Benzylarylation of N-Allyl Anilines: Synthesis of Benzylated Indolines

Article abstract of DOI:10.1021/acs.joc.9b00237

An unprecedented benzylic C-H functionalization of methyl arenes across unactivated alkenes is presented. In the presence of MnCl₂·4H₂O and di-tert-butyl peroxide, N-allyl anilines underwent benzylation/cyclization cascade to give be

Full text of DOI:10.1021/acs.joc.9b00237

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Article
Benzylarylation of N-Allyl Anilines: Synthesis of Benzylated Indolines
Wenzhong Huang, Xiulan Li, Xuemei Song, Qing Luo,
Yanping Li, Ying Dong, Deqiang Liang, and Baoling Wang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b00237 • Publication Date (Web): 25 Apr 2019
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Page 1 of 15
The Journal of Organic Chemistry
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Benzylarylation of N-Allyl Anilines: Synthesis of Benzylated Indolines
†
†
†
†
†
‡
†, ,
§
Wenzhong Huang, Xiulan Li, Xuemei Song, Qing Luo, Yanping Li, Ying Dong, Deqiang Liang, 
and Baoling Wang†,
§
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†Department of Chemistry, Kunming University, Kunming 650214, China.
‡College of Chemistry, Chemical Engineering and Materials Science, Shandong Normal University, Jinan 250014, China
§Yunnan Engineering Technology Research Center for Plastic Films, Kunming 650214, China
Supporting Information
R2
Ar
.
MnCl2 4H2O (10 mol%)
R1
H
R1
DTBP (2 equiv)
N
H
N
methyl arenes, 140 °C
R2 PG
PG
first benzylation across unactivated alkenes with toluene
benzylated indolines provided
exo selective
35 examples
ABSTRACT: An unprecedented benzylic C−H functionalization of methyl arenes across unactivated alkenes is presented. In
the presence of MnCl24H2O and di-tert-butyl peroxide (DTBP), N-allyl anilines underwent benzylation/cyclization cascade
to give benzylated indolines, which are a previously unmet synthetic goal. This protocol features simple operation, broad
substrate scope, and great exo selectivity.
most cases.4 Assisted by a directing group and metal
complexation, methyl arene derivatives were also reported
INTRODUCTION
to undergo cross-coupling with indoles,6 ferrocenes,24 and
unactivated alkylic C–H bonds.25 In 2018, an exciting
benzylation of enolates was reported by Yazaki and
Ohshima, and the reaction proceeds through dual iron
catalyst activation and is 2‑acylimidazole-dependent.8a
Since examples of nucleophile benzylation using methyl
arenes are rare,11,26 new chemistry needs to be developed.
In
the
past
decade,
dehydrogenative
C–H
functionalization has emerged as a powerful tool for C–C
bond construction, and is of fundamental interest in
organic chemistry because of remarkable atom- and step-
economy.1 The inexpensive and abundant hydrocarbon
feedstocks are considered ideal C–H sources.2 For example,
benzylic C−H functionalization of toluene has been
extensively investigated, and its C−C coupling partners
include aromatic,3,4 heteroaromatic,5,6 aldehydic,7 activated
alkylic,8,9 and activated alkenylic C–H bonds,10,11 as well as
C−halogen,12 C−B,13 C−NO2,14 C−CO2H15 and C−COMe
bonds,16 and CuIIIbpy(CF3)3.17 Radical addition of benzylic
C−H bonds across CO,18 activated alkynes19 or activated
alkenes 20,21 has also been developed.
Scheme 1. Background
a) Coupling of Unactivated Alkenes with Methyl Arenes
Bn
H
polarity
mismatching
R
Bn
R
not reported
This Work:
b)
Benzylarylation of Unactivated Alkenes
R2
Ar
In sharp contrast, benzylative coupling or addition of
methyl arenes with unactivated alkenes has never been
achieved (Scheme 1a). This could be rationalized by
polarity mismatching.22 Benzylic radicals5a,d,e,8b,10a,20c,e,g and
unactivated alkenes23 are both considered nucleophilic,22
and they tend to react with electron-deficient
species.3,5,7,8,10,12-20 The coupling of methyl arene radicals
with an electron-rich partner is a formidable challenge. In
2016, Greaney and co-workers reported an in situ
bromination protocol to effect the remarkable cross-
dehydrogenative-coupling reaction of polarity-mismatched
alkoxybenzenes with methyl arenes, wherein 2 equiv of
CuBr2 were used and still poor yields were observed in
.
MnCl2 4H2O (10 mol%)
R1
H
H
R1
DTBP (2 equiv)
N
N
methyl arenes, 140 °C
R2 PG
PG
first benzylation across unactivated alkenes with toluene
benzylated indolines provided
exo selective
35 examples
c) Synthesis of Benzylated Oxoindoles from N-Arylacrylamides
Bn
Bn
H
?
Bn
H
O
H
[H]
N
O
[O]
N
N
functional group intolerance
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Interestingly, several electron-rich activated alkenes,27
Table 1. Optimization of Reaction Conditionsa
as well as 2-biphenyl isocyanides,28 have been reported to
undergo cascade benzylic radical addition/cyclization
sequence, like electron-deficient activated alkenes do,29,30
affording valuable carbo- and heterocyclic products. It is
speculated that it might be the cyclization process which
permits such polarity-mismatched couplings. Specifically,
rapid intramolecular trapping of the transient radicals
generated by addition, and related stabilization effect of
cyclized intermediates as well as final products, might
serve as the thermodynamic reaction driving force.
Nevertheless, unactivated alkenes were not involved in
such benzylation/cyclization processes either, probably
attributed to two major problems: unfavourable polar
effect and insufficiently stabilized radicals which might be
difficult to trap in situ. In the past decades, activated olefin
difunctionalization has proven to be a powerful tool to
access molecule complexity,20,21,27,29,30 whereas the
difunctionalization across unactivated ones remains more
rudimentary.23,31
1
2
3
4
5
6
7
8
Bn
H
Bz
catalyst, oxidant
H
N
H
H
N
N
toluene, 140 °C, 6 h
Ac
Ac
2a1
Ac
1a1
3
entry
1
catalyst
none
oxidant
yield of 2a1 (%)
33 (11)b (36)c
55d (24)c
49 (8)b (21)c
32 (10)c
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
TBHPf
DCP
9
2
TBAI
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
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43
44
45
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60
3
CuBr
4
Cu(OAc)2
Cu2O
5
44 (30)c
6
AgNO3
55 (8)b (23)c
56 (trace)b (13)c
59 (8)b (24)c
32 (26)c
58 (9)b (14)c
70 (56)e (7)b (8)c
61 (8)b (12)c
56 (14)b (15)c
66 (20)c
7
FeCl36H2O
FeCl24H2O
CoCl26H2O
NiCl26H2O
MnCl24H2O
Mn(OAc)32H2O
MnO2
8
9
10
11
12
13
14
15
16
17
18
19
20g
21h
In continuation of our interest in radical chemistry,32 we
wondered whether a challenging benzylation/cyclization
sequence of unactivated alkenes could be enabled by the
simple combination of an active aryl group and a transition
metal salt. The active aryl group might function as both an
inbuilt radical trap and an intermediate stabilizer, whereas
the metal salt would facilitate final aromaticity restoration
process. We examined protected N-allyl anilines as
substrates,31,33 and to our delight, this synthetic plan was
successful executed, delivering benzylated indolines with
broad substrate scope and great exo/endo selectivity
(Scheme 1b). To the best of our knowledge, this is the first
benzylation reaction across unactivated alkenes with
methyl arenes.
KMnO4
38 (16)b
MnCl24H2O
MnCl24H2O
MnCl24H2O
MnCl24H2O
MnCl24H2O
MnCl24H2O
MnCl24H2O
15
BPO
26 (7)b (16)c
TBPB
trace
K2S2O8
DTBP
DTBP
trace (15)c
58 (17)b (7)c
46-62
aReaction conditions: 1a1 (0.25 mmol), catalyst (0.025 mmol),
The indoline is a privileged structural motif found in a
broad range of alkaloids and pharmaceuticals.34 Their
diverse biological properties and clinical applications in
turn demand highly structure-diversified indoline
derivatives as drug candidates. In indole chemistry,
however, it is significantly more challenging to construct
an indoline framework than to elaborate other indolic
counterparts such as oxoindole.35 Oxoindoles could be
prepared either by the derivatization of their parent
indolic variants,36 or through the chemistry of N-
arylacrylamides (Scheme 1c),29,37 whereas access to
indolines is mainly restricted to indole dearomatization
reactions.38 Indoline syntheses from acyclic materials are
rather limited, and transformation of oxoindoles to
indolines suffers from severe functional group intolerance
due to the strongly reducing conditions required.39 Our
protocol provides a straightforward entry to benzylated
indolines.
b
oxidant (0.5 mmol), toluene (5.0 mL), 140 C, 6 h. Yield of 3.
d
cRecovery of 1a1. The same yield was achieved when the
e
reaction was run using 20 mol% TBAI for 12 h. The reaction
f
was performed using 5.3 mmol of 1a1. 5.0−6.0 mol/L in
decane. gThe reaction was run in 2 mL toluene under
h
otherwise identical conditions. The reaction was performed
under otherwise identical conditions using
MnCl24H2O or 1.5 equiv of DTBP, or at 120 C.
5
mol%
effected, furnishing benzylated indoline 2a1 albeit in a
poor yield, along with benzoylated indoline 3 isolated in
11% yield, which might be related to the oxidation of
toluene or the initial product 2a1 (entry 1). To improve
the reaction efficiency, catalysts which might stabilize
transient radicals and/or facilitate single electron transfer
(SET) process were screened.40 The use of
tetrabutylammonium iodide (TBAI, entry 2) or various
metal salts, including CuBr (entry 3), Cu2O (entry 5),
AgNO3 (entry 6), FeCl36H2O (entry 7), FeCl24H2O (entry 8),
and NiCl26H2O(entry 10), led to better yields of indoline
2a1, while beneficial effect was not observed with
Cu(OAc)2 (entry 4) or CoCl26H2O (entry 9). Almost
identical results were obtained using 20 mol% TBAI after a
prolonged reaction time (note d, entry 2). Manganese salts
proved to be superior catalysts (entries 11-14), and use of
RESULTS AND DISCUSSION
The initial investigations were performed with N-(2-
methylallyl)-N-phenylacetamide 1a1 as the model
substrate (Table 1). To our delight, upon exposure of 1a1
to 2 equiv of di-tert-butyl peroxide (DTBP) in toluene at
140 C, the expected benzylation/cyclization reaction was
2
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The Journal of Organic Chemistry
Table 2. Synthesis of Benzylated Indolines a
poor yields, thus we focused our studies on the synthesis
of benzylated indolines 2.
1
2
3
4
5
6
7
8
Ar
.
The optimized conditions were then tested on a broad
collection of allylated anilines (Table 2). 5-Substituted
indolines 2a2-6 were prepared in 46-68% yields from N-
(2-methylallyl) acetanilides bearing a methyl, bromo,
chloro, phenyl, or methoxy group at the para position of
the N-aryl group. Substrates with an electron-deficient N-
aryl group are less reactive, and 5-trifluoromethyl indoline
2a7 was produced in a poor yield. In the case of cyano-
substituted N-allylated acetanilide, the methyl radical
derived from DTBP underwent methylarylation to afford
3-ethyl indoline 4 in 12% yield as the only product.
