Copper-Catalyzed Regio- and Stereoselective 1,6-Conjugate Addition of Aza-Heterocycles to 1-Sulfonyl-1,3-dienes

Article abstract of DOI:10.1002/adsc.201901299

An efficient and straightforward method for the synthesis of new and versatile sulfonyl-functionalized allylic amines through the selective copper-catalyzed aza-1,6-conjugate addition of heterocycles or arylamines to 1,4-disubstituted-1,3-dienyl sulfones has been developed. This catalytic process is promoted by a combination of an easily prepared and sterically demanding N-heterocyclic carbene-based copper complex and KOt-Bu under mild reaction conditions to provide a broad range of (E)-allylic amines with excellent regio- and stereoselectivities. (Figure presented.).

Full text of DOI:10.1002/adsc.201901299

Title: Copper-Catalyzed Regio- and Stereoselective 1,6-Conjugate
Addition of Aza-Heterocycles to 1-Sulfonyl-1,3-dienes
Authors: Subin Park, Hanseul Lee, and Yunmi Lee
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Adv. Synth. Catal. 10.1002/adsc.201901299
Link to VoR: http://dx.doi.org/10.1002/adsc.201901299

Advanced Synthesis & Catalysis
10.1002/adsc.201901299
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Copper-Catalyzed Regio- and Stereoselective 1,6-Conjugate
Addition of Aza-Heterocycles to 1-Sulfonyl-1,3-dienes
a
a
a
Subin Park, Hanseul Lee and Yunmi Lee *
a
Department of Chemistry, Kwangwoon University, Seoul 01897, Republic of Korea
E-mail: ymlee@kw.ac.kr
Received:
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.
Abstract. An efficient and straightforward method for the synthesis of new and versatile sulfonyl-functionalized allylic
amines through the selective copper-catalyzed aza-1,6-conjugate addition of heterocycles or arylamines to 1,4-disubstituted-
1
,3-dienyl sulfones has been developed. This catalytic process is promoted by a combination of an easily prepared and
sterically demanding N-heterocyclic carbene-based copper complex and KOt-Bu under mild reaction conditions to provide a
broad range of (E)-allylic amines with excellent regio- and stereoselectivities.
Keywords: Copper catalysis; aza-1,6-conjugate addition; regioselectivity; (E)-allylic amine; N-heterocyclic carbene
In recent studies, Jørgensen, Wang and coworkers
Introduction
developed organocatalyzed enantioselective aza-1,6-
conjugate addition/cyclization cascade reactions of N-
The formation of carbon-nitrogen bonds is crucial hydroxycarbamate derivatives with 2,4-dienals via
in the construction of natural products, therapeutic iminium ion activation and applied this reaction in the
agents and functional materials.[1] Therefore, the synthesis of isoxazolidines and aziridines. The
development of new and efficient synthetic methods selective addition of nucleophilic amines in a 1,6-
for the synthesis of versatile amines has received conjugate mode remains a topic of great interest in
[5]
[
6]
substantial attention. Among the numerous reported organic synthesis.
approaches, the conjugate addition of nucleophilic
Allylic sulfones are important intermediates in
amines to electron-deficient alkenes is a powerful and many synthetic transformations
attractive tool because it is one of the most scaffolds in biologically active molecules. Due to
straightforward and atom economical processes for their synthetic and biological significance, we devised
[7]
and valuable
[8]
[2]
selectively constructing C-N bonds. Despite great an efficient method for synthesizing new
advances involving aza-1,4-conjugate addition functionalized amine-substituted allylic sulfones
reactions, aza-1,6-additions to electron-deficient through the 1,6-conjugate addition of aza-heterocycles
dienes to generate allylic amines have rarely been or arylamines to sulfonyl-1,3-dienes, especially in a
studied due to the difficulty in controlling the copper-catalyzed manner. Copper catalysts have the
regioselectivity (β- vs. δ-addition) and stereoselectivity advantage of being easy to handle and inexpensive and
(
E- vs. Z-isomer product). For example, Back and have played crucial roles in controlling the selectivity
coworkers showed that two allylic amines could be and enhancing the reactivity of aza-Michael additions
[9]
synthesized through a K
2
CO
3
-mediated 1,6-addition of of amines under mild conditions. To the best of our
iodoaniline derivatives to (E)-1-tosyl-1,3-butadiene in knowledge, the 1,6-conjugate addition of aza-
[3]
moderate yields with high (E)-selectivity. Ukaji, heterocycles to electron-deficient dienes has not been
Inomata and coworkers reported that secondary reported. Herein, we describe an efficient and selective
aliphatic amines could be selectively added at the δ- copper-catalyzed aza-1,6-conjugate addition of azoles
position of 1-sulfonyl-1,3-dienes or 2,4-dienoate, or arylamines to 1,4-disubstituted-1,3-dienyl sulfones
affording mainly the (Z)-selective 1,6-addition promoted by a sterically demanding N-heterocyclic
products in low reaction concentration at room carbene (NHC) ligand (Scheme 1b). A wide range of
temperature (Scheme 1a).[ Although these reactions synthetically versatile functionalized allylic amines
are highly regioselective, the scope of the dienes and were synthesized in good to high yields with excellent
amines for such 1,6-additions has been limited to regio- and (E)-stereoselectivities.
terminal conjugated dienes and aliphatic amines, and
4]
controlling the stereoselectivity remains challenging.
1
This article is protected by copyright. All rights reserved.

Advanced Synthesis & Catalysis
10.1002/adsc.201901299
catalysts such as IMesCuCl and SIMesCuCl
compared to TripPy-IPrCuCl, provided certain
amounts of 1,4-addition product 4b (18-20% yield,
entries 4 and 5), indicating that the regioselectivity was
significantly influenced by the sterics of the ligand.
The results summarized by entries 10-13 indicate that
CuCl itself does not catalyze the aza-1,6-conjugate
addition of 2a (<2% conv), and an electron-donating
NHC ligand and KOt-Bu are critical to the addition of
pyrazole to sulfonyl diene 1. It is postulated that the
reaction of in situ-generated NHC-CuOt-Bu with
pyrazole forms an NHC-copper-pyrazole complex as
the main catalytic species, and this species selectively
inserts into diene 1 to construct a C-N bond at the δ-
position with concomitant generation of a C-Cu bond
or O-Cu bond. Then, the copper intermediate reacts
with pyrazole to release the protonated allylic amine
Scheme 1. Aza-1,6-conjugate additions of amines to dienes
Results and Discussion
Our initial studies focused on optimizing the
conditions for the 1,6-conjugate addition of pyrazole
(
2a) to 1-sulfonyl-1,3-diene 1, as shown in Table 1.
[13]
product and regenerate the Cu-pyrazole species.
First, we attempted to examine copper catalysts based
on 1,2-bis(diphenylphosphino)benzene (dppbz) and
bis[(2-diphenylphosphino)phenyl] ether (DPEphos),
which were highly effective in our previous studies
involving Cu-catalyzed aza-1,4-conjugate additions of
Table 1. Optimization of the Cu-catalyzed 1,6-conjugate
[
a]
addition of pyrazole to sulfonyl diene 1
(
hetero)arylamines to α,β-unsaturated carbonyls and
[9a-b]
α,β-unsaturated sulfones.
However, these bidentate
phosphine ligands in the presence of CuCl and KOt-Bu
did not promote the aza-1,6-addition of 2a to diene 1
to provide desired allylic amine product 3a (<5% conv,
<
2% of 3a). Therefore, we investigated the ability of
NHC-based copper catalysts to promote the selective
,6-conjugate addition reaction.[
10]
The strong
1
electron-donating properties of NHC ligands were
expected to be able to activate pyrazole for addition to
KOt-Bu
temp
(°C)
conv
(%)
3a:4a:4b:4c:4d
entry
NHC-CuCl
[b]
[b]
(mol %)
(%)
[c]
[11]
1
IPrCuCl
IPrCuCl
7
7
7
7
7
7
7
7
7
7
0
7
0
70
70
70
70
70
70
50
50
50
50
50
50
50
77
>98
>98
>98
79
50:5:7:3:6
50:5:8:3:17
22:2:2:4:37
20:2:18:<2:30
28:5:20:3:13
62:5:<2:5:14
93:<2:<2:3:2
2:<2:14:<2:<2
7:<2:52:<2:7
<2
diene 1 by enhancing its nucleophilicity.
