ7.33 (m, 2H), 5.00 (dd, J = 9.1, 2.6 Hz, 1H), 4.23 (dd, J = 11.7, 2.9 Hz, 1H), 4.08ꢀ3.93
1
3
(
m, 3H), 3.89ꢀ3.79 (m, 2H). C NMR (101 MHz, CDCl
3
) δ 161.7, 150.6, 140.6, 125.5, 124.7,
1
7
5
20.4, 110.9, 71.1, 68.5, 66.6, 66.4. IR (neat) ν 3007, 2981, 1658, 1530, 1472, 1347, 1311, 850,
ꢀ1
+
87, 734 cm . HRMS (ESI, m/z): calcd. for C11
H
11NO
3
Na (M+Na) : 228.0637, found: 228.0635.
1
-Phenyl-2-(tetrahydrofuran-2-yl)oxazole (3q). Colorless liquid, 65 mg, yield: 61%. H NMR
(400 MHz, CDCl ) δ 7.65 (d, J = 7.9 Hz, 2H), 7.42 (t, J = 7.6 Hz, 2H), 7.33 (t, J = 7.4 Hz, 1H),
3
7
.29 (s, 1H), 5.14ꢀ5.08 (m, 1H), 4.09 (dd, J = 14.7, 7.3 Hz, 1H), 3.99 (dd, J = 14.1, 7.5 Hz, 1H),
13
2.44ꢀ2.29 (m, 2H), 2.25ꢀ2.14 (m, 1H), 2.12ꢀ2.01 (m, 1H). C NMR (101 MHz, CDCl
3
) δ 163.7,
151.8, 128.8, 128.5, 127.9, 124.3, 121.7, 73.5, 69.0, 30.4, 25.9. IR (neat) ν 2979, 2965, 2875, 1656,
ꢀ1
2
1583, 1454, 1273, 1241, 1077, 910, 750 cm . HRMS (ESI, m/z): calcd. for C13H13NO Na
+
(M+Na) : 238.0844, found: 238.0838.
Methyl-5-phenyl-2-(tetrahydrofuran-2-yl)oxazole-4-carboxylate (3r). Colorless liquid, 89 mg,
1
yield: 65%. H NMR (400 MHz, CDCl ) δ 8.17ꢀ7.94 (m, 2H), 7.48 (ddd, J = 7.2, 4.9, 1.6 Hz, 3H),
3
5
.12 (t, J = 6.8 Hz, 1H), 4.09 (dt, J = 14.0, 7.0 Hz, 1H), 4.03ꢀ3.96 (m, 1H), 3.94 (s, 3H), 2.37 (q, J
13
=
3
7.2 Hz, 2H), 2.22ꢀ2.14 (m, 1H), 2.09ꢀ2.01 (m, 1H). C NMR (101 MHz, CDCl ) δ 162.5 155.9,
130.4, 128.4, 128.4, 126.8, 126.5, 73.3, 69.3, 52.3, 30.76, 26.0. IR (neat) ν 2954, 2930, 2873,
ꢀ1
1725, 1655, 1547, 1451, 1275, 1078, 977, 781 cm . HRMS (ESI, m/z): calcd. for C15
H15NO
4
+
(M+Na) : 296.0899, found: 296.0892.
1
6-Methyl-2-(tetrahydrofuran-2-yl)benzo[d]oxazole (3s). Colorless liquid, 86 mg, yield: 85%. H
3
NMR (400 MHz, CDCl ) δ 7.55 (d, J = 8.1 Hz, 1H), 7.29 (s, 1H), 7.10 (d, J = 8.1 Hz, 1H), 5.15 (t,
J = 6.7 Hz, 1H), 4.08 (dd, J = 14.6, 7.3 Hz, 1H), 3.97 (dd, J = 14.2, 7.5 Hz, 1H), 2.44 (s, 3H), 2.36
13
(dd, J = 14.3, 7.1 Hz, 2H), 2.18ꢀ2.10 (m, 1H), 2.07ꢀ1.98 (m, 1H). C NMR (101 MHz, CDCl
3
) δ
165.6, 151.2, 138.6, 135.5, 125.5, 119.4, 110.8, 73.9, 69.2, 30.6, 25.8, 21.7. IR (neat) ν 3015,
ꢀ1
2954, 2857, 1645, 1621, 1447, 1363, 1278, 1125, 820, 668 cm . HRMS (ESI, m/z): calcd. for
+
C
12
H
13NO
2
Na (M+Na) : 226.0844, found: 226.0839.
