Br?nsted Acid-Catalysed Allylic Amination of 1-(2-Aminoaryl)prop-2-en-1-ols to 1,2-Dihydroquinolines

Article abstract of DOI:10.1071/CH18191

A highly efficient synthetic method to prepare 1,2-dihydroquinolines that relies on trifluoromethanesulfonic acid (TfOH)-catalysed allylic amination of 1-(2-aminoaryl)prop-2-en-1-ols is described. Achieved at a catalyst loading of 0.01 mol-% under mild conditions at room temperature, the reaction was found to be robust, with a wide range of substitution patterns tolerated. The corresponding N-heterocyclic adducts were obtained in good to excellent yields of 45-93 %.

Full text of DOI:10.1071/CH18191

RESEARCH FRONT
CSIRO PUBLISHING
Aust. J. Chem.
Full Paper
https://doi.org/10.1071/CH18191
Brønsted Acid-Catalysed Allylic Amination of
1-(2-Aminoaryl)prop-2-en-1-ols to 1,2-Dihydroquinolines
A
A
B
B
David Philip Day, Stuart Adam Henry, Yichao Zhao, Jianwen Jin,
A
A B C
, ,
Guy James Clarkson, and Philip Wai Hong Chan
A
Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK.
School of Chemistry, Monash University, Clayton, Vic. 3800, Australia.
B
C
Corresponding author. Email: phil.chan@monash.edu
A highly efficient synthetic method to prepare 1,2-dihydroquinolines that relies on trifluoromethanesulfonic acid (TfOH)-
catalysed allylic amination of 1-(2-aminoaryl)prop-2-en-1-ols is described. Achieved at a catalyst loading of 0.01 mol-%
under mild conditions at room temperature, the reaction was found to be robust, with a wide range of substitution patterns
tolerated. The corresponding N-heterocyclic adducts were obtained in good to excellent yields of 45–93 %.
Manuscript received: 29 April 2018.
Manuscript accepted: 22 May 2018.
Published online:
19 June 2018.
Introduction
exploring the Brønsted acid-mediated reactivity of p-rich alco-
hols, we describe herein a significant expansion of this chemis-
try with the discovery that trifluoromethanesulfonic acid
(TfOH) can efficiently mediate the allylic amination of a variety
of 1-(2-aminoaryl)prop-2-en-1-ols (Scheme 1b).[8] Achieved at
a low catalyst loading of 0.01 mol-% in a reaction vessel open to
air at room temperature, the 1,2-dihydroquinoline products were
obtained in good to excellent yields.
Fully and partially hydrogenated quinolines are immensely
important targets in organic synthesis because of their presence
as a structural motif in an array of natural products and phar-
maceutical compounds of current biological interest.[1,2] The N-
heterocycle has also been demonstrated to be a versatile building
block in strategies to various synthetically valuable products.[2]
For these reasons, the establishment of mild and efficient syn-
thetic methods to construct this member of the heterocyclic
compound family from easily accessible substrates continues to
be actively pursued.
Results and Discussion
Recent works have illustrated allylic and homoallylic alco-
hols to be useful substrates in a wide variety of Lewis and
Brønsted acid-catalysed strategies for carbocyclic and hetero-
cyclic synthesis.[3,4] For example, we delineated one synthetic
approach to assemble 1,2-dihydroquinolines from gold(III)-cat-
alysed allylic amination of 1-(2-aminoaryl)prop-2-en-1-ols.[2h]
The potential of this synthetic method for scale-up applications,
however, was deemed low owing to the need for a high catalyst
loading and the associated cost of the metal salts.[5] In this
regard, we queried whether the development of a Brønsted acid-
catalysed version of this N-heterocyclic-forming reaction could
hold promise as the basis for re-addressing these shortcomings.
Inexpensive and commercially available along with having a
high tolerance to air and moisture, Brønsted acids have been
shown to be versatile in mediating a wide variety of functional
group transformations in excellent yields and selectivity.[6] We
were also encouraged by the findings of a control experiment in
our initial studies that showed the p-toluenesulfonic acid mono-
hydrate (pTsOHUH2O)-mediated reaction of the 1,2-amino
alcohol 1a gave the anticipated N-heterocycle 2a in 13 % yield
(Scheme 1a). Added to this is a recent study revealing a
thiourea–HBr co-catalytic protocol, although limited to aryl-
substituted substrates, that provided access to the nitrogen-
containing heterocycle.[2d,7] As part of an ongoing program
All 1-(2-aminoaryl)prop-2-en-1-ols examined in the present
work were prepared from the corresponding o-anilinyl methyl
ketone in three steps following literature procedures.[9] With 1b
as the model substrate, we began our studies by examining a
variety of Brønsted acid-mediated catalytic systems to identify
the optimum reaction conditions (Table 1). This initially
revealed treatment of the secondary alcohol with 10 mol-% of
pTsOHUH2O in toluene at room temperature for 72 h gave 2b in
32 % yield (entry 1). Comparable product yields of 20 and 33 %
were found on repeating the experiment with diphenyl phos-
phate or HCl in place of pTsOHUH2O as the catalyst and a
reaction time of 16 h (entries 2 and 3). Our investigations sub-
sequently found that the analogous reaction mediated by TfOH
for 15 min gave the best result in terms of product yield, fur-
nishing the N-heterocyclic adduct in 79 % yield (entry 4). A
similar outcome was found on gradually decreasing the catalyst
loading of TfOH from 10 to 1 to 0.1 to 0.01 mol-% with no
apparent loss in catalytic activity (entries 5–7). Although an
additional reaction time of 1 h was required each time the cat-
alyst loading was reduced 10-fold, products yields of 65–78 %
were attained. However, the analogous control reaction at a
catalyst loading of 0.01 mol-% with dichloromethane instead of
toluene as the solvent gave a lower product yield of 45 % after
6 h (entry 8). On the basis of the above results, reaction of 1b in
Journal compilation ꢀ CSIRO 2018
www.publish.csiro.au/journals/ajc

B
D. P. Day et al.
Me
p-TsOH·H2O (5 mol-%)
toluene, rt, 16 h
(a)
R1 ꢀ R3 ꢀ H
N
R2 ꢀ Me, R4 ꢀ p-tolyl
previous work: ref. [2h]
Ts
R2
HO
2a
R3
13 % yield
R1
NH
SO2R4
R3
TfOH (0.01 mol-%)
toluene, rt, 2–10 h
1
R1
(b)
this work
R2
SO2R4
N
2
Scheme 1. Brønsted acid-catalysed allylic amination of 1-(2-aminoaryl)prop-2-en-1-ols 1.
Table 1. Optimisation of the reaction conditionsA
also determined by X-ray crystallographic analysis.[10] The
present procedure was found to be limited to substrates contain-
ing an aryl-substituted alkene motif as the TfOH-catalysed
reaction of 1a was found to lead to a mixture of unknown
decomposition products. On the other hand, the above Brønsted
acid-catalysed allylic aminations demonstrated that the nitrogen
ring-forming process occurred in a highly selective manner with
the 1,2-dihydroquinoline only being obtained. In our hands, the
possible formation of by-products arising from a competitive
hydroamination, Friedel–Crafts reaction or dehydration process
OH
catalyst
Ph
N
Ph
toluene, t, rt
Ts
NHTs
1b
2b
Entry
Catalyst (mol-%)
Time t (h)
Yield (%)B
1
pTsOHUH2O (10)
(PhO)2P(O)OH (10)
conc. HCl (10)
TfOH (10)
72
16
16
0.25
1
32
20
33
79
65
76
78
45
1
2
was not observed by H NMR analysis of the crude reaction
mixtures.
3
4
Our attention next turned to attempting to develop an
asymmetric version of the present Brønsted acid-mediated N-
heterocylic-formation reaction and its versatility as a building
block of the products obtained (Scheme 2). As shown in
Scheme 2a, this revealed that the reaction of 1b in the presence
of 5 mol-% of chiral N-triflyl phosphoramide A as the catalyst in
toluene at 08C for 2 h gave the best result. Under these reaction
conditions, 1,2-dihydroquinoline 2b was afforded in 89 % yield
and with an enantiomeric excess (ee) value of 35 %. The
reactions of 2c with 3-chloroperbenzoic acid (mCPBA) or an
atmosphere of hydrogen and Pd/C under the conditions
described in Scheme 2b were also found to give the correspond-
ing epoxide 3 and 1,2,3,4-tetrahydroquinoline 4 in respective
yields of 85 and 95 %.