To our
2
3
4
5
6
7
8
delight, when the reaction was carried out in the
presence of IPrCuCl and KOt-Bu at 70 °C for 15 h,
pyrazole was added at the δ-position of diene 1,
affording desired (E)-selective allylic amine product
SIPrCuCl
IMesCuCl
SIMesCuCl
TripPy-IPrCuCl
TripPy-IPrCuCl
>98
>98
18
3
a in 50% yield with 86:14 regioselectivity (3a:4b),
albeit with the generation of 5% of (Z)-isomer 4a, 3%
of vinyl sulfone 4c and 17% of diaminated product 4d
as the main side product (entries 1 and 2). The structure
of (E)-isomer 3a and (Z)-isomer 4a was confirmed by
3
PPh + CuCl
9
dppe+ CuCl
74
1
0
1
2
3
CuCl
<2
1
1
1
TripPy-IPrCuCl
<2
<2
2D NMR (NOESY) experiment. To improve the
no
no
<2
<2
regioselectivity and stereoselectivity and suppress the
diamination reaction, various NHC-CuCl catalysts
<2
<2
were screened as illustrated in entries 3-7. Notably, a [a]Reaction conditions: sulfonyl diene 1 (0.36 mmol),
sterically demanding aryl-substituted TripPy- pyrazole (2a, 0.30 mmol), NHC-CuCl (7.5 mol %), KOt-Bu
IPrCuCl catalyst[ was found to be the most selective (7 mol %), toluene (1.0 M) under N
12]
[b]
Determined by H
1
2
.
and efficient. When the 1,6-conjugate addition of NMR analysis using 1,3,5-trimethoxybenzene as an internal
[
c]
pyrazole to 1 was carried out at 50 °C in the presence standard. The reaction time was 5 h.
of TripPy-IPrCuCl and KOt-Bu, the (E)-allylic amine
3a was obtained in 93% yield with >98:<2 regio- and
stereoselectivities (entry 7). The addition of a second
pyrazole, leading to diaminated side product 4d, was
retarded by the lower reaction temperature. Notably,
the conjugate additions of 2a with ligands (PPh or 1,2-
3
bis(diphenylphosphino)ethane (dppe)) that are
relatively less sterically demanding and less electron-
donating than NHC ligands preferentially generated
1
,4-addition product 4b (>88:<12 1,4-addition:1,6-
addition, entries 8 and 9), albeit with less efficiency. In
a similar context, the use of less bulky NHC-Cu
2
This article is protected by copyright. All rights reserved.

Advanced Synthesis & Catalysis
10.1002/adsc.201901299
After establishing the optimized reaction
conditions, the scope of aza-heterocycles and
arylamines was investigated as shown in Table 2.
Pyrazoles are valuable building blocks for
pharmaceutically active molecules and in heterocyclic
[
16]
synthesis.
Therefore, various pyrazole derivatives
(
2a-2f) were introduced in the 1,6-conjugate addition
to sulfonyl-1,3-diene 1. The catalytic reactions
successfully afforded corresponding allylic amines 3a-
3
f in 71-92% yields with excellent regio- and
stereoselectivities (>95:<5). Pyrazoles 2d-2f bearing
chloro, bromo, or ester groups were well tolerated in
this catalytic system. The Cu-catalyzed additions of
azoles, including imidazole 2g, methyl imidazole 2h,
benzimidazole 2i, and triazole 2j, worked well,
providing sulfonyl-substituted (E)-amine products 3g-
Scheme 2. One-pot Cu-catalyzed diamination with pyrazole
The generation of the diaminated side product 4d
is also indicated in Table 1. As illustrated in Scheme 2,
when allylic amine 3a was treated with pyrazole in the
presence of SIPrCuCl and KOt-Bu at 100 °C,
3
j in 72-80% yields. It was noted that the reaction of 1
with 2h gave only 4-methylimidazole product 3h
diamination product 4d was synthesized in 96%
yield,[14]
regioselectively (vs. 5-methylimidazole product),
indicating that the second amination
[17]
presumably because of steric effects. Arylamines
proceeded via allylic amine 3a. The reaction did not
proceed in the absence of an NHC-Cu catalyst. It was
assumed that allylic amine 3a was isomerized to vinyl
sulfone 4c in the presence of SIPrCuCl, KOt-Bu and
pyrazole and subsequently underwent a Cu-catalyzed
such
as
anisidine
2k,
fluoro-aniline
2l,
tetrahydroquinoline 2m and dihydroindole 2n were
efficiently and selectively transformed to the
corresponding allylic amines (3k-3n) in 84-96% yields.
However, the 1,6-addition of an indole to diene 1 was
not effective under these catalytic reaction coniditions
1
,4-addition with pyrazole to afford diaminated
[15]
product 4d. When 2.4 equiv of pyrazole was used in
the presence of SIPrCuCl, the one-pot diamination
with sulfonyl diene 1 successfully proceeded to give
the desired product 4d in 82% yield.
(
(
<2% conv). Notably, higher reaction temperatures
70 °C vs. 50 °C) were required to improve the
conversion and yield in reactions with heterocycles
such as 2d-2f, 2h-2i and 2k-2l.
Table 2. Cu-catalyzed 1,6-conjugate addition of azoles and
[a],[b]
Table 3. Cu-catalyzed 1,6-conjugate addition of pyrazole to
arylamines to sulfonyl diene 1
[
a],[b]
various sulfonyl-1,3-dienes
[a]Reaction conditions: sulfonyl diene 5 (0.36 mmol),
pyrazole (2a, 0.30 mmol), TripPy-IPrCuCl (7.5 mol %),
KOt-Bu (7 mol %), toluene (1.0 M) under N
2
. In all cases,
>
95:<5 regio- and stereoselectivities were achieved.
Yields of the isolated products.
[
b]
[a]Reaction conditions: sulfonyl diene (0.36 mmol), amine
0.30 mmol), TripPy-IPrCuCl (7.5 mol %), KOt-Bu (7
mol %), toluene (1.0 M) under N . In all cases, >95:<5 regio-
and stereoselectivities were achieved. Yields of the
(
Next, we explored the substrate scope of sulfonyl
2
dienes. As depicted in Table 3, a range of 4-
substituted-1-sulfonyl-1,3-dienes could be utilized in
the Cu-catalyzed aza-1,6-addition of pyrazole,
affording versatile and new sulfonyl-substituted (E)-
[
b]
[
c]
isolated products. Toluene (0.5 M).
3
This article is protected by copyright. All rights reserved.

Advanced Synthesis & Catalysis
10.1002/adsc.201901299
allylic amines in good to high yields. All the selectivities is the use of a copper complex based on a
transformations were carried out in the presence of 7.5 sterically demanding NHC ligand. This catalytic
mol % TripPy-IPrCuCl and 7 mol % KOt-Bu at 80°C system enables the synthesis of a wide range of new
and showed excellent regio- and (E)-stereoselectivities and versatile functionalized (E)-allylic amines bearing
(
>95:<5). Dienes 5a-5e substituted with alkyl pyrazole, imidazole, triazole, and arylamine
functionalities such as ethyl, propyl, n-hexyl, isobutyl derivatives with excellent regio- and stereoselectivities.
and phenethyl groups smoothly underwent aza-1,6- Sulfonyl-substituted allylic amines can be readily
addition to give desired products 6a-6e in 82-95% transformed to useful building blocks for the synthesis
yields. With mild reaction conditions, this copper of more complex molecules. Further efforts are
catalytic addition exhibited good compatibility with underway to expand the scope of diene substrates.
synthetically valuable functional groups such as a
chloro, benzyl ether, silyl ether, alkene, and alkyne
groups. New functionalized allylic amines 6f-6l were Experimental Section
obtained with high efficiencies and selectivities (75-
8
5% yields).
To highlight the utility of our newly developed
Cu-catalyzed aza-1,6-addition, we applied the
General: Infrared (IR) spectra were recorded on a ABB
-1
MB3000 FT-IR spectrophotometer, max in cm . Bands are
1
characterized as strong (s), medium (m), and weak (w). H
NMR spectra were recorded a JEOL JNM-AL400 (400
sulfonyl-substituted allylic amine product to the MHz) spectrometer. Chemical shifts are reported in ppm
from tetramethylsilane, with the solvent resonance as the
synthesis of cyclopropane and polysubstituted phenyl
[
18]
3
internal standard (CDCl : δ 7.27 ppm). Data are reported as
motifs, as illustrated in Scheme 3.
When allylic
follows: chemical shift, multiplicity (s = singlet, d = doublet,
t = triplet, q = quartet, quint = quintet, m = multiplet),
sulfone 3n bearing a dihydroindole group was treated
13
with trans-chalcone (7) using NaH as a base, coupling constants (Hz), and integration. C NMR spectra
were recorded on a JEOL JNM-AL400 (100 MHz)
cyclopropane product 8 was selectively generated in
spectrometer with complete proton decoupling. Chemical
8
3% yield through the base-promoted 1,4-conjugate
shifts are reported in ppm from tetramethylsilane with the
addition of sulfone 3n to the chalcone, followed by S
N
2
solvent resonance as the internal standard (CDCl : δ 77.00
3
ppm). High-resolution mass spectra (HRMS) were
performed at the Korea Basic Science Institute for technical
assistance using an electrospray ionization (ESI) time-of-
flight mass spectrometer. Unless otherwise noted, all
ring closure with the removal of a sulfonyl
substituent.[19] On the other hand, the reaction of allylic
sulfone 3n with the same chalcone in the presence of
NaOH and polyethylene glycol (PEG) 2000 provided reactions were carried out with distilled solvents under an
in 71% yield. When
cinnamaldehyde was reacted with 3n in the presence of
NaH, cyclized biphenyl product 11 was efficiently and unless otherwise specified. Dichloromethane was purified
selectively obtained in 92% yield. In the case of two by distillation from CaH
2
atmosphere of dry N in oven-dried (130 °C) glassware.
Toluene and tetrahydrofuran were purified by distillation
from sodium benzophenone ketyl immediately prior to use
terphenyl product
9
2
immediately prior to use.
Copper(I) chloride was purchased from Sigma-Aldrich
Corporation and used as received. Potassium tert-butoxide
was purchased from Sigma-Aldrich Corporation and used as
later reactions, the 1,2-additions of allylic sulfone 3n
to 7 or 10 were preferred under basic conditions. The
one-pot syntheses of polysubstituted phenyl products 9 received. Sodium hydride was purchased from Sigma-
and 11 proceeded through tandem 1,2-addition/Julia
olefination/electrocyclization/aromatization processes.
Aldrich Corporation and used as received. All work-up and
purification procedures were carried out with reagent grade
solvents in air. NHC-CuCl complexes were synthesized
[
20]
according to reported experimental procedures. A variety
of 1-sulfonyl-1,3-dienes were prepared according to
[
21]
reported experimental procedures.