Notably, this method tolerates allylated N-(pyridin-4-
yl)acetamide, and the corresponding 2,3-dihydro
pyrrolo[3,2-c]pyridine product 2b was furnished in 53%
yield. While propionyl-protected indoline 2c was also
delivered in a good yield, slightly diminished yields were
obtained when pivaloyl or long-chain N-protecting groups
(PGs), such as octanoyl, decanoyl, dodecanoyl, and stearoyl,
were used (2d1-5), probably due to steric conflict. The
allylated aniline with a tert-butyloxy-carbonyl PG reacted
with toluene to afford indoline 2e in a moderate yield,
whereas N-ethylsulfonyl indoline 2f was produced in only
a poor yield. The anilide derived from 3,5-dichloroaniline
was compatible with this transformation as well, giving the
expected benzylated indoline 2g albeit in a modest yield.
Ortho-substituted anilides proved to be challenging
substrates due to steric hindrance, and the corresponding
indoline products were not produced. Instead, severe
substrate decomposition was observe. Interestingly, in the
case of the ortho-chlorinated anilide, intramolecular
aromatic substitution occurred, furnishing aryl-
unsubstituted indoline 2c in 22% yield. As for C−H
coupling partners, methyl arenes with an electron-
donating or -withdrawing group at the para, meta, or ortho
position all worked well in this reaction to furnish the
corresponding benzylated indolines 2h-i. Reactions run in
ortho-substituted methyl arenes gave the highest yields,
whereas methyl arenes with a para-substituent were the
most unfavourable C−H sources, the origin of which is
unclear at this time. Benzylarylations using mesitylene or
2,3,4,5,6-pentafluorotoluene as the solvent also proceeded
smoothly, affording indolines 2j,k in moderate to high
yields. To our disappointment, reactions performed in
ethylbenzene or cumene, as well as the benzylarylation of
a 1,2-disubstituted alkene, hardly occurred, probably due
to steric hindrance.
MnCl2 4H2O (10 mol%)
R1
H
H
R1
DTBP (2 equiv)
N
N
methyl arenes, 140 °C
PG
1
PG
2
, R1 = H, R2 = Bn, 70%
, R1 = Me, R2 = Bn, 68%
, R1 = Br, R2 = Bn, 54%
, R1 = Cl, R2 = Bn, 60%
, R1 = Ph, R2 = Bn, 46%
, R1 = OMe, R2 = Bn, 52%
, R1 = CF3, R2 = Bn, 41%
2a1
Bn
H
2a2
2a3
2a4
2a5
2a6
2a7
4
R2
H
R1
N
H
N
H
9
N
Ac
, 53%
Ac
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
2b
, R1 = CN, R2 = Me, 12%
, R2 = nC7H15, 54%
, R2 = nC9H19, 55%
, R2 = nC11H23, 66%
, R2 = nC17H35, 57%
, R2 = t-Bu, 60%
2d1
2d2
2d3
2d4
2d5
Bn
Bn
H
H
2c
72%
H
H
N
N
Et
R2
CO
CO
Cl
Bn
H
Bn
H
Cl
Bn
H
H
H
N
H
N
N
Cl
SO2Et
COR2
Boc
, R2 = nC7H15, 41%
2g
2e
2f
, 27%
, 46%
Ar
Ar
Bn
H
H
H
H
H
H
N
N
N
COEt
R1
COEt
CO(CH2)6CH3
2i1
2i2
2i3
2i4
, Ar = 2-ClPh, 81%
, Ar = 3-ClPh, 66%
, Ar = 4-ClPh, 64%
, Ar = 4-FPh, 50%
R1 = Me, 0%
, Ar = 2-MePh, 62%
, Ar = 3-MePh, 51%
, Ar = 4-MePh, 45%
2h1
2h2
2h3
R1 = Cl, 0% ( , 22%)
2c
F
F
2
2
F
N
F
F
N
CO(CH2)6CH3
COEt
2k
, 76%
2j
, 60%
Ph
Ph
Bn
Cl
N
N
N
COEt
COEt
trace amounts of unidentified products
Ac
aReaction conditions: 1 (0.25 mmol), MnCl24H2O (0.025
mmol), DTBP (0.5 mmol), solvent (5.0 mL), 140 C, 6 h.
MnCl24H2O gave the highest yield of 70% (entry 11).
Comparison of a series of oxidants was also conducted.
Whereas poor yields of indoline 2a1 were afforded using
tert-butyl hydroperoxide (TBHP, entry 15), dicumyl
peroxide (DCP, entry 16), or benzoyl peroxide (BPO, entry
17), tert-butyl peroxybenzoate (TBPB, entry 18) and
K2S2O8 (entry 19) proved ineffective for this
transformation. When the reaction was performed in 2 mL
toluene under otherwise identical conditions, the yield of
indoline 2a1 was compromised (entry 20). Both reducing
the loading of the catalyst or DCP, and lowering the
reaction temperature, led to diminished yields (entry 21).
It is worthy of notice that this synthesis could be carried
out on a gram scale with only a slight loss of activity (note
e, entry 11), rendering it highly practical. In all these
reactions, benzoylated product 3 was produced in very
Unfortunately, no reaction occurred with aroyl-
protected allylated anilines even at an elevated
temperature (Scheme 2a), which might be attributed to
polarity mismatching during cyclizative radical trapping
process as a result of -conjugation effect. These results
further suggest that an inbuilt radical scavenger with
matched electronic property which enables the rapid
intramolecular radical trapping is the key for the title
reaction. Allylated N-methylbenzamide, however, could
undergo a similar benzylarylation reaction to afford 3,4-
3
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dihydroisoquinolin-1-ones 3a,b, albeit in lower yields
(Scheme 2b).
optimized conditions afforded benzylated indolines 4a-e in
46-62% yields. Still, formal 6-endo-trig product was not
observed.
1
2
3
4
5
6
7
8
Scheme 2.
Synthesis
of
Benzylated
3,4-
Anilides having an activated N-allyl moiety were also
tested (Table 4). While the reaction of 2-phenylallyl
acetanilide led to complex mixtures, from which we failed
to isolate any pure product, the ester group-activated
substrate33 reacted to furnish methyl indoline-3-
carboxylate 7 in 55% yield. Interestingly, when 2-
bromoallyl acetanilide was used, aromatized indole
product 8 was delivered in 67% yield, which might arise
from the HBr elimination of the initial indoline product.
dihydroisoquinolin-1-ones
a)
b)
.
O
MnCl2 4H2O (10 mol%)
DTBP (2 equiv)
R
N
nr
Tol
toluene, 160 °C, 6 h
R = H or Cl
9
O
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
N
MnCl2 4H2O (10 mol%)
DTBP (2 equiv)
N
Scheme 3. Mechanistic Investigations
Ar
methyl arenes, 140 °C, 6 h
t-Bu
a)
TEMPO (3 equiv)
or BHT (2 equiv)
5a
, Ar = Ph, 50%
, Ar = 2-MePh, 38%
5b
O
1a1
2a1
5
, 28%
, 0%
Table 3. Benzylarylation of Non-Methyl-Branched Allyl
Anilides a
standard conditions
standard conditions
Bn
t-Bu
b)
Bn
5
BHT
, 71%
Bn
R1
R1
standard
H
H
R1
Cl
c)
N
conditions
N
toluene/toluene-d8 (1:1, v/v)
N
PG
H
PG
2a4 2a4-d7
PG
formal 6-endo-trig
not detected
N
otherwise standard conditions
6
, 5-exo-trig
46%
0%
Ac
H
H
Cl
R1
Bn
H
Bn
d)
H
toluene-d8
2a4-d
7, 0%
H
H
N
N
N
otherwise standard conditions
R2
Ac
CO
Ac
, R1 = H, 50%
, R1 = Me, 57%
, R1 = Cl, 62%
, R2 = Et, 60%
6a
6b
6c
6d
D
, R2 = nC7H15, 46%
6e
e)
D
D
D
standard conditions
39%, KIE = 1
1a1-d5
aReaction conditions: substrate (0.25 mmol), MnCl24H2O
(0.025 mmol), DTBP (0.5 mmol), toluene (5.0 mL), 140 C, 6 h.
1a1
2a1
2a1-d4
+
+
N
Ac
D
Table 4. Benzylarylation of Anilides with an Activated
Allyl Moiety a
1a1
PhCH2
PhCH3 t-BuOH
f)
Ac
N
DTBP
2 t-BuO
R2
R1
.
R1
MnCl2 4H2O (10 mol%)
Bn
H
t-BuO
Bn
t-BuO
DTBP (2 equiv)
N
H
N
A
Mn2+
Bn
Mn+
Ac
toluene, 140 °C
R2 Ac
Ac
2a1
Ac
Bn
N
N
Ph
MeO2C
Bn
H
H
Bn
Bn
H
Cl
t-BuOH
H
B
C
H
H
N
N
N
Ac
complex
Ac
Ac
, R2 = Br, 67%
8
Radical trapping experiments were performed to
confirm the radical nature of this cyclizative benzylation
(Scheme 3a). As might be expected, the model reaction
under optimized conditions was completely suppressed by
7
, 55%
aReaction conditions: substrate (0.25 mmol), MnCl24H2O
(0.025 mmol), DTBP (0.5 mmol), toluene (5.0 mL), 140 C, 6 h.
In light of Baldwin's rules,41 exo- and endo-mode
cyclizations are both favoured here, thus our initial studies
focused on the benzylarylation of 2-methylallyl anilides in
order to avoid the latter mode ring closure. Inspired by the
exo selectivity achieved in all of the above reactions, we
wondered whether the non-methyl-branched allyl anilides
would be suitable substrates (Table 3). We were pleased to
find that subjecting such unactivated alkenes having an
electron-neutral, -rich, or -deficient N-aryl group to our
doping
with
either
3
equiv
of
2,2,6,6-
tetramethylpiperidine-1-oxyl (TEMPO) or 2 equiv of 2,6-
di-tert-butyl-4-methylphenol (BHT). Furthermore, benzyl-
BHT adduct 5 was isolated in 28% yield in the BHT
experiment, and subjecting BHT to our optimized
conditions afforded the same adduct as the only product in
71% yield (Scheme 3b). These suggested that methyl arene
radicals might be involved in this transformation. An
intermolecular competing kinetic isotope effect (KIE)
experiment was carried out using a toluene/toluene-d8
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mixture (1:1, v/v, Scheme 3c). Interestingly, deuterated
indoline 2a4-d7 was not observed, and control
extracted with CH2Cl2 (10.0 mL) three times. The residue
1
2
3
4
5
6
7
8
a
obtained after evaporation of the organic solvent was
purified by column chromatography on silica gel using
petroleum ether and ethyl acetate as the eluent to give
benzylated indolines 2.
experiment confirmed that the title benzylation did not
proceed in perdeuterated toluene (Scheme 3d), suggesting
that the cleavage of the benzylic C–H bond might be a rate-
influencing step. A mixture of the substrates 1a1 and 1a1-
d5 (1:1) was subjected to the standard conditions, and a
neglectable KIE was observed (Scheme 3e), indicating that
the C–H bond cleavage of anilines is not involved in the
rate-limiting step.
2a1, 1-(3-methyl-3-phenethylindolin-1-yl)ethan-1-one,
1:5 mixture of rotamers due to the slow rotation of the N–
(CO) bond,42 isolated by flash column chromatography
(petroleum ether/ethyl acetate  20:1) in 70% yield (49
1
mg), pale yellow oil. H NMR (400 MHz, CDCl3)   1.42 (s,
9
On the basis of the above results and previous reports,27-
a tentative mechanistic pathway was proposed (Scheme
3H), 1.90-2.03 (m, 2H), 2.17 (s, 3H), 2.39-2.46 (m, 1H),
2.52-2.60 (m, 1H), 3.71 (d, J  10.3 Hz, 1H), 3.89 (d, J  10.3
Hz, 1H), 7.06-7.27 (m, 8H), 8.22 (d, J  8.0 Hz, 1H); 13C{1H}
NMR (100 MHz, CDCl3)   168.7, 142.3, 141.8, 138.6,
128.5, 128.3, 128.0, 126.0, 123.9, 122.3, 117.0, 61.2, 43.7,
43.4, 31.1, 27.3, 24.3; HRMS (ESI-TOF) Calcd for C19H22NO
([MH]) 280.1696. Found 280.1695.