ACS Paragon Plus Environment

Page 17 of 22
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
1
2
-(1,3-Dioxolan-2-yl)benzo[d]oxazole (3t1). Colorless liquid, 52 mg, yield: 54%. H NMR (400
MHz, CDCl ) δ 7.80ꢀ7.73 (m, 1H), 7.63ꢀ7.53 (m, 1H), 7.43ꢀ7.33 (m, 2H), 6.21 (s, 1H), 4.34ꢀ4.27
m, 2H), 4.20ꢀ4.13 (m, 2H). C NMR (101 MHz, CDCl
120.8, 111.1, 70.5, 68.7, 65.7. IR (neat) ν 3015, 2969, 2946, 1435, 1366, 1216, 1092, 896, 764
3
13
(
3
) δ 161.9, 150.7, 140.4, 125.9, 124.7,
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
ꢀ
1
+
cm . HRMS (ESI, m/z): calcd. for C10
H
9
NO
3
Na (M+Na) : 214.0480, found: 214.0477.
1
2
-(1,3-Dioxolan-4-yl)benzo[d]oxazole (3t2). Colorless liquid, 20 mg, yield: 21%. H NMR (400
3
MHz, CDCl ) δ 7.80ꢀ7.73 (m, 1H), 7.60ꢀ7.53 (m, 1H), 7.42ꢀ7.34 (m,2H), 5.32 (dd, J = 6.7, 5.5 Hz,
13
1
1
1
2
2
H), 5.26 (s, 1H), 5.18 (s, 1H), 4.37 (dt, J = 6.8, 3.4 Hz, 2H). C NMR (101 MHz, CDCl ) δ
3
63.4, 150.9, 140.6, 125.6, 124.6, 120.4, 110.9, 70.5, 68.7, 65.7. IR (neat) ν 3015, 2969, 2946,
ꢀ1
+
435, 1366, 1216, 1092, 896, 764 cm . HRMS (ESI, m/z): calcd. for C10
H
9
3
NO Na (M+Na) :
14.0480, found: 214.0477.
-(1-Butoxyethyl)benzo[d]oxazole (3u1) and 2-(1-ethoxybutyl)benzo[d]oxazole (3u2), mixture.
1
Colorless liquid, 75 mg, yield: 69%. H NMR (400 MHz, CDCl
3
) δ 7.80ꢀ7.69 (m, 1H), 7.60ꢀ7.53
(m, 1H), 7.40ꢀ7.34 (m, 2H), 4.76 (q, J = 6.6 Hz, 0.66H), 4.62 (t, J = 6.9 Hz, 0.34H), 3.66ꢀ3.48 (m,
H), 1.68 (d, J = 6.7 Hz, 1.97H), 1.61ꢀ1.22 (m, 5.03H), 0.91 (t, J = 7.4 Hz, 1.98H), 0.97 (t, J = 7.4
2
1
3
Hz, 1.02H). C NMR (101 MHz, CDCl
3
) δ 166.4, 166.1, 150.8, 150.9, 140.8, 140.7, 125.2, 125.1,
1
1
24.4, 124.3, 120.2, 120.1, 110.8, 75.4, 71.5, 69.7, 65.6, 36.1, 31.7, 29.7, 19.6, 19.2, 18.6, 15.1,
ꢀ1
3.8. IR (neat) ν 2963, 2934, 2869, 1616, 1430, 1293, 1261, 1112, 906, 773 cm . HRMS (ESI,
+
m/z): calcd. for C13
H
17NO
2
(M+Na) : 242.1157, found: 242.1153.