Representative experimental procedure for the synthesis
of 1-sulfonyl-1,3-diene
(
((1E,3E)-Penta-1,3-dien-1-yl)sulfonyl)benzene (1). To a
solution of (E)-1-(phenylsulfonyl)pent-3-en-2-ol (500 mg,
2
6
2 2 2
.21 mmol) in CH Cl (5 mL) was added Ac O (0.63 mL,
.63 mmol) and DBU (1.32 mL, 8.84 mmol) at 0 °C. The
mixture was allowed to stir at room temperature for 3 h.
Then, the reaction was quenched by adding a saturated
aqueous solution of NaHCO
washed with CH Cl
combined, dried over MgSO
3
(5 mL), and the mixture was
2
2
(5 x 3 mL). The organic layers were
, filtered and concentrated. The
4
crude product was purified using silica gel column
chromatography (EtOAc:hexanes = 1:5), affording desired
diene product 1 (391 mg, 1.88 mmol, 85% yield) as a white
solid. This compound has been previously reported, and its
Scheme 3. Synthetic transformations
[
22] 1
spectral data match the reported values.
3
H NMR (CDCl ,
4
7
6
00 MHz): δ 7.90-7.88 (m, 2H), 7.61-7.59 (m, 1H), 7.55-
Conclusion
.52 (m, 2H), 7.29-7.23 (m, 1H), 6.29-6.23 (m, 2H), 6.16-
13
3
.13 (m, 1H), 1.88 (d, J = 6.9 Hz, 3H); C NMR (CDCl ,
In summary, we have developed an efficient and 100 MHz): δ 142.8, 142.5, 141.0, 133.1, 129.2, 127.5, 127.4,
highly regio- and stereoselective Cu-catalyzed aza-1,6- 127.3, 18.8.
conjugate addition of heterocycles or arylamines with
various 4-substituted-1-sulfonyl-1,3-dienes under mild
reaction conditions. The key to controlling the
(
((1E,3E)-Hexa-1,3-dien-1-yl)sulfonyl)benzene
(5a).
Compound
5a
was
synthesized
from
(E)-1-
(
phenylsulfonyl)hex-3-en-2-ol (1.04 g, 4.33 mmol) in 75%
4
This article is protected by copyright. All rights reserved.

Advanced Synthesis & Catalysis
10.1002/adsc.201901299
yield (722 mg, 3.25 mmol) as light yellow oil. The crude (quint, J = 7.5 Hz, 2H); 13C NMR (CDCl
, 100 MHz): δ
3
product was purified using silica gel column 147.1, 142.7, 141.7, 141.0, 133.2, 129.2, 128.4, 128.4, 127.7,
chromatography (EtOAc:hexanes = 1:5). IR (neat): 3055 127.5, 126.4, 125.9, 35.2, 32.5, 30.1; HRMS (ESI) m/z:
+
(
w), 2970 (w), 2878 (w), 1643 (m), 1589 (m), 1450 (m), [M+H] Calcd for C19
H
21
O
2
S 313.1262, Found 313.1262.
1
304 (s), 1196 (w), 1142 (s), 1088 (m), 995 (s), 910 (m), 826
-1 1
(
s) cm ; H NMR (CDCl
3
, 400 MHz): δ 7.90-7.88 (m, 2H),
.61-7.59 (m, 1H), 7.55-7.51 (m, 2H), 7.30-7.23 (m, 1H),
.33-6.25 (m, 2H), 6.14-6.10 (m, 1H), 2.22 (qd, J = 7.2, 7.2
(
(
2
((1E,3E)-9-Chloronona-1,3-dien-1-yl)sulfonyl)benzene
5f). Compound 5f was synthesized from 6-phenylhex-3-yn-
7
6
-ol (400 mg, 1.26 mmol) in 82% yield (309 mg, 1.03 mmol)
1
3
Hz, 2H), 1.05 (t, J = 7.4 Hz, 3H); C NMR (CDCl
3
, 100
as light yellow oil. The crude product was purified using
silica gel column chromatography (EtOAc:hexanes = 1:5).
IR (neat): 3055 (w), 2932 (w), 2862 (w), 1736 (w), 1643 (m),
MHz): δ 149.1, 143.0, 141.1, 133.1, 129.2, 127.5, 127.4,
+
1
25.1, 26.1, 12.6; HRMS (ESI) m/z: [M+H] Calcd for
S 223.0793, Found 223.0795.
12 15 2
C H O
1
1
589 (w), 1450 (m), 1311 (s), 1242 (w), 1196 (w), 1142 (s),
-1 1
3
088 (m), 995 (s), 825 (s), 741 (s) cm ; H NMR (CDCl ,
(
((1E,3E)-Octa-1,3-dien-1-yl)sulfonyl)benzene
(5b). 400 MHz): δ 7.91-7.88 (m, 2H), 7.60-7.59 (m, 1H), 7.56-
(E)-1- 7.51 (m, 2H), 7.25 (dd, J = 14.6, 10.5 Hz, 1H), 6.29-6.21 (m,
Compound 5b was synthesized from
(
phenylsulfonyl)oct-3-en-2-ol (500 mg, 1.86 mmol) in 82% 2H), 6.11 (dd, J = 15.0, 10.5 Hz, 1H), 3.53 (t, J = 6.6 Hz,
yield (382 mg, 1.53 mmol) as light yellow oil. The crude 2H), 2.22 (td, J = 6.9, 6.9 Hz, 2H), 1.80-1.76 (m, 2H), 1.50-
13
product was purified using silica gel column 1.44 (m, 4H); C NMR (CDCl
chromatography (EtOAc:hexanes = 1:5). IR (neat): 3055 141.0, 133.1, 129.2, 127.8, 127.5, 126.3, 44.8, 32.8, 32.3,
w), 2924 (m), 2854 (w), 1643 (m), 1589 (m), 1450 (m), 27.7, 26.3; HRMS (ESI) m/z: [M+H]+ Calcd for
311 (s), 1142 (s), 1088 (m), 995 (m), 825 (m), 756 (s), 717 S 299.0873, Found 299.0873.
3
, 100 MHz): δ 147.0, 142.6,
(
1
15 2
C H20ClO
-
1 1
(
3
m) cm ; H NMR (CDCl , 400 MHz): δ 7.90-7.88 (m, 2H),
7
1
1
.60-7.59 (m, 1H), 7.55-7.51 (m, 2H), 7.25 (dd, J = 15.1,
(
((1E,3E)-8-(Benzyloxy)octa-1,3-dien-1-
yl)sulfonyl)benzene (5g). Compound 5g was synthesized
from (E)-8-(benzyloxy)-1-(phenylsulfonyl)oct-3-en-2-ol
0.5 Hz, 1H), 6.28-6.23 (m, 2H), 6.12 (dd, J = 15.1, 11.0 Hz,
H), 2.18 (td, J = 7.2, 7.2 Hz, 2H), 1.43-1.31 (m, 4H), 0.90
1
3
(
3
t, J = 7.3 Hz, 3H); C NMR (CDCl , 100 MHz): δ 147.9,
(
500 mg, 1.33 mmol) in 75% yield (346 mg, 0.970 mmol) as
1
2
2
42.9, 141.0, 133.1, 129.2, 127.4, 127.3, 126.0, 32.7, 30.5,
light yellow oil. The crude product was purified using silica
+
19 2
2.2, 13.8; HRMS (ESI) m/z: [M+H] Calcd for C14H O S
gel column chromatography (EtOAc:hexanes = 1:5). IR
51.1106, Found 251.1107.
(
1
neat): 3055 (w), 2939 (w), 2862 (w), 1967 (w), 1898 (w),
813 (w), 1736 (m), 1643 (m), 1589 (m), 1450 (m), 1366
(
((1E,3E)-Undeca-1,3-dien-1-yl)sulfonyl)benzene (5c). (w), 1311 (m), 1142 (m), 1088 (m), 995 (m), 910 (w), 825
-1 1
Compound
5c
was
synthesized
from
3
(E)-1- (m), 741 (s) cm ; H NMR (CDCl , 400 MHz): δ 7.91-7.88
(
8
phenylsulfonyl)undec-3-en-2-ol (400 mg, 1.29 mmol) in (m, 2H), 7.61-7.59 (m, 1H), 7.55-7.54 (m, 2H), 7.35-7.22 (m,
9% yield (335 mg, 1.15 mmol) as a white solid. The crude 6H), 6.27-6.23 (m, 2H), 6.10 (dd, J = 15.1, 10.5 Hz, 1H),
product was purified using silica gel column 4.50 (s, 2H), 3.47 (t, J = 6.4 Hz, 2H), 2.21 (td, J = 7.3, 7.3
1
3
chromatography (EtOAc:hexanes = 1:5). mp 58-59 °C; IR Hz, 2H), 1.64-1.59 (m, 2H), 1.55-1.51 (m, 2H); C NMR
(
neat): 3055 (w), 2924 (m), 2854 (w), 1643 (m), 1589 (m), (CDCl
3
, 100 MHz): δ 147.3, 142.7, 141.0, 138.5, 133.1,
450 (m), 1311 (s), 1142 (s), 1088 (m), 995 (m), 825 (m), 129.2, 128.3, 127.7, 127.6, 127.5, 127.4, 126.3, 72.9, 69.9,
1
7
7
-
1
1
+
48 (s), 717 (m) cm ; H NMR (CDCl
.88 (m, 2H), 7.61-7.59 (m, 1H), 7.55-7.52 (m, 2H), 7.25 (dd,
3
, 400 MHz): δ 7.90- 32.8, 29.2, 25.1; HRMS (ESI) m/z: [M+H] Calcd for
21 25 3
C H O
S 357.1524, Found 357.1522.