As outlined in Scheme 3, we tentatively propose the mecha-
nism of the present reaction to proceed in a manner similar to that
described for the analogous metal-catalysed allylic amination of
1-(2-aminoaryl)prop-2-en-1-ols.[2h] With 1b as a representative
example, this could initially involve activation of the substrate
through protonation of the hydroxyl group by the Brønsted acid.
As a result, the ensuing protonated intermediate Ib could
subsequently undergo elimination to give the putative carboca-
tion species IIb. The newly formed cationic species might then
promote cyclisation of the pendant sulfonamide group to provide
the iminium species IIIb, deprotonation of which by the TfOꢀ
anion subsequently delivers the product 2b. The modest ee value
observed for the reaction of 1b could be due to the carbocation
IIb being associated with the N-triflyl phosphoramide anion to
give the chiral contact ion pair species IVb.[7] Added to this is
the possibility of IIb occupying a conformation that would allow
p–p stacking interactions between the two aryl ring motifs and
hydrogen-bonding interactions between the sulfonamide group
and the N-triflyl phosphoramide anion.[11]
5
TfOH (1)
6
TfOH (0.1)
2
7
8C
TfOH (0.01)
TfOH (0.01)
3
6
AAll reactions were performed using 0.2 mmol of 1b in toluene (3 mL) at
room temperature with the Brønsted acid at the catalyst loading and time
indicated in the table.
BIsolated yield.
CReaction performed with dichloromethane as the solvent.
the presence of 0.01 mol-% TfOH in toluene at room tempera-
ture for 3 h was deemed to provide the optimal conditions.
To evaluate the scope of the present procedure, we next
turned our attention to the reactions of a series of 1-(2-
aminoaryl)prop-2-en-1-ols 1a and 1c–o and the results are
summarised in Fig. 1. Overall, these experiments showed that
the TfOH-catalysed reaction conditions were broad in scope and
a wide variety of substituted 1,2-dihydroquinolines 2c–o could
be furnished in good to excellent yields. Reactions of 1c–g with
an electron-donating or withdrawing substituent at the para-
position of the styryl or anilinyl motif were shown to be well
tolerated and afforded the corresponding products 2c–g in good
to excellent yields of 64–93 %. Likewise, reactions of starting
alcohols with a nosyl protecting group (1h) or a tertiary carbinol
carbon centre occupied by an alkyl (1i, j) or cycloalkyl (1k, l)
moiety were found to proceed well, providing 2h–l in 45–80 %
yield. Similarly, the reactions were found to proceed well for
tertiary alcohols containing an aryl (1m, n) or thiophenyl (1o)
group at the carbinol carbon centre. In these reactions, the
corresponding 1,2-dihydroquinolines 2m–o were obtained in
55–92 % yield. The structures of products 2j, 2m, and 2n were

Brønsted Acid-Catalysed Allylic Amination of 1-(2-Aminoaryl)prop-2-en-1-ols
C
R3
N
HO R3
TfOH (0.01 mol-%)
R2
R1
R1
toluene, 2–10 h, rt
R2
NHSO2R4
SO2R4
1
2
Me
R
N
N
Ph
N
Ph
N
Ts
Ns
Ts
R
Ts
2a (0 %)
2h (65 %)
2c R ꢀ Cl (88 %)
2d R ꢀ Br (93 %)
2d R ꢀ OMe (71 %)
2f R ꢀ Br (64 %)
2g R ꢀ F (81 %)
Bn
Me
N
Ph
N
Ts
Ph
N
Ph
N
Ph
Ts
Ts
Ts
2i (80 %)
2j (76 %)
2k (73 %)
2l (45 %)
Ph
S
OMe
Ph
N
Ph
N
Ph
N
Ts
Ts
2o (61 %)
Ts
2m (55 %)
2n (92 %)
Fig. 1. TfOH-catalysed allylic amination of 1-(2-aminoaryl)prop-2-en-1-ols 1a and 1c–o. All reactions
were performed using 0.2 mmol of 1 and TfOH (0.01 mol-%) in toluene (3 mL) at room temperature for
2–10 h. Values in parentheses denote isolated product yields.
Ph
(R)-A ꢀ
(a)
OH
O
(R)-A (5 mol-%)
toluene, 0ꢁC, 2 h
O
O
P
Ph
N
Ph
NHTf
Ts
NHTs
1b
2b, 89 % yield, 35 % ee
Ph
(b)
O
m-CPBA
NaHCO3
H2, Pd/C
N
N
Ph
N
MeOH, rt, 2 h
CH2Cl2, 0ꢁC, 6 h
Ts
Ts
Ts
Cl
Cl
4, 95 % yield
3, 85 % yield
2c
Scheme 2. Enantioselective allylic amination of 1b catalysed by (R)-(A) and synthetic transformations.
Conclusion
direct atom-economical chemical processes that can make use of
low-cost and readily available reagents and catalysts.
In summary, we have presented a Brønsted acid-catalysed
synthetic protocol for the allylic amination of 1-(2-aminoaryl)
prop-2-en-1-ols as an expedient route to 1,2-dihydroquinolines.
The reaction was shown to be applicable to a wide variety of
substrates that complemented the metal-mediated versions of this
reaction. The efficiency of the present operationally straightfor-
ward synthetic method was exemplified by the good to excellent
product yields achieved with a low catalyst loading of 0.01 mol-
%. This is notable given the recent demand for more rapid and
Experimental
General Considerations
Unless specified, all reagents, solvents, and starting materials
were purchased from commercial sources and used as received.
The ketone precursor to substrate 1 was prepared following lit-
erature procedures.[9] Analytical thin-layer chromatography
(TLC) was performed using precoated silica gel plates and

D
D. P. Day et al.
OH
Ph
N
Ph
Ts
NHTs
2b
1b
TfOH
TfOꢂ
ꢃOH2
NH
O
P
O
ꢃ
N
Ph
Ph
O
TfN
Ts
H
ꢂ
TfOꢂ
IIIb
ꢃ
Ts
Ib
ꢃ
NH
Ts
Ph
H2O
IVb
NH
Ts
IIb
Scheme 3. Proposed mechanism for the TfOH-catalysed allylic amination of 1-(2-aminoaryl)prop-2-en-1-ols as
represented by 1b.
visualisation was achieved with UV light (254 nm). Flash
chromatography was performed using silica gel and a gradient
solvent system (toluene or EtOAc/n-hexane as eluent). H and
reduced pressure. The crude mixture was dissolved in dichlor-
omethane (10 mL mmolꢀ1), washed with water (10 mL), brine
(10 mL), dried over magnesium sulfate, filtered, and concen-
trated under reduced pressure. The crude mixture was purified
by flash column chromatography on silica gel (eluent: toluene/
dichloromethane 2 : 1) to afford the secondary alcohol substrate.
Method 2: the p-tosyl-protected 20-aminochalcone
(3.0 mmol) was dissolved in THF (60 mL mmolꢀ1) and a
solution of alkyl or aryl magnesium bromide (1 M in THF
solution, 4.5 mmol) was added at 08C and slowly warmed to
room temperature over a 30 min period. The reaction mixture
was stirred at room temperature for 24 h and the progress of the
reaction was followed by TLC analysis and mass spectrometry.
On completion, the reaction mixture was quenched with satu-
rated NH4Cl (60 mL mmolꢀ1). After additional stirring at room
temperature for 10 min, EtOAc (90 mL mmolꢀ1) was added and
the organic phase was separated. The aqueous phase was further
extracted with EtOAc (3 ꢁ 30 mL mmolꢀ1) and the combined
organic layers were washed with brine (60 mL), dried over
anhydrous Na2SO4, and concentrated under reduced pressure.
The crude mixture was purified by flash column chromatogra-
phy on silica gel (eluent: toluene/dichloromethane 2 : 1) to
afford the tertiary alcohol substrate.
