Lipophilic Indole-Catalyzed Intermolecular Bromoesterification of Olefins in Nonpolar Media

Article abstract of DOI:10.1021/acs.joc.9b00029

An environmentally benign and highly versatile catalytic protocol has been successfully applied in the intermolecular bromoesterification between various olefins and carboxylic acids. The use of a highly lipophilic indole catalyst and 1,3-dibromo-5,5-dime

Full text of DOI:10.1021/acs.joc.9b00029

Subscriber access provided by WEBSTER UNIV
Article
Lipophilic Indole-Catalyzed Intermolecular
Bromoesterification of Olefins in Nonpolar Media
YAO SHI, Jonathan Wong, Zhihai Ke, and Ying-Yeung Yeung
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b00029 • Publication Date (Web): 28 Feb 2019
Downloaded from http://pubs.acs.org on March 2, 2019
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 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 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.
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 28
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Lipophilic
Indole-Catalyzed
Intermolecular
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
Bromoesterification of Olefins in Nonpolar Media
Yao Shi,† Jonathan Wong,† Zhihai Ke,* Ying-Yeung Yeung*
Department of Chemistry, The Chinese University of Hong Kong, Shatin, NT, Hong Kong
(China)
COOMe
8
N
R
H
Indole organocatalysis
Equal molar acid and olefin
O
(5 mol %)
O
O
+
Mild reaction conditions
Excellent chemoselectivity
Br
R
OH
DBDMH
heptane
(equal molar)
ABSTRACT: An environmentally-benign and highly versatile catalytic protocol has been
successfully applied in the intermolecular bromoesterification between various olefins and
carboxylic acids. The use of a highly lipophilic indole catalyst and 1,3-dibromo-5,5-
dimethylhydantoin (DBDMH) as the bromine source allows the reaction to proceed in heptane
via a solid-liquid phase transfer mechanism, affording the corresponding bromoester products in
good-to-excellent yields.
1
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 28
1
2
3
4
1. INTRODUCTION
5
6
7
8
Electrophilic halofunctionalization of alkenes is a powerful organic transformation, permitting
the simultaneous introduction of a halogen and an additional functional group across the olefinic
substrates. The resultant 1,2-halofunctionalized compounds are valuable building blocks that can
easily be manipulated by nucleophilic substitution of the halogen.1–4 Olefinic
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
halofunctionalizations
such
as
haloetherifications,5–11
haloamidations,12–15
halo-
dearomatization16 and haloesterifications2–4,17–20 are well-documented. Amongst these reactions,
intermolecular haloesterification is challenging with a low efficiency partly due to the weak
nucleophilicity of the carboxylate group. Practically, super-stoichiometric amounts of carboxylic
acid is often required to compensate the low reaction efficiency.3,4 In addition, these reactions are
typically run in environmentally unfriendly solvents such as methylene chloride and chloroform.
A seminal work on the asymmetric bromoesterification of unactivated olefins was reported by
Shi in which the reactions proceeded smoothly with catalyst (DHQD)2PHAL in ethyl acetate
(Scheme 1, eq 1).2b. Recently, Borhan19a and Christmann19b independently reported elegant
examples of intermolecular asymmetric haloesterifications of assisting group-containing olefins
and the assisting groups were found to be crucial in facilitating the introduction of ester groups.
In our previous research efforts regarding the bromolactonization of olefinic acids 2,20 we have
demonstrated that indole-based catalyst 1a allowed the reaction to proceed efficiently in green
lipophilic solvents such as heptane21 via a solid-liquid phase transfer mechanism (Scheme 1, eq
2).22,23 Very recently, we re-engineered indole 1a to the more lipophilic catalyst 1b, which was
found to be very potent in promoting the aromatic bromination of various anisole, thioanisole
and aniline-type substrates 4 (Scheme 1, eq 3).24 Herein, we are pleased to disclose our recent
success in the application of the indole catalytic protocol to the intermolecular
2
ACS Paragon Plus Environment

Page 3 of 28
The Journal of Organic Chemistry
1
2
3
4
5
6
bromoesterification of olefinic substrates 6 in nonpolar media with equimolar amount of the
carboxylic acids 7 as the nucleophilic partners (Scheme 1, eq 4).
7
8
9
Scheme 1. Lipophilic Indole-based Catalysis in Bromination
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
Selected literature example of bromoesterification in polar media (ref 2b)
(1-Nap)
(DHQD)2PHAL
(10 mol %)
O
R1
O
O
Ar
+
(1)
Br
R1
(1-Nap)
OH
R2
PhC(O)NHBr
Ar
EtOAc, -30 o
C
R2
Previous works on indole-catalyzed bromination in lipophilic media (ref 20, 24)
COOMe
O
Me
N
HO
O
1a
(5 mol %)
H
O
(2)
(3)
Br
NBS
2
3
COOMe
Br
H
Ar
4
N
H
1b
(5 mol %)
Z
Ar
Z
NBS, heptane, 25 o
C
Z = SR, OR, NR2
5
This work
COOMe
R
N
H
O
O
O
(4)
1c
(5 mol %), DBDMH
+
Br
heptane, 25 o
C
R
OH
6
7
8
R = Ar or Alkyl
(equal molar)
2. RESULTS AND DISCUSSION
The investigation began with the intermolecular bromoesterification of styrene (6a) in heptane.
1,3-Dibromo-5,5-hydantoin (DBDMH) and benzoic acid (7a) were used as the halogen source
and the nucleophilic partner, respectively. A series of lipophilic indole-based catalysts 1a-d were
examined and the results are summarized in Table 1. The reaction was sluggish when no catalyst
was applied (Table 1, entry 1). Some common catalysts for electrophilic halogenations25–28
including Lewis base (Ph3PS), Lewis acid (FeCl3), Brønsted acid (HCl), and Brønsted base
(Na2CO3) catalysts were examined and these reactions gave inferior yields of the desired
bromoester product 8aa as compared to the lipophilic indole catalysts 1 (entries 2–5). For the
3
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 28
1
2
3
4
5
6
7
8
9
case with HCl as the catalyst, significant amounts of vicinal dibrominated side product was
detected. Indole 1a (5 mol%), which was found to be effective in promoting the
bromolactonization of olefinic acids,20 could catalyze the intermolecular bromoesterification of
6a and 7a to give bromoester 8aa with moderate yield, attributable to the moderate solubility of
1a (entry 6). To our delight, dramatic improvement of the efficiency was observed when indole
1c was used, giving the desired product 8aa in 85% yield (entry 8). This increase in activity
could be congruent with an increase in lipophilicity and hence catalyst solubility conferred upon
by the length of the alkyl chain attached at the C(2) position of the indole system. The reaction
was found to be sensitive to the lipophilicity of the catalyst; indole catalyst 1b that has a
relatively shorter hydrocarbon side-chain returned a considerable drop in yield (entry 7).
Diminishment of the reaction efficiency was observed when the sterically hindered indole 1d
was applied instead of 1c (entry 9). The performance of DBDMH was found to be superior to N-
bromosuccinimide (NBS) (entry 10), which can be ascribed to the higher reactivity of DBDMH.
Table 1. Reaction Optimizationa
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
O
HO
O
catalyst (5 mol%)
Br source,
O
+
Br
heptane, 23 oC, 24 h
6a
7a
8aa
COOMe
COOMe
COOMe
COOMe
8
4
N
N
N
N
H
H
H
H
1a
1b
1c
1d
entry
Br source
DBDMH
DBDMH
DBDMH
catalyst
yield (%)
1
2
3
-
11
31
24
Ph3PS
FeCl3
4
ACS Paragon Plus Environment