J = 14.6, 10.5 Hz, 1H), 6.30-6.22 (m, 2H), 6.10 (dd, J = 15.1,
1
7
1.0 Hz, 1H), 2.18 (td, J = 7.2, 7.2 Hz, 2H), 1.42 (quint, J =
tert-Butyldimethyl(((3E,5E)-6-(phenylsulfonyl)hexa-3,5-
dien-1-yl)oxy)silane (5h). Compound 5h was synthesized
13
.1 Hz, 2H), 1.31-1.27 (m, 8H), 0.88 (t, J = 6.8 Hz, 3H); C
, 100 MHz): δ 147.9, 143.0, 141.1, 133.1,
NMR (CDCl
3
from
(E)-6-((tert-butyldimethylsilyl)oxy)-1-
1
1
2
29.2, 127.5, 127.4, 126.0, 33.1, 31.7, 29.1, 29.0, 28.5, 22.6,
(
phenylsulfonyl)hex-3-en-2-ol (154 mg, 0.416 mmol) in
+
25 2
4.1; HRMS (ESI) m/z: [M+H] Calcd for C17H O S
7
5% yield (110 mg, 0.312 mmol) as light yellow oil. The
93.1575, Found 293.1574.
crude product was purified using silica gel column
chromatography (EtOAc:hexanes = 1:5). IR (neat): 3055
(w), 2955 (w), 2854 (w), 1643 (m), 1589 (m), 1466 (m),
(
(
(
((1E,3E)-7-Methylocta-1,3-dien-1-yl)sulfonyl)benzene
5d). Compound 5d was synthesized from (E)-7-methyl-1- 1389 (w), 1311 (m), 1250 (m), 1180 (w), 1142 (m), 1088
-
1 1
phenylsulfonyl)oct-3-en-2-ol (910 mg, 3.22 mmol) in 96% (m), 995 (s), 933 (m), 833 (s), 779 (m), 717 (m) cm ; H
yield (815 mg, 3.08mol) as light yellow oil. The crude NMR (CDCl
3
, 400 MHz): δ 7.89-7.87 (m, 2H), 7.60-7.58
product was purified using silica gel column (m, 1H), 7.54-7.52 (m, 2H), 7.25 (dd, J = 14.6, 10.5 Hz, 1H),
chromatography (EtOAc:hexanes = 1:5). IR (neat): 3055 6.29-6.23 (m, 2H), 6.15 (dd, J = 15.1, 11.0 Hz, 1H), 3.68 (t,
(
1
8
w), 2955 (w), 2870 (w), 2361 (m), 1736 (w), 1643 (m), J = 6.4 Hz, 2H), 2.38 (td, J = 6.4, 6.4 Hz, 2H), 0.87 (s, 9H),
13
589 (w), 1450 (w), 1311 (m), 1142 (s), 1088 (m), 995 (m), 0.03 (s, 6H); C NMR (CDCl
3
, 100 MHz): δ 144.1, 142.6,
-
1 1
25 (s), 748 (m), 717 (m) cm ; H NMR (CDCl
3
, 400 MHz): 140.9, 133.1, 129.2, 127.9, 127.6, 127.4, 61.7, 36.4, 25.8,
δ 7.89 (d, J = 7.3 Hz, 2H), 7.62-7.58 (m, 1H), 7.55-7.51 (m, 18.2, -5.4; HRMS (ESI) m/z: [M+H]+ Calcd for
2
6
2
H), 7.25 (dd, J = 14.6, 10.5 Hz, 1H), 6.27-6.22 (m, 2H),
.10 (dd, J = 15.1, 11.0 Hz, 1H), 2.18 (td, J = 7.3, 7.3 Hz,
H), 1.58-1.52 (m, 1H), 1.30 (td, J = 7.5, 7.5 Hz, 2H), 0.89
18 29 3
C H O SSi 353.1607, Found 353.1606.
tert-Butyldimethyl(((5E,7E)-8-(phenylsulfonyl)octa-5,7-
dien-1-yl)oxy)silane (5i). Compound 5i was synthesized
1
3
(
3
d, J = 6.4 Hz, 6H); C NMR (CDCl , 100 MHz): δ 148.0,
1
2
2
42.9, 141.1, 133.1, 129.2, 127.4, 127.4, 125.8, 37.5, 31.0,
from
(
(E)-8-((tert-butyldimethylsilyl)oxy)-1-
+
7.5, 22.3; HRMS (ESI) m/z: [M+H] Calcd for C15
H
21
O
2
S
phenylsulfonyl)oct-3-en-2-ol (475 mg, 1.19 mmol) in 82%
65.1262, Found 265.1263.
yield (373 mg, 0.980 mmol) as light yellow oil. The crude
product was purified using silica gel column
chromatography (EtOAc:hexanes = 1:5). IR (neat): 3055
(
((1E,3E)-7-Phenylhepta-1,3-dien-1-yl)sulfonyl)benzene
(
5e). Compound 5e was synthesized from (E)-7-phenyl-1- (w), 2955 (w), 2854 (w), 1643 (m), 1589 (m), 1466 (m),
(
phenylsulfonyl)hept-3-en-2-ol (580 mg, 1.76 mmol) in 1311 (m), 1250 (m), 1142 (m), 1088 (m), 995 (s), 933 (m),
-
1 1
5
3
7% yield (312 mg, 1.00 mmol) as light yellow oil. The 833 (s), 779 (m), 717 (m) cm ; H NMR (CDCl , 400 MHz):
crude product was purified using silica gel column δ 7.91-7.89 (m, 2H), 7.61-7.59 (m, 1H), 7.55-7.54 (m, 2H),
chromatography (EtOAc:hexanes = 1:5). IR (neat): 3063 7.25 (dd, J = 14.7, 10.5 Hz, 1H), 6.30-6.22 (m, 2H), 6.11 (dd,
(
(
(
(
6
2
w), 3032 (w), 2932 (w), 2862 (w), 2361 (s), 1643 (m), 1589 J = 14.6, 10.5 Hz, 1H), 3.61 (t, J = 6.0 Hz, 2H), 2.22 (td, J =
m), 1450 (m), 1311 (m), 1142 (m), 1088 (m), 995 (m), 833 6.6, 6.6 Hz, 2H), 1.52-1.48 (m, 4H), 0.89 (s, 9H), 0.04 (s,
-
1
1
13
3 3
m), 741 (s) cm ; H NMR (CDCl , 400 MHz): δ 7.91-7.89 6H); C NMR (CDCl , 100 MHz): δ 147.5, 142.8, 141.1,
m, 2H), 7.63-7.59 (m, 1H), 7.56-7.52 (m, 2H), 7.29-7.15 (m, 133.1, 129.2, 127.6, 127.5, 126.2, 62.7, 32.8, 32.2, 25.9, 24.8,
H), 6.28-6.25 (m, 2H), 6.11 (dd, J = 15.5, 10.9 Hz, 1H), 18.3, -5.3; HRMS (ESI) m/z: [M+H]+ Calcd for
.63 (t, J = 7.6 Hz, 2H), 2.22 (td, J = 7.3, 7.3 Hz, 2H), 1.77 SSi 381.1920, Found 381.1921.
20 33 3
C H O
5
This article is protected by copyright. All rights reserved.

Advanced Synthesis & Catalysis
10.1002/adsc.201901299
(
((1E,3E,7Z)-Deca-1,3,7-trien-1-yl)sulfonyl)benzene (5j). 1:1), affording desired (E)-allylic amine 3a (76.3 mg, 0.276
Compound 5j was synthesized from (3E,7Z)-1- mmol, 92% yield) as an ivory solid.
phenylsulfonyl)deca-3,7-dien-2-ol (396 mg, 1.34 mmol) in
(
6
8% yield (250 mg, 0.906 mmol) as light yellow oil. The
(
E)-1-(5-(Phenylsulfonyl)pent-3-en-2-yl)-1H-pyrazole
crude product was purified using silica gel column
(
3a). Compound 3a was synthesized from 1H-pyrazole (2a,
chromatography (EtOAc:hexanes = 1:5). IR (neat): 3055
2
0.4 mg, 0.300 mmol) and (((1E,3E)-penta-1,3-dien-1-
(
w), 3099 (w), 2962 (w), 2870 (w), 1643 (m), 1589 (m),
yl)sulfonyl)benzene (1, 75.0 mg, 0.360 mmol) in 92% yield
76.3 mg, 0.276 mmol) as an ivory solid. The crude product
was purified using silica gel column chromatography
1
450 (m), 1311 (s), 1142 (s), 1088 (m), 995 (s), 826 (s), 756
(
-1 1
(
(
s), 717 (m) cm ; H NMR (CDCl
3
, 400 MHz): δ 7.91-7.88
m, 2H), 7.61-7.59 (m, 1H), 7.56-7.52 (m, 2H), 7.25 (dd, J
(
EtOAc:hexanes = 1:1). mp 69-70 °C; IR (neat): 3140 (w),
=
14.6, 10.5 Hz, 1H), 6.28-6.24 (m, 2H), 6.12 (dd, J = 15.1,
1
1
986 (w), 1520 (w), 1443 (m), 1396 (m), 1304 (s), 1142 (s),
1
2
0.5 Hz, 1H), 5.43-5.41 (m, 1H), 5.30-5.27 (m, 1H), 2.26-
-1 1
3
088 (s), 972 (s), 779 (s) cm ; H NMR (CDCl , 400 MHz):
.17 (m, 4H), 2.05-2.01 (m, 2H), 0.96 (t, J = 7.5 Hz, 3H);
δ 7.82 (d, J = 7.3 Hz, 2H), 7.65 (t, J = 7.3 Hz, 1H), 7.54 (t, J
13
3
C NMR (CDCl , 100 MHz): δ 147.0, 142.7, 141.0, 133.1,
=
7.8 Hz, 2H), 7.50 (d, J = 2.1 Hz, 1H), 7.30 (d, J = 2.1 Hz,
1
1
2
32.9, 129.2, 127.7, 127.5, 127.2, 126.3, 33.1, 26.0, 20.6,
1
5
1
H), 6.24 (t, J = 2.1 Hz, 1H), 5.74 (dd, J = 15.3, 6.2 Hz, 1H),
+
21 2
4.2; HRMS (ESI) m/z: [M+H] Calcd for C16H O S
.51 (dtd, J = 15.4, 7.5, 1.1 Hz, 1H), 4.89 (quint, J = 6.7 Hz,
77.1262, Found 277.1262.