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
30
3f). At the beginning, tert-butoxyl radical was generated by
thermal decomposition of DTBP. Hydrogen atom transfer
from a benzylic C–H bond to this radical affords a methyl
arene radical, addition of which across the tethered double
bond leads to radical intermediate A possessing a newly
formed C–C bond. Rapid intramolecular radical trapping by
the N-aryl group ensues, furnishing ring closure
intermediate B. Subsequent single-electron transfer from
B to Mn2 affords cationic intermediate C as well as Mn.
Finally, deprotonation of C gives the benzylated indoline
2a1. Mn is oxidized to Mn2 by tert-butoxyl radical to
finish the catalytic cycle.
2a1-d4,
1-(3-methyl-3-phenethylindolin-1-yl-4,5,6,7-
d4)ethan-1-one, 1:5 mixture of rotamers, isolated by flash
column chromatography (petroleum ether/ethyl acetate 
1
20:1) in 40% yield (28 mg), pale yellow oil. H NMR (400
MHz, CDCl3)   1.42 (s, 3H), 1.87-2.05 (m, 2H), 2.17 (s, 3H),
2.39-2.44 (m, 1H), 2.52-2.60 (m, 1H), 3.71 (d, J  10.3 Hz,
1H), 3.89 (d, J  10.3 Hz, 1H), 7.10 (d, J  7.0 Hz, 2H), 7.17
(dd, J  7.3, 7.3 Hz, 1H), 7.26 (dd, J  8.1, 6.6 Hz, 2H); 13C{1H}
NMR (100 MHz, CDCl3)   168.6, 142.2, 141.8, 138.5,
128.5, 128.2, 126.0, 61.2, 43.7, 43.4, 31.1, 27.2, 24.2; HRMS
(ESI-TOF) Calcd for C19H18D4NO ([MH]) 284.1947.
Found 284.1944.
CONCLUSIONS
To conclude, a benzylarylation reaction of N-allyl
anilines has been developed. This is the first benzylic C−H
functionalization of methyl arenes across unactivated
alkenes, which provides a direct and straightforward
access to benzylated indolines. This protocol features
broad substrate scope and simple operation, and exo-
selectivity was always achieved even using non-methyl-
branched allyl anilines.
2a2, 1-(3,5-dimethyl-3-phenethylindolin-1-yl)ethan-1-
one, 1:4 mixture of rotamers, isolated by flash column
chromatography (petroleum ether/ethyl acetate  24:1) in
68% yield (50 mg), colorless oil. 1H NMR (400 MHz, CDCl3)
  1.40 (s, 3H), 1.88-2.01 (m, 2H), 2.15 (s, 3H), 2.33 (s, 3H),
2.39-2.48 (m, 1H), 2.52-2.60 (m, 1H), 3.68 (d, J  10.3 Hz,
1H), 3.87 (d, J  10.3 Hz, 1H), 6.93 (s, 1H), 7.02 (d, J  8.5
Hz, 1H), 7.10 (d, J  7.2 Hz, 2H), 7.16 (dd, J  7.2, 7.2 Hz,
1H), 7.25 (dd, J  7.5, 7.3 Hz, 2H), 8.09 (d, J  8.2 Hz, 1H);
13C{1H} NMR (100 MHz, CDCl3)   168.3, 141.8, 140.0,
138.7, 133.4, 128.5, 128.4, 128.2, 126.0, 122.9, 116.7, 61.4,
43.6, 43.3, 31.1, 27.2, 24.1, 21.2; HRMS (ESI-TOF) Calcd for
C20H24NO ([MH]) 294.1852. Found 294.1864.
EXPERIMENTAL SECTION
General. Chemicals were all purchased from commercial
sources and used without treatment. Reactions were
monitored by Thin Layer Chromatography (TLC) using
silica gel F254 plates. Products were purified by column
chromatography over 300-400 mesh silica gel. 1H NMR, 19
F
NMR, 13C NMR and DEPT NMR spectra were recorded at 25
C on a Bruker AscendTM 400 spectrometer using TMS as
internal standard. The term "stack" is used to describe a
region where resonances arising from nonequivalent
nuclei are coincident, and multiplet, m, to describe a region
where resonances arising from a single nucleus (or
equivalent nuclei) are coincident but coupling constants
cannot be readily assigned. High-resolution mass spectra
(HRMS) were obtained using a Bruker microTOF II Focus
spectrometer (ESI).
2a3,
1-(5-bromo-3-methyl-3-phenethylindolin-1-
yl)ethan-1-one, isolated by flash column chromatography
(petroleum ether/ethyl acetate  24:1) in 54% yield (48
1
mg), colorless oil. H NMR (400 MHz, CDCl3)   1.41 (s,
3H), 1.88-2.02 (m, 2H), 2.15 (s, 3H), 2.40-2.48 (m, 1H),
2.52-2.60 (m, 1H), 3.70 (d,  10.3 Hz, 1H), 3.88 (d, J  10.3
Hz, 1H), 7.11 (d, J  7.1 Hz, 2H), 7.18 (dd, J  7.2, 7.2 Hz,
1H), 7.22-7.29 (m, 3H), 7.33 (dd, J  2.0, 8.6 Hz, 1H), 8.10 (d,
J  8.6 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3)   168.7,
141.4, 141.3, 141.0, 130.9, 128.5, 128.2, 126.1, 125.6, 118.4,
116.2, 61.2, 43.8, 43.2, 31.0, 27.2, 24.1; HRMS (ESI-TOF)
Calcd for C19H21BrNO ([MH]) 358.0801. Found 358.0799.
Synthesis of Benzylated Indolines and 3,4-
dihydroisoquinolin-1-ones. To a screw-capped vial with
a magnetic stirring bar were added N-allylated amines 1
(0.25 mmol), MnCl24H2O (5 mg, 0.025 mmol), DTBP (73
mg, 0.50 mmol) and methylarene solvent (5.0 mL) under
argon. The mixture was stirred at 140 C (oil bath
temperature) for 6 h, then it was quenched with saturated
aqueous Na2S2O3 (1.0 mL) and water (10.0 mL), and
2a4,
1-(5-chloro-3-methyl-3-phenethylindolin-1-
yl)ethan-1-one, isolated by flash column chromatography
(petroleum ether/ethyl acetate  24:1) in 60% yield (47
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1
mg), colorless oil. H NMR (400 MHz, CDCl3)   1.41 (s,
3H), 1.89-2.02 (m, 2H), 2.15 (s, 3H), 2.40-2.48 (m, 1H),
2.52-2.60 (m, 1H), 3.71 (d, J  10.3 Hz, 1H), 3.89 (d, J  10.3
Hz, 1H), 7.08 (d, J  2.0 Hz, 1H), 7.11 (d, J  7.0 Hz, 2H),
7.16-7.20 (m, 2H), 7.25-7.28 (m, 2H), 8.15 (d, J  8.6 Hz,
1H); 13C{1H} NMR (100 MHz, CDCl3)   168.7, 141.4, 140.9,
140.6, 128.7, 128.5, 128.2, 128.0, 126.1, 122.7, 118.0, 61.3,
43.8, 43.2, 31.0, 27.2, 24.1; HRMS (ESI-TOF) Calcd for
C19H21ClNO ([MH]) 314.1306. Found 314.1298.
CDCl3)   1.39 (s, 3H), 1.87-1.99 (m, 2H), 2.09 (s, 3H),
1
2
3
4
5
6
7
8
2.35-2.53 (m, 2H), 3.64 (d, J  10.2 Hz, 1H), 3.81 (d, J  10.2
Hz, 1H), 7.02 (d, J  7.1 Hz, 2H), 7.09 (dd, J  7.2, 7.2 Hz,
1H), 7.18 (dd, J  7.5, 7.2 Hz, 2H), 7.94 (d, J  4.9 Hz, 1H),
8.28 (s, 1H), 8.34 (d, J  5.3 Hz, 1H); 13C{1H} NMR (100 MHz,
CDCl3)   168.7, 148.9, 147.8, 143.3, 140.1, 132.9, 127.5,
127.2, 125.1, 110.3, 60.3, 42.2, 42.1, 30.0, 26.3, 23.2; HRMS
(ESI-TOF) Calcd for C18H21N2O ([MH]) 281.1648. Found
281.1659.
9
2a5,
1-(3-methyl-3-phenethyl-5-phenylindolin-1-
2c, 1-(3-methyl-3-phenethylindolin-1-yl)propan-1-one,
isolated by flash column chromatography (petroleum
ether/ethyl acetate  75:1) in 72% yield (53 mg), pale
yellow oil. 1H NMR (400 MHz, CDCl3)   1.22 (t, J  7.4 Hz,
3H), 1.42 (s, 3H), 1.89-2.00 (m, 2H), 2.33-2.46 (m, 3H),
2.51-2.59 (m, 1H), 3.69 (d, J  10.3 Hz, 1H), 3.89 (d, J  10.3
Hz, 1H), 7.05-7.11 (m, 3H), 7.13-7.18 (m, 2H), 7.21-7.27 (m,
3H), 8.25 (d, J  8.1 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3)
  172.0, 142.5, 141.8, 138.5, 128.5, 128.2, 128.0, 126.0,
123.7, 122.3, 116.9, 60.3, 43.7, 43.5, 31.1, 29.2, 27.2, 8.7;
HRMS (ESI-TOF) Calcd for C20H24NO ([MH]) 294.1852.
Found 294.1864.
yl)ethan-1-one, isolated by flash column chromatography
(petroleum ether/ethyl acetate  30:1) in 46% yield (41
mg), white solid: mp 137-138 C. 1H NMR (400 MHz, CDCl3)
  1.48 (s, 3H), 1.95-2.08 (m, 2H), 2.19 (s, 3H), 2.45-2.53
(m, 1H), 2.57-2.65 (m, 1H), 3.76 (d, J  10.3 Hz, 1H), 3.94 (d,
J  10.3 Hz, 1H), 7.12 (d, J  7.0 Hz, 2H), 7.17 (dd, J  7.3, 7.2
Hz, 1H), 7.24-7.28 (m, 2H), 7.30-7.35 (m, 2H), 7.43 (dd, J 
7.8, 7.4 Hz, 2H), 7.48 (dd, J  1.8, 8.4 Hz, 1H), 7.58 (d, J  7.4
Hz, 2H), 8.27 (d, J  8.4 Hz, 1H); 13C{1H} NMR (100 MHz,
CDCl3)   168.6, 141.71, 141.66, 141.0, 139.3, 137.1, 128.8,
128.5, 128.3, 127.00, 126.96, 126.9, 126.0, 121.0, 117.1,
61.5, 43.8, 43.4, 31.1, 27.3, 24.2; HRMS (ESI-TOF) Calcd for
C25H26NO ([MH]) 356.2009. Found 356.2012.