Page 5 of 28
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
4b
5
DBDMH
DBDMH
DBDMH
DBDMH
DBDMH
DBDMH
NBS
HCl
Na2CO3
1a
12
22
6
35
7
1b
61
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
8
1c
85
9
1d
40
10
1c
trace
a
Reactions were carried out with styrene (6a) (0.36 mmol), benzoic acid (7a) (0.3 mmol),
catalyst (5 mol%), and Br source (0.315 mmol) in n-heptane (1.0 mL) at 23 oC in the absence of
light for 24 h. b Olefinic dibromination of styrene (6a) was observed.
With the optimized reaction conditions in hand, the substrate scope of the intermolecular
bromoesterification reaction catalyzed by indole catalyst 1c was investigated (Table 2). Benzoic
acid derivatives 7 carrying electron donating or withdrawing substituents with styrene (6a) as the
reacting partner gave the corresponding bromoesters 8aa-8ad with excellent yields. In all cases,
the reactions were regioselective for the Markovnikov product and no aromatic bromination side
products were observed. The sterically demanding 2,6-disubstituted benzoic acid 7b was well
tolerated, giving 8ab in 97% yield. 3,5-dibromo-2-hydroxybenzoic acid (7d) underwent
preferential nucleophilic attack from the carboxylate group to yield bromoester 8ad, attributed to
the intramolecular hydrogen-bonding which could favor the nucleophilic attack of the
carboxylate.29 Other aliphatic acids such as 7e, 7f and heterocyclic acid such as 2-
thiophenecarboxylic acid (7j) were also found to react smoothly under these conditions to give
8ae, 8af and 8aj, respectively. However, 4-nitrobenzoic acid and 4-methylcinnamic acid gave
sluggish reactions with very low conversions (<5%).
5
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 28
1
2
3
4
Table 2. Substrate Scopea
5
6
7
8
9
R
O
O
HO
O
1c
(5 mol %), DBDMH
Br
heptane, 23 o
C
+
R
7
6
8
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
O
, R2 = H
6a
6b
6c
6d
6e
, R = H
7a
7b
7c
7d
7g
7h
7i
Me
Me
, R2 = 2,4-Me2
, R2 = 2,6-F2
, R2 = 2-OH-3,5-Br2
, R2 = 4-COOMe
, R2 = 2-Br
R3
OH
, R = 4-Me
, R = 2-Me
, R = 4-Br
, R = 4-Cl
, R = 3-Cl
O
R1
2
2
5
Me
3
4
7e
7f
Ph
, R3 = H
, R3 = CH2Ph
3
OH
R
Me
6k
R2
, R1 = Me
, R1 = NO2
4
6g
6h
COOH
S
6i
6j
6l
6m
6f
6n
, R2 = 2-C(O)Me
7j
, R = 3-NO2
Br
Me
F
Ph
O
OH
O
O
O
O
O
S
O
Br
O
O
O
O
Me
O
F
O
Br
Br
Br
Br
Br
Br
O
Br
8aa
8ab
8ac
8ad
8ae
8af
(63%)
(85%)
O
(97%)
Me
(88%)
(87%)
(57%)
8aj
(69%)
O
Me
Me
Ph
O
MeO
O
O
O
O
O
Br
O
Me
O
Me
O
Br
Br
O
Br
Me
O
Br
Br
Me
Br
Me
Me
(93%)
Br
(91%)
Me
8ba
8bb
8bg
8cb
8da
(86%)
8db
(87%)
(74%)
(90%)
Me
Me
O
O
O
O
O
O
Me
Br
NO2
Br
Br
O
O
Me
O
O
Br
Br
Br
Me
O
O
O
Br
Br
Cl
O
Br
Cl
Cl
8ia
8dh
8ea
8eb
8fb
8ga
8ha
(64%)
(88%)
O
(87%)
(89%)
(92%)
(90%)
O
(87%, dr 12:1)
O
Me
Me
O
Br
O
O
O
O
Br
O
Br
Me Me
Br
Br
O
O
Me
O
O
O
Br
O
Me Me
Br
NO2
8na
(50%)
8ib
8ii
8ja
8ka
8la
8ma
(50%)
(90%)
(89%)
(76%)
(89%)
(95%)
a Reactions were carried out with 6 (0.36 mmol), 7 (0.3 mmol), catalyst 1c (0.015 mmol), and
DBDMH (0.315 mmol) in n-heptane (1 mL) for 24 h at 23 oC in the absence of light.
Styrene derivatives carrying electron rich substituents on the aromatic ring such as 4-
methylstyrene (6b) and 2-methylstyrene (6c) reacted with benzoic derivatives to give the
6
ACS Paragon Plus Environment

Page 7 of 28
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
corresponding bromoesters 8ba, 8bb, 8bg, and 8cb in good-to-excellent yields. Olefins with
electron-deficient substituents such as 4-bromo, 4-chloro, and 3-chlorostyrene (6d, 6e, and 6f,
respectively) also worked well under the mild and pH neutral conditions, furnishing bromoesters
8da, 8db, 8dh, 8ea, 8eb and 8fb in excellent yields. β-Substituted styrene derivatives such as
trans-1-phenyl-1-propene (6g) and trans-1-nitro-2-phenylethylene (6h) reacted with benzoic acid
(7a) to give bromoesters 8ga (dr 12:1) and 8ha in 87% and 64% yields, respectively. The
decrease in yield was consistent with the strong electron-withdrawing nature of the nitro
substituent in 6h, which could deactivate the olefin towards bromination. Other olefinic partners
such as cyclohexene (6i), indene (6j), 2,3-dimethyl-2-butene (6k) and cis-3-hexene (6l) were
also subjected to the reaction, producing bromoesters 8ii, 8ja, 8ka, and 8la, respectively, in
appreciable conversions. The reaction with the bulkier trisubstituted olefin 1-methyl-1-
cyclohexene (6m) gave bromoester 8ma in 50% yield. The use of a highly electron-deficient
olefin 6n still gave the desired product 8na in 50% yield. However, reactions using methyl
cinnamate/acrylate or 2-vinylpyridine were sluggish. 1-Hexene was also examined but low
reaction yield (c.a. 10%) and regioselectivity (3:2) were observed.
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
The indole-catalyzed bromoesterification could also be scaled up while retaining
regioselectivity and yield. For example, the scaled-up reaction using styrene (6a) (3.6 mmol) and
benzoic acid (7a) (3 mmol), produced 8aa in 87% yield (Scheme 2).
7
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 28
1
2
3
4
Scheme 2. Scale-up Reaction
5
6
7
8
9
O
HO
O
1c
DBDMH (1.05 equiv),
(5 mol %)
O
+
Br
heptane, 23 oC, 24 h
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
6a
7a
(3 mmol)
(3.6 mmol)
8aa
87% yield
Based on our previous experience on the indole-catalyzed bromination reactions,20,24,30 we
believe that indole 1c might react with DBDMH to give the 3-bromoindole16 active species 1c-
Br through a solid-liquid phase transfer mechanism (Scheme 3). The existence of 1c-Br was
evidenced by NMR and HRMS analysis. Unlike other intermolecular bromoesterification
reaction, the indole catalytic protocol does not require excess amount of carboxylic acid.3,4 We
speculate that the active species 1c-Br might interact with the carboxylic acid which could
facilitate the reaction. Thus, an 13C NMR experiment on a 1:1 mixture of 1c-Br and benzoic acid
(7a) was conducted and a measurable downfield-shift of the C(2) signal was observed (Figure
1). A possible explanation is that the Schiff base in 1c-Br might interact with the acidic proton of
benzoic acid (7a) to give species A, which would lead to the deshielding of the C(2) in 1c-Br.
Subsequently, the olefinic substrate 6 might then be brominated to give the corresponding
bromiranium species B, which could be attacked by the carboxylate group in a Markovnikov-
fashion to yield product 8. The high reaction efficiency by just employing an equal molar of
olefinic substrates 6 and carboxylic acids 7 could be attributed to the close proximity of the
bromiranium ion and the carboxylate group in the putative species B. However, a more detailed
study is needed in order to elucidate a clearer mechanistic picture.
8
ACS Paragon Plus Environment