13
H), 3.79 (d, J = 7.3 Hz, 2H), 1.54 (d, J = 6.9 Hz, 3H);
C
NMR (CDCl
3
, 100 MHz): δ 140.7, 139.2, 137.9, 133.8,
(
(
(
((1E,3E)-Tetradeca-1,3,13-trien-1-yl)sulfonyl)benzene
129.1, 128.4, 127.2, 118.2, 105.5, 59.4, 58.4, 20.1; HRMS
+
5k). Compound 5k was synthesized (E)-1- (ESI) m/z: [M+H] Calcd for C14
17 2 2
H N O S 277.1011, Found
phenylsulfonyl)tetradeca-3,13-dien-2-ol (570 mg, 1.63 277.1010.
mmol) in 94% yield (510 mg, 1.53 mmol) as a white solid.
The crude product was purified using silica gel column
chromatography (EtOAc:hexanes = 1:5). mp 38-39 °C; IR
(
(
Z)-1-(5-(Phenylsulfonyl)pent-3-en-2-yl)-1H-pyrazole
4a). The product was purified using silica gel column
(
neat): 3078 (m), 2924 (s), 2854 (m), 1643 (m), 1589 (m),
chromatography (EtOAc:hexanes = 1:1). IR (neat): 3070
1
450 (m), 1311 (s), 1142 (s), 1088 (m), 995 (s), 910 (m), 833
(
(
w), 2978 (w), 1651 (m), 1512 (w), 1304 (m), 1250 (s), 1142
-1 1
(
s), 756 (m), 717 (m) cm ; H NMR (CDCl
3
, 400 MHz): δ
.91-7.88 (m, 2H), 7.61-7.59 (m, 1H), 7.55-7.51 (m, 2H),
.25 (dd, J = 14.6, 11.0 Hz, 1H), 6.29-6.22 (m, 2H), 6.09 (dd,
-1 1
3
s), 1041 (m), 957 (m), 748 (s) cm ; H NMR (CDCl , 400
7
7
MHz): δ 7.90 (d, J = 7.8 Hz, 2H), 7.63 (t, J = 7.8 Hz, 1H),
7
=
.56 (t, J = 7.8 Hz, 2H), 7.47 (s, 1H), 7.30 (s, 1H), 6.21 (d, J
J = 15.1, 11.0 Hz, 1H), 5.81 (ddt, J = 17.0, 10.3, 6.7 Hz, 1H),
1.4 Hz, 1H), 5.98 (t, J = 9.2 Hz, 1H), 5.61-5.54 (m, 1H),
4
.99 (dq, J = 17.2, 1.8 Hz, 1H), 4.93 (ddt, J = 10.2, 2.2, 1.1
4
3
3
1
.97 (quint, J = 7.4 Hz, 1H), 4.01 (dd, J = 14.3, 9.1 Hz, 1H),
Hz, 1H), 2.18 (td, J = 7.2, 7.2 Hz, 2H), 2.04-2.01 (m, 2H),
.82 (dd, J = 14.3, 7.1 Hz, 1H), 1.44 (dd, J = 6.9, 1.4 Hz,
1
3
1
.43-1.41 (m, 4H), 1.27 (s, 8H); C NMR (CDCl
3
, 100
13
H); C NMR (CDCl
3
, 100 MHz): δ 139.2, 138.7, 138.5,
MHz): δ 148.0, 142.9, 141.0, 139.2, 133.1, 129.2, 127.4,
33.9, 129.2, 128.3, 126.9, 117.5, 105.5, 54.9, 54.0, 20.6;
1
2
3
27.3, 126.0, 114.1, 33.8, 33.0, 29.3, 29.3, 29.1, 29.0, 28.8,
+
HRMS (ESI) m/z: [M+H] Calcd for C14
H
17
N
2
O
2
S 277.1011,
+
29 2
8.4; HRMS (ESI) m/z: [M+H] Calcd for C20H O S
Found 277.1009.
33.1888, Found 333.1889.
(
(
E)-1-(1-(Phenylsulfonyl)pent-3-en-2-yl)-1H-pyrazole
4b). The product was purified using silica gel column
(
((1E,3E)-Octa-1,3-dien-7-yn-1-yl)sulfonyl)benzene (5l).
5l was synthesized from (E)-1-
Compound
chromatography (EtOAc:hexanes = 1:1). IR (neat): 3001
(
phenylsulfonyl)oct-3-en-7-yn-2-ol (1.10 g, 4.16 mmol) in
(
w), 2924 (w), 2854 (w), 1512 (w), 1450 (m), 1396 (m),
9
8% yield (1.00 g, 4.08 mmol) as light yellow oil. The crude
-1
1288 (s), 1142 (s), 1080 (s), 964 (m), 810 (m), 741 (s) cm ;
product was purified using silica gel column
1
H NMR (CDCl
.55 (t, J = 7.5 Hz, 1H), 7.45-7.41 (m, 2H), 7.35 (d, J = 2.1
Hz, 1H), 7.24 (d, J = 2.1 Hz, 1H), 6.1 (t, J = 2.1 Hz, 1H),
.70-5.56 (m, 2H), 5.31-5.27 (m, 1H), 4.24 (dd, J = 14.6, 8.7
3
, 400 MHz): δ 7.67 (d, J = 8.2 Hz, 2H),
chromatography (EtOAc:hexanes = 1:5). IR (neat): 3302
7
(
(
(
w), 3055 (w), 2978 (w), 2916 (w), 2847 (w), 2114 (w), 1736
m), 1643 (m), 1589 (m), 1443 (m), 1304 (s), 1142 (s), 1088
5
-
1 1
3
m), 995 (s), 825 (s), 741 (s) cm ; H NMR (CDCl , 400
Hz, 1H), 3.58 (dd, J = 14.6, 4.6 Hz, 1H), 1.65 (d, J = 5.0 Hz,
MHz): δ 7.90 (d, J = 7.3 Hz, 2H), 7.62 (t, J = 7.3 Hz, 1H),
13
3
1
3
H); C NMR (CDCl , 100 MHz): δ 139.9, 139.3, 133.4,
7
6
2
.55 (t, J = 7.3 Hz, 2H), 7.26 (dd, J = 14.6, 10.5 Hz, 1H),
.37-6.27 (m, 2H), 6.20 (dd, J = 15.6, 11.0 Hz, 1H), 2.42-
30.3, 129.1, 128.9, 127.9, 127.6, 105.5, 59.6, 58.8, 17.6;
+
HRMS (ESI) m/z: [M+H] Calcd for C14
H
17
N
2
O
2
S 277.1011,
13
.39 (m, 2H), 2.35-2.32 (m, 2H), 2.03 (s, 1H); C NMR
Found 277.1009.
(
CDCl
3
, 100 MHz): δ 144.3, 142.0, 140.7, 133.1, 129.1,
28.4, 127.3, 127.0, 82.6, 69.3, 31.4, 17.6; HRMS (ESI)
1
+
(E)-1-(5-(Phenylsulfonyl)pent-4-en-2-yl)-1H-pyrazole
4c). The product was purified using silica gel column
chromatography (EtOAc:hexanes = 1:1). IR (neat): 3005
w), 2964 (w), 1641 (w), 1512 (w), 1450 (m), 1375 (m),
m/z: [M+H] Calcd for C14
H
15
O
2
S 247.0793, Found
(
2
47.0794.