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
2d1, 1-(3,5-dimethyl-3-phenethylindolin-1-yl)octan-1-
one, isolated by flash column chromatography (petroleum
ether/ethyl acetate  90:1) in 54% yield (51 mg), colorless
2a6,
1-(5-methoxy-3-methyl-3-phenethylindolin-1-
1
oil. H NMR (400 MHz, CDCl3)   0.88 (t, J  6.8 Hz, 3H),
yl)ethan-1-one, 1:5 mixture of rotamers, isolated by flash
column chromatography (petroleum ether/ethyl acetate 
15:1) in 52% yield (40 mg), pale yellow oil. H NMR (400
1.26-1.36 (m, 8H), 1.40 (s, 3H), 1.68-1.75 (m, 2H), 1.87-
2.00 (m, 2H), 2.29-2.48 (m, 6H), 2.52-2.60 (m, 1H), 3.68 (d,
J  10.3 Hz, 1H), 3.88 (d, J  10.3 Hz, 1H), 6.92 (s, 1H), 7.02
(d, J  8.5 Hz, 1H), 7.10 (d, J  7.1 Hz, 2H), 7.16 (dd, J  7.4,
7.2 Hz, 1H), 7.25 (dd, J  7.0, 7.7 Hz, 2H), 8.12 (d, J  8.2 Hz,
1H); 13C{1H} NMR (100 MHz, CDCl3)   171.1, 141.9, 140.2,
138.7, 133.3, 128.5, 128.4, 128.3, 125.9, 122.9, 116.7, 60.6,
43.6, 43.4, 36.0, 31.8, 31.1, 29.4, 29.2, 27.2, 24.7, 22.7, 21.2,
14.1; HRMS (ESI-TOF) Calcd for C26H36NO ([MH])
378.2791. Found 378.2791.
1
MHz, CDCl3)   1.41 (s, 3H), 1.85-2.01 (m, 2H), 2.15 (s, 3H),
2.40-2.47 (m, 1H), 2.53-2.61 (m, 1H), 3.70 (d, J  10.3 Hz,
1H), 3.80 (s, 3H), 3.88 (d, J  10.3 Hz, 1H), 6.69 (d, J  2.5
Hz, 1H), 6.76 (dd, J  2.6, 8.7 Hz, 1H), 7.11 (d, J  7.1 Hz,
2H), 7.17 (dd, J  7.3, 7.3 Hz, 1H), 7.26 (dd, J  7.8, 7.0 Hz,
2H), 8.14 (d, J  8.8 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3)
  167.9, 156.5, 141.7, 140.3, 136.1, 128.5, 128.2, 126.0,
117.6, 112.1, 108.9, 61.4, 55.7, 43.8, 43.3, 31.1, 27.2, 24.0;
HRMS (ESI-TOF) Calcd for C20H24NO2 ([MH]) 310.1802.
Found 310.1806.

2d2, 1-(3,5-dimethyl-3-phenethylindolin-1-yl)decan-1-
one, isolated by flash column chromatography (petroleum
ether/ethyl acetate  90:1) in 55% yield (56 mg), colorless
2a7,
1-(3-methyl-3-phenethyl-5-
1
oil. H NMR (400 MHz, CDCl3)   0.88 (t, J  7.0 Hz, 3H),
(trifluoromethyl)indolin-1-yl)ethan-1-one, 1:5 mixture of
rotamers, isolated by flash column chromatography
(petroleum ether/ethyl acetate  12:1) in 41% yield (36
1.27-1.36 (m, 12H), 1.40 (s, 3H), 1.68-1.75 (m, 2H), 1.87-
2.00 (m, 2H), 2.26-2.48 (m, 6H), 2.52-2.60 (m, 1H), 3.68 (d,
J  10.3 Hz, 1H), 3.89 (d, J  10.3 Hz, 1H), 6.92 (s, 1H), 7.03
(d, J  8.4 Hz, 1H), 7.11 (d, J  7.0 Hz, 2H), 7.16 (dd, J  7.3,
7.3 Hz, 1H), 7.25 (dd, J  7.6, 7.1 Hz, 2H), 8.12 (d, J  8.2 Hz,
1H); 13C{1H} NMR (100 MHz, CDCl3)   171.2, 141.9, 140.2,
138.7, 133.3, 128.5, 128.4, 128.2, 125.9, 122.9, 116.7, 60.6,
43.6, 43.4, 36.0, 31.9, 31.1, 29.52, 29.46, 29.3, 27.1, 24.7,
22.7, 21.2, 14.1; HRMS (ESI-TOF) Calcd for C28H40NO
([MH]) 406.3104. Found 406.3108.
1
mg), colorless oil. H NMR (400 MHz, CDCl3)   1.45 (s,
3H), 1.92-2.08 (m, 2H), 2.18 (s, 3H), 2.40-2.48 (m, 1H),
2.53-2.61 (m, 1H), 3.75 (d, J  10.3 Hz, 1H), 3.94 (d, J  10.3
Hz, 1H), 7.10 (d, J  7.1 Hz, 2H), 7.18 (dd, J  7.3, 7.3 Hz,
1H), 7.27 (dd, J  7.5, 7.2 Hz, 2H), 7.35 (s, 1H), 7.50 (dd, J 
0.8, 8.5 Hz, 1H), 8.30 (d, J  8.4 Hz, 1H); 13C{1H} NMR (100
MHz, CDCl3)   169.2, 145.0, 141.2, 139.4, 128.6, 128.2,
126.6 (q, J(C–F)  274.3 Hz), 126.2, 125.75 (q, J(C–F)  3.3
Hz), 119.42 (q, 3J(C–F)  3.1 Hz), 116.7, 61.3, 43.7, 43.2, 31.0,
27.2, 24.3; 19F NMR (376 MHz, CDCl3)   –61.52 (s, 3F);
HRMS (ESI-TOF) Calcd for C20H21F3NO ([MH]) 348.1570.
Found 348.1567.
1
3
2d3, 1-(3,5-dimethyl-3-phenethylindolin-1-yl)dodecan-
1-one, isolated by flash column chromatography
(petroleum ether/ethyl acetate  90:1) in 66% yield (72
mg), colorless oil. 1H NMR (400 MHz, CDCl3)   0.88 (t, J 
7.0 Hz, 3H), 1.26-1.38 (m, 16H), 1.40 (s, 3H), 1.68-1.75 (m,
2H), 1.87-2.00 (m, 2H), 2.27-2.46 (m, 6H), 2.52-2.60 (m,
1H), 3.68 (d, J  10.3 Hz, 1H), 3.89 (d, J  10.3 Hz, 1H), 6.92
(s, 1H), 7.03 (d, J  8.4 Hz, 1H), 7.11 (d, J  7.0 Hz, 2H), 7.16
2b,
1-(3-methyl-3-phenethyl-2,3-dihydro-1H-
pyrrolo[3,2-c]pyridin-1-yl)ethan-1-one, isolated by flash
column chromatography (petroleum ether/ethyl acetate 
1:1) in 53% yield (37 mg), yellow oil. H NMR (400 MHz,
1
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(dd, J  7.3, 7.3 Hz, 1H), 7.25 (dd, J  7.6, 7.2 Hz, 2H), 8.11 2H), 3.73 (d, J  10.1 Hz, 1H), 3.98 (d, J  10.1 Hz, 1H), 7.09
(d, J  8.2 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3)   171.2,
141.9, 140.2, 138.7, 133.3, 128.5, 128.4, 128.2, 125.9, 122.9,
116.7, 60.6, 43.6, 43.4, 36.0, 31.9, 31.1, 29.7, 29.64, 29.56,
29.53, 29.46, 29.4, 27.1, 24.7, 22.7, 21.2, 14.1; HRMS (ESI-
TOF) Calcd for C30H44NO ([MH]) 434.3417. Found
434.3419.
(d, J  2.1 Hz, 1H), 7.12 (d, J  7.0 Hz, 2H), 7.15-7.20 (m, 2H),
7.25-7.27 (m, 2H), 7.30 (d, J  8.5 Hz, 1H); 13C{1H} NMR
(100 MHz, CDCl3)   141.3, 140.4, 140.1, 128.54, 128.45,
128.20, 128.18, 126.1, 123.6, 114.1, 62.0, 44.2, 43.9, 42.8,
31.0, 26.5, 7.8; HRMS (ESI-TOF) Calcd for C19H23ClNO2S
([MH]) 364.1133. Found 364.1131.
1
2
3
4
5
6
7
8
9
2d4,
1-(3,5-dimethyl-3-phenethylindolin-1-
isolated by flash column
2g,
1-(4,6-dichloro-3-methyl-3-phenethylindolin-1-
yl)octadecan-1-one,
yl)octan-1-one, isolated by flash column chromatography
(petroleum ether/ethyl acetate  100:1) in 41% yield (44
mg), colorless oil. 1H NMR (400 MHz, CDCl3)   0.89 (t, J 
7.0 Hz, 3H), 1.30-1.37 (m, 8H), 1.52 (s, 3H), 1.67-1.74 (m,
2H), 1.89-1.99 (m, 1H), 2.24-2.51 (m, 5H), 3.70 (d, J  10.3
Hz, 1H), 3.93 (d, J  10.3 Hz, 1H), 7.01 (d, J  1.8 Hz, 1H),
7.11 (d, J  7.0 Hz, 2H), 7.17 (dd, J  7.3, 7.3 Hz, 1H), 7.26
(dd, J  7.3, 7.3 Hz, 2H), 8.31 (s, 1H); 13C{1H} NMR (100
MHz, CDCl3)   171.8, 145.3, 141.4, 134.4, 132.0, 130.4,
128.5, 128.3, 126.1, 124.7, 116.0, 60.8, 45.3, 40.3, 36.1,
31.7, 31.5, 29.3, 29.2, 26.4, 24.4, 22.7, 14.1; HRMS (ESI-TOF)
Calcd for C25H32Cl2NO ([MH]) 432.1855. Found
432.1871.
chromatography (petroleum ether/ethyl acetate  95:1) in
57% yield (74 mg), colorless oil. 1H NMR (400 MHz, CDCl3)
  0.88 (t, J  7.0 Hz, 3H), 1.25-1.36 (m, 28H), 1.40 (s, 3H),
1.68-1.75 (m, 2H), 1.87-2.00 (m, 2H), 2.29-2.49 (m, 6H),
2.52-2.60 (m, 1H), 3.68 (d, J  10.3 Hz, 1H), 3.89 (d, J  10.3
Hz, 1H), 6.92 (s, 1H), 7.03 (d, J  8.4 Hz, 1H), 7.11 (d, J  7.0
Hz, 2H), 7.16 (dd, J  7.3, 7.3 Hz, 1H), 7.25 (dd, J  7.6, 7.1
Hz, 2H), 8.11 (d, J  8.2 Hz, 1H); 13C{1H} NMR (100 MHz,
CDCl3)   171.1, 141.9, 140.2, 138.7, 133.3, 128.5, 128.4,
128.2, 125.9, 122.9, 116.7, 60.6, 43.6, 43.4, 36.0, 31.9, 31.1,
29.71, 29.67, 29.6, 29.52, 29.46, 29.4, 27.1, 24.7, 22.7, 21.2,
14.1; HRMS (ESI-TOF) Calcd for C36H56NO ([MH])
518.4356. Found 518.4352.
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
2h1, 1-(3,5-dimethyl-3-(2-methylphenethyl)indolin-1-
yl)octan-1-one, isolated by flash column chromatography
(petroleum ether/ethyl acetate  50:1) in 62% yield (61
mg), pale yellow oil. 1H NMR (400 MHz, CDCl3)   0.88 (t, J
 7.0 Hz, 3H), 1.30-1.40 (m, 8H), 1.41 (s, 3H), 1.68-1.78 (m,
2H), 1.80-1.91 (m, 2H), 2.20 (s, 3H), 2.27-2.42 (m, 6H),
2.52-2.59 (m, 1H), 3.73 (d, J  10.3 Hz, 1H), 3.95 (d, J  10.3
Hz, 1H), 6.94 (s, 1H), 6.99-7.12 (m, 5H), 8.12 (d, J  8.2 Hz,
1H); 13C{1H} NMR (100 MHz, CDCl3)   171.1, 140.2, 140.0,
138.7, 135.6, 133.3, 130.3, 128.7, 128.5, 126.1, 122.9, 116.8,
60.6, 43.6, 42.2, 36.0, 31.8, 29.4, 29.2, 28.4, 26.9, 24.7, 22.7,
21.2, 19.1, 14.1; HRMS (ESI-TOF) Calcd for C27H38NO
([MH]) 392.2948. Found 392.2949.