Page 9 of 28
The Journal of Organic Chemistry
1
2
3
4
Scheme 3. A Plausible Reaction Mechanism
5
6
7
8
9
O
COOMe
3
Br
O2CR1
Br
N
DBDMH
8
2
N
R2
N
Br
O
H
O
8
1c
H
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
N
N
R2
Br
O
O
R1
Br
O
COOMe
R
Br
MeOOC
H
N
C
8
N
B
180.5 ppm
1c-Br
HRMS
calcd m/z 402.1039
found m/z 402.1037
R2
180.7 ppm
O
R1
6
Br
O
R
N
O
MeOOC
R = n-nonyl
C
H
R1
O
H
7
A
Figure 1. 13C NMR study on a 1:1 mixture of 1c-Br and benzoic acid (7a) [the C(2) signal of
1c-Br]
3. CONCLUSIONS
In summary, we have developed an efficient electrophilic intermolecular bromoesterification
between various olefins and carboxylic acids, using a lipophilic indole as a solid-liquid phase
9
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 28
1
2
3
4
5
6
7
8
9
transfer catalyst, DBDMH as the bromine source, and the lipophilic green solvent, heptane, as
the reaction media. This process is highly regioselective, producing the corresponding 1,2-
bromoester products with good to excellent yields. Mechanistic studies suggest that a 3-
bromoindole intermediate may act as the active electrophilic brominating species with a
mechanism analogous to that previously reported by our group. Thus far, we have successfully
applied the indole-catalyzed electrophilic bromination protocol to bromolactonization, aromatic
bromination and intermolecular bromoesterification reactions. As such, this bromination protocol
may represent a highly general method for various bromination reactions, and applications in
other reactions and their asymmetric variants are currently being investigated.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
EXPERIMENTAL SECTION
General Information.
All reactions requiring anhydrous conditions were conducted by standard procedures under
nitrogen atmosphere. Commercially available reagents were used as received. The solvents were
dried over a solvent purification system from Innovative Technology. Melting points were
determined on a BÜCHI B-540b melting point apparatus. 1H NMR, 13C{1H} NMR spectra were
recorded on a Bruker AMX500 (500 MHz) spectrometer or a Bruker AMX400 (400 MHz)
spectrometer. Proton and carbon chemical shifts are reported in parts per million (ppm) values
downfield from TMS (δ 0.00) and referenced to residual protons in NMR solvents (CDCl3 at 
7.26, CD2Cl2 at  5.36) or carbon signals in NMR solvent (CDCl3 at  77.16, CD2Cl2 at  55.42).
High resolution mass spectra were obtained on a Thermo Finnigan MAT95XL Magnetic Sector
Mass Spectrometer (ionization mode: EI) or a Thermo Q Exactive Hybrid Quadrupole-Orbitrap
Mass Spectrometer (ESI ). Analytical thin layer chromatography (TLC) was performed with
10
ACS Paragon Plus Environment

Page 11 of 28
The Journal of Organic Chemistry
1
2
3
4
5
6
Merck pre-coated TLC plates, silica gel 60F-254, layer thickness 0.25 mm. Flash
chromatography separations were performed on Merck 60 (0.040-0.063 mm) mesh silica gel.
7
8
9
Representative procedure for the synthesis of indole catalyst 1c. A mixture of methyl 3-
oxododecanoate (1 mmol), aniline (1.5 mmol) and acetic acid (0.1 mmol) in a 5 mL eggplant-
shaped flask was placed in an ultrasound bath under sonication at 22 oC for ~3 h and the reaction
was monitored by TLC. Upon completion of the reaction, the product mixture was diluted with
EtOH (5 mL), dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure.
The residue was briefly purified by column chromatography through silica gel (hexanes/ethyl
acetate 20:1) to give the corresponding enamine, methyl 3-(phenylamino)dodec-2-enoate, which
was used immediately in the next step.
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
A solution of the methyl 3-(phenylamino)dodec-2-enoate (1.0 mmol) in DMF (3 mL) was
transferred with a syringe into a 50 mL resealable tube containing Pd(OAc)2 (22.5 mg, 0.1 mmol,
10 mol%), Cu(OAc)2 (0.54 g, 3.0 mmol, 3.0 equiv), K2CO3 (0.41 g, 3.0 mmol, 3.0 equiv), DMF
(7 mL) and a magnetic stir bar (Teflon-coated) under a nitrogen atmosphere. The resealable tube
was degassed by evacuation under high vacuum and refilled with nitrogen gas. The step was
repeated three times before closing the screw cap tightly. The resealable tube was then placed in
o
a preheated oil bath at 140 C and allowed to stir for 1 h (no more enamine substrate detectable
by TLC). The product mixture was allowed to cool to room temperature then filtered through a
thin plug of celite eluted with EtOAc (3 x 10 mL). The filtrate was washed with saturated
aqueous NH4Cl (5 mL) and brine (5 mL), dried over anhydrous MgSO4, filtered, and
concentrated under reduced pressure. The residue was purified by flash column chromatography
through silica gel (hexanes/ethyl acetate 10:1) to give indole 1c. 1a, 1b, and 1d were prepared
according to above procedure starting from the corresponding -ketoesters.
11
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 28
1
2
3
4
5
6
7
8
9
1
Methyl 2-pentyl-indole-3-carboxylate (1b). Yield: 87%, 214 mg; Yellow oil. H NMR (400
MHz, CDCl3):  8.97 (s, 1H), 8.15 (d, J = 7.5 Hz, 1H), 7.32 (d, J = 7.5 Hz, 1H), 7.18−7.24 (m,
2H), 3.95 (s, 3H), 3.14 (t, J = 7.8 Hz, 2H), 1.68−1.73 (m, 2H), 1.29−1.34 (m, 4H), 0.86 (t, J =
6.7 Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3):  166.7, 149.1, 134.7, 127.2, 122.3, 121.7,
121.3, 110.8, 103.5, 50.8, 31.6, 29.0, 28.0, 22.4, 14.0. HRMS (EI) m/z: [M]+ calcd for
C15H19NO2 245.1410, found 245.1414.
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
Methyl 2-decyl-indole-3-carboxylate (1c). Yield: 85%, 257 mg; Orange oil. H NMR (400
MHz, CDCl3):  9.18 (s, 1H), 8.16 (d, J = 7.7 Hz, 1H), 7.31 (d, J = 7.7 Hz, 1H), 7.17−7.24 (m,
2H), 3.95 (s, 3H), 3.14 (t, J = 7.6 Hz, 2H), 1.67−1.74 (m, 2H), 1.22−1.33 (m, 12H), 0.89 (t, J =
6.7 Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3):  166.8, 149.3, 134.7, 127.2, 122.3, 121.6,
121.3, 110.9, 103.4, 50.8, 31.9, 29.6, 29.6, 29.5, 29.4, 29.3, 28.0, 22.7, 14.4. HRMS (EI) m/z:
[M]+ calcd for C19H27NO2 301.2036, found 301.2033.
1
Methyl 2-ethylpropyl-indole-3-carboxylate (1d). Yield: 85%, 209 mg; Pale yellow oil. H
NMR (400 MHz, CDCl3):  9.31 (s, 1H), 8.24 (d, J = 5.3 Hz, 1H), 7.41 (s, 1H), 7.28 (s, 2H),
4.01 (s, 4H), 1.76−1.87 (m, 4H), 0.92 (s, 6H). 13C{1H} NMR (100 MHz, CDCl3):  167.1, 151.8,
135.0, 127.0, 122.3, 121.5, 110.9, 105.0, 50.8, 40.0, 29.7, 27.8, 11.9. HRMS (EI) m/z: [M]+
calcd for C15H19NO2 245.1410, found 245.1412.
General Procedure for the intermolecular bromoesterification reactions.
1,3-dibromo-5,5-dimethydantoin (90 mg, 0.315 mmol) was added to a mixture of alkene 6
(0.36 mmol), carboxylic acid 7 (0.3 mmol) and indole catalyst 1c (4.52 mg, 0.015 mmol) in
heptane (1.0 mL) at 23 oC in the absence of light. The resultant mixture was allowed to stir at 23
oC and the reaction was monitored by TLC. The product mixture was concentrated under
12
ACS Paragon Plus Environment