(
Representative experimental procedure for the Cu-
catalyzed 1,6-conjugate addition of heterocycles to
sulfonyl dienes
-1
1
243 (s), 1142 (s), 1080 (s), 910 (m), 805 (m), 741 (s) cm ;
1
H NMR (CDCl
.62 (t, J = 7.3 Hz, 1H), 7.54-7.50 (m, 3H), 7.46 (s, 1H), 6.78
dt, J = 15.0, 7.4 Hz, 1H), 6.19 (d, J = 15.0 Hz, 1H), 6.16 (s,
TripPy-IPrCuCl (13.1 mg, 22.5 x 10 mmol), KOt-Bu (2.36 1H), 4.49-4.48 (m, 1H), 2.90-2.83 (m, 1H), 2.73-2.67 (m,
3
, 400 MHz): δ 7.76 (d, J = 7.3 Hz, 2H),
7
(
-
3
-
3
13
3
mg, 21.0 x 10 mmol), and 1H-pyrazole (2a, 20.4 mg, 0.300 1H), 1.57 (d, J = 6.4 Hz, 3H); C NMR (CDCl , 100 MHz):
mmol) were added to a vial (4 mL) charged with a magnetic δ 141.5, 140.1, 133.9, 133.3, 133.2, 129.2, 128.5, 127.6,
+
bar in a glove box. The vial was sealed with a cap (phenolic 105.5, 58.0, 38.7, 20.7; HRMS (ESI) m/z: [M+H] Calcd for
open-top cap with gray PTFE/silicone) and was removed
14 17 2 2
C H N O S 277.1011, Found 277.1010.
from the glove box. After the vial was purged with N
2
gas
. The
for 5 min, toluene (0.2 mL) was added to vial under N
2
1
,1'-(1-(Phenylsulfonyl)pentane-2,4-diyl)bis(1H-
solution was allowed to premix for 20 min and then a
solution of sulfonyl diene (1, 75.0 mg, 0.360 mmol) in
toluene (0.1 mL) was added to the reaction vial using a
syringe. Then, the mixture was allowed to stir at 50 °C for
pyrazole) (4d) Compound 4d was synthesized from 1H-
pyrazole (2a, 24.5 mg, 0.360 mmol) and (E)-1-(5-
(
phenylsulfonyl)pent-3-en-2-yl)-1H-pyrazole (3a, 82.9 mg,
.300 mmol) in 96% yield (99.2 mg, 0.288 mmol) as an
0
1
5 h. After that time, the reaction solution was quenched by
ivory solid. The crude product was purified using silica gel
column chromatography (EtOAc:hexanes = 1:1). mp 61-
adding a saturated aqueous solution of NH
4
Cl (1 mL), and
the mixture was washed with CH Cl (3 x 3 mL). The
2
2
6
2 °C; IR (neat): 3109 (w), 2993 (w), 2932 (w), 1512 (w),
organic layers were combined, dried over MgSO
4
, filtered,
-
1
396 (m), 1288 (s), 1142 (s), 1088 (m), 933 (m), 741 (s) cm
and concentrated in vacuo. The crude product was purified
1
1
;
3
H NMR (CDCl , 400 MHz), a 1:1 mixture of
using silica gel column chromatography (EtOAc:hexanes =
diastereomers: δ 7.61-7.50 (m, 7H), 7.46 (d, J = 1.4 Hz, 1H),
7
.41-7.37 (m, 4H), 7.32 (s, 1H), 7.28 (d, J = 2.3 Hz, 1H),
6
This article is protected by copyright. All rights reserved.

Advanced Synthesis & Catalysis
10.1002/adsc.201901299
7
1
.25 (s, 1H), 7.20 (d, J = 2.3 Hz, 1H), 7.18 (d, J = 2.3 Hz, (t, J = 7.3 Hz, 1H), 7.55-7.53 (m, 2H), 7.42 (s, 1H), 7.22 (s,
H), 7.12 (d, J = 2.3 Hz, 1H), 6.25 (t, J = 1.8 Hz, 1H), 6.18 1H), 5.67 (dd, J = 15.5, 6.0 Hz, 1H), 5.54 (dd, J = 15.5, 7.3
(
t, J = 1.8 Hz, 1H), 6.05 (t, J = 1.8 Hz, 1H), 6.02 (t, J = 1.8 Hz, 1H), 4.82 (quint, J = 6.6 Hz, 1H), 3.79 (d, J = 6.9 Hz,
13
Hz, 1H), 4.70-4.63 (m, 1H), 4.32-4.25 (m, 1H), 4.12-4.03 (m, 2H), 1.51 (d, J = 6.9 Hz, 3H); C NMR (CDCl
3
, 100 MHz):
1
1
H), 3.97-3.88 (m, 2H), 3.66-3.58 (m, 1H), 3.43 (dd, J = δ 139.7, 139.7, 137.8, 133.9, 129.2, 128.4, 127.4, 119.1, 93.1,
+
4.6, 3.7 Hz, 1H), 3.38 (dd, J = 14.9, 3.9 Hz, 1H), 2.60-2.30 59.3, 59.1, 19.8; HRMS (ESI) m/z: [M+H] Calcd for
S 355.0116, Found 355.0119.
(
m, 4H), 1.43 (d, J = 6.9 Hz, 3H), 1.34 (d, J = 6.9 Hz, 3H);
14 2 2
C H16BrN O
13
3
C NMR (CDCl , 100 MHz), a 1:1 mixture of
diastereomers: δ 140.7, 140.3, 139.6, 139.3, 139.0, 139.0,
Ethyl
(E)-1-(5-(phenylsulfonyl)pent-3-en-2-yl)-1H-
1
1
4
33.5, 133.5, 131.4, 129.8, 128.2, 127.6, 127.5, 127.5, 105.4,
05.3, 105.3, 104.8, 60.1, 59.4, 54.2, 54.2, 53.8, 53.8, 42.4,
pyrazole-4-carboxylate (3f). Compound 3f was
synthesized from 1H-pyrazole-4-carboxylate (2f, 40.0 mg,
+
1.6, 21.9, 20.5; HRMS (ESI) m/z: [M+H] Calcd for
0
.300
mmol)
and
(((1E,3E)-penta-1,3-dien-1-
C
17
H
21
N
4
O
2
S 345.1385, Found 345.1386.
yl)sulfonyl)benzene (1, 75.0 mg, 0.360 mmol) in 79% yield
82.6 mg, 0.237 mmol) as ivory solid. The crude product was
purified using silica gel column chromatography
(
(
E)-4-Methyl-1-(5-(phenylsulfonyl)pent-3-en-2-yl)-1H-
pyrazole (3b). Compound 3b was synthesized from 4- (EtOAc:hexanes = 1:1). mp 82-83 °C; IR (neat): 3124 (w),
methyl-1H-pyrazole (2b, 24.6 mg, 0.300 mmol) and 2978 (w), 1705 (s), 1551 (m), 1443 (m), 1404 (m), 1304 (s),
-
1
(
((1E,3E)-penta-1,3-dien-1-yl)sulfonyl)benzene (1, 75.0 mg, 1219 (s), 1180 (s), 1142 (s), 1026 (s), 980 (m), 771 (s) cm ;
1
0
.360 mmol) in 90% yield (78.0 mg, 0.269 mmol) as light
3
H NMR (CDCl , 400 MHz): δ 7.85 (s, 1H), 7.80 (s, 1H),
yellow oil. The crude product was purified using silica gel 7.77 (d, J = 7.8 Hz, 2H), 7.62 (t, J = 7.8 Hz, 1H), 7.51 (t, J
column chromatography (EtOAc:hexanes = 1:1). IR (neat): = 7.8 Hz, 2H), 5.69 (dd, J = 15.3, 6.4 Hz, 1H), 5.54 (dt, J =
3
9
070 (w), 2978 (w), 1628 (m), 1450 (m), 1311 (s), 1149 (s), 15.3, 7.4 Hz, 1H), 4.85 (quint, J = 6.6 Hz, 1H), 4.28 (q, J =
-1 1
3
80 (m), 910 (m), 733 (s) cm ; H NMR (CDCl , 400 MHz): 6.9 Hz, 2H), 3.78 (d, J = 7.4 Hz, 2H), 1.51 (d, J = 6.9 Hz,
13
δ 7.81 (d, J = 7.8 Hz, 2H), 7.63 (t, J = 7.3 Hz, 1H), 7.54-7.50 3H), 1.33 (t, J = 7.1 Hz, 3H); C NMR (CDCl
3
, 100 MHz):
m, 2H), 7.26 (s, 1H), 7.02 (s, 1H), 5.69 (dd, J = 15.6, 6.4 δ 162.8, 140.8, 139.4, 137.8, 133.9, 130.6, 129.1, 128.3,
Hz, 1H), 5.47 (dt, J = 15.6, 7.3 Hz, 1H), 4.77 (quint, J = 6.6 119.2, 115.0, 60.1, 59.2, 59.0, 19.9, 14.3; HRMS (ESI) m/z:
(
+
Hz, 1H), 3.77 (d, J = 7.3 Hz, 2H), 2.03 (s, 3H), 1.47 (d, J = [M+H] Calcd for C17
H
21
N
2
O
4
S 349.1222, Found 349.1222.
13
6
1
1
2
3
.9 Hz, 3H); C NMR (CDCl , 100 MHz): δ 140.8, 139.4,
37.9, 133.7, 129.0, 128.4, 125.9, 117.9, 115.9, 59.3, 58.1,
(
(
E)-1-(5-(Phenylsulfonyl)pent-3-en-2-yl)-1H-imidazole
3g). Compound 3g was synthesized from 1H-imidazole (2g,
+
19 2 2
9.9, 8.8; HRMS (ESI) m/z: [M+H] Calcd for C15H N O S
91.1167, Found 291.1168.