2d5,
1-(3,5-dimethyl-3-phenethylindolin-1-yl)-2,2-
dimethylpropan-1-one, isolated by flash column
chromatography (petroleum ether/ethyl acetate  60:1) in
60% yield (50 mg), white solid: mp 59-60 C. 1H NMR (400
MHz, CDCl3)   1.36 (s, 9H), 1.38 (s, 3H), 1.84-1.99 (m, 2H),
2.33 (s, 3H), 2.44-2.51 (m, 1H), 2.59-2.66 (m, 1H), 3.85 (d, J
 10.2 Hz, 1H), 4.11 (d, J  10.2 Hz, 1H), 6.93 (s, 1H), 7.02
(d, J  7.8 Hz, 1H), 7.11 (d, J  7.2 Hz, 2H), 7.16 (dd, J  7.4,
7.2 Hz, 1H), 7.25 (dd, J  7.7, 7.0 Hz, 2H), 8.10 (d, J  8.2 Hz,
1H); 13C{1H} NMR (100 MHz, CDCl3)   176.1, 141.9, 141.6,
138.5, 133.4, 128.5, 128.3, 128.2, 126.0, 122.6, 118.2, 61.9,
44.2, 42.5, 40.1, 31.2, 27.7, 25.4, 21.1; HRMS (ESI-TOF)
Calcd for C23H30NO ([MH]) 336.2322. Found 336.2322.
2h2, 1-(3,5-dimethyl-3-(3-methylphenethyl)indolin-1-
yl)octan-1-one, isolated by flash column chromatography
(petroleum ether/ethyl acetate  60:1) in 51% yield (50
mg), colorless oil. 1H NMR (400 MHz, CDCl3)   0.88 (t, J 
6.8 Hz, 3H), 1.30-1.39 (m, 11H), 1.68-1.75 (m, 2H), 1.86-
1.99 (m, 2H), 2.30-2.43 (m, 9H), 2.49-2.56 (m, 1H), 3.68 (d,
J  10.3 Hz, 1H), 3.89 (d, J  10.3 Hz, 1H), 6.90-7.03 (m, 5H),
7.14 (dd, J  7.8, 7.8 Hz, 1H), 8.11 (d, J  8.2 Hz, 1H); 13C{1H}
NMR (100 MHz, CDCl3)   171.1, 141.8, 140.2, 138.7,
138.0, 133.3, 129.1, 128.4, 128.3, 126.7, 125.2, 122.9, 116.7,
60.6, 43.6, 43.4, 36.0, 31.8, 31.0, 29.4, 29.2, 27.1, 24.7, 22.7,
21.4, 21.2, 14.1; HRMS (ESI-TOF) Calcd for C27H38NO
([MH]) 392.2948. Found 392.2946.
2e,
tert-butyl
3,5-dimethyl-3-phenethylindoline-1-
carboxylate, 1:1 mixture of rotamers due to the slow
rotation of the N–(CO) bond, isolated by flash column
chromatography (petroleum ether/ethyl acetate  300:1)
1
in 46% yield (40 mg), colorless oil. H NMR (400 MHz,
CDCl3)   1.36 (s, 3H), 1.57 (s, 9H), 1.83-1.96 (m, 2H), 2.31
(s, 3H), 2.35-2.43 (m, 1H), 2.56-2.63 (m, 1H), 3.64 (brs, 1H),
3.86 (brs, 0.5H), 3.94 (brs, 0.5H), 6.90 (s, 1H), 6.99 (d, J 
7.7 Hz, 1H), 7.12 (d, J  7.2 Hz, 2H), 7.15 (dd, J  7.3, 7.3 Hz,
1H), 7.25 (dd,
J  7.6, 7.2 Hz, 2H), 7.33 (brs,
unexchangeable, 0.5H), 7.73 (brs, unexchangeable, 0.5H);
13C{1H} NMR (100 MHz, CDCl3)   152.5 (br), 142.2, 140.0-
138.4 (brm), 131.8, 128.4, 128.3, 125.8, 123.3 (br), 123.1
(br), 114.4, 81.4 (br), 80.4 (br), 60.1 (br), 59.8 (br), 43.6,
42.9 (br), 42.2 (br), 31.0, 28.5, 27.2, 21.0; HRMS (ESI-TOF)
Calcd for C23H30NO2 ([MH]) 352.2271. Found 352.2273.
2h3, 1-(3,5-dimethyl-3-(4-methylphenethyl)indolin-1-
yl)octan-1-one, isolated by flash column chromatography
(petroleum ether/ethyl acetate  60:1) in 45% yield (44
mg), pale yellow oil. 1H NMR (400 MHz, CDCl3)   0.88 (t, J
 6.8 Hz, 3H), 1.30-1.39 (m, 11H), 1.68-1.75 (m, 2H), 1.86-
1.94 (m, 2H), 2.30-2.42 (m, 9H), 2.48-2.56 (m, 1H), 3.67 (d,
J  10.3 Hz, 1H), 3.88 (d, J  10.3 Hz, 1H), 6.92 (s, 1H), 6.98-
7.07 (m, 5H), 8.11 (d, J  8.2 Hz, 1H); 13C{1H} NMR (100
MHz, CDCl3)   171.1, 140.2, 138.77, 138.75, 135.4, 133.3,
129.1, 128.4, 128.1, 122.9, 116.7, 60.6, 43.6, 43.5, 36.0,
2f,
5-chloro-1-(ethylsulfonyl)-3-methyl-3-
isolated by flash column
phenethylindoline,
chromatography (petroleum ether/ethyl acetate  30:1) in
27% yield (25 mg), colorless oil. 1H NMR (400 MHz, CDCl3)
  1.41 (s, 3H), 1.42 (t, J  7.4 Hz, 3H), 1.86-2.01 (m, 2H),
2.40-2.47 (m, 1H), 2.62-2.70 (m, 1H), 3.12 (q, J  7.4 Hz,
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31.8, 30.6, 29.4, 29.2, 27.2, 24.7, 22.7, 21.2, 21.0, 14.1;
(petroleum ether/ethyl acetate  30:1) in 60% yield (61
HRMS (ESI-TOF) Calcd for C27H38NO ([MH]) 392.2948.
mg), pale yellow oil. 1H NMR (400 MHz, CDCl3)   0.88 (t, J
 6.8 Hz, 3H), 1.26-1.39 (m, 11H), 1.68-1.76 (m, 2H), 1.85-
1.97 (m, 2H), 2.17-2.42 (m, 12H), 2.45-2.52 (m, 1H), 3.67
(d, J  10.3 Hz, 1H), 3.89 (d, J  10.3 Hz, 1H), 6.72 (s, 2H),
6.80 (s, 1H), 6.92 (s, 1H), 7.02 (d, J  8.4 Hz, 1H), 8.11 (d, J 
8.2 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3)   171.1, 141.8,
140.2, 138.8, 137.9, 133.2, 128.4, 127.6, 126.1, 122.9, 116.7,
60.6, 43.6, 43.5, 36.0, 31.8, 30.9, 29.4, 29.2, 27.1, 24.7, 22.7,
21.24, 21.17, 14.1; HRMS (ESI-TOF) Calcd for C28H40NO
([MH]) 406.3104. Found 406.3108.
1
2
3
4
5
6
7
8
Found 392.2940.
2i1,
1-(3-(2-chlorophenethyl)-3,5-dimethylindolin-1-
yl)propan-1-one, isolated by flash column chromatography
(petroleum ether/ethyl acetate  20:1) in 81% yield (69
mg), colorless oil. 1H NMR (400 MHz, CDCl3)   1.24 (t, J 
7.4 Hz, 3H), 1.41 (s, 3H), 1.82-1.95 (m, 2H), 2.33 (s, 3H),
2.41-2.53 (m, 3H), 2.65-2.73 (m, 1H), 3.72 (d, J  10.4 Hz,
1H), 4.01 (d, J  10.3 Hz, 1H), 6.95 (s, 1H), 7.03 (d, J  8.4
Hz, 1H), 7.08-7.17 (m, 3H), 7.31 (dd, J  2.0, 7.0 Hz, 1H),
8.12 (d, J  8.2 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3)  
171.7, 140.2, 139.4, 138.5, 133.7, 133.3, 130.3, 129.5, 128.5,
127.5, 126.9, 122.9, 116.7, 60.2, 43.7, 41.7, 29.22, 29.16,
27.0, 21.2, 8.8; HRMS (ESI-TOF) Calcd for C21H25ClNO
([MH]) 342.1619. Found 342.1622.
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
2k,
1-(3,5-dimethyl-3-(2-
(perfluorophenyl)ethyl)indolin-1-yl)propan-1-one,
isolated by flash column chromatography (petroleum
ether/ethyl acetate  20:1) in 76% yield (76 mg), colorless
crystal: mp 94-95 C. 1H NMR (400 MHz, CDCl3)   1.25 (t,
J  7.4 Hz, 3H), 1.41 (s, 3H), 1.80-1.92 (m, 2H), 2.33 (s, 3H),
2.40-2.52 (m, 3H), 2.59-2.69 (m, 1H), 3.76 (d, J  10.4 Hz,
1H), 3.98 (d, J  10.5 Hz, 1H), 6.92 (s, 1H), 7.04 (d, J  8.3
Hz, 1H), 8.11 (d, J  8.2 Hz, 1H); 13C{1H} NMR (100 MHz,
CDCl3)   171.6, 140.2, 137.4, 133.5, 128.8, 122.7, 116.7,
59.9, 43.6, 40.7, 29.2, 27.2, 21.1, 18.0, 8.8; 19F NMR (376
MHz, CDCl3)   –144.93 (m, 2F), –157.53 (m, 1F), –162.59
(m, 2F); HRMS (ESI-TOF) Calcd for C21H21F5NO ([MH])
398.1538. Found 398.1540.
2i2,
1-(3-(3-chlorophenethyl)-3,5-dimethylindolin-1-
yl)propan-1-one, isolated by flash column chromatography
(petroleum ether/ethyl acetate  20:1) in 66% yield (56
mg), colorless oil. 1H NMR (400 MHz, CDCl3)   1.23 (t, J 
7.4 Hz, 3H), 1.40 (s, 3H), 1.85-1.98 (m, 2H), 2.33 (s, 3H),
2.35-2.42 (m, 3H), 2.49-2.56 (m, 1H), 3.70 (d, J  10.4 Hz,
1H), 3.88 (d, J  10.4 Hz, 1H), 6.91 (s, 1H), 6.96 (d, J  6.9
Hz, 1H), 7.04 (d, J  8.4 Hz, 1H), 7.09 (s, 1H), 7.13-7.19 (m,
2H), 8.12 (d, J  8.2 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3)
  171.6, 143.9, 140.2, 138.2, 134.2, 133.3, 129.7, 128.6,
128.3, 126.5, 126.1, 122.9, 116.7, 60.4, 43.6, 43.2, 30.8,
29.1, 27.2, 21.2, 8.8; HRMS (ESI-TOF) Calcd for C21H25ClNO
([MH]) 342.1619. Found 342.1634.