Page 13 of 28
The Journal of Organic Chemistry
1
2
3
4
reduced pressure and the residue was purified by flash column chromatography through silica gel
5
6
(hexanes/ethyl acetate 10:1) to give the corresponding product 8.
7
8
9
2-bromo-1-phenylethyl benzoate (8aa). Yield: 85%, 78 mg; Colorless oil. 1H NMR (400 MHz,
CDCl3):  8.18 (d, J = 7.3 Hz, 2H), 7.63 (t, J = 7.4 Hz, 1H), 7.49−7.53 (m, 4H), 7.37−7.45 (m,
3H), 6.26−6.29 (m, 1H), 3.84−3.88 (m, 1H), 3.76−3.80 (m, 1H). 13C{1H} NMR (100 MHz,
CDCl3):  165.5, 137.8, 133.4, 130.0, 129.8, 129.0, 128.9, 128.6, 126.6, 75.4, 34.6. HRMS (ESI-
Q-orbitrap) m/z: [M+Na]+ calcd for C15H13BrO2Na 326.9991, found 326.9995.
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
2-bromo-1-phenylethyl 2,6-dimethylbenzoate (8ab). Yield: 97%, 97 mg; Colorless oil. H
NMR (400 MHz, CDCl3):  7.39−7.48 (m, 5H), 7.21 (t, J = 7.6 Hz, 1H), 7.05 (d, J = 7.6 Hz,
13
2H), 6.27−6.31 (m, 1H), 3.67−3.71 (m, 1H), 3.78−3.83 (m, 1H), 2.28 (s, 6H). C{1H} NMR
(100 MHz, CDCl3):  169.1, 137.6, 135.0, 133.5, 129.5, 129.2, 128.9, 127.6, 127.0, 76.2, 33.9,
19.9. HRMS (ESI-Q-orbitrap) m/z: [M+Na]+ calcd for C17H17BrO2Na 355.0304, found
355.0304.
1
2-bromo-1-phenylethyl 2,6-difluorobenzoate (8ac). Yield: 88%, 90 mg; Pale yellow oil. H
NMR (400 MHz, CDCl3):  7.37−7.48 (m, 6H), 6.97 (t, J = 8.3 Hz, 2H), 6.27 (dd, J = 8.0, 4.7
13
Hz, 1H), 3.78 (dd, J = 11.0, 8.1 Hz, 1H), 3.70 (dd, J = 11.0, 4.7 Hz, 1H). C{1H} NMR (100
1
3
MHz, CDCl3):  162.3, 161.0 (d, JC-F = 256 Hz), Hz, 160.4, 137.1, 133.3 (t, JC-F = 10.5 Hz),
2
2
128.9 (d, JC-F = 25 Hz), 126.7, 112.2 (d, JC-F = 25 Hz), 112.1, 76.7, 33.8. HRMS (ESI-Q-
orbitrap) m/z: [M+Na]+ calcd for C15H11BrF2O2Na 362.9803, found 362.9808.
2-bromo-1-phenylethyl 3,5-dibromo-2-hydroxybenzoate (8ad). Yield: 87%, 125 mg; Yellow
oil. 1H NMR (400 MHz, CDCl3):  11.16 (s, 1H), 8.06 (d, J = 2.4 Hz, 1H), 7.86 (d, J = 2.4 Hz,
13
1H), 7.39−7.43 (m, 5H), 6.20−6.23 (m, 1H), 3.81−3.86 (m, 1H), 3.70−3.74 (m, 1H). C{1H}
13
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 28
1
2
3
4
NMR (100 MHz, CDCl3):  167.8, 157.8, 141.5, 136.6, 131.5, 129.6, 129.2, 126.6, 114.3, 112.6,
5
6
111.1, 33.5. HRMS (EI) m/z: [M]+ calcd for C15H11Br3O3 477.8232, found 477.8231.
7
8
9
2-bromo-1-phenylethyl propionate (8ae). Yield: 57%, 44 mg; Yellow oil. 1H NMR (400 MHz,
CDCl3):  7.34−7.40 (m, 5H), 5.99−6.01 (m, 1H), 3.59−3.68 (m, 2H), 2.38−2.50 (m, 2H), 1.18
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
(t, J = 7.6 Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3):  173.3, 137.9, 128.9, 128.8, 126.6, 74.7,
34.5, 27.7, 9.2. HRMS (ESI-Q-orbitrap) m/z: [M+Na]+ calcd for C11H13BrO2Na 278.9991, found
278.9994.
1
2-bromo-1-phenylethyl 4-phenylbutanoate (8af). Yield: 63%, 66 mg; Yellow oil. H NMR
(500 MHz, CDCl3):  7.32−7.41 (m, 5H), 7.26−7.30 (m, 2H), 7.21 (d, J = 7.4 Hz, 1H), 7.17 (d, J
= 7.4, 2H), 6.00−6.02 (m, 1H), 3.59−3.68 (m, 2H), 2.66 (t, J = 7.6 Hz, 2H), 2.37−2.49 (m, 2H),
1.97−2.03 (m, 2H). 13C{1H} NMR (125 MHz, CDCl3):  172.4, 141.4, 137.9, 129.0, 128.9,
128.6, 128.5, 126.7, 126.1, 74.9, 35.2, 34.5, 33.7, 26.6. HRMS (ESI-Q-orbitrap) m/z: [M+Na]+
calcd for C18H19BrO2Na 369.0461, found 369.0461.
1
2-bromo-1-phenylethyl thiophene-2-carboxylate (8aj). Yield: 69%, 64 mg; Yellow oil. H
NMR (400 MHz, CDCl3):  7.89 (dd, J = 3.8, 1.2 Hz, 1H), 7.60 (dd, J = 5.0, 1.2 Hz, 2H),
7.33−7.45(m, 5H), 7.13 (dd, J = 4.9, 3.9 Hz, 2H), 3.69−3.81 (m, 2H). 13C{1H} NMR (125 MHz,
CDCl3):  161.0, 137.6, 134.1, 133.1, 133.0, 129.0, 128.8, 127.9, 126.6, 75.5, 34.3. HRMS (ESI-
Q-orbitrap) m/z: [M+Na]+ calcd for C13H11BrO2SNa 334.9535, found 334.9532.
1
2-bromo-1-(p-tolyl)ethyl benzoate (8ba). Yield: 87%, 83 mg; Colorless oil. H NMR (400
MHz, CDCl3):  8.15 (d, J = 7.3 Hz, 2H), 7.60 (t, J = 7.3 Hz, 1H), 7.48 (t, J = 7.7 Hz, 2H), 7.37
(d, J = 8.0 Hz, 2H), 7.22 (d, J = 8.0 Hz, 2H), 6.21−6.24 (m, 1H), 3.81−3.86 (m, 1H), 3.72−3.76
14
ACS Paragon Plus Environment