1
13C NMR spectra were measured on 300-, 400-, and 500-MHz
spectrometers. Chemical shifts (ppm) were recorded with respect
to TMS in CDCl3. Multiplicities are given as: s (singlet), brs
(broad singlet), d (doublet), t (triplet), q (quartet), m (multiplet),
dd (doublet of doublets), ddd (doublet of doublets of doublets), or
dt (doublet of triplets). The number of protons (n) for a given
resonance is indicated by nH. Coupling constants are reported as
a J value in hertz. Infrared spectra were recorded on an IR
spectrometer. Low- and high-resolution mass spectra (electro-
spray ionisation, ESI) were obtained using a liquid chromatog-
raphy-high-resolution mass spectrometry (LC-HRMS) time-of-
flight (TOF) spectrometer fitted with an analytical electrospray
source using NaI for accurate mass calibration. Mass spectral
data are reported in units of mass to charge ratio (m/z).
General Experimental Procedure for the Synthesis of Allylic
Alcohol Substrate 1[9]
To an EtOH (10 mL mmolꢀ1) solution containing the aldehyde
(1 mmol) and 20-aminoacetophenone (1 mmol) at room tem-
perature was added 2.5 M NaOH (0.6 mL mmolꢀ1) and the
resulting reaction mixture was stirred for 4 h. On completion, the
reaction mixture was quenched by the addition of 1 M HCl
(10 mL mmolꢀ1) and the solvent was removed under reduced
pressure. The crude 20-aminochalcone was taken up in pyridine
(0.4 mL) and p-toluenesulfonyl chloride (1.6 mmol) was added
in one portion at room temperature under a nitrogen atmosphere.
The resulting reaction mixture was then stirred at room tem-
perature for 4 h, after which the solvent was removed under
reduced pressure and the crude mixture was purified by flash
column chromatography on silica gel with dichloromethane as
eluent. At this point, one of two methods was employed:
Method 1: the p-tosyl-protected 20-aminochalcone
(3.0 mmol) was dissolved in methanol (30 mL mmolꢀ1) and
cooled to 08C. Sodium borohydride (3.9 mmol) was added in one
portion and the reaction mixture was stirred for 3 h. On
completion, the reaction mixture was quenched by the addition
of water (1 mL mmolꢀ1) and the solvent was removed under
N-(2-(2-Hydroxybut-3-en-2-yl)phenyl)-4-
methylbenzenesulfonamide (1a)[2h]
Method 2: white solid (0.85 g, 90 % yield); mp 140–1448C. dH
(500 MHz, [D6]acetone) 9.95 (s, 1H), 7.74 (d, J 8.3, 2H), 7.59
(dd, J 8.2 and 1.2, 1H), 7.31 (d, J 8.0, 2H), 7.19 (ddd, J 15.3, 7.7
and 1.5, 2H), 6.96 (td, J 7.6, 1.3, 1H), 5.94 (dd, J 17.3 and 10.6,
1H), 5.17 (dd, J 17.4 and 1.1, 1H), 5.00 (dd, J 10.7 and 1.1, 1H),
2.35 (s, 3H), 1.61 (s, 3H). dC (125 MHz, [D6]acetone) 143.4,
143.3, 137.3, 136.8, 132.7, 129.2, 127.8, 127.2, 126.8, 122.6,
118.4, 111.9, 76.0, 27.9, 20.3.
(E)-N-(2-(1-Hydroxy-3-phenylallyl)phenyl)-4-
methylbenzenesulfonamide (1b)[2h]
Method 1: white solid (1.02 g, 90 % yield); mp 84–868C. dH
(400 MHz, [D6]acetone) 7.70–7.63 (m, 2H), 7.52 (d, J 8.1, 1H),

Brønsted Acid-Catalysed Allylic Amination of 1-(2-Aminoaryl)prop-2-en-1-ols
E
7.40–7.31 (m, 4H), 7.21 (dt, J 23.7 and 8.0, 6H), 7.06 (t, J 7.6,
1H), 6.59 (dd, J 15.8 and 2.0, 1H), 6.20 (dd, J 16.1 and 5.5, 1H),
5.47 (d, J 5.7, 1H), 2.29 (s, 3H). dC (100 MHz, [D6]acetone)
143.5, 137.3, 136.7, 136.2, 132.8, 130.5, 129.7, 129.4, 128.5,
128.4, 128.1, 127.6, 127.1, 126.5, 124.2, 120.7, 73.7, 20.5.
132.5, 131.4 (d, J 3.0), 129.8, 128.8, 128.5, 128.2, 127.4, 126.9,
125.5 (d, J 8.0), 115.7 (d, J 23.0), 115.2 (d, J 24.0), 73.5, 21.7.
dF(dH) (282 MHz, CDCl3) ꢀ116.0. m/z (HRMS ESI) 420.1036
[M þ Na]þ; calc. for C22H20FNNaO3S: 420.1040 [M þ Na]þ.
(E)-N-(2-(1-Hydroxy-3-phenylallyl)phenyl)-2-
nitrobenzenesulfonamide (1h)
(E)-N-(2-(3-(4-Chlorophenyl)-1-hydroxyallyl)phenyl)-4-
methylbenzenesulfonamide (1c)[2h]
Method 1: light orange oil (0.65 g, 53 % yield). nmax (film)/cmꢀ1
3482, 3217, 2926, 1693, 1586, 1538, 1493, 1303, 1163, 1124,
966, 853, 752, 732, 693, 584, 559. dH (500 MHz, [D6]acetone)
7.93–7.95 (1H, m), 7.73–7.75 (1H, m), 7.58–7.67 (4H, m), 7.47–
7.52 (2H, m), 7.28–7.31 (5H, m), 7.18 (1H, d, J 7.5), 6.48 (1H, d,
J 16.0 Hz), 6.35 (1H, dd, J 16.0, 6.0), 5.56 (1H, d, J 6.0). dC
(125 MHz, [D6]acetone) 136.1, 134.8, 134.5, 133.8, 132.7,
131.8, 131.2, 129.3, 129.11, 129.09, 128.9, 128.7, 128.4, 128.2,
126.8, 126.3, 125.4, 123.8, 73.3. m/z (HRMS ESI) 433.0831
[M þ Na]þ; calc. for C21H18N2O5SNa: 433.0834 [M þ Na]þ.
Method 1: colourless oil (1.04 g, 84 % yield). dH (500 MHz, [D6]
acetone) 7.69–7.65 (m, 2H), 7.51 (d, J 7.8, 1H), 7.38 (s, 4H), 7.2
8–7.19 (m, 4H), 7.09 (dd, J 8.2 and 6.8, 1H), 6.60 (dd, J 15.9 and
1.8, 1H), 6.25 (dd, J 15.9, 5.5, 1H), 5.51 (dd, J 5.4 and 1.7, 1H),
2.32 (s, 3H). dC (125 MHz, [D6]acetone) 143.6, 137.4, 136.1,
135.6, 132.9, 132.7, 131.6, 129.5, 128.6, 128.4, 128.2, 128.1,
127.1, 124.4, 121.1, 73.4, 20.5.
(E)-N-(2-(3-(4-Bromophenyl)-1-hydroxyallyl)phenyl)-4-
methylbenzenesulfonamide (1d)[2h]
(E)-N-(2-(2-Hydroxy-4-phenylbut-3-en-2-yl)phenyl)-4-
methylbenzenesulfonamide (1i)[2d]
Method 1: colourless oil (1.12 g, 82 % yield). dH (500 MHz, [D6]
acetone) 7.69–7.62 (m, 2H), 7.55–7.48 (m, 3H), 7.34–7.28 (m,
3H), 7.28–7.15 (m, 5H), 7.07 (td, J 7.5 and 1.2, 1H), 6.57 (dd, J
15.9, 1.6, 1H), 6.25 (dd, J 15.9 and 5.5, 1H), 5.49 (dd, J 5.5 and
1.7, 1H), 2.30 (s, 3H). dC (125 MHz, [D6]acetone) 143.6, 137.4,
136.1, 136.0, 132.9, 131.7, 131.6, 129.5, 128.5, 128.4, 128.3,
128.2, 127.2, 124.4, 121.1, 120.8, 73.4, 20.6.
Method 1: pale yellow oil (0.89 g, 76 % yield). dH (500 MHz,
[D6]acetone) 10.03 (s, 1H), 7.64 (t, J 8.8, 3H), 7.40–7.32 (m,
4H), 7.28 (dd, J 7.7 and 1.5, 2H), 7.20 (td, J 7.8 and 1.5, 1H),
7.05 (d, J 8.0, 2H), 6.98 (td, J 7.6 and 1.3, 1H), 6.61 (d, J 16.1,
1H), 6.36 (d, J 16.0, 1H), 5.77 (s, 1H), 2.24 (s, 3H), 1.75 (s, 3H).
dC (125 MHz, [D6]acetone) 143.3, 137.1, 136.9, 136.7, 135.0,
133.0, 129.2, 128.5, 128.0, 127.5, 127.2, 127.0, 126.5, 122.8,
118.3, 76.0, 28.6, 20.4.