3, 2-(1-acetyl-3-methylindolin-3-yl)-1-phenylethan-1-
one, isolated by flash column chromatography (petroleum
ether/ethyl acetate  15:1) in 17% yield (12 mg), colorless
oil. 1H NMR (400 MHz, CDCl3)   1.50 (s, 3H), 2.23 (s, 3H),
3.24 (d, J  17.3 Hz, 1H), 3.53 (d, J  17.3 Hz, 1H), 4.06 (d, J
 11.0 Hz, 1H), 4.20 (d, J  11.0 Hz, 1H), 7.06 (dd, J  6.8,
6.8 Hz, 1H), 7.18-7.25 (m, 2H), 7.46 (dd, J  7.5, 7.5 Hz, 2H),
7.57 (dd, J  7.4, 7.4 Hz, 1H), 7.91 (d, J  7.3 Hz, 2H), 8.21 (d,
J  8.0 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3)   198.3,
168.9, 141.6, 139.2, 137.2, 133.4, 128.7, 128.3, 128.0, 123.8,
122.1, 117.2, 61.3, 48.1, 42.2, 26.4, 24.3; HRMS (ESI-TOF)
Calcd for C19H20NO2 ([MH]) 294.1489. Found 294.1490.
2i3,
1-(3-(4-chlorophenethyl)-3,5-dimethylindolin-1-
yl)propan-1-one, isolated by flash column chromatography
(petroleum ether/ethyl acetate  20:1) in 64% yield (55
mg), colorless oil. 1H NMR (400 MHz, CDCl3)   1.22 (t, J 
7.4 Hz, 3H), 1.40 (s, 3H), 1.83-1.97 (m, 2H), 2.33 (s, 3H),
2.35-2.43 (m, 3H), 2.45-2.56 (m, 1H), 3.68 (d, J  10.3 Hz,
1H), 3.86 (d, J  10.3 Hz, 1H), 6.91 (s, 1H), 7.01-7.04 (m,
3H), 7.21 (d, J  8.3 Hz, 2H), 8.12 (d, J  8.2 Hz, 1H); 13C{1H}
NMR (100 MHz, CDCl3)   171.6, 140.3, 138.3, 133.3,
131.7, 129.6, 128.6, 128.5, 122.9, 116.7, 60.4, 43.6, 43.4,
30.5, 29.1, 27.2, 21.2, 8.7; HRMS (ESI-TOF) Calcd for
C21H25ClNO ([MH]) 342.1619. Found 342.1618.
4,
1-acetyl-3-ethyl-3-methylindoline-5-carbonitrile,
isolated by flash column chromatography (petroleum
ether/ethyl acetate  20:1) in 12% yield (7 mg), colorless
1
oil. H NMR (400 MHz, CDCl3)   0.83 (t, J  7.5 Hz, 3H),
1.36 (s, 3H), 1.68 (q, J  7.5 Hz, 2H), 2.26 (s, 3H), 3.74 (d, J 
10.3 Hz, 1H), 3.92 (d, J  10.3 Hz, 1H), 7.34 (s, 1H), 7.52 (dd,
J  1.7, 8.4 Hz, 1H), 8.27 (d, J  8.4 Hz, 1H); 13C{1H} NMR
(100 MHz, CDCl3)   169.4, 145.9, 140.1, 132.9, 126.3,
119.4, 117.1, 106.6, 61.0, 43.9, 34.0, 26.6, 24.3, 8.8; HRMS
(ESI-TOF) Calcd for C14H17N2O ([MH]) 229.1335. Found
229.1346
2i4,
1-(3-(4-fluorophenethyl)-3,5-dimethylindolin-1-
yl)propan-1-one, isolated by flash column chromatography
(petroleum ether/ethyl acetate  20:1) in 50% yield (41
mg), pale yellow oil. 1H NMR (400 MHz, CDCl3)   1.22 (t, J
 7.4 Hz, 3H), 1.40 (s, 3H), 1.84-1.97 (m, 2H), 2.33-2.41 (m,
6H), 2.48-2.56 (m, 1H), 3.68 (d, J  10.3 Hz, 1H), 3.87 (d, J 
10.3 Hz, 1H), 6.91-6.95 (m, 3H), 7.02-7.06 (m, 3H), 8.12 (d,
J  8.2 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3)   171.6,
5a, 2,4-dimethyl-4-phenethyl-3,4-dihydroisoquinolin-
1(2H)-one, isolated by flash column chromatography
(petroleum ether/ethyl acetate  20:1) in 50% yield (35
1
4
162.3 (d, J(C–F)  242.2 Hz), 140.2, 138.4, 137.4 (d, J(C–F)

3.0 Hz), 133.3, 129.6 (d, 3J(C–F)  7.7 Hz), 128.5, 122.9, 116.7,
2
1
115.1 (d, J(C–F)  21.0 Hz), 60.4, 43.6, 30.3, 29.1, 27.2, 21.2,
mg), yellow oil. H NMR (400 MHz, CDCl3)   1.41 (s, 3H),
8.8; 19F NMR (376 MHz, CDCl3)   –117.54 (m, 1F); HRMS
(ESI-TOF) Calcd for C21H25FNO ([MH]) 326.1915. Found
326.1919.
1.86-2.02 (m, 2H), 2.37-2.44 (m, 1H), 2.55-2.62 (m, 1H),
3.14 (s, 3H), 3.30 (d, J  12.5 Hz, 1H), 3.51 (d, J  12.6 Hz,
1H), 7.08 (d, J  7.3 Hz, 2H), 7.16 (dd, J  7.4, 7.4 Hz, 1H),
7.23 (dd, J  7.5, 7.5 Hz, 2H), 7.29 (d, J  7.8 Hz, 1H), 7.35
(dd, J  7.5, 7.6 Hz, 1H), 7.48 (dd, J  7.5, 7.5 Hz, 1H), 8.13
2j, 1-(3-(3,5-dimethylphenethyl)-3,5-dimethylindolin-1-
yl)octan-1-one, isolated by flash column chromatography
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(d, J  7.7 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3)   164.5,
145.1, 141.8, 131.7, 128.7, 128.5, 128.3, 128.2, 126.9, 126.0,
124.3, 58.6, 41.6, 37.3, 35.3, 31.0, 23.2; HRMS (ESI-TOF)
Calcd for C19H22NO ([MH]) 280.1696. Found 280.1692.
3H), 2.40 (q, J  7.4 Hz, 2H), 2.69-2.73 (m, 2H), 3.35-3.42
1
2
3
4
5
6
7
8
(m, 1H), 3.66 (dd, J  5.9, 10.3 Hz, 1H), 4.11 (dd, J  9.9, 9.9
Hz, 1H), 6.98-7.02 (m, 2H), 7.19-7.22 (m, 3H), 7.28-7.32 (m,
2H), 8.11 (d, J  8.2 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3)
  171.6, 141.4, 140.7, 134.7, 133.1, 128.5, 128.40, 128.35,
126.1, 124.4, 116.6, 54.1, 39.7, 37.0, 33.3, 29.1, 21.1, 8.8;
HRMS (ESI-TOF) Calcd for C20H24NO ([MH]) 294.1852.
Found 294.1850.
5b,
2,4-dimethyl-4-(2-methylphenethyl)-3,4-
dihydroisoquinolin-1(2H)-one, isolated by flash column
chromatography (petroleum ether/ethyl acetate  20:1) in
38% yield (28 mg), colorless oil. 1H NMR (400 MHz, CDCl3)
  1.44 (s, 3H), 1.77-1.92 (m, 2H), 2.13 (s, 3H), 2.34-2.42
(m, 1H), 2.53-2.61 (m, 1H), 3.16 (s, 3H), 3.31 (d, J  12.5 Hz,
1H), 3.55 (d, J  12.5 Hz, 1H), 7.00-7.19 (m, 4H), 7.31 (d, J 
7.7 Hz, 1H), 7.36 (dd, J  6.8, 7.5 Hz, 1H), 7.48 (ddd, J  1.2,
7.6, 7.4 Hz, 1H), 8.14 (d, J  6.8 Hz, 1H); 13C{1H} NMR (100
MHz, CDCl3)   164.5, 145.1, 139.9, 135.6, 131.7, 130.3,
128.8, 128.7, 128.3, 126.9, 126.2, 126.1, 124.3, 58.7, 40.5,
37.3, 35.4, 28.2, 22.9, 19.0; HRMS (ESI-TOF) Calcd for
C20H24NO ([MH]) 294.1852. Found 294.1851.
6e,
1-(5-methyl-3-phenethylindolin-1-yl)octan-1-one,
9
isolated by flash column chromatography (petroleum
ether/ethyl acetate  55:1) in 46% yield (42 mg), colorless
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
oil. H NMR (400 MHz, CDCl3)   0.89 (t, J  6.8 Hz, 3H),
1.29-1.40 (m, 8H), 1.68-1.75 (m, 2H), 1.83-1.92 (m, 1H),
2.11-2.19 (m, 1H), 2.30 (s, 3H), 2.36 (t, J  7.6 Hz, 2H), 2.71
(t, J  6.9 Hz, 2H), 3.34-3.41 (m, 1H), 3.66 (dd, J  6.0, 10.3
Hz, 1H), 4.11 (dd, J  9.8, 9.9 Hz, 1H), 6.97-7.01 (m, 2H),
7.19-7.22 (m, 3H), 7.28-7.32 (m, 2H), 8.10 (d, J  8.1 Hz,
1H); 13C{1H} NMR (100 MHz, CDCl3)   171.1, 141.4, 140.6,
134.8, 133.1, 128.5, 128.38, 128.36, 126.1, 124.4, 116.7,
54.3, 39.7, 37.0, 36.0, 33.3, 31.8, 29.4, 29.2, 24.7, 22.7, 21.1,
14.1; HRMS (ESI-TOF) Calcd for C25H34fNO ([MH])
364.2635. Found 364.2628.
6a, 1-(3-phenethylindolin-1-yl)ethan-1-one, isolated by
flash column chromatography (petroleum ether/ethyl
acetate  20:1) in 50% yield (33 mg), colorless oil. 1H NMR
(400 MHz, CDCl3)   1.86-1.95 (m, 1H), 2.13-2.18 (m, 1H),
2.20 (s, 3H), 2.72 (t, J  7.4 Hz, 2H), 3.40-3.47 (m, 1H), 3.68
(dd, J  6.0, 10.3 Hz, 1H), 4.14 (dd, J  9.9, 9.9 Hz, 1H), 7.03
(dd, J  7.4, 7.4 Hz, 1H), 7.17-7.23 (m, 5H), 7.31 (dd, J  7.1,
7.6 Hz, 2H), 8.20 (d, J  8.0 Hz, 1H); 13C{1H} NMR (100 MHz,
CDCl3)   168.7, 142.7, 141.3, 134.7, 128.6, 128.4, 128.0,
126.2, 123.8, 123.7, 117.0, 55.0, 39.7, 37.0, 33.2, 24.3;
HRMS (ESI-TOF) Calcd for C18H20NO ([MH]) 266.1539.
Found 266.1538.