Page 15 of 28
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
13
(m, 1H), 2.37 (s, 3H). C{1H} NMR (100 MHz, CDCl3):  165.5, 138.8, 134.9, 133.3, 129.9,
129.5, 128.5, 126.6, 75.4, 34.6, 21.3. HRMS (ESI-Q-orbitrap) m/z: [M+Na]+ calcd for
C16H15BrO2Na 341.0147, found 341.0148.
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
2-bromo-1-(p-tolyl)ethyl 2,6-dimethylbenzoate (8bb). Yield: 93%, 97 mg; Colorless oil. H
NMR (400 MHz, CDCl3):  7.33 (d, J = 8.0 Hz, 2H), 7.20 (t, J = 8.0 Hz, 3H), 7.03 (d, J = 7.6
Hz, 2H), 6.22−6.26 (m, 1H), 3.75−3.80 (m, 1H), 3.64−3.67 (m, 1H), 2.38 (s, 3H), 2.26 (s, 6H).
13C{1H} NMR (100 MHz, CDCl3):  169.1, 139.1, 135.1, 134.7, 133.6, 129.6, 129.5, 127.6,
127.0, 76.1, 34.0, 21.4, 19.9. HRMS (ESI-Q-orbitrap) m/z: [M+Na]+ calcd for C18H19BrO2Na
369.0461, found 369.0454.
1
2-bromo-1-(p-tolyl)ethyl methyl terephthalate (8bg). Yield: 74%, 84 mg; Colorless oil. H
NMR (400 MHz, CDCl3):  8.10−8.17 (m, 4H), 7.33 (d, J = 7.9 Hz, 2H), 7.20 (d, J = 7.9 Hz,
2H), 6.17-6.20 (m, 1H), 3.95 (s, 3H), 3.79−3.84 (m, 1H), 3.69−3.73 (m, 1H), 2.35 (s, 3H).
13C{1H} NMR (100 MHz, CDCl3):  166.3, 164.8, 139.1, 134.6, 134.3, 133.7, 129.9, 129.7,
129.6, 126.6, 76.0, 52.6, 34.4, 21.4. HRMS (EI) m/z: [M]+ calcd for C18H17BrO4 376.0305,
found 376.0305.
1
2-bromo-1-(o-tolyl)ethyl 2,6-dimethylbenzoate (8cb). Yield: 90%, 94 mg; Colorless oil. H
NMR (400 MHz, CDCl3):  7.42 (d, J = 7.2 Hz, 1H), 7.21−7.29 (m, 4H), 7.06 (d, J = 7.6 Hz,
2H), 6.50−6.53 (m, 1H), 3.74−3.80 (m, 1H), 3.61−3.64 (m, 1H), 2.57 (s, 3H), 2.30 (s, 6H).
13C{1H} NMR (100 MHz, CDCl3):  169.1, 136.2, 135.7, 135.0, 133.6, 130.9, 129.5, 128.9,
127.6, 126.4, 126.0, 73.1, 33.3, 19.9, 19.4. HRMS (ESI-Q-orbitrap) m/z: [M+Na]+ calcd for
C18H19BrO2Na 369.0461, found 369.0459.
15
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 28
1
2
3
4
1
2-bromo-1-(4-bromophenyl)ethyl benzoate (8da). Yield: 86%, 99 mg; Colorless oil. H NMR
5
6
(400 MHz, CDCl3):  8.11 (d, J = 7.2 Hz, 2H), 7.60 (t, J = 7.4 Hz, 1H), 7.46−7.54 (m, 4H), 7.33
7
8
9
(d, J = 8.4 Hz, 2H), 6.15−6.18 (m, 1H), 3.69−3.81 (m, 2H). 13C{1H} NMR (100 MHz, CDCl3): 
165.4, 136.8, 133.6, 132.0, 129.9, 129.8, 129.5, 128.6, 128.4, 123.0, 74.7, 34.2. HRMS (ESI-Q-
orbitrap) m/z: [M+Na]+ calcd for C15H12Br2O2Na 406.9076, found 406.9075.
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
2-bromo-1-(4-bromophenyl)ethyl 2,6-dimethylbenzoate (8db). Yield: 91%, 113 mg; Colorless
oil. 1H NMR (400 MHz, CDCl3):  7.55 (d, J = 8.3 Hz, 2H), 7.33 (d, J = 8.3 Hz, 2H), 7.22 (t, J =
7.6 Hz, 1H), 7.05 (d, J = 7.6 Hz, 2H), 6.22−6.25 (m, 1H), 3.73−3.78 (m, 1H), 3.63−3.67 (m, 1H),
2.28 (s, 6H). 13C{1H} NMR (100 MHz, CDCl3):  168.9, 136.6, 135.0, 132.2, 132.0, 129.6,
128.7, 127.7, 123.2, 75.3, 33.5, 19.9. HRMS (EI) m/z: [M]+ calcd for C17H16Br2O2 411.9491,
found 411.9495.
2-bromo-1-(4-bromophenyl)ethyl 2-bromobenzoate (8dh). Yield: 87%, 121 mg; Pale yellow
oil. 1H NMR (400 MHz, CDCl3):  7.89−7.91 (m, 1H), 7.67 (d, J = 6.9 Hz, 1H), 7.53 (d, J = 8.3
Hz, 2H), 7.33-7.41 (m, 4H), 6.15−6.18 (m, 1H), 3.75−3.80 (m, 1H), 3.68−3.71 (m, 1H). 13C{1H}
NMR (100 MHz, CDCl3):  164.8, 136.3, 134.7, 133.2, 132.1, 131.8, 131.3, 128.6, 127.4, 123.2,
122.1, 75.6, 33.8. HRMS (EI) m/z: [M]+ calcd for C15H11Br3O2 461.8283, found 461.8286.
1
2-bromo-1-(4-chlorophenyl)ethyl benzoate (8ea). Yield: 89%, 91 mg; Colorless oil. H NMR
(400 MHz, CDCl3):  8.21 (d, J = 7.5 Hz, 2H), 7.60 (t, J = 7.5 Hz, 1H), 7.48 (t, J = 7.5 Hz, 2H),
13
7.36−7.41 (m, 4H), 6.17−6.20 (m, 1H), 3.77−3.81 (m, 1H), 3.70−3.74 (m, 1H). C{1H} NMR
(100 MHz, CDCl3):  165.4, 136.3, 134.8, 133.6, 129.9, 129.6, 129.1, 128.6, 128.1, 74.7, 34.2.
HRMS (ESI-Q-orbitrap) m/z: [M+Na]+ calcd for C15H12BrClO2Na 362.9580, found 362.9591.
16
ACS Paragon Plus Environment

Page 17 of 28
The Journal of Organic Chemistry
1
2
3
4
2-bromo-1-(4-chlorophenyl) ethyl 2,6-dimethylbenzoate (8eb). Yield: 92%, 102 mg; Colorless
5
6
1
oil. H NMR (400 MHz, CDCl3):  7.40 (m, 4H), 7.22 (t, J = 7.6 Hz, 1H), 7.04 (d, J = 7.6 Hz,
7
8
9
13
2H), 6.22−6.26 (m, 1H), 3.73−3.79 (m, 1H), 3.63−3.67 (m, 1H), 2.27 (s, 6H). C{1H} NMR
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
(100 MHz, CDCl3):  168.9, 136.1, 135.0, 133.2, 129.7, 129.1, 128.4, 127.7, 75.3, 33.5, 19.9.
HRMS (ESI-Q-orbitrap) m/z: [M+Na]+ calcd for C17H16BrClO2Na 390.9893, found 390.9896.
2-bromo-1-(3-chlorophenyl)ethyl 2,6-dimethylbenzoate (8fb). Yield: 90%, 99 mg; Colorless
1
oil. H NMR (400 MHz, CDCl3):  7.46 (s, 1H), 7.34−7.37 (m, 3H), 7.22 (t, J = 7.6 Hz, 1H),
7.05 (d, J = 7.6 Hz, 2H), 6.21−6.24 (m, 1H), 3.73−3.78 (m, 1H), 3.64−3.68 (m, 1H), 2.28 (s,
6H). 13C{1H} NMR (100 MHz, CDCl3):  168.9, 139.6, 135.1, 134.8, 133.2, 130.2, 129.7, 129.4,
127.7, 127.2, 125.3, 75.3, 33.5, 19.9. HRMS (ESI-Q-orbitrap) m/z: [M+Na]+ calcd for
C17H16BrClO2Na 390.9893, found 390.9892.
1
2-bromo-1-phenylpropyl benzoate (8ga). Yield: 87%, 83 mg; Colorless oil. H NMR (400
MHz, CDCl3):  8.15 (d, J = 7.6 Hz, 2H), 7.60 (t, J = 7.2 Hz, 1H), 7.45−7.51 (m, 4H), 7.34−7.40
(m, 3H), 6.21−6.23 (m, 1H), 4.50−4.54 (m, 1H), 1.75 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3):
 165.3, 137.1, 133.4, 130.0, 128.7, 128.6, 128.5, 127.2, 78.8, 50.4, 21.0. HRMS (ESI-Q-
orbitrap) m/z: [M+Na]+ calcd for C16H15BrO2Na 341.0148, found 341.0145.
1
2-bromo-2-nitro-1-phenylethyl benzoate (8ha). Yield: 64%, 67 mg; Pale yellow oil. H NMR
(400 MHz, CDCl3):  8.01 (d, J = 13.7 Hz, 1H), 7.54−7.61 (m, 2H), 7.45−7.51 (m, 2H),
13
7.37−7.43 (m, 3H), 7.26−7.28 (m, 2H), 5.87−5.91 (m, 1H), 5.01−5.05 (m, 1H). C{1H} NMR
(100 MHz, CDCl3):  139.2, 137.2, 132.2, 131.9, 130.1, 129.5, 129.4, 129.3, 129.1, 127.2, 82.3,
47.4. HRMS (EI) m/z: [M]+ calcd for C15H12BrNO4 348.9944, found 348.9944.
17
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 18 of 28
1
2
3
4
5
6
7
8
9
1
2-bromocyclohexyl benzoate (8ia). Yield: 88%, 75 mg; Colorless oil. H NMR (400 MHz,
CDCl3):  8.07 (d, J = 7.2 Hz, 2H), 7.56 (t, J = 7.2 Hz, 1H), 7.44 (t, J = 7.8 Hz, 2H), 5.10−5.16
(m, 1H), 4.12−4.18 (m, 1H), 2.38−2.42 (m, 1H), 2.25−2.31 (m, 1H), 1.89−1.99 (m, 3H),
1.75−1.81 (m, 2H), 1.53−1.56 (m, 1H). 13C{1H} NMR (100 MHz, CDCl3):  165.7, 133.2, 130.3,
129.8, 128.5, 76.5, 52.8, 35.7, 31.2, 25.5, 23.4. HRMS (ESI-Q-orbitrap) m/z: [M+Na]+ calcd for
C13H15BrO2Na 305.0148, found 305.0150.
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
2-bromocyclohexyl 2,6-dimethylbenzoate (8ib). Yield: 90%, 84 mg; Colorless oil. H NMR
(400 MHz, CDCl3):  7.20 (t, J = 7.6 Hz, 1H), 7.03 (d, J = 7.6 Hz, 2H), 5.17−5.23 (m, 1H),
4.00−4.07 (m, 1H), 2.38−2.42 (m, 8H), 1.89−1.99 (m, 1H), 1.74−1.83 (m, 2H), 1.46−1.57 (m,
2H), 1.29−1.38 (m, 1H). 13C{1H} NMR (100 MHz, CDCl3):  169.1, 134.7, 134.0, 129.3, 127.6,
76.8, 52.5, 36.2, 31.7, 25.8, 23.5, 19.8. HRMS (ESI-Q-orbitrap) m/z: [2M+Na]+ calcd for
C30H38Br2O4Na 645.1011, found 645.1009.
1
2-bromocyclohexyl 2-acetylbenzoate (8ii). Yield: 89%, 87 mg; Colorless oil. H NMR (400
MHz, CDCl3):  7.86 (d, J = 7.4 Hz, 1H), 7.47−7.56 (m, 2H), 7.41 (d, J = 7.4 Hz, 1H), 5.06−5.11
(m, 1H), 4.05−4.11 (m, 1H), 2.54 (s, 3H), 2.27−2.37 (m, 2H), 1.84−1.94 (m, 3H), 1.70−1.78 (m,
3H). 13C{1H} NMR (100 MHz, CDCl3):  166.1, 142.3, 132.0, 130.2, 129.7, 129.2, 126.6, 52.6,
35.7, 30.9, 25.5, 24.1, 23.3. HRMS (ESI-Q-orbitrap) m/z: [M+Na]+ calcd for C15H17BrO3Na
347.0253, found 347.0253.
1
2-bromo-2,3-dihydro-1H-inden-1-yl benzoate (8ja). Yield: 76%, 72 mg; Colorless oil. H
NMR (400 MHz, CDCl3):  8.04 (d, J = 7.4 Hz, 2H), 7.57 (t, J = 7.4 Hz, 1H), 7.27−7.48 (m,
6H), 6.59 (d, J = 3.6 Hz, 1H), 4.65−4.68 (m, 1H), 3.77−3.83 (m, 1H), 3.33−3.38 (m, 1H).
13C{1H} NMR (100 MHz, CDCl3):  166.1, 141.4, 138.5, 133.5, 130.0, 129.9, 129.7, 128.6,
18
ACS Paragon Plus Environment