Methyl-2-(1-methoxybutyl)benzo[d]oxazole-6-carboxylate (3v). Colorless liquid, 75 mg, yield:
1
57%. H NMR (400 MHz, CDCl ) δ 8.25 (s, 1H), 8.09 (dd, J = 8.4, 1.1 Hz, 1H), 7.77 (d, J = 8.4
3
Hz, 1H), 4.56ꢀ4.51 (m, 1H), 3.97 (s, 3H), 3.44 (s, 3H), 2.07ꢀ1.93 (m, 2H), 1.55ꢀ1.39 (m, 2H), 0.97
13
(t, J = 7.4 Hz, 3H). C NMR (101 MHz, CDCl
3
) δ 168.5, 166.5, 150.5, 144.6, 127.4, 126.2,
1
1
2
2
19.8, 112.6, 77.1, 57.9, 52.4, 35.8, 18.4, 13.7. IR (neat) ν 3073, 2961, 2926, 2867, 1724, 1606,
ꢀ1
+
432, 1297, 1263, 1071, 977, 742 cm . HRMS (ESI, m/z): calcd. for C14
4
H17NO Na (M+Na) :
86.1056, found: 286.1051.
1
-(1,2-Dimethoxyethyl)benzo[d]oxazole (3w1). Colorless liquid, 55 mg, yield: 53%. H NMR (400
MHz, CDCl ) δ 7.74 (dd, J = 5.3, 3.7 Hz, 1H), 7.56 (dd, J = 5.8, 3.3 Hz, 1H), 7.39ꢀ7.30 (m, 2H),
3
4
.74 (dd, J = 6.8, 4.9 Hz, 1H), 3.88 (ddd, J = 15.2, 10.3, 5.9 Hz, 2H), 3.49 (s, 3H), 3.42 (s, 3H).
13
C NMR (101 MHz, CDCl
3
) δ 163.3, 150.8, 140.7, 125.4, 124.5, 120.3, 110.9, 76.5, 73.3, 59.5,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 18 of 22
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
ꢀ1
5
8.3. IR (neat) ν 2999, 2969, 2939, 1611, 1454, 1365, 1228, 1112, 765, 539 cm . HRMS (ESI,
+
m/z): calcd. for C11
H
13NO
3
Na (M+Na) : 230.0793, found: 230.0789.
1
2
-((2-Methoxyethoxy)methyl)benzo[d]oxazole (3w2). Colorless liquid, 30 mg, yield: 28%. H
NMR (400 MHz, CDCl ) δ 7.75 (dd, J = 5.6, 3.2 Hz, 1H), 7.57 (dd, J = 5.7, 2.9 Hz, 1H), 7.37 (dd,
J = 6.4, 2.7 Hz, 2H), 4.86 (s, 2H), 3.83 (dd, J = 5.4, 3.6 Hz, 2H), 3.64 (dd, J = 5.4, 3.6 Hz, 2H),
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
3
3
7
3
.41 (s, 3H). C NMR (101 MHz, CDCl ) δ 162.6, 151.1, 140.8, 125.4, 124.5, 120.3, 110.8, 71.8,
ꢀ1
0.7, 65.8, 59.1. IR (neat) ν 3015, 2969, 2945, 1536, 1435, 1358, 1205, 1092, 899, 754, 539 cm .
+
HRMS (ESI, m/z): calcd. for C H NO Na (M+Na) : 230.0793, found: 230.0790.