7, methyl 1-acetyl-5-chloro-3-phenethylindoline-3-
carboxylate, isolated by flash column chromatography
(petroleum ether/ethyl acetate  20:1) in 53% yield (49
mg), white solid: mp 154-155 C. 1H NMR (400 MHz, CDCl3)
  2.11-2.18 (m, 1H), 2.21 (s, 3H), 2.45-2.58 (m, 3H), 3.76
(s, 3H), 3.84 (d, J  10.8 Hz, 1H), 4.71 (d, J  10.8 Hz, 1H),
7.13-7.15 (m, 2H), 7.18-7.25 (m, 2H), 7.29 (dd, J  7.6, 7.6
Hz, 2H), 7.38 (d, J  2.1 Hz, 1H), 8.15 (d, J  8.7 Hz, 1H);
13C{1H} NMR (100 MHz, CDCl3)   172.5, 168.5, 140.9,
140.2, 133.7, 129.3, 128.8, 128.6, 128.3, 126.5, 124.6, 118.0,
56.3, 54.9, 53.1, 40.5, 31.3, 24.1; HRMS (ESI-TOF) Calcd for
C20H21ClNO3 ([MH]) 358.1204. Found 358.1207.
6b, 1-(5-methyl-3-phenethylindolin-1-yl)ethan-1-one,
isolated by flash column chromatography (petroleum
ether/ethyl acetate  40:1) in 57% yield (40 mg), pale
yellow oil. 1H NMR (400 MHz, CDCl3)   1.84-1.93 (m, 1H),
2.12-2.20 (m, 4H), 2.31 (s, 3H), 2.69-2.74 (m, 2H), 3.36-
3.43 (m, 1H), 3.66 (dd, J  6.0, 10.4 Hz, 1H), 4.12 (dd, J  9.9,
9.9 Hz, 1H), 6.98-7.02 (m, 2H), 7.19-7.23 (m, 3H), 7.29-7.32
(m, 2H), 8.07 (d, J  8.2 Hz, 1H); 13C{1H} NMR (100 MHz,
CDCl3)   168.3, 141.4, 140.4, 134.9, 133.3, 128.6, 128.39,
128.35, 126.2, 124.4, 116.7, 55.1, 39.7, 37.0, 33.3, 24.1,
21.1; HRMS (ESI-TOF) Calcd for C19H22NO ([MH])
280.1696. Found 280.1699.
8, 1-(3-phenethyl-1H-indol-1-yl)ethan-1-one, isolated by
flash column chromatography (petroleum ether/ethyl
1
acetate  24:1) in 67% yield (44 mg), pale yellow oil. H
NMR (400 MHz, CDCl3)   2.54 (s, 3H), 3.01 (s, 4H), 7.07
(brs, 1H, unexchangeable), 7.20-7.24 (m, 3H), 7.26-7.37 (m,
4H), 7.52 (d, J  7.8 Hz, 1H), 8.43 (brd, J  6.5 Hz, 1H,
unexchangeable); 13C{1H} NMR (100 MHz, CDCl3)   168.4,
141.6, 136.0, 130.6, 128.5, 126.2, 125.3, 123.4, 122.4, 122.0,
118.9, 116.7, 35.5, 27.0, 24.0; HRMS (ESI-TOF) Calcd for
C18H18NO ([MH]) 264.1383. Found 264.1382.
6c,
1-(5-chloro-3-phenethylindolin-1-yl)ethan-1-one,
isolated by flash column chromatography (petroleum
ether/ethyl acetate  30:1) in 62% yield (46 mg), white
solid: mp 88-89 C. 1H NMR (400 MHz, CDCl3)   1.85-1.95
(m, 1H), 2.10-2.23 (m, 4H), 2.69-2.74 (m, 2H), 3.37-3.44 (m,
1H), 3.69 (dd, J  6.1, 10.4 Hz, 1H), 4.14 (dd, J  9.9, 9.9 Hz,
1H), 7.13-7.24 (m, 5H), 7.29-7.33 (m, 2H), 8.13 (d, J  8.6
Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3)   168.6, 141.4,
140.9, 136.7, 128.6, 128.5, 128.3, 127.9, 126.3, 124.0, 118.0,
55.1, 39.5, 36.8, 33.1, 24.1; HRMS (ESI-TOF) Calcd for
C18H19ClNO ([MH]) 300.1150. Found 300.1161.
9,
4-benzyl-2,6-di-tert-butyl-4-methylcyclohexa-2,5-
dien-1-one, isolated by flash column chromatography
(pure petroleum ether) in 71% yield (55 mg), yellow solid:
1
mp 83-84 C. H NMR (400 MHz, CDCl3)   1.14 (s, 18H),
1.27 (s, 3H), 2.82 (s, 2H), 6.47 (s, 2H), 6.94-6.97 (m, 2H),
7.12-7.20 (m, 3H); 13C{1H} NMR (100 MHz, CDCl3)   186.1,
146.1, 145.9, 136.7, 130.1, 127.5, 126.6, 48.1, 40.9, 34.6,
29.3, 26.2; HRMS (ESI-TOF) Calcd for C22H31O ([MH])
311.2369. Found 311.2371.
6d, 1-(5-methyl-3-phenethylindolin-1-yl)propan-1-one,
isolated by flash column chromatography (petroleum
ether/ethyl acetate  40:1) in 60% yield (44 mg), white
Synthesis of Allyl Amines 1. Substrates 1 were
prepared from anilides and allyl bromides according to the
literature procedure, and spectral data of known
compounds match those described.32a-c Spectral data of
1
solid: mp 83-84 C. H NMR (400 MHz, CDCl3)   1.22 (t, J
 7.4 Hz, 3H), 1.83-1.92 (m, 1H), 2.11-2.20 (m, 1H), 2.31 (s,
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2H); 13C{1H} NMR (100 MHz, CDCl3)   177.7, 141.2, 137.7,
129.5, 129.2, 112.3, 58.6, 41.1, 29.6, 21.1, 20.4; HRMS (ESI-
TOF) Calcd for C16H24NO ([MH]) 246.1852. Found
246.1856.
new compounds or known compounds prepared by the
new method are shown below.
1
2
3
4
5
6
7
8
1a1-d5,
N-(2-methylallyl)-N-(phenyl-d5)acetamide,
isolated by flash column chromatography (petroleum
ether/ethyl acetate  15:1) in 92% yield (2681 mg),
1e, tert-butyl (2-methylallyl)(p-tolyl)carbamate, isolated
1
colorless oil. H NMR (400 MHz, CDCl3)   1.76 (s, 3H),
by flash column chromatography (petroleum ether/ethyl
1.90 (s, 3H), 4.29 (s, 2H), 4.70 (s, 1H), 4.81 (s, 1H); 13C{1H}
NMR (100 MHz, CDCl3)   170.3, 143.0, 140.7, 129.0 (t, J(C–
D)  24.1 Hz), 127.3 (t, J(C–D)  24.5 Hz), 127.2 (t, J(C–D)  23.7
Hz), 113.1, 55.0, 22.7, 20.3; HRMS (ESI-TOF) Calcd for
C12H11D5NO ([MH]) 195.1540. Found 195.1542.
1
acetate  300:1) in 81% yield (3176 mg), colorless oil. H
NMR (400 MHz, CDCl3)   1.44 (s, 9H), 1.74 (d, J  0.5 Hz,
3H), 2.31 (s, 3H), 4.14 (s, 2H), 4.79-4.81 (m, 1H), 4.83-4.84
(m, 1H), 7.10 (s, 4H); 13C{1H} NMR (100 MHz, CDCl3)  
154.8, 141.8, 140.3, 135.2, 129.1, 125.9, 111.3, 80.2, 55.9,
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

28.3, 21.0, 20.1; HRMS (ESI-TOF) Calcd for C16H24NO2
([MH]) 262.1802. Found 262.1809.
1a6, N-(4-methoxyphenyl)-N-(2-methylallyl)acetamide,
isolated by flash column chromatography (petroleum
ether/ethyl acetate  20:1) in 88% yield (2895 mg), white
1f,
N-(4-chlorophenyl)-N-(2-
1
solid: mp 60-61 C. H NMR (400 MHz, CDCl3)   1.75 (s,
methylallyl)ethanesulfonamide, isolated by flash column
chromatography (petroleum ether/ethyl acetate  24:1) in
87% yield (3573 mg), yellow oil. 1H NMR (400 MHz, CDCl3)
  1.38 (t, J  7.4 Hz, 3H), 1.74 (s, 3H), 3.04 (q, J  7.4 Hz,
2H), 4.27 (s, 2H), 4.78 (s, 1H), 4.81 (s, 1H), 7.27-7.35 (m,
4H); 13C{1H} NMR (100 MHz, CDCl3)   139.8, 137.6, 133.4,
129.42, 129.38, 115.4, 57.2, 45.3, 19.8, 8.0; HRMS (ESI-TOF)
Calcd for C12H17ClNO2S ([MH]) 274.0663. Found
274.0663.
3H), 1.88 (s, 3H), 3.82 (s, 3H), 4.24 (s, 2H), 4.69 (s, 1H),
4.81 (s, 1H), 6.89 (ddd, J  3.4, 2.2, 8.9 Hz, 2H), 7.07 (ddd, J
 3.4, 2.2, 8.9 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3)  
170.8, 158.8, 140.9, 136.0, 128.9, 114.6, 113.2, 55.4, 55.1,

22.7, 20.3; HRMS (ESI-TOF) Calcd for C13H18NO2 ([MH])
220.1332. Found 220.1333.
1a7,
N-(2-methylallyl)-N-(4-
(trifluoromethyl)phenyl)acetamide, isolated by flash
column chromatography (petroleum ether/ethyl acetate 
1g, N-(3,5-dichlorophenyl)-N-(2-methylallyl)octanamide,
isolated by flash column chromatography (petroleum
ether/ethyl acetate  80:1) in 91% yield (4672 mg), pale
yellow oil. 1H NMR (400 MHz, CDCl3)   0.86 (t, J  7.0 Hz,
3H), 1.23-1.27 (m, 8H), 1.60 (s, 2H), 1.74 (s, 3H), 2.13 (s,
2H), 4.22 (s, 2H), 4.71 (s, 1H), 4.88 (s, 1H), 7.08 (s, 2H),
7.33 (s, 1H); 13C{1H} NMR (100 MHz, CDCl3)   172.6,
144.8, 140.3, 135.4, 128.0, 126.7, 113.5, 55.2, 34.4, 31.6,
29.2, 29.0, 25.4, 22.6, 20.3, 14.1; HRMS (ESI-TOF) Calcd for
C18H26Cl2NO ([MH]) 342.1386. Found 342.1385.
1
20:1) in 90% yield (3473 mg), colorless oil. H NMR (400
MHz, CDCl3)   1.67 (s, 3H), 1.86 (s, 3H), 4.22 (s, 2H), 4.63
(s, 1H), 4.76 (s, 1H), 7.25 (d, J  8.2 Hz, 2H), 7.58 (d, J  8.2
Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3)   169.8, 146.2,
1
140.3, 129.5, 128.1, 126.6, 123.7 (q, J(C–F)  270.5 Hz),
113.4, 54.8, 22.7, 20.1; 19F NMR (376 MHz, CDCl3)   –
62.64 (s, 3F); HRMS (ESI-TOF) Calcd for C13H15F3NO
([MH]) 258.1100. Found 258.1106.
N-(4-Cyanophenyl)-N-(2-methylallyl)acetamide, isolated
by flash column chromatography (petroleum ether/ethyl
acetate  20:1) in 76% yield (2443 mg), white solid: mp
122-123 C. 1H NMR (400 MHz, CDCl3)   1.75 (s, 3H), 2.01
(s, 3H), 4.29 (s, 2H), 4.73 (s, 1H), 4.88 (s, 1H), 7.33 (d, J 
8.2 Hz, 2H), 7.69 (d, J  8.2 Hz, 2H); 13C{1H} NMR (100 MHz,
CDCl3)   169.8, 147.1, 140.2, 133.4, 128.1, 118.1, 113.4,
55.2, 22.8, 20.2; HRMS (ESI-TOF) Calcd for C13H15N2O
([MH]) 215.1179. Found 215.1171.