2
0.4 mg, 0.300 mmol) and (((1E,3E)-penta-1,3-dien-1-
yl)sulfonyl)benzene (1, 75.0 mg, 0.360 mmol) in 75% yield
(62.5 mg, 0.226 mmol) as yellow oil. The crude product was
(
E)-3,5-Dimethyl-1-(5-(phenylsulfonyl)pent-3-en-2-yl)-
1
H-pyrazole (3c). Compound 3c was synthesized from 3,5- purified using silica gel column chromatography (10%
dimethyl-1H-pyrazole (2c, 28.8 mg, 0.300 mmol) and MeOH in EtOAc). IR (neat): 3078 (w), 2986 (w), 1643 (w),
(
-
1 1
((1E,3E)-penta-1,3-dien-1-yl)sulfonyl)benzene (1, 75.0 mg, 1497 (m), 1304 (s), 1142 (s), 910 (m), 741 (s) cm ; H NMR
0
3
.360 mmol) in 71% yield (65.0 mg, 0.213 mmol) as an (CDCl , 400 MHz): δ 7.75 (d, J = 7.8 Hz, 2H), 7.61 (t, J =
ivory solid. The crude product was purified using silica gel 7.3 Hz, 1H), 7.51-7.47 (m, 2H), 7.34 (s, 1H), 6.97 (s, 1H),
column chromatography (EtOAc:hexanes = 1:1). mp 91- 6.74 (s, 1H), 5.62 (dd, J = 15.3, 6.0 Hz, 1H), 5.44 (dt, J =
9
1
(
2 °C; IR (neat): 2955 (w), 2878 (w), 1551 (w), 1443 (m), 15.3, 7.4 Hz, 1H), 4.66 (quint, J = 6.6 Hz, 1H), 3.75 (d, J =
-
1
1
1
3
296 (s), 1142 (s), 1080 (m), 980 (m), 733 (s) cm ; H NMR 7.4 Hz, 2H), 1.44 (d, J = 6.9 Hz, 3H); C NMR (CDCl
3
, 100
CDCl
3
, 400 MHz): δ 7.76 (d, J = 7.8 Hz, 2H), 7.59 (t, J = MHz): δ 140.1, 137.8, 135.2, 133.8, 129.1, 128.1, 127.3,
+
7
1
.3 Hz, 1H), 7.50-7.46 (m, 2H), 5.74 (s, 1H), 5.69 (dd, J = 118.5, 116.9, 58.9, 53.7, 20.4; HRMS (ESI) m/z: [M+H]
5.6, 5.9 Hz, 1H), 5.31 (dt, J = 15.6, 7.6 Hz, 1H), 4.66 (quint, Calcd for C14 S 277.1011, Found 277.1012.
17 2 2
H N O
J = 6.7 Hz, 1H), 3.72 (d, J = 7.6 Hz, 2H), 2.15 (s, 3H), 2.14
1
3
(
s, 3H), 1.46 (d, J = 6.9 Hz, 3H); C NMR (CDCl
3
, 100
(
E)-4-Methyl-1-(5-(phenylsulfonyl)pent-3-en-2-yl)-1H-
MHz): δ 147.2, 141.1, 138.2, 137.9, 133.6, 128.9, 128.3,
imidazole (3h). Compound 3h was synthesized from 4-
methyl-1H-imidazole (2h, 24.6 mg, 0.300 mmol) and
1
16.9, 105.1, 59.3, 54.4, 19.8, 13.5, 10.8; HRMS (ESI) m/z:
+
[
21 2 2
M+H] Calcd for C16H N O S 305.1324, Found 305.1324.
(
((1E,3E)-penta-1,3-dien-1-yl)sulfonyl)benzene (1, 75.0 mg,
.360 mmol) in 80% yield (70.0 mg, 0.241 mmol) as yellow
0
(
E)-4-Chloro-1-(5-(phenylsulfonyl)pent-3-en-2-yl)-1H-
oil. The crude product was purified using silica gel column
pyrazole (3d). Compound 3d was synthesized from 4- chromatography (10% MeOH in EtOAc). IR (neat): 3109
chloro-1H-pyrazole (2d, 30.8 mg, 0.300 mmol) and (w), 2978 (w), 1643 (m), 1450 (m), 1304 (s), 1149 (s), 910
-
1 1
(
3
((1E,3E)-penta-1,3-dien-1-yl)sulfonyl)benzene (1, 75.0 mg, (m), 733 (s) cm ; H NMR (CDCl , 400 MHz): δ 7.75 (d, J
0
.360 mmol) in 75% yield (70.0 mg, 0.225 mmol) as an = 7.8 Hz, 2H), 7.61 (t, J = 7.3 Hz, 1H), 7.49 (t, J = 7.8 Hz,
ivory solid. The crude product was purified using silica gel 2H), 7.21 (s, 1H), 6.43 (s, 1H), 5.69 (dd, J = 15.6, 5.9 Hz,
column chromatography (EtOAc:hexanes = 1:1). mp 122- 1H), 5.43 (dt, J = 15.6, 7.3 Hz, 1H), 4.56 (quint, J = 6.4 Hz,
1
1
23 °C; IR (neat): 3124 (w), 2993 (w), 1443 (m), 1304 (s), 1H), 3.77 (d, J = 7.3 Hz, 2H), 2.13 (s, 3H), 1.40 (d, J = 7.3
-1 1 13
3 3
142 (s), 972 (m), 741 (s) cm ; H NMR (CDCl , 400 Hz, 3H); C NMR (CDCl ,100 MHz): δ 140.3, 137.8, 134.3,
MHz): δ 7.80 (d, J = 7.3 Hz, 2H), 7.64 (t, J = 7.3 Hz, 1H), 133.7, 129.0, 128.1, 127.3, 118.3, 113.4, 59.0, 53.5, 20.3,
+
7
1
.55-7.51 (m, 2H), 7.36 (s, 1H), 7.19 (s, 1H), 5.66 (dd, J = 13.6; HRMS (ESI) m/z: [M+H] Calcd for C15
5.5, 6.4 Hz, 1H), 5.52 (dt, J = 15.5, 7.6 Hz, 1H), 4.78 (quint, 291.1167, Found 291.1169.
19 2 2
H N O S
J = 6.5 Hz, 1H), 3.78 (d, J = 7.3 Hz, 2H), 1.48 (d, J = 6.9 Hz,
1
3
3
1
H); C NMR (CDCl
3
, 100 MHz): δ 139.7, 137.8, 137.4,
(
E)-1-(5-(Phenylsulfonyl)pent-3-en-2-yl)-1H-
33.9, 129.1, 128.3, 125.3, 119.0, 109.8, 59.2, 59.1, 19.7;
benzo[d]imidazole (3i). Compound 3i was synthesized
from 1H-benzo[d]imidazole (2i, 35.4 mg, 0.300 mmol) and
+
HRMS (ESI) m/z: [M+H] Calcd for C14
H
2
16ClN O
2
S
3
11.0621, Found 311.0623.
(
((1E,3E)-penta-1,3-dien-1-yl)sulfonyl)benzene (1, 75.0 mg,
.360 mmol) in 77% yield (75.6 mg, 0.232 mmol) as ivory
0
(
E)-4-Bromo-1-(5-(phenylsulfonyl)pent-3-en-2-yl)-1H-
oil. The crude product was purified using silica gel column
pyrazole (3e). Compound 3e was synthesized from 4- chromatography (10% MeOH in EtOAc). IR (neat): 3094
bromo-1H-pyrazole (2e, 44.1 mg, 0.300 mmol) and (w), 2986 (w), 1620 (w), 1489 (m), 1311 (s), 1227 (m), 1149
-
1 1
(
3
((1E,3E)-penta-1,3-dien-1-yl)sulfonyl)benzene (1, 75.0 mg, (s), 1088 (m), 910 (s), 741 (s) cm ; H NMR (CDCl , 400
0
.360 mmol) in 86% yield (92.0 mg, 0.259 mmol) as an MHz): δ 7.83-7.80 (m, 1H), 7.77 (s, 1H), 7.68 (d, J = 7.3 Hz,
ivory solid. The crude product was purified using silica gel 2H), 7.56 (t, J = 7.3 Hz, 1H), 7.38 (t, J =7.8 Hz, 2H), 7.31-
column chromatography (EtOAc:hexanes = 1:1). mp 121- 7.30 (m, 3H), 5.77 (dd, J = 15.6, 5.9 Hz, 1H), 5.53 (dtd, J =
1
1
22 °C; IR (neat): 3124 (w), 2986 (w), 1435 (m), 1304 (s), 15.6, 7.3, 1.4 Hz, 1H), 5.01 (quint, J = 6.5 Hz, 1H), 3.78 (d,
-
1
1
1
3
142 (s), 972 (s), 949 (s), 818 (m), 849 (m), 741 (s) cm ; H J = 7.3 Hz, 2H), 1.67 (d, J = 7.3 Hz, 3H); C NMR (CDCl
3
,
NMR (CDCl
3
, 400 MHz): δ 7.81 (d, J = 7.8 Hz, 2H), 7.66 100 MHz): δ 144.0, 140.4, 139.4, 137.8, 133.9, 129.1, 128.2,
7
This article is protected by copyright. All rights reserved.

Advanced Synthesis & Catalysis
10.1002/adsc.201901299
1
23.0, 122.4, 120.6, 119.1, 110.2, 59.2, 52.4, 19.7; HRMS 129.0, 128.6, 128.3, 126.6, 126.1, 125.5, 117.6, 60.9, 59.8,
+ +
(
ESI) m/z: [M+H] Calcd for C18
27.1169.
H
19
N
2
O
2
S 327.1167, Found 52.4, 46.8, 29.1, 17.0; HRMS (ESI) m/z: [M+H] Calcd for
S 342.1528, Found 342.1530.
3
20 2
C H24NO
(
E)-1-(5-(Phenylsulfonyl)pent-3-en-2-yl)-1H-1,2,3-
triazole (3j). Compound 3j was synthesized from 1H-1,2,3- Compound 3n was synthesized from indoline (2n, 33.7 μL,
triazole (2j, 17.4 μL, 0.300 mmol) and (((1E,3E)-penta-1,3- 0.300 mmol) and (((1E,3E)-penta-1,3-dien-1-
dien-1-yl)sulfonyl)benzene (1, 75.0 mg, 0.360 mmol) in yl)sulfonyl)benzene (1, 75.0 mg, 0.360 mmol) in 92% yield
(E)-1-(5-(Phenylsulfonyl)pent-3-en-2-yl)indoline
(3n).
