Selective Cleavage of Inert Aryl C-N Bonds in N-Aryl Amides

Article abstract of DOI:10.1021/acs.joc.7b02880

A highly selective, IBX-promoted reaction has been developed for the oxidative cleavage of inert C(aryl)-N bonds on secondary amides while leaving the C(carbonyl)-N bond unchanged. This metal-free reaction proceeds under mild conditions (HFIP/H₂O, 25 °C), providing facile access to various useful primary amides, some of which would be otherwise unattainable using conventional aminolysis and hydrolysis approaches.

Full text of DOI:10.1021/acs.joc.7b02880

Subscriber access provided by READING UNIV
Article
Selective Cleavage of Inert Aryl C-N Bonds in N-Aryl Amides
Zhiguo Zhang, Dan Zheng, Yameng Wan, Guisheng Zhang, Jingjing Bi, Qingfeng Liu, Tongxin Liu, and Lei Shi
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b02880 • Publication Date (Web): 05 Jan 2018
Downloaded from http://pubs.acs.org on January 5, 2018
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
Selective Cleavage of Inert Aryl C−N Bonds in NꢀAryl Amides
1
2
3
4
a,b
a
a
a
a
a
a
Zhiguo Zhang,* Dan Zheng, Yameng Wan, Guisheng Zhang,* Jingjing Bi, Qingfeng Liu, Tongxin Liu, and
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
a
Lei Shi
a
Henan Key laboratory of Organic Functional Molecule and Drug Innovation, Collaborative Innovation Center
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
of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and
Reactions, Ministry of Education, School of Chemistry and Chemical Engineering, Henan Normal University,
Xinxiang, Henan 453007, China. Fax: (+86)ꢀ373ꢀ332ꢀ5250; Eꢀmail: zhangzg@htu.edu.cn or
zgs6668@yahoo.com
b
Jilin Province Key Laboratory of Organic Functional Molecular Design & Synthesis, Northeast Normal Univerꢀ
sity, Jilin, Changchun, 130024, China.
Abstract: A highly selective, IBXꢀpromoted reaction has been developed for the oxidative cleavage of
inert C(aryl)−N bonds on secondary amides whilst leaving the C(carbonyl)−N bond unchanged. This
metalꢀfree reaction proceeds under mild conditions (HFIP/H O, 25 °C), providing facile access to variꢀ
2
ous useful primary amides, some of which would be otherwise unattainable using conventional aminolꢀ
ysis and hydrolysis approaches.
Keywords: IBX; C(aryl)ꢀN bond cleavage; Oxidation; Metalꢀfree; Amides
INTRODUCTION
The cleavage of C(aryl)−N bonds could become an important process for the selective fragmentation
of Nꢀaryl amides into smaller molecules, which could be used as building blocks in synthetic organic
1
2
chemistry and further transformed into highꢀvalue chemicals. Furthermore, the development of a proꢀ
cess of this type could add considerable value to organic synthesis, because it could be used to expand
the utility of aryl substituents as removable protecting group. However, the cleavage of the inert
3
C(aryl)−N bonds of Nꢀaryl amides has been largely unexplored to date for two main reasons: (i)
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 22
C(carbonyl)–N bonds are generally broken prior to C(aryl)−N bonds in Nꢀaryl amide when they are atꢀ
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
tacked by a suitable nucleophile (such as amide hydrolysis) because of the low bond dissociation enerꢀ
5
gy of the former (95 kcal/mol) compared with the latter (104 kcal/mol) (Scheme 1); (ii) it can be diffiꢀ
6
cult to stop reactions of this type at the C(aryl)−N bond cleavage stage without further derivatization. A
review of the literature revealed that there is an urgent need for the development of a new method for
the cleavage of the inert C(aryl)−N bonds of Nꢀaryl amides using a highly selective and simplified cataꢀ
lyst system.
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
Scheme 1. Dissociation energies of CꢀN bonds of amides.
Existing C(aryl)−N bond cleavage reactions are limited to a specific set of reagents, including aroꢀ
7
8
matic hydrazines and N,N’ꢀdimethyl substituted aromatic compounds. Compounds belonging to these
two classes can be readily reacted with an electrophilic partner such as an aryl halide, aryl triflate or arꢀ
ylboronic acid in the presence of a suitable metal catalyst to afford the corresponding crossꢀcoupling
9
products (Eq. 1). Besides, the numbered cases of cleavage of the C(aryl)−N bond of some certain terꢀ
6
10
tiary Nꢀaryl amides with the help of a nickel(0) catalyst and ceric ammonium nitrate (CAN) are reꢀ
ported. Thus it can be seen that development of new methods to cleave the inert C(aryl)−N bonds using
more types of Nꢀaryl amides whilst leaving the C(carbonyl)−N bond unchanged are highly desirable.
Herein, we report the development of a highly selective, 2ꢀiodoxybenzoic acid (IBX)ꢀmediated reaction
for the oxidative cleavage of inert C(aryl)−N bonds in electronically neutral secondary aromatic amides
in a mixed solvent system of hexafluoroisopropanol (HFIP) and water at 25 °C (Eq. 2). This novel metꢀ
alꢀfree method allows for the regioselective cleavage of inert C(aryl)−N bonds, thereby allowing the arꢀ
yl groups to be used as removable protecting groups. This method could therefore be used to achieve the
synthesis of a wide range of primary amides, and represents a valuable addition to the limited number of
11
methods currently available for the cleavage of C(aryl)−N bonds.
ACS Paragon Plus Environment

Page 3 of 22
The Journal of Organic Chemistry
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
1
2
IBX is a commercially available hypervalent iodine(V) reagent that has been widely used in organic
synthesis to achieve a variety of different transformations, including the oxidization of alcohols to aldeꢀ
1
3
14
hydes and the oxidative cleavage of the C–C bonds of glycols to give two aldehydes or ketones. A
review of the literature revealed that there are currently no methods available for the selective oxidative
cleavage of the inert C(aryl)−N bonds in Nꢀaryl amides using a hypervalent iodine reagent. We recently
established two new reliable, efficient and green methods for the synthesis of 1Hꢀindazoles and spirocyꢀ
clopropane quinolinediones under mild conditions. Notably, both of these methods required the presence
of a hypervalent iodine reagent and proceeded via an intramolecular oxidative C–N bond forming reacꢀ
15
tion. Encouraged by these results, we became interested in expanding the scope of organoiodine reaꢀ
gents in organic synthesis.
RESULTS AND DISCUSSION
We initiated our study using IBX with amide 1l as a model substrate. After several screening experiꢀ
ments, we found that the cleavage reaction occurred regiospecifically at the C(aryl)−N bond of the amꢀ
ide substrate when it was treated with 2.2 equiv. of IBX in a 2:1 (v/v) mixture of HFIP and H O at 25 °C
2
for 29 h. Furthermore, this reaction gave the desired primary amide in 83% yield (Table 1, entry 5).
Given that IBX is insoluble in water, most of the amide substrate 1l was recovered when the reaction
was performed in water (Table 1, entry 1). Interestingly, the reaction also failed to any of the desired
product when it was conducted in HFIP (Table 1, entry 2). These preliminary results indicated that water
plays an important role in the transformation. Further investigation revealed that the relative proportion
of HFIP to H O had a pronounced influence on the outcome of the reaction. (Table 1, entries 3 and 4).
2
Increasing or decreasing the amount of IBX led to a decrease in the yield of 2l (Table 1, entries 6 and 7).
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 22
Accordingly, the optimum amount of IBX was determined to be 2.2 equiv. in terms of the yield of 2l.