N-(But-2-en-1-yl)-N-(4-chlorophenyl)acetamide,
4:17
mixture of Z/E isomers, isolated by flash column
chromatography (petroleum ether/ethyl acetate  12:1) in
1
82% yield (2752 mg), colorless oil. H NMR (400 MHz,
CDCl3)   1.46 (d, J  6.7 Hz, 3H minor), 1.60-1.68 (m, 3H
major), 1.84 (s, 3H major and 3H minor), 4.16-4.23 (m, 2H
major), 4.33 (d, J  7.0 Hz, 2H minor), 5.42-5.63 (stack, 2H
major and 2H minor), 7.08-7.13 (stack, 2H major and 2H
minor), 7.37 (d, J  8.5 Hz, 2H major and 2H minor); 13C{1H}
NMR (100 MHz, CDCl3)   169.8 (minor), 169.7 (major),
141.54 (major), 141.50 (minor), 133.7 (minor), 133.6
(major), 129.8 (minor), 129.7 (major), 129.6 (major),
129.5 (minor), 128.2 (minor), 125.5 (major), 124.8
(minor), 51.2 (major), 45.4 (minor), 22.7 (major), 22.6
(minor), 17.7 (major), 12.7 (minor); HRMS (ESI-TOF) Calcd
for C12H15ClNO ([MH]) 224.0837. Found 224.0831.
1b,
N-(2-methylallyl)-N-(pyridin-4-yl)acetamide,
isolated by flash column chromatography (petroleum
ether/ethyl acetate  1:1) in 44% yield (1256 mg), brown
oil. 1H NMR (400 MHz, CDCl3)   1.75 (s, 3H), 2.09 (s, 3H),
4.29 (s, 2H), 4.77 (s, 1H), 4.90 (s, 1H), 7.18 (d, J  5.5 Hz,
2H), 8.62 (d, J  4.8 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3)
  169.9, 151.0, 150.5, 140.1, 121.2, 112.9, 54.8, 22.9, 20.2;
HRMS (ESI-TOF) Calcd for C11H15N2O ([MH]) 191.1179.
Found 191.1180.
3-Chloro-N-(2-methylallyl)-N-(p-tolyl)benzamide,
isolated by flash column chromatography (petroleum
ether/ethyl acetate  60:1) in 86% yield (3867 mg), pale
1d5, N-(2-methylallyl)-N-(p-tolyl)pivalamide, prepared
from 4-methyl-N-(2-methylallyl)aniline and pivaloyl
chloride and isolated by flash column chromatography
(petroleum ether/ethyl acetate  60:1) in 77% yield (2834
1
yellow solid: mp 43-44 C. H NMR (400 MHz, CDCl3)  
1.81 (s, 3H), 2.27 (s, 3H), 4.46 (s, 2H), 4.87 (s, 1H), 4.90 (s,
1H), 6.90 (d, J  8.1 Hz, 2H), 7.01 (d, J  8.1 Hz, 2H), 7.05-
7.13 (m, 2H), 7.21 (ddd, J  1.6, 1.6, 7.6 Hz, 1H), 7.37 (s, 1H);
13C{1H} NMR (100 MHz, CDCl3)   168.9, 140.8, 140.6,
1
mg), yellow oil. H NMR (400 MHz, CDCl3)   1.04 (s, 9H),
1.74 (s, 3H), 2.36 (s, 3H), 4.18 (s, 2H), 4.67 (s, 1H), 4.80 (s,
1H), 7.06 (ddd, J  1.6, 1.6, 8.2 Hz, 2H), 7.14 (d, J  8.0 Hz,
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The Journal of Organic Chemistry
21.1, 14.1; HRMS (ESI-TOF) Calcd for C18H28NO ([MH])
274.2165. Found 274.2168.
N-Phenyl-N-(2-phenylallyl)acetamide,43 isolated by flash
138.0, 136.7, 133.9, 129.7, 129.6, 129.0, 128.9, 126.9, 126.7,
112.8, 55.8, 21.0, 20.5; HRMS (ESI-TOF) Calcd for
C18H19ClNO ([MH]) 300.1150. Found 300.1154.
1
2
3
4
5
6
7
8
N-Methyl-N-(2-methylallyl)benzamide, 2:3 mixture of
rotamers, isolated by flash column chromatography
(petroleum ether/ethyl acetate  40:1) in 88% yield (2498
column chromatography (petroleum ether/ethyl acetate 
1
32:1) in 77% yield (2903 mg), pale yellow oil. H NMR
(400 MHz, CDCl3)   1.79 (s, 3H), 4.87 (s, 2H), 5.00 (s, 1H),
5.33 (s, 1H), 6.90-6.92 (s, 2H), 7.25-7.35 (s, 6H), 7.40-7.42
(m, 2H); 13C{1H} NMR (100 MHz, CDCl3)   170.3, 143.8,
142.2, 138.5, 129.3, 128.4, 128.2, 127.9, 127.8, 126.4, 115.9,
51.9, 22.8; HRMS (ESI-TOF) Calcd for C17H18NO ([MH])
252.1383. Found 252.1392.
1
mg), pale yellow oil. H NMR (400 MHz, CDCl3)   1.60 (s,
3H major), 1.78 (s, 3H minor), 2.88 (s, 3H minor), 3.04 (s,
3H major), 3.77 (s, 2H major), 4.13 (s, 2H minor), 4.89 (s,
1H minor), 4.92 (s, 1H major), 4.97 (s, 1H minor), 4.98 (s,
1H major), 7.36-7.44 (stack, 5H major and 5H minor);
13C{1H} NMR (100 MHz, CDCl3)   172.3 (major), 171.4
(minor), 140.5 (major), 140.2 (minor), 136.4 (minor),
136.2 (major), 129.6 (major), 129.5 (minor), 128.3 (major
and minor), 126.8 (minor), 126.6 (major), 112.5 (minor),
112.2 (major), 57.3 (major), 52.8 (minor), 36.8 (minor),
33.2 (major), 19.90 (minor), 19.86 (major); HRMS (ESI-
TOF) Calcd for C12H16NO ([MH]) 190.1226. Found
190.1225.
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
Methyl
2-((N-(4-
chlorophenyl)acetamido)methyl)acrylate, prepared from
methyl 2-(((4-chlorophenyl)amino)methyl)acrylate and
acetyl chloride and isolated by flash column
chromatography (petroleum ether/ethyl acetate  16:1) in
1
90% yield (3614 mg), white solid: mp 63-64 C. H NMR
(400 MHz, CDCl3)   1.91 (s, 3H), 3.70 (s, 3H), 4.57 (s, 2H),
5.74 (d, J  1.0 Hz, 1H), 6.32 (s, 1H), 7.10 (d, J  8.5 Hz, 2H),
7.37 (d, J  8.5 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3)  
170.3, 166.3, 141.6, 135.4, 133.9, 129.9, 129.2, 127.3, 52.0,
50.0, 22.7; HRMS (ESI-TOF) Calcd for C13H15ClNO3 ([MH])
268.0735. Found 268.0741.
N-Allyl-N-(p-tolyl)acetamide, isolated by flash column
chromatography (petroleum ether/ethyl acetate  40:1) in
93% yield (2640 mg), yellow oil. 1H NMR (400 MHz, CDCl3)
  1.85 (s, 3H), 2.37 (s, 3H), 4.27 (d, J  6.3 Hz, 2H), 5.04-
5.11 (m, 2H), 5.80-5.90 (m, 1H), 7.03 (d, J  8.2 Hz, 2H),
7.19 (d, J  8.0 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3)  
170.3, 140.4, 137.8, 133.3, 130.2, 127.8, 117.7, 52.0, 22.6,
21.1; HRMS (ESI-TOF) Calcd for C12H16NO ([MH])
190.1226. Found 190.1223.
N-(2-Bromoallyl)-N-phenylacetamide,44 isolated by flash
column chromatography (petroleum ether/ethyl acetate 
1
16:1) in 42% yield (1601 mg), pale yellow oil. H NMR
(400 MHz, CDCl3)   1.91 (s, 3H), 4.60 (s, 2H), 5.51 (s, 1H),
5.65 (s, 1H), 7.24-7.27 (m, 2H), 7.34-7.44 (m, 3H); 13C{1H}
NMR (100 MHz, CDCl3)   170.5, 142.2, 129.7, 128.6,
128.2, 128.0, 119.5, 56.3, 22.7; HRMS (ESI-TOF) Calcd for
C11H13BrNO ([MH]) 254.0175. Found 254.0177.
N-Allyl-N-(4-chlorophenyl)acetamide, isolated by flash
column chromatography (petroleum ether/ethyl acetate 
60:1) in 90% yield (2831 mg), yellow solid: mp 45-46 C.
1H NMR (400 MHz, CDCl3)   1.86 (s, 3H), 4.27 (ddd, J 
1.2, 1.2, 6.2 Hz, 2H), 5.04-5.13 (m, 2H), 5.79-5.89 (m, 1H),
7.10 (d, J  8.5 Hz, 2H), 7.38 (d, J  8.6 Hz, 2H); 13C{1H} NMR
(100 MHz, CDCl3)   169.9, 141.5, 133.8, 132.9, 129.8,
129.5, 118.2, 52.0, 22.7; HRMS (ESI-TOF) Calcd for
C11H13ClNO ([MH]) 210.0680. Found 210.0682.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website.
1H, 19F, 13C and DEPT NMR Spectra (PDF)
N-Allyl-N-(p-tolyl)propionamide, isolated by flash
column chromatography (petroleum ether/ethyl acetate 
AUTHOR INFORMATION
Corresponding Author
1
60:1) in 89% yield (2714 mg), pale yellow oil. H NMR
(400 MHz, CDCl3)   1.04 (t, J  7.5 Hz, 3H), 2.06 (q, J  7.4
Hz, 2H), 2.37 (s, 3H), 4.27 (d, J  6.3 Hz, 2H), 5.03-5.10 (m,
2H), 5.81-5.91 (m, 1H), 7.03 (d, J  8.2 Hz, 2H), 7.19 (d, J 
8.0 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3)   173.7, 140.0,
137.7, 133.4, 130.1, 128.0, 117.6, 52.2, 27.7, 21.1, 9.6;
HRMS (ESI-TOF) Calcd for C13H18NO ([MH]) 204.1383.
Found 204.1377.
liangdq695@nenu.edu.cn
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
We gratefully acknowledge the financial support from the
National Natural Science Foundation of China (21702083), the
Yunnan Ten Thousand Talent Program for Young Top-Notch
Talents, and the Program for Innovative Research Team (in
Science and Technology) in Universities of Yunnan Province.
N-Allyl-N-(p-tolyl)octanamide, isolated by flash column
chromatography (petroleum ether/ethyl acetate  60:1) in
1
85% yield (3486 mg), pale yellow oil. H NMR (400 MHz,
CDCl3)   0.84 (t, J  6.8 Hz, 3H), 1.18-1.26 (m, 8H), 1.52-
1.59 (m, 2H), 2.04 (t, J  7.7 Hz, 2H), 2.37 (s, 3H), 4.26 (ddd,
J  1.1, 1.1, 6.3 Hz, 2H), 5.03-5.10 (m, 2H), 5.80-5.90 (m,
1H), 7.01 (d, J  8.1 Hz, 2H), 7.19 (d, J  8.0 Hz, 2H); 13C{1H}
NMR (100 MHz, CDCl3)   173.0, 140.1, 137.7, 133.5,
130.1, 128.1, 117.6, 52.2, 34.3, 31.6, 29.2, 29.0, 25.5, 22.6,
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