Page 19 of 28
The Journal of Organic Chemistry
1
2
3
4
5
6
127.8, 126.1, 125.0, 84.6, 50.0, 41.7. HRMS (ESI-Q-orbitrap) m/z: [M+Na]+ calcd for
C16H13BrO2Na 338.9991, found 338.9995.
7
8
9
1
3-bromo-2,3-dimethylbutan-2-yl benzoate (8ka). Yield: 89%, 76 mg; Colorless oil. H NMR
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
(400 MHz, CDCl3):  8.04−8.06 (m, 2H), 7.53−7.57 (m, 1H), 7.42−7.46 (m, 2H), 1.94 (s, 6H),
1.84 (s, 6H). 13C{1H} NMR (100 MHz, CDCl3):  165.3, 132.9, 131.8, 129.7, 128.5, 86.5, 73.1,
30.0, 21.9. HRMS (ESI-Q-orbitrap) m/z: [M+Na]+ calcd for C13H17BrO2Na 307.0304, found
307.0319.
1
4-bromohexan-3-yl benzoate (8la). Yield: 95%, 81 mg; Colorless oil. H NMR (400 MHz,
CDCl3):  8.10 (d, J = 7.7 Hz, 2H), 7.58 (t, J = 7.3 Hz, 1H), 7.46 (t, J = 7.7 Hz, 2H), 5.17 (td, J =
6.7, 3.1 Hz, 1H), 4.09−4.13 (m, 1H), 1.82−1.96 (m, 4H), 1.08 (t, J = 7.3 Hz, 3H), 0.97 (t, J =
13
7.3Hz, 3H). C{1H} NMR (100 MHz, CDCl3):  166.1, 133.3, 130.0, 129.9, 128.6, 76.7, 59.5,
28.9, 25.8, 12.7, 9.9. HRMS (ESI-Q-orbitrap) m/z: [M+Na]+ calcd for C13H17BrO2Na 307.0304,
found 307.0304.
2-bromo-1-methylcyclohexyl benzoate (8ma). Yield: 50%, 45 mg; Colorless oil. 1H NMR (400
MHz, CDCl3):  8.01 (d, J = 7.7 Hz, 2H), 7.55 (t, J = 7.3 Hz, 1H), 7.44 (t, J = 7.6 Hz, 2H), 4.86
(dd, J = 8.4, 3.9 Hz, 1H), 2.46−2.50 (m, 1H), 2.05-2.10 (m, 1H), 1.94−2.01 (m, 1H), 1.69−1.82
13
(m, 5H), 1.45−1.58 (m, 3H). C{1H} NMR (100 MHz, CDCl3):  165.4, 132.9, 131.5, 129.7,
128.5, 84.1, 57.9, 34.3, 33.2, 31.1, 23.7, 22.1. HRMS (ESI-Q-orbitrap) m/z: [M+Na]+ calcd for
C14H17BrO2Na 319.0304, found 319.0305.
1
2-bromo-1-(3-nitrophenyl)ethyl benzoate (8na). Yield: 50%, 53 mg; Colorless oil. H NMR
(500 MHz, CDCl3):  8.34 (t, J = 1.9 Hz, 1H), 8.23 (dq, J = 8.2, 1.1 Hz, 1H), 8.12 (dd, J = 8.3,
1.3 Hz, 2H), 7.80 (d, J = 7.8 Hz, 1H), 7.58−7.64 (m, 2H), 7.49 (t, J = 7.8 Hz, 2H), 6.29 (dd, J =
19
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 20 of 28
1
2
3
4
5
6
7
8
9
6.6, 5.4 Hz 1H), 3.77−3.85 (m, 2H). 13C{1H} NMR (125 MHz, CDCl3):
            . HRMS (ESI-
Q-orbitrap) m/z: [M+Na]+ calcd for C15H12BrNO4Na 371.9842, found 371.9840.
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
Procedure for the preparation compound 1c-Br.
1,3-Dibromo-5,5-dimethylhydantoin (20.9 mg, 0.073 mmol, 1.1 equiv) was added to a mixture
o
of indole catalyst 1c (0.066 mmol, 16.3 mg, 1.0 equiv) in dichloromethane (0.22 mL) at 23 C
and allowed to stir for 15 minutes in the absence of light. The product mixture was then
concentrated under reduced pressure and the yellow solid residue was diluted in hexanes. The
solution was filtered and concentrated under reduced pressure to give compound 1c-Br as a
yellow oil with 79% yield.
1
Methyl 3-bromo-2-nonyl-3H-indole-3-carboxylate (1c-Br). Yield: 79%, 20 mg; Yellow oil. H
NMR (500 MHz, CDCl3):  7.58 (d, J = 7.5, 1H), 7.55 (d, J = 7.5 Hz, 1H), 7.40 (t, J = 7.5 Hz,
1H), 7.24 (t, J = 7.5 Hz, 1H), 3.76 (s, 3H), 2.92−2.99 (m, 1H), 2.73−2.80 (m, 1H), 1.83−1.94 (m,
2H), 1.25−1.46 (m, 12 H), 0.88 (t, J = 6.8 Hz, 3H). 13C{1H} NMR (125 MHz, CDCl3):  180.5,
166.6, 153.6, 136.4, 131.0, 126.8, 124.5, 121.1, 60.2, 54.2, 32.0, 30.3, 29.65, 29.59, 29.53, 29.4,
26.7, 22.8, 14.3. HRMS (ESI-Q-orbitrap) m/z: [M+Na]+ calcd for C19H26BrNO2Na 402.1039,
found 402.1037.
20
ACS Paragon Plus Environment