Several other hypervalent iodine reagents were also screened against this reaction, including [bisꢀ
(trifluoroacetoxy)iodo]benzene (PIFA), phenyliodonium diacetate (PIDA), 1,1,1ꢀtriacetoxyꢀ1,1ꢀdihydroꢀ
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
,2ꢀbenziodoxolꢀ3(1H)ꢀone (DMP) and PhIO, but were all found to be much less efficient than IBX
Table 1, entries 8−11). The reaction was also screened against a variety of different mixed solvents at a
ratio of 2:1, including TFE/H O, 2,2,3,3ꢀtetrafluoroꢀ1ꢀpropanol (TFP)/H O, 2,2,3,3,4,4,5,5ꢀoctafluoroꢀ1ꢀ
(
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
2
pentanol (OFP)/H O, trifluoroacetic acid ethyl ester (TFAET)/H O, DMSO/H O, DMF/H O and
2
2
2
2
DMF/H O. However, all of these systems were found to be much less efficient than HFIP/H O (Table 1,
2
2
entries 12−17). It is noteworthy that this reaction was found to be amenable to gramꢀscale synthesis, as
exemplified by the reaction of 1l (10.2 g, 40 mmol), which afforded 2l in 78% yield (5.18 g, 31 mmol).
a
Table 1. Survey of the Reaction Conditions
Entry
Oxidant (equiv)
IBX (2.2)
IBX (2.2)
IBX (2.2)
IBX (2.2)
IBX (2.2)
IBX (1.2)
IBX (3.2)
PIFA (2.2)
PIDA (2.2)
DMP (2.2)
Solvent
Time
3 d
2l/%
0
Recovered of 1l/%
1
2
H O
2
90
92
28
21
0
HFIP
3 d
0
3
HFIP/H O = 1:1
29 h
29 h
29 h
3 d
58
69
83
46
56
50
59
45
2
4
HFIP/H O = 3:1
2
5
HFIP/H O = 2:1
2
6
HFIP/H O = 2:1
40
28
31
32
40
2
7
HFIP/H O = 2:1
3 d
2
8
HFIP/H O = 2:1
29 h
29 h
29 h
2
9
HFIP/H O = 2:1
2
10
HFIP/H O = 2:1
2
ACS Paragon Plus Environment

Page 5 of 22
The Journal of Organic Chemistry
1
1
PhIO (2.2)
IBX (2.2)
IBX (2.2)
IBX (2.2)
IBX (2.2)
IBX (2.2)
IBX (2.2)
HFIP/H O = 2:1
29 h
2.5 d
29 h
3 d
22
78
trace
10
0
0
2
1
2
3
4
5
6
7
8
9
1
2
TFE/H O = 2:1
0
2
13
TFP/H O = 2:1
75
67
80
78
72
2
14
15
16
17
OFP/H O = 2:1
2
TFAET/H O = 2:1
3 d
2
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
DMSO/H O = 2:1
3 d
0
2
DMF/H O = 2:1
3 d
0
2
a
Unless otherwise indicated, all of these reactions were conducted with 1l (0.2 mmol) in 2 mL of solꢀ
vent at 25 °C.
With the optimized conditions in hand (Table 1, entry 5), we proceeded to investigate the scope of
this intramolecular C(aryl)−N bond cleavage reaction (Table 2). We initially investigated the scope of
2
the R group using a variety of different secondary amides (1a–f) bearing an electronꢀdonating group
(EDG) (e.g., ꢀMe and ꢀOMe) at their paraꢀ, orthoꢀ or metaꢀposition. We also investigated the unsubstiꢀ
tuted system 1g for comparison. Pleasingly, all of these substrates afforded the desired products in 68–
7
8% yields. It is noteworthy that compound 1a was recovered in 19% yield and that this material could
not be converted to 2a even after a prolonged reaction time of 5 days. Compound 1g also behaved in a
similar manner. However, substrate 1h bearing a weak electronꢀwithdrawing group (EWG) (ꢀCl) at its
paraꢀposition and 1i (aliphatic amide) failed to afford the desired products, with the majority of these
starting materials being recovered unchanged. This limitation suggested that IBX exhibited its activity
via the formation of an interaction with the phenyl ring of the substrate (with the exception of phenyl
rings bearing EWG). Based on these results, the pꢀmethylphenyl group was selected as the best leaving
1
group to investigate the scope of the R group. The results revealed that substituted phenyl groups bearꢀ
ing an EDG (e.g., 1j: ꢀOMe, 1k: ꢀNH ) or EWG (e.g., 1l−n: ꢀNO ) at their orthoꢀ, metaꢀ or paraꢀ
2
2
position were tolerated, affording the desired amides in moderate to good yields (67–88%). Several othꢀ
er secondary amides (1o–u) also reacted smoothly under the optimized conditions to afford the correꢀ
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 22
sponding amides in 44–85% yields. It is noteworthy that no excessive oxidation products were generatꢀ
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
6
17
18
ed for the cinnamic acid amide (1q), thiobenzamide (1s), 2ꢀphenylꢀNꢀ(pꢀtolyl)acetamide (1t) and
1
9
dodecanamide (1u) substrates. These results therefore highlight the selectivity of this new method.
Further investigation revealed that this reaction was not amenable to the tertiary amide 1v or annular
amide 1w, with most of these starting materials being recovered. The results therefore demonstrated that
an IBXꢀoxidizable N−H moiety was important to the success of this reaction and that IBX could interact
more effectively with acyclic amides.
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 2. Extension of the Reaction Scope
b
1
b: 2 d, 75%
1d: 28 h, 78%
1e: 32 h, 72%
1
a: 2 d, 77%
1c: 2 d, 70%
c
e
d
1
g: 2 d, 72%
1i: 5 d, NR
1f: 34 h, 68%
1k: 4.5 h, 79%
1h: 5 d, NR
1
j: 28 h, 67%
1
m: 22 h, 79%
1o: 6 h, 79%
1l: 29 h, 83%
1q: 8 h, 83%
1n: 16 h, 88%
f
1t: 48 h, 85%
1p: 48 h, 44%
1s: 2 d, 74%
1
r: 3 d, 76%
g
h
1u: 32 h, 72%
1v: 5 d, NR
i
1w: 5 d, NR
ACS Paragon Plus Environment

Page 7 of 22
The Journal of Organic Chemistry
a
Unless otherwise indicated, all of these reactions were conducted with 1 (0.2 mmol) and IBX (2.2
1
2
b
equiv.) in 2 mL of the mixed solvent system (VHFIP/VH2O = 2 : 1) at 25 °C. Compound 1a was recovꢀ
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
c
d
ered in 19% yield. Compound 1g was recovered in 9% yield. Compound 1h was recovered in 88%
e
f
g
yield. Compound 1i was recovered in 83% yield. Compound 1p was recovered in 38% yield.
h
i
Compound 1u was recovered in 16% yield. Compound 1v was recovered in 82% yield. Compound
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
w was recovered in 73% yield.
A control experiment was performed with Nꢀ(naphthalenꢀ1ꢀyl)benzamide (1x) under the optimized
conditions, resulting in the formation of benzamide in 72% yield, along with the corresponding 1,4ꢀ
2
0
naphthoquinone byꢀproduct, which was isolated in 60% yield (Eq. 3). A separate experiment starting
from 1ꢀnaphthalenol also resulted in the formation of 1,4ꢀnaphthoquinone in 63% yield (Eq. 4). This
result revealed that the aryl group on the nitrogen atom of compound 1 was being released in the form
of the corresponding phenol. This result therefore explains why this reaction requires 2.2 equivalents of
IBX. To further investigate the source of the oxygen atom incorporated in the 1,4ꢀnaphthoquinone, we
1
8
conducted an experiment using Oꢀlabeled H O (Eq. 5). Mass spectrometry (MS) analysis of the two
2
18
products generated during this transformation suggested that
O was incorporated in 1,4ꢀ
naphthoquinone, indicating that H O was acting as a nucleophilic oxygen donor and attacking the aryl
2
group of the amides. It is noteworthy that 2ꢀiodobenzoic acid was detected by TLC and HRMS in all of
these reactions.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 22
a
Table 3. Radical Trapping Experiments
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
Radical donors
None
83
TEMPO
78
PBN
70
DPE
80
Galvinoxyl
76
Yield of 2l/%
a
All of these reactions were conducted with 1l (0.2 mmol), IBX (2.2 equiv.) and radical trapping agents
(1 equiv.) in 2 mL of the mixed solvent system (VHFIP/VH2O = 2 : 1) at 25 °C. Yields were that of isolatꢀ
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
ed products.