1
1
13
3
1
2
-(1-(2-Ethoxyethoxy)ethyl)benzo[d]oxazole (3x). Colorless liquid, 92 mg, yield: 78%. H NMR
400 MHz, CDCl ) δ 7.78ꢀ7.66 (m, 1H), 7.61ꢀ7.46 (m, 1H), 7.41ꢀ7.30 (m, 2H), 4.84 (q, J = 6.7
Hz, 1H), 3.72 (t, J = 4.8 Hz, 2H), 3.63ꢀ3.58 (m, 2H), 3.50 (q, J = 7.0 Hz, 2H), 1.70 (d, J = 6.7 Hz,
(
3
13
3H), 1.17 (t, J = 7.0 Hz, 3H). C NMR (101 MHz, CDCl
3
) δ 166.0, 150.8, 140.7, 125.2, 124.4,
120.2, 110.8, 71.9, 69.7, 69.2, 66.6, 19.5, 15.1. IR (neat) ν 2969, 2932, 2869, 1646, 1621, 1488,
ꢀ1
+
3
1455, 1365, 1228, 1112, 765, 688 cm . HRMS (ESI, m/z): calcd. for C13H17 NO Na (M+Na) :
2
2
2
58.1106, found: 258.1105.
-(2-methyltetrahydrofuran-2-yl)benzo[d]oxazole (3y1) and
-(5-methyltetrahydrofuran-2-yl)benzo[d]oxazole (3y2), mixture.
1
Light yellow liquid, 74 mg, yield: 73%. H NMR (400 MHz, CDCl ) δ 7.66ꢀ7.60 (m, 1H),
3
7
0
.45ꢀ7.40 (m, 1H), 7.24ꢀ7.18 (m, 2H), 5.20 (t, J = 7.0 Hz, 0.26H), 5.07 (dd, J = 7.9, 5.5 Hz,
.04H), 4.32ꢀ4.22 (m, 0.27H), 4.18ꢀ4.08 (m, 0.06H), 4.02ꢀ3.88 (m, 1.36H), 2.68ꢀ2.55 (m, 0.63H),
2.41ꢀ2.28 (m, 0.59H), 2.20ꢀ2.09 (m, 0.32 H), 2.09ꢀ1.86 (m, 2.11H), 1.68 (s, 2.03H), 1.52 (ddd, J =
1
3
17.0, 12.2, 8.6 Hz, 0.44H), 1.29 (d, J = 6.1 Hz, 0.13H), 1.24 (d, J = 6.1 Hz, 0.79H). C NMR (101
MHz, CDCl ) δ 168.9, 166.5, 150.9, 150.8, 140.8, 125.0, 124.9, 124.2, 124.2, 120.0, 110.6, 80.3,
7.5, 77.4, 76.5, 74.0, 73.6, 68.9, 37.3, 33.3, 32.9, 30.9, 30.8, 26.0, 25.6, 20.9, 20.6. IR (neat) ν
3
7
3
ꢀ1
011, 2959, 2866, 1621, 1451, 1366, 1275, 1128, 925, 670 cm . HRMS (ESI, m/z): calcd. for
+
C
12
H
13NO
2
Na (M+Na) : 226.0844, found: 226.0841.
Supporting Information
ACS Paragon Plus Environment

Page 19 of 22
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Experimental details and NMR spectra. This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
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
Corresponding Author
*
Email: hongjianlu@nju.edu.cn; guigen.li@ttu.edu.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
We are grateful for financial support by National Natural Science Foundation of China (21332005,
21472085) and Qing Lan Project.
REFERENCES
(
1) For selected recent reviews: (a) Gensch, T.; Hopkinson, M. N.; Glorius, F.; WencelꢀDelord, J.
Chem.Soc. Rev. 2016, 45, 2900ꢀ2936. (b) Liu, W.; Ackermann, L. ACS Catal. 2016, 6, 3743ꢀ3752.
c) Ca, N. D.; Fontana, M.; Motti, E.; Catellani, M. Acc. Chem. Res. 2016, 49, 1389ꢀ1400. (d) He,
(
G.; Wang, B.; Nack, W. A.; Chen, G. Acc. Chem. Res. 2016, 49, 635ꢀ645. (e) Minami, Y.; Hiyama,
T. Acc. Chem. Res. 2016, 49, 67ꢀ77. (f) Zheng, Q.; Jiao, N. Chem. Soc. Rev. 2016, 45, 4590ꢀ4627.
(2) For recent reviews of Coꢀcatalyzed C−H bond functionalization, see: (a) Moselage, M.; Li, J.;
Ackermann, L. ACS Catal. 2016, 6, 498ꢀ525. (b) Wei, D.; Zhu, X.; Niu, J. L.; Song, M. P.