(E)-N-(2-(1-Hydroxy-3-(4-methoxyphenyl)allyl)phenyl)-4-
methylbenzenesulfonamide (1e)[2d]
Method 1: yellow oil (1.04 g, 85% yield). dH (500 MHz, [D6]
acetone) 8.39 (d, J 5.5, 1H), 7.67–7.61 (m, 2H), 7.26–7.05 (m,
12H), 6.87–6.80 (m, 3H), 6.44 (dd, J 15.9and 1.3, 1H), 6.04(dd, J
15.9 and 6.3, 1H), 5.25 (d, J 6.2, 1H), 3.80 (s, 3H), 2.31 (s, 3H). dC
(125 MHz, [D6]acetone)131.2, 129.6, 129.6, 129.3, 129.1, 129.1,
128.9, 128.8, 128.3, 128.2, 128.0, 127.3, 127.2, 127.1, 126.6,
125.3, 124.5, 121.6, 114.0, 113.9, 113.8, 74.9, 55.3, 55.3, 21.6.
(E)-N-(2-(3-Hydroxy-1,5-diphenylpent-1-en-3-yl)phenyl)-4-
methylbenzenesulfonamide (1j)
Method 2: colourless oil (0.74 g, 51 % yield). nmax (film)/cmꢀ1
3479, 3171, 3061, 3027, 2926, 1651, 1601, 1578, 1494, 1452,
1334, 1159, 1119, 752, 700, 565. dH (500 MHz, [D6]acetone)
11.41 (s, 1H), 8.02 (dd, J 8.1, 1.5, 1H), 7.66 (d, J 8.3, 1H), 7.60 (d,
J 8.0, 2H), 7.55–7.49 (m, 1H), 7.32 (d, J 4.4, 4H), 7.29–7.18 (m,
6H), 7.18–7.08 (m, 4H), 3.41 (d, J 6.0, 2H), 3.33 (td, J 8.5, 7.7 and
3.7, 1H), 2.48 (td, J 9.5 and 6.1, 2H), 2.28 (s, 3H). dC (125 MHz,
[D6]acetone) 144.4, 144.0, 142.1, 139.7, 136.5, 134.6, 131.7,
129.7, 128.4, 128.2, 127.8, 127.1, 126.3, 125.7, 122.9, 122.7,
118.9, 46.2, 40.9, 38.0, 33.4, 20.4. m/z (HRMS ESI) 506.1763
[Mþ Na]þ; calc. for C30H29NNaO3S: 506.1760 [Mþ Na]þ.
(E)-N-(4-Bromo-2-(1-hydroxy-3-phenylallyl)phenyl)-4-
methylbenzenesulfonamide (1f)
Method 1: yellow oil (1.03 g, 88 % yield). nmax (film)/cmꢀ1
3471, 3232, 2925, 2855, 1597, 1487, 1384, 1330, 1161, 1091,
905, 729, 650. dH (500 MHz, [D6]acetone) 7.62 (2H, d, J 8.5),
7.43 (1H, d, J 8.5), 7.28–7.37 (7H, m), 7.08 (2H, d, J 8.0), 6.53
(1H, d, J 16.0), 6.11 (1H, dd, J 16.0, 6.0), 5.24 (1H, d, J 5.5), 2.32
(3H, s), 2.04 (1H, s), 1.26–1.28 (1H, m). dC (125 MHz, [D6]
acetone) 162.5, 144.1, 135.9, 135.2, 133.6, 132.3, 131.9, 131.3,
129.8, 128.8, 128.5, 128.1, 127.4, 126.9, 123.4, 117.7, 74.3,
21.7. m/z (HRMS ESI) 480.0240, 482.0222 [M þ Na]þ; calc. for
C22H20BrNNaO3S: 480.0239/482.0221 [M þ Na]þ.
(E)-N-(2-(1-Cyclopropyl-1-hydroxy-3-phenylallyl)phenyl)-
4-methylbenzenesulfonamide (1k)
Method 2: off-white oil (0.80 g, 63 % yield). nmax (film)/cmꢀ1
3456, 3217, 3081, 3026, 2923, 2854, 1599, 1583, 1558, 1494,
1449, 1402, 1334, 1159, 1091, 975, 929, 751, 661, 566, 545. dH
(500 MHz, [D6]acetone) 9.18 (1H, s), 7.63 (2H, dd, J 19.5 and
8.0), 7.55 (2H, d, J 8.0), 7.30–7.34 (3H, m), 7.14–7.24 (3H, m),
7.02 (1H, d, J 8.0), 6.82 (1H, d, J 8.0), 6.51 (1H, d, J 16.0), 5.83
(1H, d, J 16.0), 2.38 (1H, bs), 2.19 (3H, m), 0.78–0.86 (2H, m),
0.54–0.57 (2H, m), 0.41–0.46 (1H, m). dC (125 MHz, [D6]
acetone) 143.3, 136.8, 136.2, 132.0, 130.5, 129.8, 129.4, 128.8,
128.7, 128.1, 127.7, 127.5, 126.9, 123.2, 119.2, 78.9, 29.9, 22.4,
21.6, 3.9, 0.2. m/z (HRMS ESI) 442.1446 [M þ Na]þ; calc. for
C25H25NNaO3S: 442.1447 [M þ Na]þ.
(E)-N-(4-Fluoro-2-(1-hydroxy-3-phenylallyl)phenyl)-4-
methylbenzenesulfonamide (1g)
Method 1: pale yellow oil (0.86 g, 72 % yield). nmax (film)/cmꢀ1
3471, 3266, 2960, 2924, 2853, 1597, 1496, 1393, 1330, 1159,
1091, 908, 796, 693, 664, 549. dH (500 MHz, CDCl3) 7.78 (1H,
s), 7.61 (2H, d, J 8.0), 7.39–7.42 (1H, m), 7.28–7.37 (5H, m),
7.15 (2H, d, J 8.0), 6.93 (2H, d, J 8.0), 6.54 (1H, d, J 16.0), 6.13
(1H, dd, J 16.0, 6.5), 5.16–5.28 (1H, m), 2.41 (1H, d, J 3.5), 2.36
(3H, s), 7.43 (1H, d, J 8.5, 7.28–7.37 (7H, m), 7.08 (2H, d, J 8.0),
6.53 (1H, d, J 16.0), 6.11 (1H, dd, J 16.0, 6.0), 5.24 (1H, d, J 5.5),
2.32 (3H, s), 2.04 (1H, s), 1.26–1.28 (1H, m). dC (125 MHz,
CDCl3) 160.2 (d, J 246), 144.0, 136.7, 135.9, 135.8 (d, J 7),
(E)-N-(2-(1-Cyclopentyl-1-hydroxy-3-phenylallyl)phenyl)-
4-methylbenzenesulfonamide (1l)
Method 2: yellow oil (0.92 g, 69 % yield). nmax (film)/cmꢀ1
3438, 2952, 1700, 1649, 1493, 1451, 1335, 1246, 1159, 1090,

F
D. P. Day et al.
916, 813, 756, 701, 657, 628, 562, 544. dH (500 MHz, [D6]
acetone) 11.41 (s, 1H), 8.03 (dd, J 8.0 and 1.6, 1H), 7.63 (d, J 8.4,
1H), 7.58 (d, J 8.1, 2H), 7.52–7.46 (m, 1H), 7.25 (dd, J 6.0 and
2.9, 6H), 7.16 (dq, J 5.7 and 2.9, 1H), 7.13–7.07 (m, 1H), 3.53
(dd, J 16.9 and 9.7, 1H), 3.39 (dd, J 17.0 and 4.2, 1H), 3.09 (td, J
9.8 and 4.2, 1H), 2.32 (s, 3H), 2.22–2.12 (m, 1H), 2.05 (q, J 2.2,
1H), 1.92 (dt, J 7.9 and 4.1, 1H), 1.67 (ddd, J 10.7, 7.4 and 4.3,
1H), 1.56 (ddt, J 11.9, 8.2 and 4.2, 2H), 1.44 (dtd, J 8.3, 5.6 and
2.6, 1H), 1.30 (dqd, J 18.0, 8.6 and 3.6, 2H), 1.11–1.01 (m, 1H).
dC (125 MHz, [D6]acetone) 204.3, 144.8, 144.0, 139.7, 136.5,
131.8, 129.7, 128.1, 128.0, 127.1, 126.0, 122.8, 122.7, 118.7,
47.2, 46.2, 45.2, 31.3, 31.2, 25.0, 24.6, 20.5. m/z (HRMS ESI)
446.1791 [M – Hþ]; calc. for C27H28NO3S: 446.1795 [M – Hþ].
analysis. The crude mixture was quenched with water (2 mL per
0.2 mmol of substrate), extracted with EtOAc (3 ꢁ 10 mL), and
concentrated under reduced pressure. Purification by flash col-
umn chromatography on silica gel (eluent: toluene or n-hexane/
EtOAc 10 : 1) furnished the title compound.