2
1
Kits’s work showed that 1,4ꢀnaphthoquinone could be generated from 1ꢀnaphthalenol or naphthaꢀ
lene free radicals. With this in mind, we investigated the effects of adding four different radical scavenꢀ
gers (100 mol%) to the reaction of 1l under the optimized conditions to determine whether it proceeded
via a radical intermediate (Table 3). The results revealed that the reaction proceed smoothly in the presꢀ
ence of 2,2,6,6ꢀtetramethylꢀ1ꢀpiperidinyloxy (TEMPO), Nꢀbenzylideneꢀtertꢀbutylamine Nꢀoxide (PBN),
1
,1ꢀdiphenylethylene (DPE) and galvinoxyl radical scavengers, which suggested that this reaction did
not involve a radical species.
21ꢀ
Based on the results of the current study, as well as previously published results from the literature,
2
2
we proposed a plausible mechanism for this reaction (Scheme 2). The initial interaction of IBX with 1
21ꢀ22
would result in formation of the annular π–complex species A,
which would be attacked by the hyꢀ
droxy derived from H O, resulting in the regioselective cleavage of the C(aryl)−N bond in intermediate
2
A to provide primary amide 2, 2ꢀiodobenzoic acid and phenol, and the resulting phenol generated in site
2
3
was then oxidized rapidly to the quinones by the excessive IBX (Scheme 2). The poor reactivity of
substrates 1h, 1i and 1w could be attributed to their inability to form the π−complex A. The fact of
C(aryl)−N bond of compound 1v being not cleaved indicated that secondary amides conducive to the
formation of intermediate A.
ACS Paragon Plus Environment

Page 9 of 22
The Journal of Organic Chemistry
Scheme 2. Proposed Mechanism.
1
2
a
Table 4. Application of the C(aryl)−N bond cleavage reaction
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
2
a’: 3 h, 86%
2c’: 29 h, 71%
2h’: 37 h, 77%
2d’: 2 d, 68%
2i’: 48 h, 80%
2
e’: 15 h, 68%
2
b’: 15 h, 88%
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
f’: 24 h, 73%
2g’: 36 h, 82%
2j’: 45 h, 65%
[
b]
2
k’: 5 h, 42%
2
l’: 48 h, 79%
Unless otherwise indicated, all of these reactions were conducted with 1 (0.2 mmol), IBX (2.2
equiv.) in 2 mL of the mixed solvent system (VHFIP/VH2O = 2 : 1) at 25 °C, and with the 4ꢀMeꢀC H ꢀ
a
6
4
b
group serving as the leaving group. Starting material 1k’ was recovered in 19% yield.
Pleasingly, our newly developed method provided facile access to several primary amide derivatives
2
4
that were otherwise difficult or impossible to prepare using conventional methods (Table 4). For exꢀ
ample, this new strategy provided access to a variety of useful cyclopropylꢀcontaining βꢀketo amides
25
1
a–e’ in moderate to good yields (65–88%) from the corresponding doubly activated cyclopropanes
2
6
27
without affecting the highly reactive cyclopropyl or oxime ether moieties. However, the reaction of
1
8a
the benzyl alcohol analogue 3a’ still afforded the βꢀketo amide 2a’ (Eq. 6).
Notably, we successfully extended this reaction to a wide variety of αꢀmonoꢀ and α,αꢀdisubstituted βꢀ
2
8
ketoamides (1f’–j’), which afforded the desired amides in satisfactory yields (65–82%). Pleasingly,
this method also allowed for the successful construction of 3ꢀoxoꢀ3ꢀphenylpropanamide (2k’), however,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 22
2
k’ decomposed when the reaction time was extended to more than 5 h. αꢀOxo ketene dithioacetal 1l’
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
also reacted smoothly to give the corresponding product 2l’ in 79% yield without oxidizing the dithioꢀ
2
9
acetal moiety. This result contrasted with that of our previous report, where IBX oxidized thiols to the
3
0
corresponding disulfides. To further demonstrate the synthetic potential of this chemistry, we investiꢀ
gated the conversion of the Lꢀlysine derivative (S)ꢀ1m’ under the standard reaction conditions. The reꢀ
sults revealed that the 4ꢀmethylphenyl group of (S)ꢀ1m’ was readily removed and gave the desired
product (S)ꢀ2m’ in 81% yield based on the 69% conversion rate of (S)ꢀ1m’ after 48 h, without change
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
31
the enantiopurity (Eq. 7). This case highlighted key benefit of this C−N bond cleavage strategy in
terms of its regioselectivity for C(aryl)−N bonds over other C−N bond types.
CONCLUSION
In summary, we have developed a highly selective, IBXꢀpromoted reaction for the oxidative cleavage
of the inert C(aryl)−N bond of electronically neutral and structurally simple Nꢀaryl amides. In contrast
6
to previously reported nickel catalysts, the use of IBX offers operational convenience, as well as being
unique in terms of its effectiveness for the cleavage of C(aryl)−N bonds of secondary amides whilst
leaving the C(carbonyl)−N bond untouched. Notably, this study represents the first reported example of
the use of an aryl group as a removable protecting group in the absence of metal catalyst under mild
conditions. Although some of the aryl groups evaluated in the currently study reacted inefficiently, this
method could be used to remove a variety of different aryl groups from the N atom of amides. Overall,
we have developed a new strategy for the cleavage of the C(aryl)−N bonds of secondary amides to give
the corresponding primary amides. Notably, this route provided access to 2ꢀoxoamides and αꢀsubstituted
benzoylacetamides, which are otherwise unattainable using conventional aminolysis and hydrolysis
methods.
EXPERIMENTAL SECTION
ACS Paragon Plus Environment

Page 11 of 22
The Journal of Organic Chemistry
General Remarks. All reactions were carried out under air atmosphere, unless otherwise indicated.
1
2
Other all reagents were purchased from commercial sources and used without further treatment, unless
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
o
otherwise indicated. Petroleum ether (PE) used refers to the 60ꢀ90 C boiling point fraction of petroleꢀ
1
13
1
1
13
1
um. H NMR and C{ H} NMR spectra were recorded on Bruker Avance/600 ( H: 600 MHz, C{ H}:
1
13
1
1
50 MHz at 25 ºC) or Bruker Avance/400 ( H: 400 MHz, C{ H}: 100 MHz at 25 ºC) and TMS as inꢀ
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
ternal standard. Data are represented as follows: chemical shift, integration, multiplicity (br = broad, s =
singlet, d = doublet, dd = double doublet, t = triplet, q = quartet, m = multiplet), coupling constants in
Hertz (Hz). All highꢀresolution mass spectra (HRMS) were measured on a mass spectrometer by using
electrospray ionization (ESIꢀoaꢀTOF), and the purity of all samples used for HRMS (>95%) were
1
13
1
confirmed by H NMR and C{ H} NMR spectroscopic analysis. Melting points were measured on a
melting point apparatus equipped with a thermometer and were uncorrected. All reactions were moniꢀ
tored by TLC with GF254 silica gel coated plates. Flash chromatography was carried out on SiO (silica
2
gel 200ꢀ300 mesh).
Typical Experimental Procedure For 2 (2l as an example). To a roundꢀbottom flask (25 mL) was
added 4ꢀnitroꢀNꢀ(pꢀtolyl)benzamide 1l (51.2 mg, 0.2 mmol), and IBX (123 mg, 0.44 mmol), then the
o
mixture was well stirred for 29 h in 2 mL mixedꢀsolvent (VHFIP/VH2O = 2 : 1) at 25 C (the whole proꢀ
cess was closely monitored by TLC). Afterward the resulting solution was filtered through a plug of
celite and the residue was washed with ethyl acetate (EA) (4 mL × 3). Then the organic solvent was
concentrated in vacuo. The residue was purified by flash column chromatography with EA and PE as
eluent to give primary amide 2l as white solid (27.6 mg, 83%).