ChemCatChem. 2016, 8, 1242ꢀ1263. (c) Hyster, T. K. Catal. Lett. 2015, 145, 458ꢀ467. (d)
Daugulis, O.; Roane, J.; Tran, L. D. Acc. Chem. Res. 2015, 48, 1053ꢀ1064.
(3) For selected recent examples of Coꢀcatalyzed C−H bond activation, see: (a) Li, L.; Wang, H.;
Yu, S.; Yang, X.; Li, X. Org. Lett. 2016, 18, 3662ꢀ3665. (b) Wang, F.; Wang, H.; Wang, Q.; Yu,
S.; Li, X. Org. Lett. 2016, 18, 1306ꢀ1309. (c) Sen, M.; Emayavaramban, B.; Barsu, N.; Richard
Premkumar, J.; Sundararaju, B. ACS Catal. 2016, 6, 2792ꢀ2796. (d) Kong, D.; Cheng, L.; Yue, T.;
Wu, H.; Feng, W.; Wang, D.; Liu, L. J. Org. Chem. 2016, 81, 5337ꢀ5344. (e) Zhang, J.; Chen, H.;
Li, C.; Liu, Z. X.; Wang, C.; Zhang,Y. J. Am. Chem. Soc. 2015, 137, 12990ꢀ12996 and
references cited therein.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 20 of 22
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
(
4) For the first example of cobaltꢀcatalyzed C−H functionalization, see: Murahashi, S. J. Am.
Chem. Soc. 1955, 77, 6403ꢀ6404.
5) For selected reviews: (a) Liu, C.; Yuan, J.; Gao, M.; Tang, S.; Li, W.; Shi, R.; Lei, A. Chem.
(
Rev. 2015, 115, 12138ꢀ12204. (b) Yeung, C. S.; Dong, V. M. Chem. Rev. 2011, 111, 1215ꢀ1292.
(c) Scheuermann, C. Chem. Asian J. 2010, 5, 436ꢀ451. (d) Li, C. J. Acc. Chem. Res. 2009, 42,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
3
35ꢀ344.
(6) Coꢀcatalyzed CDC reaction for C−X bond formation. C−S bond: (a) Gensch,T.; Klauck,J. R.;
Glorius, F. Angew. Chem., Int. Ed. 2016, 55, 11287ꢀ11291. C−N bond: (b) Yan, Q.; Xiao, T.; Liu,
Z.; Zhang, Y. Adv. Syn. Catal. 2016, 358, 2707ꢀ2711. (c) Shang, X.; Liu, Z. Tetrahedron Lett.
2
015, 56, 482ꢀ484. C−O bond: (d) Ye, Y.; Zhang, J.; Wang, G.; Chen, S.; Yu, X. Tetrahedron.
011, 67, 4649ꢀ4654.
2
(7) (a) Li, Z.; Li, C. J. J. Am. Chem. Soc. 2006, 128, 56ꢀ57. (b) Wu, C.; Zhong, J.; Meng, Q.; Lei,
T.; Gao, X.; Tung, C.; Wu, L. Org. Lett. 2015, 17, 884ꢀ887. (c) Tan, G.; He, S.; Huang, X.; Liao,
X.; Cheng, Y.; You, J. Angew. Chem. Int. Ed. 2016, 55, 10414ꢀ10418. (d) Dian, L.; Zhao, H.;
ZhangꢀNegrerie, D.; Du, Y. Adv. Syn. Catal. 2016, 358, 2422ꢀ2426.
(8) (a) Jiang, J.; Zou, H.; Dong, Q.; Wang, R.; Lu, L.; Zhu, Y.; He, W. J. Org. Chem. 2016, 81,
5
1ꢀ56. (b) Haffner, C. D.; Becherer, J. D.; Boros, E. E.; Cadilla, R.; Carpenter, T.; Cowan, D.;
Deaton, D. N.; Guo, Y.; Harrington, W.; Henke, B. R.; Jeune, M. R.; Kaldor, I.; Milliken, N.;
Petrov, K. G.; Preugschat, F.; Schulte, C.; Shearer, B. G.; Shearer, T.; Smalley, T. L.; Stewart, E.