2-Phenyl-1-tosyl-1,2-dihydroquinoline (2b)[2h]
Reaction time 3 h; colourless oil (0.054 g, 75 % yield). dH
(400 MHz, [D6]acetone) 7.63 (d, J 8.0, 1H), 7.39 (ddd, J 18.4,
7.8 and 1.8, 4H), 7.33–7.22 (m, 6H), 7.19 (d, J 7.5, 1H), 7.09 (d, J
7.4, 1H), 6.40 (d, J 9.3, 1H), 6.17–6.07 (m, 2H), 2.38 (s, 3H). dC
(100 MHz, [D6]acetone) 143.7, 139.3, 136.6, 133.1, 129.2,
128.9, 128.4, 127.9, 127.7, 127.2, 127.1 126.5, 126.4, 125.0,
56.9, 20.5.
(E)-N-(2-(1-Hydroxy-1,3-diphenylallyl)phenyl)-4-
methylbenzenesulfonamide (1m)
2-(4-Chlorophenyl)-1-tosyl-1,2-dihydroquinoline (2c)[2h]
Method 2: colourless oil (0.87 g, 64 % yield). nmax (film)/cmꢀ1
3444, 3207, 3060, 3027, 2923, 1600, 1583, 1493, 1449, 1402,
1331, 1282, 1156, 1091, 976, 941, 907, 752, 733, 700, 662, 565,
545. dH (400 MHz, CDCl3) 8.97 (1H, s), 7.62 (1H, d, J 8.0),
7.18–7.34 (14H, m), 7.07 (1H, d, J 8.0), 6.94 (2H, d, J 8.5), 6.63
(1H, d, J 16.0), 6.24 (1H, d, J 16.0), 3.00 (1H, s), 2.27 (3H, s). dC
(100 MHz, CDCl3) 143.8, 143.3, 136.8, 136.4, 136.1, 133.8,
132.3, 130.9, 129.5, 129.3, 129.1, 128.8, 128.7, 128.3, 128.0,
127.5, 127.0, 126.8, 122.7, 119.2, 81.3, 21.6. m/z (HRMS ESI)
478.1445 [M þ Na]þ; calc. for C28H25NNaO3S: 478.1447
[M þ Na]þ.
Reaction time 5 h; colourless crystalline solid (0.07 g, 88 %
yield); mp 135–1378C. dH (400 MHz, CDCl3) 7.64 (1H, d, J 8.0),
7.32 (2H, d, J 8.5), 7.28 (2H, d, J 8.5), 7.19–7.21 (3H, m), 7.08–
7.16 (3H, m), 6.97 (1H, dd, J 7.5 and 1.0), 6.30 (1H, d, J 9.5),
5.98 (1H, d, J 6.0), 5.85 (1H, dd, J 9.5, 6.0), 2.35 (3H, s). dC
(100 MHz, CDCl3) 143.7, 137.0, 136.1, 133.9, 132.8, 129.3,
129.0, 128.7, 128.6, 127.7, 127.3, 126.8, 126.5, 126.2, 126.1,
126.0, 56.3, 21.7.
2-(4-Bromophenyl)-1-tosyl-1,2-dihydroquinoline (2d)[2h]
Reaction time 5 h; colourless oil (0.082 g, 93 % yield). dH
(400 MHz, CDCl3) 7.64 (1H, d, J 8.0), 7.31–7.37 (4H, m), 7.20–
7.22 (3H, m), 7.08–7.14 (3H, m), 6.97 (1H, dd, J 7.5, 1.0), 6.30
(1H, d, J 9.5), 5.97 (1H, d, J 6.0), 5.85 (1H, dd, J 9.5, 6.0), 2.35
(3H, s). dC (100 MHz, CDCl3) 143.7, 137.6, 136.1, 132.8, 131.7,
129.3, 129.3, 128.6, 128.6, 127.7, 127.4, 126.8, 126.5, 126.1,
125.9, 122.1, 56.4, 21.7.
(E)-N-(2-(1-Hydroxy-1-(2-methoxyphenyl)-3-phenylallyl)
phenyl)-4-methylbenzenesulfonamide (1n)
Method 1: colourless oil (0.97 g, 66 % yield). nmax (film)/cmꢀ1
3473, 3212, 3028, 2926, 2856, 1599, 1583, 1490, 1455, 1401,
1336, 1284, 1236, 1159, 1092, 910, 753, 661, 565, 545. dH
(400 MHz, CDCl3) 9.73 (1H, bs), 7.71 (1H, d, J 8.0), 7.57 (2H, d,
J 8.0), 7.28–7.41 (5H, m), 7.19 (1H, t, J 8.0), 6.79–7.04 (7H, m),
6.69 (1H, d, J 8.0), 6.52 (1H, d, J 16.0), 6.18 (1H, d, J 16.0), 5.67
(1H, s), 3.74 (3H, s), 2.24 (3H, s). dC (100 MHz, CDCl3) 157.1,
143.2, 137.3, 136.9, 136.4, 132.4, 131.9, 131.5, 130.9, 129.8,
129.4, 128.9, 128.9, 128.7, 128.6, 128.1, 127.5, 127.1, 122.4,
121.3, 118.5, 112.4, 81.9, 56.0, 21.6. m/z (HRMS ESI) 508.1553
[M þ Na]þ; calc. for C29H27NNaO4S: 508.1553 [M þ Na]þ.
2-(4-Methoxyphenyl)-1-tosyl-1,2-dihydroquinoline (2e)[2d]
Reaction time 3 h; viscous colourless oil (0.056 g, 71 % yield).
dH (500 MHz, CDCl3) 7.62 (1H, d, J 8.0), 7.32 (2H, d, J 8.0),
7.18–7.25 (3H, m), 7.08–7.14 (3H, m), 6.97 (1H, d, J 7.5), 6.76
(2H, d, J 9.0), 6.27 (1H, d, J 9.5), 5.97 (1H, d, J 6.0), 5.84 (1H,
dd, J 9.5 and 6.0), 3.73 (3H, s), 2.35 (3H, s). dC (125 MHz,
CDCl3) 159.5, 143.5, 136.4, 132.9, 130.4, 129.2, 129.0, 128.8,
128.4, 127.9, 127.4, 126.9, 126.6, 126.3, 125.5, 113.9, 56.8,
55.3, 21.7.
(E)-N-(2-(1-Hydroxy-3-phenyl-1-(thiophen-2-yl)allyl)
phenyl)-4-methylbenzenesulfonamide (1o)
Method 2: pale yellow oil (1.05 g, 76 % yield). nmax (film)/cmꢀ1
3426, 3238, 3064, 3029, 2924, 1650, 1600, 1583, 1494, 1452,
6-Bromo-2-phenyl-1-tosyl-1,2-dihydroquinoline (2f)
1403, 1333, 1158, 1091, 972, 911, 828, 752, 704, 566, 545 cmꢀ1
.