Benzamide (2a). The product was isolated by flash chromatography (eluent: EA:PE = 1:2) as a white
o
1
solid (19 mg, 77%); mp: 127ꢀ128 C; H NMR (600 MHz, DMSO) δ 7.98 (s, 1H), 7.88 (d, J = 7.8 Hz,
1
3
2H), 7.51 (t, J = 6.9 Hz, 1H), 7.44 (t, J = 7.5 Hz, 2H), 7.38 (s, 1H). C NMR (150 MHz, CDCl ) δ
3
+
1
1
69.6, 133.4, 132.0, 128.6, 127.4. HRMS (ESI), m/z calcd. for C H NNaO ([M+Na] ) 144.0420, found:
7
7
44.0425.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 22
3
2
4
ꢀMethoxybenzamide (2j). The product was isolated by flash chromatography (eluent: EA:PE = 1:2)
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
o
1
as a white solid (20 mg, 67%); mp: 166ꢀ167 C; H NMR (600 MHz, CDCl ) δ 7.78 (d, J = 8.4 Hz, 2H),
3
1
3
6.94 (d, J = 8.4 Hz, 2H), 5.97 (s, 1H), 5.75 (s, 1H), 3.86 (s, 3H). C NMR (150 MHz, CDCl ) δ 168.9,
3
+
1
62.6, 129.3, 125.6, 113.8, 55.5. HRMS (ESI), m/z calcd. for C H NNaO ([M+Na] ) 174.0525, found:
8
9
2
1
74.0525.
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
2
2
ꢀAminobenzamide (2k). The product was isolated by flash chromatography (eluent: EA:PE = 1:2)
o
1
as a white solid (21 mg, 79%); mp: 111ꢀ114 C; H NMR (600 MHz, DMSO) δ 7.72 (s, 1H), 7.53 (d, J =
7
.8 Hz, 1H), 7.13 (t, J = 7.5 Hz, 1H), 7.06 (s, 1H), 6.68 (d, J = 7.8 Hz, 1H), 6.55 (s, 2H), 6.48 (t, J = 7.5
13
Hz, 1H). C NMR (100 MHz, CDCl ) δ 171.6, 149.4, 133.0, 128.0, 117.4, 116.4, 114.0. HRMS (ESI),
3
+
m/z calcd. for C H N NaO ([M+Na] ) 159.0529, found: 159.0529.
7
8
2
3
2
4ꢀNitrobenzamide (2l). The product was isolated by flash chromatography (eluent: EA:PE = 1:2) as
o
1
a white solid (27 mg, 83%); mp: 198ꢀ202 C; H NMR (600 MHz, DMSOꢀd ) δ 8.30 (t, J = 9.0 Hz, 3H),
6
1
3
8
.10 (d, J = 8.4 Hz, 2H), 7.73 (s, 1H). C NMR (150 MHz, DMSOꢀd ) δ 166.7, 149.5, 140.5, 129.4,
6
+
123.9. HRMS (ESI), m/z calcd. for C H N O ([M+H] ) 167.0451, found: 167.0452.
7
7
2
3
3
2
3
ꢀNitrobenzamide (2m). The product was isolated by flash chromatography (eluent: EA:PE = 1:2)
o
1
as a white solid (26 mg, 79%); mp: 140ꢀ144 C; H NMR (600 MHz, CDCl ) δ 8.65 (s, 1H), 8.40 (d, J =
3
1
3
8
.4 Hz, 1H), 8.20 (d, J = 7.8 Hz, 1H), 7.68 (t, J = 7.8 Hz, 1H), 6.23 (s, 1H), 5.89 (s, 1H). C NMR (150
MHz, CDCl ) δ 166.6, 134.9, 133.5, 130.0, 126.6, 122.3. HRMS (ESI), m/z calcd. for C H N NaO
3
7
6
2
3
+
(
[M+Na] ) 189.0271, found: 189.0270.
3
3
2
ꢀNitrobenzamide (2n). The product was isolated by flash chromatography (eluent: EA:PE = 1:2) as
o
1
a white solid (29 mg, 88%); mp: 175ꢀ179 C; H NMR (600 MHz, DMSOꢀd ) δ 8.14 (s, 1H), 7.99 (d, J
6
1
3
=
7.8 Hz, 1H), 7.78ꢀ7.75 (m, 1H), 7.69 (s, 1H), 7.68ꢀ7.65 (m, 1H), 7.63 (d, J = 7.8, 1H). C NMR (150
MHz, DMSOꢀd ) δ 167.6, 147.7, 133.8, 133.1, 131.1, 129.3, 124.4. HRMS (ESI), m/z calcd. for
6
+
C H N NaO ([M+Na] ) 189.0271, found: 189.0270.
7
6
2
3
3
4
Furanꢀ2ꢀcarboxamide (2o). The product was isolated by flash chromatography (eluent: EA:PE =
ACS Paragon Plus Environment

Page 13 of 22
The Journal of Organic Chemistry
o
1
1
:2) as a light yellow solid (17 mg, 79%); mp: 138ꢀ142 C; H NMR (600 MHz, CDCl ) δ 7.46 (s, 1H),
3
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
3
7
.18ꢀ7.14 (m, 1H), 6.51 (d, J = 3.6 Hz, 1H), 6.29 (s, 1H), 6.11 (s, 1H). C NMR (150 MHz, CDCl ) δ
3
+
160.2, 147.4, 144.4, 115.2, 112.3. HRMS (ESI), m/z calcd. for C H NNaO ([M+Na] ) 134.0212, found:
5
5
2
1
34.0206.
Quinolineꢀ2ꢀcarboxamide (2p). The product was isolated by flash chromatography (eluent: EA:PE =
32
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
o
1
1
:2) as a white solid (15 mg, 44%); mp: 146ꢀ148 C; H NMR (600 MHz, CDCl ) δ 8.35 – 8.27 (m, 2H),
3
8
.12 (s, 1H), 8.10 (d, J = 8.4 Hz, 1H), 7.86 (d, J = 7.8 Hz, 1H), 7.75 (t, J = 7.5 Hz, 1H), 7.61 (t, J = 7.5
13
Hz, 1H), 6.35 (s, 1H). C NMR (150 MHz, CDCl ) δ 166.9, 149.4, 146.7, 137.5, 130.2, 129.9, 129.4,
3
+
1
28.1, 127.8, 118.8. HRMS (ESI), m/z calcd. for C H N O ([M+H] ) 173.0709, found: 173.0717.
10
9
2
3
4
Cinnamamide (2q). The product was isolated by flash chromatography (eluent: EA:PE = 1:2) as a
o
1
white solid (24 mg, 83%); mp: 146ꢀ150 C; H NMR (600 MHz, CDCl ) δ 7.65 (d, J = 15.6 Hz, 1H),
3
13
7
.55ꢀ7.49 (m, 2H), 7.37 (d, J = 3.6 Hz, 3H), 6.47 (d, J = 15.6 Hz, 1H), 5.84 (s, 1H), 5.71 (s, 1H). C
NMR (150 MHz, CDCl ) δ 167.9, 142.5, 134.5, 130.0, 128.8, 127.9, 119.5. HRMS (ESI), m/z calcd. for
3
+
C H NO ([M+H] ) 148.0757, found: 148.0775.
9
9
35
2
ꢀOxoꢀ2ꢀphenylacetamide (2r). The product was isolated by flash chromatography (eluent: EA:PE =
o
1
1
:2) as a white solid (23 mg, 76%); mp: 90ꢀ93 C; H NMR (600 MHz, CDCl ) δ 8.13 (d, J = 7.2 Hz,
3
13
2H), 7.62 (t, J = 7.2 Hz, 1H), 7.49 (t, J = 7.8 Hz, 2H). C NMR (150 MHz, CDCl ) δ 163.1, 134.3,
3
1
29.8, 128.9, 125.7.
Benzothioamide (2s). The product was isolated by flash chromatography (eluent: EA:PE = 1:2) as a
o
1
yellow solid (20 mg, 74%); mp: 114ꢀ117 C; H NMR (600 MHz, CDCl ) δ 7.86 (d, J = 8.4 Hz, 2H),
3
1
3
7.82 (s, 1H), 7.50 (t, J = 7.2 Hz, 1H), 7.40 (t, J = 7.8 Hz, 2H), 7.24 (s, 1H). C NMR (150 MHz, CDCl )
3
δ 202.9, 139.2, 132.0, 128.5, 126.9.