L.; Stuart, J. D.; Ulrich, J. C. J. Med. Chem. 2015, 58, 3548ꢀ3571. (c) Kim, M.; Jeon, J.; Song, J.;
Suh, K. H.; Kim, Y. H.; Min, K. H.; Lee, K. O. Bioorg. Med. Chem. Lett. 2013, 23, 3140ꢀ3144.
(d) Mandadapu, S. R.; Weerawarna, P. M.; Gunnam, M. R.; Alliston, K. R.; Lushington, G. H.;
Kim, Y.; Chang, K.; Groutas, W. C. Bioorg. Med. Chem. Lett. 2012, 22, 4820ꢀ4826. (e) Rusch,
M.; Zahov, S.; Vetter, I. R.; Lehr, M.; Hedberg, C. Bioorg. Med. Chem. 2012, 20, 1100ꢀ1112. (f)
He, T.; Li, H.; Li, P.; Wang, L. Chem. Commun. 2011, 47, 8946ꢀ8948.
(9) (a) Vechorkin, O.; Proust, V.; Hu, X. Angew. Chem., Int. Ed. 2010, 49, 3061ꢀ3064. (b) Yao, T.;
Hirano, K.; Satoh, T.; Miura, M. Chem. Eur. J. 2010, 16, 12307ꢀ12311. (c) Ackermann, L.; Punji,
B.; Song, W. Adv. Synth. Catal. 2011, 353, 3325ꢀ3329. (d) Ren, P.; Isuf Salihu, Scopelliti, R.; Hu,
X. Org. Lett. 2012, 14, 1748ꢀ1751. (e) Wu, X.; See, J. W. T.; Xu, K.; Hirao, H.; Roger, J.; Hierso,
J.; Zhou, J. S. Angew. Chem. Int. Ed. 2014, 53, 13573ꢀ13577. (f) Wu, X.; Lei, C.; Yue, G.; Zhou,
ACS Paragon Plus Environment

Page 21 of 22
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
J. S. Angew. Chem, Int. Ed. 2015, 54, 9601ꢀ9605. (g) McCallum, T.; Barriault, L. Chem. Sci. 2016,
7
, 4754ꢀ4758.
(10) Filloux, C. M.; Rovis, T. J. Am. Chem. Soc. 2015, 137, 508ꢀ517.
(11) Zhao, W.; Chen, X.; Yuan, J.; Qu, L.; Duana, L; Zhao, Y. Chem. Commun. 2014, 50,
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
2018ꢀ2020.
(12) (a) Zhao, X.; Wu, G.; Zhang, Y.; Wang, J. J. Am. Chem. Soc. 2011, 133, 3296ꢀ3299. (b) Hu,
F.; Yang, J.; Xia, Y.; Ma, C.; Xia, H.; Zhang Y.; Wang, J. Organometallics. 2016, 35, 1409ꢀ1414.
(
(
c) Yao, T.; Hirano, K.; Satoh, T.; Miura, M. Angew. Chem. Int. Ed. 2012, 51, 775ꢀ779.
13) (a) Gillard, R. M.; Sperry, J. J. Org. Chem. 2015, 80, 2900ꢀ2906. (b) Holmes, M.; Kwon, D.;
Taron, M.; Britton, R. Org. Lett. 2015, 17, 3868ꢀ3871. (c) Wan, M.; Meng, Z.; Lou, H.; Liu, L.
Angew. Chem. Int. Ed. 2014, 53, 13845ꢀ13849. (d) Chen, W.; Xie, Z.; Zheng, H.; Lou, H.; Liu, L.
Org. Lett. 2014, 16, 5988ꢀ5991. (e) Miles, S. M.; Marsden, S. P. J. Org. Chem. 2004, 69,
6874ꢀ6882.