H (500 MHz, [D6]acetone) 9.22 (1H, bs), 7.67 (1H, d, J 8.0),
Reaction time 6 h; pale yellow oil (0.056 g, 64 % yield). nmax
(film)/cmꢀ1 3062, 2922, 1644, 1598, 1484, 1343, 1089, 813,
685. dH (400 MHz, CDCl3) 7.52 (1H, d, J 8.5), 7.36 (2H, d, J
8.5), 7.31 (3H, dd, J 8.5, 2.0), 7.22–7.24 (3H, m), 7.12–7.14 (3H,
m), 6.23 (1H, d, J 9.5), 6.02 (1H, d, J 6.0), 5.93 (1H, dd, J 9.5,
6.0), 2.37 (3H, s). dC (100 MHz, CDCl3) 143.9, 138.0, 136.1,
132.1, 131.2, 130.4, 129.5, 129.4, 129.1, 128.7, 128.3, 128.2,
127.5, 127.3, 124.7, 120.0, 57.1, 21.7. m/z (HRMS ESI)
462.0137 [M þ Na]þ; calc. for C22H18BrNNaO2S: 462.0134
[M þ Na]þ.
d
7.49 (2H, d, J 8.0), 7.31–7.33 (6H, m), 7.14–7.23 (2H, m), 7.04
(1H, d, J 8.0), 6.93–6.96 (4H, m), 6.79 (1H, d, J 3.5), 6.62 (1H, d,
J 16.0), 6.33 (1H, d, J 16.0), 2.26 (3H, s). dC (125 MHz, [D6]
acetone) 149.1, 143.4, 136.7, 136.6, 135.9, 132.9, 131.7, 131.2,
129.5, 129.3, 129.0, 128.8, 128.4, 127.5, 127.1, 127.0, 126.5,
126.4, 122.9, 119.3, 79.9, 21.60. m/z (HRMS ESI) 460.1040
[M – Hþ]; calc. for C26H22NO3S2: 460.1047 [M – Hþ].
General Experimental Procedure for the TfOH-Catalysed
Allylic Amination of 1
6-Fluoro-2-phenyl-1-tosyl-1,2-dihydroquinoline (2g)
To a round-bottom flask containing 1 (0.2 mmol) open to the air
was added 2 mL of TfOH (0.01 mol-%) from a stock solution
containing 0.88 mL of TfOH in 1 L of toluene at room temper-
ature. Reaction progress was monitored to completion by TLC
Reaction time 6 h; colourless oil (0.061 g, 81 % yield). nmax
(film)/cmꢀ1 3062, 3031, 2962, 2924, 1612, 1598, 1578, 1484,
1451, 1345, 1262, 1165, 1045, 810, 709, 576 cmꢀ1. dH
(400 MHz, CDCl3) 7.52 (1H, m), 7.15–7.23 (7H, m), 7.04 (2H,

Brønsted Acid-Catalysed Allylic Amination of 1-(2-Aminoaryl)prop-2-en-1-ols
G
d, J 7.5), 6.82 (1H, d, J 8.5), 6.60 (1H, d, J 8.5), 6.14 (1H, d, J
9.5), 5.94 (1H, d, J 5.5), 5.83–5.85 (1H, m), 2.29 (3H, s). dC
(125 MHz, CDCl3) 161.0 (d, J 246), 143.8, 137.9, 136.0, 130.4
(d, J 9), 129.8 (d, J 9), 129.3, 128.8 (d, J 3), 128.6, 128.2, 128.1,
127.6, 127.4, 125.0 (d, J 2), 115.1 (d, J 23), 112.7 (d, J 23), 57.1,
21.7. m/z (HRMS ESI) 402.0938 [M þ Na]þ; calc. for
C22H18FNNaO2S: 402.0934 [M þ Na]þ.
5.99 (1H, d, J 6.5), 5.71 (1H, dd, J 6.5, 1.5), 2.77–2.83 (1H, m),
2.33 (3H, s), 1.80–1.86 (1H, m), 1.58–1.64 (2H, m), 1.48–1.54
(2H, m), 1.34–1.42 (2H, m), 0.33–0.38 (1H, m). dC (125 MHz,
CDCl3) 143.4, 139.3, 138.9, 136.6, 133.2, 130.8, 129.2, 128.6,
128.4, 127.9, 127.8, 127.7, 127.5, 126.5, 123.7, 119.7, 56.9,
39.8, 31.9, 31.2, 25.4, 25.0, 21.6. m/z (HRMS ESI) 452.1659
[M þ Na]þ; calc. for C27H27NNaO2S: 452.1655 [M þ Na]þ.
1-((2-Nitrophenyl)sulfonyl)-2-phenyl-1,2-dihydroquinoline
2,4-Diphenyl-1-tosyl-1,2-dihydroquinoline (2m)
(2h)
Reaction time 3 h; colourless crystalline solid (0.051 g, 55 %
yield); mp 195–1978C. nmax (film)/cmꢀ1 3058, 3031, 2917,
2849, 1738, 1594, 1491, 1329, 1151, 1062, 988, 805, 753. dH
(400 MHz, CDCl3) 7.71 (1H, d, J 8.0), 7.38 (4H, t, J 8.5), 7.27–
7.30 (4H, m), 7.24–7.25 (3H, m), 7.03–7.11 (3H, m), 6.84–6.88
(3H, m), 6.18 (1H, d, J 6.5), 5.89 (1H, d, J 6.5), 2.31 (3H, s). dC
(100 MHz, CDCl3) 143.6, 138.7, 138.4, 138.3, 136.0, 133.4,
130.3, 129.3, 128.79, 128.76, 128.64, 128.60, 128.2, 128.1,
127.9, 127.71, 127.65, 126.6, 125.9, 124.4, 56.8, 21.5. m/z
(HRMS ESI) 460.1333 [M þ Na]þ; calc. for C28H23NNaO2S:
460.1342 [M þ Na]þ.
Reaction time 4 h; colourless oil (0.051 g, 65 % yield). nmax
(film)/cmꢀ1 3088, 3062, 2960, 2925, 1679, 1603, 1542, 1371,
1265, 1173, 1060, 1023, 766, 697, 584. dH (400 MHz, CDCl3)
7.65 (1H, d, J 8), 7.59 (1H, td, J 1 and 8), 7.48 (1H, dd, J 1 and 8),
7.29–7.36 (3H, m), 7.17–7.25 (6H, m), 7.05 (1H, dd, J 2, 7), 6.36
(1H, d, J 10), 6.17 (1H, m), 6.10 (1H, d, J 6); dC (125 MHz,
CDCl3) 137.6, 133.8, 132.0, 131.1, 130.71, 130.69, 129.5,
129.2, 128.67, 128.64, 128.31, 128.30, 127.7, 127.53, 127.3,
126.6, 125.0, 123.7, 57.3. m/z (HRMS ESI) 415.0722 [M þ
Na]þ; calc. for C21H16N2NaO4S: 415.0723 [M þ Na]þ.
4-Methyl-2-phenyl-1-tosyl-1,2-dihydroquinoline (2i)[2d]
4-(2-Methoxyphenyl)-2-phenyl-1-tosyl-1,2-
dihydroquinoline (2n)
Reaction time 4 h; colourless oil (0.06 g, 80 % yield). dH
(400 MHz, CDCl3) 7.61 (1H, d, J 7.5), 7.05–7.28 (12H, m), 5.90
(1H, d, J 6.0), 5.62 (1H, d, J 6.0), 2.34 (3H, s), 1.72 (3H, s). dC
(75 MHz, CDCl3) 143.2, 138.8, 135.9, 133.0, 131.2, 130.8,
128.9, 128.3, 128.18, 128.08, 127.7, 127.5, 127.4, 126.6,
123.08, 122.99, 56.7, 21.5, 17.9.
Reaction time 5 h; off-white crystalline solid (0.086 g, 92 %
yield); mp 203–2058C. nmax (film)/cmꢀ1 3067, 3027, 2917,
1580, 1492, 1351, 1254, 1162, 988, 787, 700, 565. dH (400 MHz,
CDCl3) 7.67 (1H, d, J 8.0), 7.56 (2H, d, J 7.0), 7.09–7.48 (10H,
m), 7.01 (1H, t, J 7.5), 6.93 (1H, d, J 8.0), 6.86 (1H, m), 6.67 (1H,
d, J 8.0), 6.15 (1H, d, J 6.0), 5.89 (1H, d, J 6.0), 3.71 (3H, bs),
2.38 (3H, s). dC (100 MHz, CDCl3) 157.5, 143.4, 132.8, 130.8,
129.3, 128.5, 128.2, 128.1, 128.0, 127.7, 127.1, 126.3, 125.8,
125.6, 120.3, 111.1, 57.0, 55.5, 21.6. m/z (HRMS ESI) 490.1438
[M þ Na]þ; calc. for C29H25NNaO3S: 490.1447 [M þ Na]þ.