3
5
2
ꢀPhenylacetamide (2t). The product was isolated by flash chromatography (eluent: EA:PE = 1:2)
o
1
as a white solid (23 mg, 85%); mp: 157ꢀ159 C; H NMR (600 MHz, CDCl ) δ 7.35 (d, J = 6.0 Hz, 2H),
3
1
3
7
.27 (d, J = 6.6 Hz, 3H), 5.89 (s, 1H), 5.43 (s, 1H), 3.58 (s, 2H). C NMR (150 MHz, CDCl ) δ 173.65,
3
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 22
+
1
34.89, 129.40, 129.06, 127.44, 43.35. HRMS (ESI), m/z calcd. for C H NNaO ([M+Na] ) 158.0576,
8 9
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
found: 158.0581.
3
6
Dodecanamide (2u). The product was isolated by flash chromatography (eluent: EA:PE = 1:2) as a
o
1
white solid (29 mg, 72%); mp: 100ꢀ103 C; H NMR (600 MHz, CDCl ) δ 5.70 (s, 1H), 5.46 (s, 1H),
3
13
2
.26ꢀ2.15 (m, 2H), 1.62 (d, J = 7.2 Hz, 2H), 1.35ꢀ1.21 (m, 16H), 0.87 (t, J = 6.6 Hz, 3H). C NMR (150
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
MHz, CDCl ) δ 175.88, 35.99, 31.91, 29.61, 29.48, 29.34 (d, J = 1.7 Hz), 29.3, 25.6, 22.7, 14.1. HRMS
3
+
(ESI), m/z calcd. for C H NNaO ([M+Na] ) 222.1828, found: 222.1826.
1
2
25
26
1
ꢀBenzoylcyclopropaneꢀ1ꢀcarboxamide (2a’). The product was isolated by flash chromatography
o
1
(eluent: EA:PE = 1:2) as a white solid (32 mg, 86%); mp: 127ꢀ128 C; H NMR (600 MHz, CDCl ) δ
3
7.92 (d, J = 7.2 Hz, 2H), 7.57 (t, J = 7.5 Hz, 1H), 7.47 (t, J = 7.8 Hz, 2H), 5.85 (s, 1H), 5.58 (s, 1H),
13
1
.66 (dd, J = 4.8 Hz, J = 2.8 Hz, 2H), 1.43 (dd, J = 5.0 Hz, J = 2.6 Hz, 2H). C NMR (150 MHz,
1
2
1
2
CDCl ) δ 197.9, 171.8, 136.1, 133.3, 128.8, 128.7, 34.6, 15.8. HRMS (ESI), m/z calcd. for
3
+
C H NNaO ([M+Na] ) 212.0682, found: 212.0691.
11
11
2
1
ꢀ(4ꢀMethoxybenzoyl)cyclopropaneꢀ1ꢀcarboxamide (2b’). The product was isolated by flash chromaꢀ
o
1
tography (eluent: EA:PE = 1:2) as a white solid (39 mg, 88%); mp: 143ꢀ145 C; H NMR (600 MHz,
6
DMSOꢀd ) δ 7.90ꢀ7.84 (m, 2H), 7.20 (s, 1H), 7.05 (s, 1H), 7.05ꢀ7.01 (m, 2H), 3.83 (s, 3H), 1.36 (dd, J1
13
=
7.2 Hz, J = 4.2 Hz, 2H), 1.21 (dd, J = 7.2 Hz, J = 4.2 Hz, 2H). C NMR (150 MHz, DMSOꢀd ) δ
2 2 2 6
1
94.5, 172.3, 163.4, 131.2, 129.8, 114.2, 56.0, 35.0, 14.0. HRMS (ESI), m/z calcd. for C H NNaO
12 13 3
+
(
[M+Na] ) 242.0788, found: 242.0788.
3
7
1ꢀAcetylcyclopropaneꢀ1ꢀcarboxamide (2c’). The product was isolated by flash chromatography (elꢀ
o
1
uent: EA:PE = 1:2) as a white solid (18 mg, 71%); mp: 85ꢀ87 C; H NMR (600 MHz, CDCl ) δ 8.68 (s,
3
1
H), 5.82 (s, 1H), 1.97 (s, 3H), 1.86 (dd, J = 7.2 Hz, J = 3.6 Hz, 2H), 1.53 (dd, J = 6.6 Hz, J = 4.2 Hz,
1 2 1 2
1
3
2H). C NMR (150 MHz, CDCl ) δ 207.0, 171.3, 34.3, 24.9, 19.51 19.50. HRMS (ESI), m/z calcd. for
3
+
C H NNaO ([M+Na] ) 150.0525, found: 150.0529.
6
9
2
ACS Paragon Plus Environment

Page 15 of 22
The Journal of Organic Chemistry
1
ꢀCyanocyclopropaneꢀ1ꢀcarboxamide (2d’). The product was isolated by flash chromatography (eluꢀ
1
2
o
1
ent: EA:PE = 1:2) as a white solid (15 mg, 68%); mp: 105ꢀ108 C; H NMR (400 MHz, CDCl ) δ 6.41
3
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
3
(s, 1H), 5.94 (s, 1H), 1.70 (dd, J = 8.0 Hz, J = 4.4 Hz, 2H), 1.55 (dd, J = 8.0 Hz, J = 4.4 Hz, 2H). C
1
2
1
2
+
NMR (150 MHz, CDCl ) δ 167.4, 120.1, 18.1, 13.1. HRMS (ESI), m/z calcd. for C H N O ([M+H] )
3
5
6
2
1
11.0553, found: 111.0561.
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
(
Z)ꢀ1ꢀ((Acetoxyimino)(phenyl)methyl)cyclopropaneꢀ1ꢀcarboxamide(2e’). The product was isolated by
o
1
flash chromatography (eluent: EA:PE = 1:2) as a white solid (50 mg, 68%); mp: 172ꢀ175 C; H NMR
(
600 MHz, CDCl ) δ 7.52 (s, 1H), 7.44 (s, 3H), 7.37 (d, J = 5.4 Hz, 2H), 5.51 (s, 1H), 2.02 (s, 3H), 1.69
3
1
3
(
s, 2H), 1.14 (s, 2H). C NMR (150 MHz, CDCl ) δ 172.18, 168.18, 167.79, 131.16, 130.20, 128.46,
3
+
127.91, 29.13, 19.37, 16.54. HRMS (ESI), m/z calcd. for C H N NaO ([M+Na] ) 269.0897, found:
1
3
14
2
3
2
69.0895.
ꢀbenzoylcyclopentaneꢀ1ꢀcarboxamide (2f’). The product was isolated by flash chromatography (eluꢀ
1
o
1
ent: EA:PE = 1:2) as a white solid (32 mg, 73%); mp: 132ꢀ135 C; H NMR (600 MHz, CDCl ) δ 7.92
3
(
d, J = 8.4 Hz, 2H), 7.52 (t, J = 7.2 Hz, 1H), 7.40 (t, J = 7.8 Hz, 2H), 5.67 (s, 1H), 5.50 (s, 1H), 2.40ꢀ
13
2
.30 (m, 4H), 1.74ꢀ1.67 (m, 2H), 1.62ꢀ1.54 (m, 2H). C NMR (150 MHz, CDCl ) δ 199.5, 174.6, 135.2,
3
+
1
33.0, 129.3, 128.4, 65.8, 34.8, 26.0. HRMS (ESI), m/z calcd. for C H NNaO ([M+Na] ) 240.0995,
13 15
2
found: 240.1003.