(14) For our related work in cobalt catalyzed C−H activation, see: (a) Li, Q.; Li, Y.; Hu, W.; Hu,
R.; Li, G.; Lu, H. Chem. - Eur. J. 2016, 22, 12286ꢀ12289. (b) Yang, K.; Chen, X.; Wang, Y.; Li,
W.; Kadi, A.; Fun, H.; Sun, H.; Zhang,Y.; Li, G.; Lu, H. J. Org. Chem. 2015, 80, 11065ꢀ11072.
(15) For our related work in cobalt catalyzed C−H insertion, see: (a) Lu, H.; Lang, K.; Jiang, H.;
Wojtas, L.; Zhang, X. P. Chem. Sci. 2016, DOI: 10.1039/C6SC02231F. (b) Lu, H.; Li, C.; Jiang,
H.; Lizardi, C.; Zhang X. Angew. Chem. Int. Ed. 2014, 53, 7028ꢀ7032. (c) Lu, H.; Hu, Y.; Jiang,
H.; Wojtas, L.; Zhang, X. P. Org. Lett. 2012, 14, 5158ꢀ5161. (d) Lu, H.; Li, C.; Jiang, H.; Hu, Y.;
Lizardi, C.; Zhang X. P. Chem. Sci., 2011, 2, 2361ꢀ2366. (e) Lu, H.; Jiang, H.; Wojtas, L.; Zhang,
X. P. Angew. Chem., Int. Ed. 2010, 49, 10192ꢀ10196. (f) Lu, H.; Zhang, X. Chem. Soc. Rev. 2011,
40, 1899ꢀ19091.
(16) (a) Jiang, J.; Zou, H.; Dong, Q.; Wang, R.; Lu, L.; Zhu, Y.; He, W. J. Org. Chem. 2016, 81,
51ꢀ56. (b) Mammoli, V.; Bonifazi, A.; Del Bello, F.; Diamanti, E.; Giannella, M.; Hudson, A. L.;
Mattioli, L.; Perfumi, M.; Piergentili, A.; Quaglia, W.; Titomanlio, F.; Pigini, M. Bioorg. Med.
Chem. 2012, 20, 2259ꢀ2265. (c) Nakata, T. Chem. Rev. 2005, 105, 4314ꢀ4347.
(17) Wang et al. reported that C−C bonds between azoles and ethers were formed without any
catalyst, see: He, T., Yu, L.; Zhang, L.; Wang, L.; Wang, M. Org. Lett. 2011, 13, 5016ꢀ5019.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 22 of 22
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
(
18) (a) Kim, J.; Cho, S.; Joseph, J.; Chang, S. Angew. Chem, Int. Ed. 2010, 49, 9899ꢀ9903. (b)
Turrà, N.; Neuenschwander, U.; Baiker, A.; Peeters, J.; Hermans, I. Chem. - Eur. J. 2010, 16,
3226ꢀ13235.
1
(19) Wu, X.; Yang, K.; Zhao, Y.; Sun, H.; Li, G.; Ge, H. Nat. Commun. 2015, 6, 6462ꢀ6471.
(20) (a) Wertz, S.; Kodama, S.; Studer, A. Angew. Chem., Int. Ed. 2011, 50, 11511ꢀ11515. (b)
Suzuki, M.; Iwasaki, T.; Miyoshi, M.; Okumura, K.; Matsumoto, K. J. Org. Chem. 1973, 38,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
3
571ꢀ3575. (c) Pippel, D. J.; Mapes, C. M.; Mani, N. S. J. Org. Chem. 2007, 72, 5828ꢀ5831. (d)
Chen, L.; Ju, L.; Bustin, K. A.; Hoover, J. M. Chem. Commun., 2015, 51, 15059ꢀ15062. (e) Yang,
K.; Wang, P.; Zhang, C.; Kadi, A. A.; Fun, H. K.; Zhang, Y.; Lu, H. Eur. J. Org. Chem. 2014, 34,
7
586ꢀ7589.
ACS Paragon Plus Environment