Page 21 of 28
The Journal of Organic Chemistry
1
2
3
4
5
6
ASSOCIATED CONTENT
Supporting Information
7
8
9
1H and 13C{1H} NMR spectra for all new compounds. This material is available free of charge
via the Internet at http://pubs.acs.org.
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
AUTHOR INFORMATION
Corresponding Author
*E-mail: chmkz@cuhk.edu.hk; yyyeung@cuhk.edu.hk
Notes
The authors declare no competing financial interest.
†These authors contributed equally in this project.
ACKNOWLEDGMENT
We thank the financial support from RGC General Research Fund of HKSAR (CUHK
14306916) and The Chinese University of Hong Kong Direct Grant (project code: 4053193).
Equipment was partially supported by the Faculty Strategic Fund for Research from the Faculty
of Science of the Chinese University of Hong Kong, China.
REFERENCES
(1) (a) Rodríguez, F.; Fańanás, F. J.; Ma, S. Handbook of Cyclization Reactions, Vol. 4, Wiley-
VCH, Weinheim, 2010, pp. 951–990. (b) Saikia, I; Borah, A. J.; Phukan, P. Use of Bromine and
Bromo-Organic Compounds in Organic Synthesis. Chem. Rev. 2016, 116, 6837–7042. (c)
21
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 22 of 28
1
2
3
4
5
6
7
8
9
Ranganathan, S.; Muraleedharan, K. M.; Vaish, N. K.; Jayaraman, N. Halo- and
selenolactonisation: the two major strategies for cyclofunctionalisation. Tetrahedron 2004, 60,
5273–5308. (d) Chemler, S. R.; Bovino, M. T. Catalytic Aminohalogenation of Alkenes and
Alkynes. ACS Catal. 2013, 3, 1076–1091. (e) Denmark, S. E.; Kuester, W. E.; Burk, M. T.
Catalytic, Asymmetric Halofunctionalization of Alkenes—A Critical Perspective. Angew. Chem.
Int. Ed. 2012, 51, 10938–10953. (f) Cheng, Y. A.; Yu, W. Z.; Yeung, Y.-Y. Recent advances in
asymmetric intra- and intermolecular halofunctionalizations of alkenes. Org. Biomol. Chem.
2014, 12, 2333–2343. (g) Zheng, S.; Schienebeck, C. M.; Zhang, W.; Wang, H.-Y.; Tang, W.
Cinchona Alkaloids as Organocatalysts in Enantioselective Halofunctionalization of Alkenes and
Alkynes. Asian. J. Org. Chem. 2014, 3, 366–376. (h) Murai, K.; Fujioka, H. Recent Progress in
Organocatalytic Asymmetric Halocyclization. Heterocycles 2013, 87, 763–805. (i) Hennecke, U.
New Catalytic Approaches towards the Enantioselective Halogenation of Alkenes. Chem. Asian.
J. 2012, 7, 456–465.
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
(2) (a) Li, G.; Fu, Q.; Zhang, X.; Jiang, J.; Tang, Z. First asymmetric intermolecular
bromoesterification catalyzed by chiral Brønsted acid. Tetrahedron: Asymmetry 2012, 23, 245–
251. (b) Li, L.; Su, C.; Liu, X.; Tian, H.; Shi, Y. Catalytic Asymmetric Intermolecular
Bromoesterification of Unfunctionalized Olefins. Org. Lett. 2014, 16, 3728–3731.
(3) (a) Ahmad, S. M.; Braddock, D. C.; Cansell, G.; Hermitage S. A. Dimethylformamide,
dimethylacetamide and tetramethylguanidine as nucleophilic organocatalysts for the transfer of
electrophilic bromine from N-bromosuccinimide to alkenes. Tetrahedron Lett. 2007, 48, 915–
918. (b) Ahmad, S. M.; Braddock, D. C.; Cansell, G.; Hermitage S. A.; Redmond, J. M.; White,
A. J. P. Amidines as potent nucleophilic organocatalysts for the transfer of electrophilic bromine
from N-bromosuccinimide to alkenes. Tetrahedron Lett. 2007, 48, 5948–5952. (c) Chen, F.;
22
ACS Paragon Plus Environment

Page 23 of 28
The Journal of Organic Chemistry
1
2
3
4
Jiang, X.; Er, J. C.; Yeung, Y.-Y. Molecular sieves as an efficient and recyclable catalyst for
5
6
bromolactonization and bromoacetoxylation reactions. Tetrahedron Lett. 2010, 51, 3433–3435.
7
8
9
(4) (a) Saikia, I.; Rajbongshi, K. K.; Phukan, P. A simple and efficient bromoformyloxylation
and bromoacetoxylation reaction using TsNBr2. Tetrahedron Lett. 2012, 53, 758–761. (b)
Agrawal, M. K.; Adimurthy, S.; Ganguly, B.; Ghosh, P. K. Comparative study of the vicinal
functionalization of olefins with 2:1 bromide/bromate and iodide/iodate reagents. Tetrahedron
2009, 65, 2791–2797. (c) Dulcère, J.-P.; Rodriguez, J. Cohalogenation of Alkenes by N-
Bromosuccinimide in Acetic Acid Derivatives: An Efficient Method for the Synthesis of trans-ß-
Bromoacetic Ester Precursors of cis-1,2-diols. Synlett 1992, 347–348. (d) Negoro, T.; Ikeda, Y.
Bromochlorination of Alkenes with Dichlorobromate(1−) Ion. V. Regio- and Stereochemistry for
the Bromochlorination of Styrene Derivatives with Dichlorobromate(1−) Ion in Protic Solvents.
Bull. Chem. Soc. Jpn. 1986, 59, 3519–3522. (e) Uemura, S.; Ohe, K.; Fukuzawa, S.; Patil, S. R.;
Sugita, N. Dominant cis-diacetoxylation of alkenes with tellurium(IV) oxide and lithium
bromide in acetic acid. J. Organomet. Chem. 1986, 316, 67–78. (f) Pimenta, L. S.; Gusevskaya,
E. V.; Alberto, E. E. Intermolecular Halogenation/Esterification of Alkenes
with N‐Halosuccinimide and Acetic Acid Catalyzed by 1,4‐Diazabicyclo[2.2.2]octane. Adv.
Synth. Catal. 2017, 359, 2297–2303. (g) Crespo, L. T. C.; Nogueira, G. P.; de Mattos, M. C. S.;
Esteves, P. M. Reaction of trihaloisocyanuric acids with alkynes: an efficient methodology for
preparation of β-haloenol acetates. Arkivoc 2018, ii, 205–214.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(5) Ke, Z.; Yeung, Y.-Y. NBS-Initiated Electrophilic Phenoxyetherification of Olefins. Org. Lett.
2013, 15, 1906–1909.
23
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 24 of 28
1
2
3
4
5
6
7
8
9
(6) Ke, Z.; Tan, C. K.; Chen, F.; Yeung, Y.-Y. Catalytic Asymmetric Bromoetherification and
Desymmetrization of Olefinic 1,3-Diols with C2-Symmetric Sulfides. J. Am. Chem. Soc. 2014,
136, 5627–5630.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(7) He, X.; Wang, X.; Tse, Y.-L.; Ke, Z.; Yeung, Y.-Y. Applications of Selenonium Cations as
Lewis Acids in Organocatalytic Reactions. Angew. Chem. Int. Ed. 2018, 57, 12869–12873.
(8) Huang, D.; Wang, H.; Xue, F.; Guan, H.; Li, L.; Peng, X.; Shi, Y. Enantioselective
Bromocyclization of Olefins Catalyzed by Chiral Phosphoric Acid. Org. Lett. 2011, 13, 6350–
6353.
(9) Zeng, X.; Miao, C.; Wang, S.; Xia, C.; Sun, W. Asymmetric 5-endo chloroetherification of
homoallylic alcoholstoward the synthesis of chiral β-chlorotetrahydrofurans. Chem. Commun.
2013, 49, 2418–2420.
(10) Ke, Z.; Tan, C. K.; Liu, Y.; Lee, K. G. Z.; Yeung, Y.-Y. Catalytic and enantioselective
bromoetherification of olefinic 1,3-diols: mechanistic insight. Tetrahedron 2016, 72, 2683–2689.
(11) Singh, S.; Bhadani, A.; Kamboj, R. Synthesis of β-Bromo Glycerol Monoethers from α-
Olefins. Ind. Eng. Chem. Res. 2008, 47, 8090–8094.
(12) Wu, X.-L.; Xia, J.-J.; Wang, G.-W. Aminobromination of olefins with TsNH2 and NBS as
the nitrogenand bromine sources mediated by hypervalent iodine in a ball mill. Org. Biomol.
Chem. 2008, 6, 548–553.
24
ACS Paragon Plus Environment