2
ꢀBenzoylꢀ2ꢀethylbutanamide (2g’). The product was isolated by flash chromatography (eluent:
o
1
EA:PE = 1:2) as a white solid (36 mg, 82%); mp: 125ꢀ130 C; H NMR (400 MHz, CDCl ) δ 77.95ꢀ
3
7.88 (m, 2H), 7.53 (t, J = 7.2 Hz, 1H), 7.42 (t, J = 7.6 Hz, 2H), 5.57 (s, 1H), 5.49 (s, 1H), 2.15ꢀ2.00 (m,
13
4
H), 0.76 (t, J = 7.6 Hz, 6H). C NMR (100 MHz, DMSOꢀd ) δ 198.7, 174.2, 136.1, 132.5, 128.4,
6
+
1
28.1, 61.5, 23.9, 7.7. HRMS (ESI), m/z calcd. for C H NNaO ([M+Na] ) 242.1151, found: 242.1158.
1
3
17
2
3
8
2ꢀBenzoylbutanamide (2h’). The product was isolated by flash chromatography (eluent: EA:PE =
o
1
1
:2) as a white solid (29 mg, 77%); mp: 146ꢀ149 C; H NMR (400 MHz, CDCl ) δ 8.03 (d, J = 7.2 Hz,
3
2
H), 7.62 (t, J = 7.4 Hz, 1H), 7.50 (t, J = 7.6 Hz, 2H), 6.60 (s, 1H), 5.50 (s, 1H), 4.29 (t, J = 7.2 Hz, 1H),
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 22
1
3
2
.14 – 1.94 (m, 2H), 1.00 (t, J = 7.0 Hz, 3H). C NMR (100 MHz, DMSOꢀd ) δ 195.8, 170.7, 136.4,
6
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
33.2, 128.6, 128.1, 56.0, 21.9, 11.9. HRMS (ESI), m/z calcd. for C H NO ([M+H] ) 192.1019, found:
1
1
14
2
192.1024.
2
,2ꢀDifluoroꢀ3ꢀoxoꢀ3ꢀphenylpropanamide (2i’). The product was isolated by flash chromatography
o
1
(
eluent: EA:PE = 1:2) as a white solid (30 mg, 80%); mp: 93ꢀ96 C; H NMR (600 MHz, CDCl ) δ 8.13
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
13
(
d, J = 7.8 Hz, 2H), 7.66 (t, J = 7.8 Hz, 1H), 7.51 (t, J = 7.8 Hz, 2H), 6.55 (s, 1H), 6.47 (s, 1H). C
NMR (150 MHz, CDCl ) δ 187.0 (t, J = 27.0 Hz), 163.6 (t, J = 27.9 Hz), 135.1, 131.5, 130.4 (t, J = 2.8
3
+
Hz), 128.9, 110.7 (t, J = 264.0 Hz). HRMS (ESI), m/z calcd. for C H F NNaO ([M+Na] ) 222.0337,
9
7
2
2
found: 222.0341.
2ꢀFluoroꢀ3ꢀoxoꢀ3ꢀphenylpropanamide (2j’). The product was isolated by flash chromatography (eluꢀ
o
1
ent: EA:PE = 1:2) as a white solid (24 mg, 65%); mp: 124ꢀ127 C; H NMR (600 MHz, DMSOꢀd ) δ
6
8
.05ꢀ8.02 (m, 2H), 8.01 (s, 1H), 7.79 (s, 1H), 7.72ꢀ7.69 (m, 1H), 7.57 (t, J = 7.8 Hz, 2H), 6.40 (d, J =
1
3
48.0 Hz, 1H). C NMR (150 MHz, DMSOꢀd ) δ 192.2 (d, J = 18.0 Hz), 166.7 (d, J = 20.7 Hz), 134.7,
6
+
1
34.5, 129.8, 129.1, 90.7 (d, J = 192.3 Hz). HRMS (ESI), m/z calcd. for C H FNNaO ([M+Na] )
9
8
2
2
04.0431, found: 204.0437.
ꢀOxoꢀ3ꢀphenylpropanamide (2k’). The product was isolated by flash chromatography (eluent:
3
9
3
o
1
EA:PE = 1:2) as a white solid (14 mg, 42%); mp: 103ꢀ106 C; H NMR (600 MHz, CDCl ) δ 7.99 (d, J
3
=
7.8 Hz, 2H), 7.62 (t, J = 7.2 Hz, 1H), 7.50 (t, J = 7.8 Hz, 2H), 7.12 (s, 1H), 5.80 (s, 1H), 3.98 (s, 2H).
1
3
C NMR (150 MHz, CDCl ) δ 195.6, 168.1, 136.1, 134.1, 128.9, 128.5, 45.0. HRMS (ESI), m/z calcd.
3
+
for C H NO ([M+H] ) 164.0706, found: 164.0714.
9
10
2
40
2
ꢀ(1,3ꢀDithiolanꢀ2ꢀylidene)ꢀ3ꢀoxobutanamide(2l’). The product was isolated by flash chromatogꢀ
o
1
raphy (eluent: EA:PE = 1:2) as a white solid (32 mg, 79%); mp: 217ꢀ220 C; H NMR (600 MHz,
DMSOꢀd ) δ 7.79 (s, 1H), 7.49 (s, 1H), 3.37 (d, J = 3.6 Hz, 2H), 3.35 (d, J = 3.6 Hz, 2H), 2.17 (s, 3H).
6
1
3
C NMR (150 MHz, DMSOꢀd ) δ 190.7, 169.6, 165.9, 124.9, 38.6, 36.4, 28.0. HRMS (ESI), m/z calcd.
6
+
for C H NNaO S ([M+Na] ) 225.9967, found: 225.9971.
7
9
2 2
ACS Paragon Plus Environment

Page 17 of 22
The Journal of Organic Chemistry
(
9HꢀFluorenꢀ9ꢀyl)methyl tertꢀbutyl (6ꢀoxoꢀ6ꢀ(pꢀtolylamino)hexaneꢀ1,5ꢀdiyl)(S)ꢀdicarbamate [(S)-
1
2
1
m’]. The product was isolated by flash chromatography (eluent: EA:PE = 1:2) as a white solid (1.25 g,
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
o
1
90%); mp: 136ꢀ139 C; H NMR (400 MHz, CDCl ) δ 8.24 (s, 1H), 7.75 (d, J = 7.6 Hz, 2H), 7.61ꢀ7.54
3
(
m, 2H), 7.38 (t, J = 8.4 Hz, 4H), 7.29 (d, J = 7.6 Hz, 2H), 7.10 (d, J = 8.0 Hz, 2H), 5.63 (s, 1H), 4.64 (s,
1
1
1
2
H), 4.41 (s, 2H), 4.28 (s, 1H), 4.20 (t, J = 6.8 Hz, 1H), 3.13ꢀ3.06 (m, 2H), 2.30 (s, 3H), 1.97 (s, 1H),
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
.70 (s, 1H), 1.50 (s, 2H), 1.43 (s, 9H), 1.31ꢀ1.22 (m, 2H). C NMR (100 MHz, CDCl ) δ 169.9, 156.3,
3
43.7, 141.3, 135.0, 134.1, 129.5, 127.8, 127.1, 125.1, 120.1, 120.0, 79.4, 67.2, 55.5, 47.1, 39.6, 31.8,
+
9.5, 28.4, 22.5, 20.9. HRMS (ESI), m/z calcd. for C H N O ([M+H] ) 558.2968, found: 558.2970.
33
40
3
5
Chiral HPLC purity: 100% ee (254 nm) [t (major) = 11.37 min].