4-Phenethyl-2-phenyl-1-tosyl-1,2-dihydroquinoline (2j)
Reaction time 4 h; colourless crystalline solid (0.071 g, 76 %
yield); mp 135–1378C. nmax (film)/cmꢀ1 3060, 3023, 2923,
2851, 1643, 1596, 1490, 1451, 1342, 1163, 1087, 1032, 976,
808, 682, 570, 544. dH (400 MHz, CDCl3) 7.68 (1H, d, J 8.0),
7.34 (2H, d, J 8.0), 7.27–7.31 (4H, m), 7.15–7.24 (7H, m), 7.11
(4H, d, J 8), 6.00 (1H, d, J 6.0), 5.76 (1H, d, J 6.0), 2.44–2.46
(3H, m), 2.32 (3H, s), 2.13–2.15 (1H, m); dC (100 MHz, CDCl3)
143.5, 141.7, 138.7, 136.5, 135.2, 133.4, 129.9, 129.2, 128.74,
128.68, 128.4, 128.3, 128.1, 127.9, 127.6, 126.8, 126.3, 123.0,
122.7, 56.8, 34.5, 33.6, 21.6. m/z (HRMS ESI) 488.1655 [M
þ Na]þ; calc. for C30H27NNaO2S: 488.1655 [M þ Na]þ.
2-Phenyl-4-(thiophen-2-yl)-1-tosyl-1,2-dihydroquinoline (2o)
Reaction time 4 h; black crystalline solid (0.054 g, 61 % yield);
mp 158–1608C. nmax (film)/cmꢀ1 3062, 3029, 2922, 2853, 1623,
1598, 1449, 1347, 1164, 1089, 1062, 808, 698, 566. dH
(400 MHz, CDCl3) 7.70 (1H, d, J 8.0), 7.34–7.37 (4H, m), 7.15–
7.30 (9H, m), 7.06 (2H, d, J 8.0), 6.99 (1H, dd, J 5.0 and 3.5),
6.69 (1H, dd, J 3.5 and 1.0), 6.14 (1H, d, J 6.5), 6.01 (1H, d, J
6.5), 2.27 (3H, s). dC (100 MHz, CDCl3) 143.7, 139.6, 138.0,
135.7, 133.4, 131.6, 129.8, 129.4, 128.9, 128.9, 128.6, 128.1,
127.7, 127.4, 127.0, 126.8, 126.8, 125.7, 125.6, 125.3, 56.7,
21.6. m/z (HRMS ESI) 466.0910 [M þ Na]þ; calc. for
C26H21NNaO2S2: 466.0906 [M þ Na]þ.
4-Cyclopropyl-2-phenyl-1-tosyl-1,2-dihydroquinoline (2k)
Reaction time 3 h; orange solid (0.059 g, 73 % yield); mp 116–
1188C. nmax (film)/cmꢀ1 3063, 3030, 2920, 2851, 1736, 1638,
1599, 1449, 1345, 1163, 1008, 782, 698, 575. dH (400 MHz,
CDCl3) 7.55 (1H, dd, J 7.5 and 1.5), 7.40 (1H, dd, J 7.5 and 1.5),
7.11–7.21 (10H, m), 7.01 (2H, d, J 8.0), 5.89 (1H, d, J 6.0), 5.55
(1H, dd, J 6.0, 1.5), 2.28 (3H, s), 1.30–1.32 (1H, m), 0.65–0.67
(1H, m), 0.44–0.47 (1H, m), 0.10–0.14 (1H, m), ꢀ0.30–ꢀ0.33
(1H, m). dC (100 MHz, CDCl3) 143.5, 138.8, 136.8, 136.2,
132.9, 130.9, 129.1, 128.5, 128.2, 128.1, 127.9, 127.6, 127.5,
126.7, 123.7, 121.9, 56.8, 21.6, 11.9, 6.2, 4.3, 1.2. m/z (HRMS
ESI) 424.1342 [M þ Na]þ; calc. for C25H23NNaO2S: 424.1342
[M þ Na]þ.
Experimental Procedure for the Preparation of 2-Phenyl-
1-tosyl-1,2-dihydroquinoline (2b) Mediated by Chiral
Brønsted Acid (R)-A
To a solution of toluene (2 mL) containing 1b (0.023 g,
0.06 mmol) was added N-((4S)-2,6-di([1,10-biphenyl]-4-yl)-4-
oxidodinaphtho[2,1-d:10,20-f][1,3,2]dioxaphosphepin-4-yl)-1,1,1-
trifluoromethanesulfonamide ((R)-A) (0.002 g, 0.003 mmol)
in one portion at 08C. On monitoring the reaction mixture to
completion by TLC analysis, after 2 h, the solvent was removed
under reduced pressure and the resulting crude mixture was
purified by flash column chromatography on silica gel (eluent: n-
hexane/EtOAc 10 : 1) to afford the title compound. Colourless oil
(0.019 g, 89 % yield). Enantiomeric excess is 35 % as determined
by HPLC (Daicel Chiralpak IC column, n-hexane/2-propanol
4-Cyclopentyl-2-phenyl-1-tosyl-1,2-dihydroquinoline (2l)
Reaction time 10 h; pale yellow oil (0.041 g, 45 % yield). nmax
(film)/cmꢀ1 3061, 2955, 2916, 2866, 1598, 1492, 1450, 1348,
1165, 1053, 809, 755, 704. dH (500 MHz, CDCl3) 7.64 (1H, d, J
7.5), 7.15–7.22 (6H, m), 7.28–7.33 (4H, m), 7.08 (1H, d, J 8.0),

H
D. P. Day et al.
85 : 15, flow rate 1.0 mL minꢀ1, 254 nm): major isomer: tR
15.3 min; minor isomer: tR 13.4 min.
(b) V. Sridharan, P. A. Suryavanshi, J. C. Menendez, Chem. Rev. 2011,
111, 7157. doi:10.1021/CR100307M
(c) A. G. Montalban, in Heterocycles in Natural Product Synthesis
(Eds K. C. Majumdar, S. K. Chattopadhyay) 2011, Ch. 9, 299–339
(Wiley-VCH: Weinheim).
Experimental Procedure for the Preparation of 2-(4-
Chlorophenyl)-3-tosyl-1a,2,3,7b-tetrahydrooxireno[2,3-c]
quinoline (3) from 2e
(d) J. P. Michael, Nat. Prod. Rep. 2008, 25, 166. doi:10.1039/
B612168N
To a solution of dichloromethane (5 mL) containing 2e was
added NaHCO3 (0.005 g, 0.06 mmol) and mCPBA (0.01 g,
0.06 mmol) in one portion at 08C. On monitoring the reaction
mixture to completion by TLC analysis, after 6 h, the solvent
was removed under reduced pressure and the resulting crude
mixture was purified by flash column chromatography on silica
gel (eluent: n-hexane/EtOAc 5 : 1) to afford the title compound.
Colourless oil (0.022 g, 85 % yield). nmax (film)/cmꢀ1 3069,
3032, 2923, 1598, 1491, 1343, 1162, 1091, 976, 807, 760, 676,
569, 547. dH (500 MHz, CDCl3) 7.74 (1H, d, J 8.0), 7.48 (2H, d,
J 8.0), 7.30–7.35 (2H, m), 7.14–7.25 (7H, m), 5.87 (1H, d, J 2.0),
3.89–3.97 (1H, m), 3.81 (1H, d, J 4.0), 2.37 (3H, s). dC
(125 MHz, CDCl3) 143.7, 135.7, 135.1, 134.5, 133.6, 130.1,
129.9, 129.2, 129.13, 129.10, 128.0, 127.3, 126.4, 126.1, 62.1,
55.0, 50.8, 21.8. m/z (HRMS ESI) 434.0590 [M þ Na]þ; calc.
for C22H18ClNNaO3S: 434.0588 [M þ Na]þ.
[2] Selected recent examples: (a) X. Chen, J. T. Merrett, P. W. H. Chan,
Org. Lett. 2018, 20, 1542. doi:10.1021/ACS.ORGLETT.8B00267
(b) J. Zhou, H. Xie, Org. Biomol. Chem. 2018, 16, 380. doi:10.1039/
C7OB02599H
(c) T. Ramanivas, G. Gayatri, D. Priyanka, V. L. Nayak, K. K.