Page 25 of 28
The Journal of Organic Chemistry
1
2
3
4
(13) Yu, W. Z.; Chen, F.; Cheng, Y. A.; Yeung, Y.-Y. Catalyst-Free and Metal-Free
5
6
Electrophilic
Bromoamidation
of
Unactivated
Olefins
Using
the N-
7
8
9
Bromosuccinimide/Sulfonamide Protocol. J. Org. Chem. 2015, 80, 2815–2821.
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
(14) Wang, Z.; Zhang, Y.; Fu, H.; Jiang, Y.; Zhao, Y. FeCl2-Catalyzed Aminobromination of
Alkenes Using Amides or Sulfonamides and NBS as the Nitrogen and Bromine Sources. Synlett
2008, 2667–2670.
(15) (a) Wei, Y.; Liang, F.; Zhang, X. N-Bromoimide/DBU Combination as a New Strategy for
Intermolecular Allylic Amination. Org. Lett. 2013, 15, 5186–5189. (b) Talluri, S. K.; Sudalai, A.
NBS-Catalyzed Hydroamination and Hydroalkoxylation of Activated Styrenes. Org. Lett. 2005,
7, 855–857.
(16) (a) Liang, X.-W.; Zheng, C.; You, S.-L. Dearomatization through Halofunctionalization
Reactions. Chem. Eur. J. 2016, 22, 11918–11933. (b) Cai, Q.; Yin, Q.; You. S.-L.
Chiral‐Amine‐Catalyzed Asymmetric Bromocyclization of Tryptamine Derivatives. Asian J.
Org. Chem. 2014, 3, 408–411. (c) Xie, W.; Jiang, G.; Liu, H.; Hu, J.; Pan, X.; Zhang, H.; Wan,
X.; Lai, Y.; Ma, D. Highly Enantioselective Bromocyclization of Tryptamines and Its
Application in the Synthesis of (−)‐Chimonanthine. Angew. Chem. Int. Ed. 2013, 52, 12924–
12927. (d) Feng, X.; Jiang, G.; Xia, Z.; Hu, J.; Wan, X.; Gao, J.-M.; Lai, Y.; Xie, W. Total
Synthesis of (−)-Conolutinine. Org. Lett. 2015, 17, 4428–4431.
(17) (a) Chen, T.; Yeung, Y.-Y. Trifluoroacetic acid catalyzed highly regioselective
bromocyclization of styrene-type carboxylic acid. Org. Biomol. Chem. 2016, 14, 4571–4575. (b)
Naresh, M.; Swamy, P.; A. Kumar, M.; M. Reddy, M.; Srujana, K.; Narender. N. A simple and
facile method for regio- and stereoselective bromoformyloxylation and bromoacetoxylation of
25
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 26 of 28
1
2
3
4
5
6
7
8
9
olefins using NH4Br and oxone®. Tetrahedron Lett. 2014, 55, 3926–3933. (c) de Almeida, L. S.;
Esteves, P. M.; de Mattos, M. C. S. Tribromoisocyanuric Acid: A New Reagent for
Regioselective Cobromination of Alkenes. Synlett 2006, 1515–1518. (d) de Almeida, L. S.;
Esteves, P. M.; de Mattos, M. C. S. Efficient Electrophilic Cobromination of Alkenes and
Bromination of Activated Arenes with Bromodichloroisocyanuric Acid under Mild Conditions.
Synlett 2007, 1687–1690. (e) Wang, H.-Y.; Zhang, W.; Schienebeck, C. M.; Bennett, S. R.;
Tang, W. Intermolecular bromoesterification of conjugated enynes: an efficient synthesis of
bromoallenes. Org. Chem. Front. 2014, 1, 386–390. (f) Balkrishna, S. J.; Prasad, Ch D.; Panini,
P.; Detty, M. R.; Chopra, D.; Kumar, S. Isoselenazolones as Catalysts for the Activation of
Bromine: Bromolactonization of Alkenoic Acids and Oxidation of Alcohols. J. Org.
Chem. 2012, 77, 9541–9552.
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
(18) Zhang, W.; Liu, N.; Schienebeck, C. M.; Zhou, X.; Izhar, I. I.; Guzei, I. A.; Tang, W.
Enantioselective intermolecular bromoesterification of allylic sulfonamides. Chem. Sci. 2013, 4,
2652–2656.
(19) (a) Soltanzadeh, B; Jaganathan, A.; Staples, R. J.; Borhan, B. Highly Stereoselective
Intermolecular Haloetherification and Haloesterification of Allyl Amides. Angew. Chem. Int. Ed.
2015, 54, 9517–9522. (b) Cao, Y.-M.; Lentz, D.; Christmann, M. Synthesis of Enantioenriched
Bromohydrins via Divergent Reactions of Racemic Intermediates from Anchimeric Oxygen
Borrowing. J. Am. Chem. Soc. 2018, 140, 10677–10681.
(20) Chen, T.; Foo, T. J. Y.; Yeung, Y.-Y. Indole-Catalyzed Bromolactonization in Lipophilic
Solvent: A Solid–Liquid Phase Transfer Approach. ACS Catal. 2015, 5, 4751–4755.
26
ACS Paragon Plus Environment

Page 27 of 28
The Journal of Organic Chemistry
1
2
3
4
(21) Capello, C.; Fischer, U.; Hungerbühler, K. What is a green solvent? A comprehensive
5
6
framework for the environmental assessment of solvents. Green Chem. 2007, 9, 927–934.
7
8
9
(22) Hashimoto, T.; Maruoka, K. Recent Development and Application of Chiral Phase-Transfer
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
Catalysts. Chem. Rev. 2007, 107, 5656–5682.
(23) Ooi, T.; Maruoka, K. Recent Advances in Asymmetric Phase-Transfer Catalysis. Angew.
Chem. Int. Ed. 2007, 46, 4222–4266.
(24) Shi, Y.; Ke, Z.; Yeung, Y.-Y. Environmentally Benign Indole-Catalyzed Position-Selective
Halogenation of Thioarenes and Other Aromatics. Green Chem. 2018, 20, 4448–4452.
(25) Vedejs, E.; Denmark, S. E. Lewis Base Catalysis in Organic Synthesis, Wiley-VCH,
Weinheim, 2016.
(26) Dawson, R. F.; Christman, D. R.; Anderson, R. C. Alkaloid Biogenesis. IV. The Non-
availability of Nicotinic Acid-Carboxyl-C14 and its Ethyl Ester for Nicotine Biosynthesis1. J. Am.
Chem. Soc. 1953, 75, 5114–5116.
(27) Andersh, B.; Murphy, D. L.; Olson, R. J. Hydrochloric Acid Catalysis of N-
Bromosuccinimide (NBS) Mediated Nuclear Aromatic Brominations in Acetone. Synth.
Commun. 2000, 30, 2091–2098.
(28) Tanemura, K.; Suzuki, T.; Nishida, Y.; Satsumabayashi, K.; Horaguchi, T. Halogenation of
Aromatic Compounds by N-chloro-, N-bromo-, and N-iodosuccinimide. Chem. Lett. 2003, 32,
932–933.
27
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 28 of 28
1
2
3
4
(29) Chen, J.; Chng, S.; Zhou, L.; Yeung, Y.-Y. Scope and Mechanistic Studies of Electrophilic
5
6
Alkoxyetherification. Org. Lett. 2011, 13, 6456–6459.
7
8
9
(30) Ke, Z.; Chen, T.; Yeung, Y.-Y. Indole-Catalyzed Bromolactonization: Preparation of
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
Bromolactone in Lipophilic Media. Org. Synth. 2018, 95, 256–266.
28
ACS Paragon Plus Environment