R
(9HꢀFluorenꢀ9ꢀyl) methyl tertꢀbutyl (6ꢀaminoꢀ6ꢀoxohexaneꢀ1,5ꢀdiyl)(S)ꢀdicarbamate [(S)-2m’]. The
product was isolated by flash chromatography (eluent: EA:PE = 7:10) as a white solid (42 mg, 45%);
o
1
mp: 118ꢀ120 C; H NMR (400 MHz, CDCl ) δ 7.75 (d, J = 7.6 Hz, 2H), 7.58 (d, J = 7.2 Hz, 2H), 7.39
3
(t, J = 7.6 Hz, 2H), 7.30 (t, J = 7.2 Hz, 2H), 6.22 (s, 1H), 5.68 (d, J = 6.8 Hz, 2H), 4.66 (s, 1H), 4.42ꢀ
4
.40 (m, 2H), 4.19 (t, J = 6.4 Hz, 2H), 4.15ꢀ4.09 (m, 1H), 3.09 (s, 2H), 1.86ꢀ1.81 (m, 2H), 1.72ꢀ1.68 (m,
13
1
H), 1.42 (s, 9H), 1.26 (t, J = 7.1 Hz, 2H). C NMR (100 MHz, CDCl ) δ 174.28, 156.30, 143.75 (d, J
3
=
3.4 Hz), 141.3, 127.8, 127.1, 125.1, 120.0, 67.0, 60.4, 54.4, 47.2, 39.8, 31.7, 29.6, 28.4, 22.4, 14.2.
+
HRMS (ESI), m/z calcd. for C H N O ([M+H] ) 468.2498, found: 468.2495. Chiral HPLC purity:
2
6
34
3
5
9
9.43% ee (254 nm) [t (major) = 16.47 min, t (minor) = 12.87 min].
R R
(
9HꢀFluorenꢀ9ꢀyl)methyl tertꢀbutyl (6ꢀoxoꢀ6ꢀ(pꢀtolylamino)hexaneꢀ1,5ꢀdiyl)(R)ꢀdicarbamate [(R)-
1m’]. The product was isolated by flash chromatography (eluent: EA:PE = 1:2) as a white solid (1.28 g,
o
1
9
2%); mp: 162ꢀ164 C; H NMR (600 MHz, CDCl ) δ 8.21 (s, 1H), 7.75 (d, J = 6.6 Hz, 2H), 7.58 (s,
3
2
H), 7.39 (s, 4H), 7.28 (s, 2H), 7.10 (d, J = 7.8 Hz, 2H), 5.61 (s, 1H), 4.64 (s, 1H), 4.42 (s, 2H), 4.28 (s,
1H), 4.21 (t, J = 6.6 Hz, 1H), 3.16 (s, 1H), 3.10 (s, 1H), 2.31 (s, 3H), 1.98 (s, 1H), 1.67 (s, 2H), 1.53 (s,
1
3
2
1
H), 1.43 (s, 9H). C NMR (150 MHz, CDCl ) δ 169.9 156.6, 156.3, 143.7, 141.3, 135.0, 134.1, 129.4,
3
27.7, 127.1, 125.0, 120.1, 120.0, 79.3, 67.2, 55.4, 47.1, 39.6, 31.7, 29.5, 28.4, 22.4, 20.9. HRMS (ESI),
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 18 of 22
+
m/z calcd. for C H N NaO ([M+Na] ) 580.2782, found: 580.2782. Chiral HPLC purity: 100% ee (254
3
3
39
3
5
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
nm) [t (major) = 9.97 min].
R
(9HꢀFluorenꢀ9ꢀyl)methyl tertꢀbutyl (6ꢀaminoꢀ6ꢀoxohexaneꢀ1,5ꢀdiyl)(R)ꢀdicarbamate [(R)-2m’]. The
product was isolated by flash chromatography (eluent: EA:PE = 7:10) as a white solid (61 mg, 65%);
o
1
mp: 105ꢀ108 C; H NMR (600 MHz, CDCl ) δ 7.76 (d, J = 7.2 Hz, 2H), 7.59 (d, J = 6.6 Hz, 2H), 7.39
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
(t, J = 7.2 Hz, 2H), 7.31 (t, J = 7.2 Hz, 2H), 6.18 (s, 1H), 5.59 (s, 2H), 4.64 (s, 1H), 4.49ꢀ4.35 (m, 2H),
1
3
4
.19 (m, 2H), 3.11 (s, 2H), 1.87 (s, 1H), 1.72 (s, 3H), 1.50 (s, 2H), 1.42 (s, 9H), 1.39 (s, 2H). C NMR
(
150 MHz, CDCl ) δ 174.5, 156.5, 156.3, 143.8, 141.3, 127.8, 127.1, 125.1, 120.0, 79.3, 67.0, 54.4, 47.2,
3
+
3
9.8, 31.7, 29.6, 28.4, 22.4. HRMS (ESI), m/z calcd. for C H N NaO ([M+Na] ) 490.2303, found:
2
6
33
3
5
490.2312. Chiral HPLC purity: 99.75% ee (254 nm) [t (major) = 12.83 min, t (minor) = 16.48 min].
R
R
1
ꢀ(Hydroxy(phenyl)methyl)ꢀNꢀ(pꢀtolyl)cyclopropaneꢀ1ꢀcarboxamide (3a’). The product was isolated
o
1
by flash chromatography (eluent: EA:PE = 3:10) as a white solid (0.74 g, 88%); mp: 133ꢀ137 C; H
NMR (600 MHz, CDCl ) δ 8.94 (s, 1H), 7.46 (d, J = 7.8 Hz, 2H), 7.33 (t, J = 7.2 Hz, 2H), 7.29ꢀ7.25 (m,
3
3
1
1
H), 7.04 (d, J = 7.8 Hz, 2H), 4.58 (s, 1H), 3.19 (s, 1H), 2.26 (s, 3H), 1.61ꢀ1.18 (m, 1H), 1.23ꢀ1.16 (m,
13
H), 0.90ꢀ0.83 (m, 1H), 0.83ꢀ0.76 (m, 1H). C NMR (150 MHz, CDCl ) δ 170.4, 140.3, 135.5, 133.5,
3
18 19
29.3, 128.5, 127.9, 126.1, 120.0, 29.9, 20.8, 14.0, 11.4. HRMS (ESI), m/z calcd. for C H NNaO2
+
(
[M+Na] ) 304.1308, found: 304.1308.
ASSOCIATED CONTENT
S Supporting Information
The Supporting Information is available free of charge on the ACS Publications website at DOI:
0.1021/acs.joc.*******.
Radical trapping experiments; Copies of HPLC spectra for racemic and enantiomerically enriched comꢀ
*
1
1
13
pounds 1m and 2m; H and C NMR spectra for all compounds (PDF)
AUTHOR INFORMATION
Corresponding Authors
ACS Paragon Plus Environment

Page 19 of 22
The Journal of Organic Chemistry
*
*
Eꢀmail: zhangzg@htu.edu.cn. Fax: (+86)ꢀ373ꢀ332ꢀ5250.
Eꢀmail: zgs6668@yahoo.com.
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
ORCID
Zhiguo Zhang: 0000ꢀ0001ꢀ6920ꢀ0471
ACKNOWLEDGMENT
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
We thank the NSFC (21272057, 21372065, 21772032, 21702051 and U1604285), Natural Science
Foundation of Henan (162300410180), Henan Provincial Natural Science Foundation (162300410180),
Young Backbone Teachers Fund of Henan (2014GGJSꢀ049), Science & Technology Innovation Talents
in Universities of Henan (17HASTIT002), and Outstanding Young Talent Cultivation Project Funding
of Henan Normal University (14YR002), and Jilin Province Key Laboratory of Organic Functional Moꢀ
lecular Design & Synthesis (130028742).
REFERENCES
(1) (a) Berrino, R.; Cacchi, S.; Fabrizi, G.; Goggiamani, A. J. Org. Chem. 2012, 77, 2537; (b) García, J.
M.; García, F. C.; Serna, F.; de la Peña, J. L. Prog. Polym. Sci. 2010, 35, 623; (c) Xie, L.ꢀY.; Duan,
Y.; Lu, L.ꢀH.; Li, Y.ꢀJ.; Peng, S.; Wu, C.; Liu, K.ꢀJ.; Wang, Z.; He, W.ꢀM. ACS Sustainable Chem.
Eng. 2017, 5, 10407.
(2) (a) Xie, P.; Wang, Z.ꢀQ.; Deng, G.ꢀB.; Song, R.ꢀJ.; Xia, J.ꢀD.; Hu, M. Li, J.ꢀH. Adv. Synth. Catal.
2
013, 355, 2257; (b) Hu, M.; Fan, J.ꢀH.; Liu, Y.; Ouyang, X.ꢀH.; Song, R.ꢀJ.; Li, J.ꢀH. Angew. Chem.