Singarapu, A. K. Srivastava, RSC Adv. 2015, 5, 73373. doi:10.1039/
C5RA11144G
(d) H. J. Lee, D. E. Lee, D. Y. Kim, Bull. Korean Chem. Soc. 2015, 36,
370. doi:10.1002/BKCS.10014
(e) Z. Wang, S. Li, B. Yu, H. Wu, Y. Wang, X. Sun, J. Org. Chem.
2012, 77, 8615. doi:10.1021/JO301560W
(f) W. Rao, P. Kothandaraman, C. B. Koh, P. W. H. Chan, Adv. Synth.
Catal. 2010, 352, 2521. doi:10.1002/ADSC.201000450
(g) P. D. Macleod, A. M. Reckling, C.-J. Li, Heterocycles 2010, 80,
1319. doi:10.3987/COM-09-S(S)123
(h) P. Kothandaraman, S. J. Foo, P. W. H. Chan, J. Org. Chem. 2009,
74, 5947. doi:10.1021/JO900917Q
[3] Selected recent reviews on the use of p-rich alcohols as pro-electro-
philes: (a) L. Zhang, G. Fang, R. K. Kumar, X. Bi, Synthesis 2015,
2317. doi:10.1055/S-0034-1378852
Experimental Procedure for the Preparation of 2-Phenyl-1-
tosyl-1,2,3,4-tetrahydroquinoline (4) from 2e
(b) B. J. Ayers, P. W. H. Chan, Synlett 2015, 1305. doi:10.1055/S-
0034-1380402
To a round-bottom flask containing Pd/C (0.10 g, 10 wt-%) in
methanol (5 mL) and previously purged three times with nitrogen
gas was added 2e (0.025 g, 0.06 mmol) dissolved in methanol
(5 mL). A hydrogen atmosphere was then introduced into the
vessel over the stirring solution and the resulting reaction mixture
was stirred at room temperature for 2 h. On completion, the
reaction mixture was filtered through a pad of Celite and con-
centrated under reduced pressure. Purification by flash column
chromatography on silica gel (eluent:n-hexane/EtOAc 5 : 1)gave
the title compound. Pale yellow oil (0.021 g, 95 % yield). nmax
(film)/cmꢀ1 3063, 3030, 2950, 2869, 1599, 1487, 1454, 1346,
1162, 1090, 972, 813, 794, 699, 660, 570. dH (500 MHz, CDCl3)
7.87 (1H, d, J 8.0), 7.43 (2H, d, J 6.0), 7.28–7.31 (5H, m), 7.18–
7.22 (3H, m), 7.10 (1H, t, J 7.5), 6.96 (1H, d, J 7.5), 5.36 (1H, bs),
2.39(3H, s), 2.31–2.34 (1H, m), 2.18 (1H, bs), 1.79–1.88 (2H, m).
dC (125 MHz, CDCl3) 143.6, 142.6, 136.4, 136.3, 134.1, 129.6,
128.7, 128.1, 127.4, 127.2, 127.1, 126.9, 126.3, 125.7, 59.8, 32.1,
25.5, 21.7. m/z (HRMS ESI) 386.1187 [Mþ Na]þ; calc. for
C22H21NNaO2S: 386.1185 [Mþ Na]þ.
(c) N. Ljungdahl, N. Kann, Angew. Chem. Int. Ed. 2009, 48, 642.
doi:10.1002/ANIE.200804114
(d) M. Bandini, N. Tragni, Org. Biomol. Chem. 2009, 7, 1501. doi:10.
1039/B823217B
[4] Selected recent examples, see refs [2b], [2d–f], [2h], and: (a) L.
Lempenauer, E. Dunach, G. Lemiere, Chem. – Eur. J. 2017, 23,
10285. doi:10.1002/CHEM.201702601
(b) J. Xu, J. Sun, J. Zhao, B. Huang, X. Li, Y. Sun, RSC Adv. 2017, 7,
36242. doi:10.1039/C7RA06425J
(c) A. Baeza, C. Na´jera, Synthesis 2014, 25. doi:10.1055/S-0033-
1340316
(d) X. Zhang, Z. P. Yang, C. Liu, S. L. You, Chem. Sci. 2013, 4, 3239.
doi:10.1039/C3SC51313K
(e) X. Zhou, H. Zhang, X. Xie, Y. Li, J. Org. Chem. 2008, 73, 3958.
doi:10.1021/JO800232P
[5] AuCl3: A$296 for 1 g; AgSbF6: A$39.50 for 1 g (source: Sigma–
Aldrich, Australia: https://www.sigmaaldrich.com/australia.html).
[6] Selected reviews on Brønsted acid catalysis: (a) J. Merad, C. Lalli,
G. Bernadat, J. Maury, G. Masson, Chem. – Eur. J. 2018, 24, 3925.
doi:10.1002/CHEM.201703556
(b) T. James, M. van Gemmeren, B. List, Chem. Rev. 2015, 115, 9388.
doi:10.1021/ACS.CHEMREV.5B00128
Supplementary Material
1H and 13C NMR spectra for all starting materials and products
as well as the ORTEP drawings of 2j, 2m, and 2n are available
on the Journal’s website.
(c) T. Akiyama, K. Mori, Chem. Rev. 2015, 115, 9277. doi:10.1021/
ACS.CHEMREV.5B00041
(d) D. Parmar, E. Sugiono, S. Raja, M. Rueping, Chem. Rev. 2014, 114,
9047. doi:10.1021/CR5001496
(e) C. H. Cheon, H. Yamamoto, Chem. Commun. 2011, 3043. doi:10.
1039/C0CC04867D
Conflicts of Interest
(f) M. Terada, Chem. Commun. 2008, 4097. doi:10.1039/B807577H
(g) Lewis Acids in Organic Synthesis (Ed. H. Yamamoto)2008 (Wiley-
VCH: Weinheim).
The authors declare no conflicts of interest.
Acknowledgements
[7] During the completion of this work, Zhou and Xie reported the chiral
Brønsted acid-catalysed enantioselective allylic amination of 1,3-
diaryl-substituted allylic alcohols to 1,2-dihydroquinolines; see
ref. [2b].
This work is supported by a Start-Up Grant from the Department of
Chemistry, University of Warwick, and a Discovery Project Grant
(DP160101682) from the Australian Research Council.
[8] Selected examples: (a) J. Jin, Y. Zhao, A. Gouranourimi, A. Ariafard,
P. W. H. Chan, J. Am. Chem. Soc. 2018, 140, 5834. doi:10.1021/JACS.
8B02339
References
[1] Selected reviews: (a) S. M. Prajapati, K. D. Patel, R. H. Vekariya, S. N.
Panchala, H. D. Patel, RSC Adv. 2014, 4, 24463. doi:10.1039/
C4RA01814A
(b) D. Susanti, L. L. R. Ng, P. W. H. Chan, Adv. Synth. Catal. 2014,
356, 353. doi:10.1002/ADSC.201300911

Brønsted Acid-Catalysed Allylic Amination of 1-(2-Aminoaryl)prop-2-en-1-ols
I
(c) S. R. Mothe, P. Kothandaraman, S. J. L. Lauw, P. W. H. Chan,
J. Org. Chem. 2012, 77, 6937. doi:10.1021/JO301093F
(d) S. R. Mothe, P. Kothandaraman, W. Rao, P. W. H. Chan, J. Org.
[9] For the synthesis of substrate 1, see refs [2d], [2h] and:
P. Kothandaraman, C. Huang, D. Susanti, W. Rao, P. W. H. Chan,
Chem. – Eur. J. 2011, 17, 10081. doi:10.1002/CHEM.201101363
Chem. 2011, 76, 2521. doi:10.1021/JO102374Z
(e) X. Zhang, W. T. Teo, P. W. H. Chan, J. Org. Chem. 2010, 75, 6290.
doi:10.1021/JO101292R
(f) S. R. Mothe, P. W. H. Chan, J. Org. Chem. 2009, 74, 5887.
doi:10.1021/JO9008244
[10] See Figs S32–S34 in the Supplementary Material for the ORTEP
drawings of the crystal structures for 2j, 2m, and 2n.
[11] M. Rueping, U. Uria, M. Y. Lin, I. Atodiresei, J. Am. Chem. Soc. 2011,
133, 3732. doi:10.1021/JA110213T