Int. Ed. 2015, 54, 9577; (c) Yang, X.ꢀH.; Song, R.ꢀJ.; Xie, Y.ꢀX.; Li, J.ꢀH. Chemcatchem 2016, 8,
2429.
(
3) Wang, Q.; Su, Y.; Li, L.; Huang, H. Chem. Soc. Rev. 2016, 45, 1257.
4) Robins, L. I.; Fogle, E. J.; Marlier, J. F. Biochim. Biophys. Acta 2015, 1854, 1756.
(
(5) (a) R. T. Sanderson, Polar Covalence, 1983. (b) R. T. Sanderson, Chemical Bonds and Bond Energy,
976.
1
(6) Tobisu, M.; Nakamura, K.; Chatani, N. J. Am. Chem. Soc. 2014, 136, 5587.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 20 of 22
(
7) Taniguchi, T.; Imoto, M.; Takeda, M.; Matsumoto, F.; Nakai, T.; Mihara, M.; Mizuno, T.; Nomoto,
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
A.; Ogawa, A. Tetrahedron 2016, 72, 4132.
(8) Azzena, U.; Cattari, M.; Melloni, G.; Pisano, L. Synthesis 2003, 2003, 2811.
(
9) (a) Koreeda, T.; Kochi, T.; Kakiuchi, F. J. Organomet. Chem. 2013, 741–742, 148; (b) Koreeda, T.;
Kochi, T.; Kakiuchi, F. Organometallics 2013, 32, 682; (c) Koreeda, T.; Kochi, T.; Kakiuchi, F. J.
Am. Chem. Soc. 2009, 131, 7238; (d) Ueno, S.; Chatani, N.; Kakiuchi, F. J. Am. Chem. Soc. 2007,
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
29, 6098.
(
10) Kronenthal, D. R.; Han, C. Y.; Taylor, M. K. J. Org. Chem. 1982, 47, 2765; b) Berger, M.; Chauꢀ
han, R.; Rodrigues, C. A. B.; Maulide, N. Chem. Eur. J. 2016, 22, 16805; c) Lee, W. C. C.; Tehrani,
A.; Li, J. J. Synthesis 2017, 49, 2865.
(
11) Ouyang, K.; Hao, W.; Zhang, W.ꢀX.; Xi, Z. Chem. Rev. 2015, 115, 12045.
12) (a) Robert K. Boeckman, J.; Shao, P.; Mullins, J. J. Org. Synth. 2000, 77, 141; (b) Frigerio, M.;
Santagostino, M.; Sputore, S. J. Org. Chem. 1999, 64, 4537.
(
(13) Frigerio, M.; Santagostino, M. Tetrahedron Lett. 1994, 35, 8019.
(14) de Graaff, C.; Bensch, L.; van Lint, M. J.; Ruijter, E.; Orru, R. V. A. Org. Biomol. Chem. 2015, 13,
1
0108.
15) (a) Zhang, Z.; Gao, X.; Li, Z.; Zhang, G.; Ma, N.; Liu, Q.; Liu, T. Org. Chem. Front. 2016, 4, 404.
b) Zhang, Z.; Huang, Y.; Guoqing, H.; Zhang, G.; Liu, Q. J. Heterocyclic Chem. 2017, 54, 2426.
(
(
(
16) (a) Baran, P. S. Zhong, Y.ꢀL. J. Am. Chem. Soc. 2001, 123, 3183; (b) Nicolaou, K. C.; Baran, P. S.;
Zhong, Y. L.; Barluenga, S.; Hunt, K. W.; Kranich, R.; Vega, J. A. J. Am. Chem. Soc. 2002, 124,
2
233.
(17) Huang, P.; Fu, X.; Liang, Y.; Zhang, R.; Dong, D. Aust. J. Chem. 2012, 65, 121.
(18) (a) Duschek, A.; Kirsch, S. F. Angew. Chem. Int. Ed. 2011, 50, 1524ꢀ1552; (b) Qian, P.ꢀC.; Liu, Y.;
Song, R.ꢀJ.; Hu, M.; Yang, X.ꢀH.; Xiang, J.ꢀN.; Li, J.ꢀH. Eur J. Org. Chem. 2015, 1680.
(19) Nicolaou, K. C. Zhong, Y. L. Baran, P. S. J. Am. Chem. Soc. 2000, 122, 7596.
ACS Paragon Plus Environment

Page 21 of 22
The Journal of Organic Chemistry
(
20) We have tried hard to isolate phenolic byproducts, but they are very unstable in the reaction mixꢀ
ture. This was confirmed by a separate experiment with phenol under the optimized conditions. A
very complexed and unstable mixture was afforded rather than benzoquinones.
21) Kita, Y.; Tohma, H.; Hatanaka, K.; Takada, T.; Fujita, S.; Mitoh, S.; Sakurai, H.; Oka, S. J. Am.
Chem. Soc. 1994, 116, 3684.
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
22) (a) Kita, Y.; Takada, T.; Tohma, H. Pure Appl. Chem. 1996, 68, 627. (b) Tohma, H.; Morioka, H.;
Takizawa, S.; Arisawa, M.; Kita, Y. Tetrahedron 2001, 57, 345.
(23) Zheng, X.; Kerr, M. A. Org. Lett. 2006, 8, 3777.
(24) Zhang, Z.; Zhang, Q.; Sun, S.; Xiong, T.; Liu, Q. Angew. Chem. Int. Ed. 2007, 46, 1726.
(25) Zhang, D.; Zhang, R.; Xiang, D.; Zhang, N.; Liang, Y.; Dong, D. Synthesis 2012, 705.
(26) (a) Chandrasekhar S.; Gopalaiah, K. Tetrahedron Lett. 2002, 43, 4023; (b) Shirini, F.; Zolfigol, M.
A.; Azadbar, M. R. Synth. Commun. 2002, 32, 315.
(27) Zhao, X.; Liu, T.ꢀX.; Ma, N.; Zhang, Z.; Zhang, G. Tetrahedron 2016, 72, 4938.
(28) (a) L. Pan, X. Bi, Q. Liu, Chem. Soc. Rev. 2013, 42, 1251; (b) Zhang, L.; Dong, J.; Xu, X.; Liu, Q.
Chem. Rev. 2016, 116, 287.
(
29) Moss, R. A.; MoralesꢀRojas, H.; Zhang, H.; Park, B.ꢀD. Langmuir 1999, 15, 2738.
30) Isolated yield of (S)ꢀ2m’ is 45%, and HPLC yield of (S)ꢀ2m’ is 56%, along with 31% of recovered
(
(S)ꢀ1m’. And for more information, please see SI.
(31) Battilocchio, C.; Hawkins, J. M.; Ley, S. V. Org. Lett. 2014, 16, 1060.
(32) Islam, S. M.; Ghosh, K.; Singha Roy, A.; Molla, R. A. Appl. Organometal. Chem. 2014, 28, 900.
(
33) Marce, P.; Lynch, J.; Blacker, A. J.; Williams, J. M. J. Chem. Commun. 2016, 52, 1436.
34) Tinnis, F.; Lundberg, H.; Adolfsson, H. Adv. Synth. Catal. 2012, 354, 2531.
(
(35) Gipson, R. M.; Pettit, F. H.; Skinner, C. G.; Shive, W. J. Org. Chem. 1963, 28, 1425.
(
36) YuLin, W.; JingLi, Z. Chin. J. Org. Chem. 1986, 6, 153.
37) Gotor, V.; Liz, R.; Testera, A. M. Tetrahedron 2004, 60, 607.
(
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 22 of 22
(
38) Zheng, C.; Zhang, X.; Ijaz Hussain, M.; Huang, M.; Liu, Q.; Xiong, Y.; Zhu, X. Tetrahedron Lett.
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
2
017, 58, 574.
(39) Li, Y.; Zhang, Q.; Cheng, X.; Liu, Q.; Xu, X. H. Synthesis 2009, 824.
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
ACS Paragon Plus Environment