7
2% yield (60.0 mg, 0.216 mmol) as ivory solid. The crude (90.4 mg, 0.276 mmol) as ivory solid. The crude product was
product was purified using silica gel column purified using silica gel column chromatography
chromatography (EtOAc:hexanes = 1:1). mp 46-47 °C; IR (EtOAc:hexanes = 1:1). mp 88-89 °C; IR (neat): 3016 (w),
(
neat): 3063 (w), 2986 (w), 1450 (m), 1420 (w), 1304 (s), 2970 (w), 1605 (m), 1489 (m), 1389 (m), 1296 (s), 1142 (s),
-
1
-1 1
1
3
142 (s), 1080 (m), 964 (m), 818 (s), 741 (s), 710 (m) cm ; 1011 (m), 987 (m), 872 (m), 741 (s) cm ; H NMR (CDCl ,
1
H NMR (CDCl
3
, 400 MHz): δ 7.81 (d, J = 7.8 Hz, 2H), 400 MHz): δ 7.79 (d, J = 7.8 Hz, 2H), 7.63 (t, J = 7.4 Hz,
.62 (t, J = 7.4 Hz, 1H), 7.57 (s, 2H), 7.53-7.49 (m, 2H), 5.74 1H), 7.49 (t, J = 7.8 Hz, 2H), 7.06-7.02 (m, 2H), 6.64 (t, J =
dd, J = 15.5, 6.9 Hz, 1H), 5.55 (dt, J = 15.5, 7.4 Hz, 1H), 7.3 Hz, 1H), 6.36 (d, J = 7.8 Hz, 1H), 5.66-5.55 (m, 2H),
.21 (quint, J = 6.7 Hz, 1H), 3.77 (d, J = 7.3 Hz, 2H), 1.57 4.17-4.11 (m, 1H), 3.79 (d, J = 5.9 Hz, 2H), 3.32-3.26 (m,
7
(
5
1
3
(
d, J = 6.9 Hz, 3H); C NMR (CDCl , 100 MHz): δ 141.2, 1H), 3.07-3.00 (m, 1H), 2.95-2.81 (m, 2H), 1.24 (d, J = 6.9
3
13
1
1
2
39.2, 137.8, 133.9, 133.7, 129.0, 128.5, 119.0, 61.6, 59.3, Hz, 3H); C NMR (CDCl
3
,100 MHz): δ 150.5, 140.8, 138.0,
+
9.9; HRMS (ESI) m/z: [M+H] Calcd for C13
H
16
N
3
O
2
S
133.5, 130.0, 129.0, 128.4, 127.2, 124.5, 117.6, 117.4, 107.3,
+
78.0963, Found 278.0965.
59.8, 51.5, 46.8, 28.0, 16.1; HRMS (ESI) m/z: [M+H]
2
Calcd for C19H22NO S 328.1371, Found 328.1373.
(
E)-4-Methoxy-N-(5-(phenylsulfonyl)pent-3-en-2-
yl)aniline (3k). Compound 3k was synthesized from 4- (E)-1-(6-(Phenylsulfonyl)hex-4-en-3-yl)-1H-pyrazole
methoxyaniline (2k, 36.9 mg, 0.300 mmol) and (((1E,3E)- (6a). Compound 6a was synthesized from 1H-pyrazole (2a,
penta-1,3-dien-1-yl)sulfonyl)benzene (1, 75.0 mg, 0.360 20.4 mg, 0.300 mmol) and (((1E,3E)-hexa-1,3-dien-1-
mmol) in 88% yield (87.6 mg, 0.264 mmol) as orange oil. yl)sulfonyl)benzene (5a, 80.0 mg, 0.360 mmol) in 95% yield
The crude product was purified using silica gel column (82.8 mg, 0.285 mmol) as ivory oil. The crude product was
chromatography (EtOAc:hexanes = 1:5). IR (neat): 3001 purified using silica gel column chromatography
(
(
w), 2908 (w), 1512 (s), 1443 (w), 1296 (m), 1234 (s), 1142 (EtOAc:hexanes = 1:1). IR (neat): 2978 (w), 1512 (w), 1450
-1 1
m), 1034 (m), 972 (m), 910 (m), 818 (m), 733 (s) cm ; H (w), 1396 (m), 1304 (s), 1142 (s), 1088 (s), 972 (s), 910 (m),
-1 1
NMR (CDCl
3
, 400 MHz): δ 7.76 (d, J = 7.3 Hz, 2H), 7.61 733 (s) cm ; H NMR (CDCl
3
, 400 MHz): δ 7.78 (d, J = 7.8
(
t, J = 7.8 Hz, 1H), 7.47 (t, J = 7.8 Hz, 2H), 6.76 (d, J = 8.9 Hz, 2H), 7.61 (t, J = 7.3 Hz, 1H), 7.51-7.47 (m, 3H), 7.28 (d,
Hz, 2H), 6.49 (d, J = 8.9 Hz, 2H), 5.59 (dt, J = 15.5, 7.3 Hz, J = 1.8 Hz, 1H), 6.22 (t, J = 1.8 Hz, 1H), 5.74 (dd, J = 15.6,
1
1
3
1
5
H), 5.50 (dd, J = 15.5, 5.5 Hz, 1H), 3.84 (quint, J = 6.3 Hz, 6.9 Hz, 1H), 5.49 (dt, J = 15.6, 7.4 Hz, 1H), 4.55 (q, J = 7.2
H), 3.76-3.73 (m, 5H), 3.21 (br s, 1H), 1.17 (d, J = 6.9 Hz, Hz, 1H), 3.77 (d, J = 7.4 Hz, 2H), 1.94 (dquint, J = 14.0, 7.8
1
3
H); C NMR (CDCl , 100 MHz): δ 152.1, 143.9, 140.9, Hz, 1H), 1.77 (dquint, J = 14.0, 7.0 Hz, 1H), 0.75 (t, J = 7.3
3
13
38.0, 133.5, 128.9, 128.4, 115.9, 114.7, 114.6, 59.5, 55.7, Hz, 3H); C NMR (CDCl
3
,100 MHz): δ 139.6, 139.1, 137.9,
+
0.8, 21.5; HRMS (ESI) m/z: [M+H] Calcd for 133.7, 129.0, 128.3, 127.8, 118.8, 105.2, 64,9, 59.3, 27.6,
+
C
18
H
22NO
3
S 332.1320, Found 332.1320.
10.3; HRMS (ESI) m/z: [M+H] Calcd for C15
91.1167, Found 291.1169.
19 2 2
H N O S
2
(
E)-2-Fluoro-N-(5-(phenylsulfonyl)pent-3-en-2-
yl)aniline (3l). Compound 3l was synthesized from 2- (E)-1-(1-(Phenylsulfonyl)oct-2-en-4-yl)-1H-pyrazole (6b).
fluoroaniline (2l, 29.0 μL, 0.300 mmol) and (((1E,3E)- Compound 6b was synthesized from 1H-pyrazole (2a, 20.4
penta-1,3-dien-1-yl)sulfonyl)benzene (1, 75.0 mg, 0.360 mg, 0.300 mmol) and (((1E,3E)-octa-1,3-dien-1-
mmol) in 84% yield (80.5 mg, 0.252 mmol) as ivory solid. yl)sulfonyl)benzene (5b, 90.1 mg, 0.360 mmol) in 82% yield
The crude product was purified using silica gel column (78.0 mg, 0.245 mmol) as light yellow oil. The crude product
chromatography (EtOAc:hexanes = 1:5). mp 49-50 °C; IR was purified using silica gel column chromatography
(
neat): 3371 (br), 3124 (w), 2962 (w), 1620 (w), 1512 (m), (EtOAc:hexanes = 1:1). IR (neat): 2932 (w), 2862 (w), 1512
-
1 1
1
296 (s), 1142 (s), 1080 (m), 980 (m), 741 (s) cm ; H NMR (w), 1450 (w), 1304 (s), 1234 (w), 1142 (s), 1088 (m), 972
-1 1
(
CDCl
3
, 400 MHz): δ 7.75 (d, J = 7.3 Hz, 2H), 7.61 (t, J = (s), 918 (w), 733 (s) cm ; H NMR (CDCl
3
, 400 MHz): δ
7
6
7
6
.8 Hz, 1H), 7.46 (t, J = 7.8 Hz, 2H), 7.00-6.95 (m, 2H), 7.79 (d, J = 7.8 Hz, 2H), 7.62 (t, J = 7.3 Hz, 1H), 7.53-7.49
.67-6.63 (m, 1H), 6.57 (t, J = 8.5 Hz, 1H), 5.61 (dt, J = 15.1, (m, 3H), 7.29 (s, 1H), 6.23 (s, 1H), 5.74 (dd, J = 15.6, 6.9
.3 Hz, 1H), 5.50 (dd, J = 15.1, 5.5 Hz, 1H), 3.94 (quint, J = Hz, 1H), 5.49 (dt, , J = 15.6, 7.4 Hz, 1H), 4.63 (q, J = 7.3 Hz,
13
.1 Hz, 1H), 3.78-3.77 (m, 3H), 1.24 (d, J = 6.9 Hz, 3H); C 1H), 3.77 (d, J = 7.4 Hz, 2H), 1.97-1.88 (m, 1H), 1.77-1.69
NMR (CDCl
3
, 100 MHz): δ 151.3 (JC-F = 23.9 Hz), 143.1, (m, 1H), 1.30-1.15 (m, 2H), 1.17-1.02 (m, 2H), 0.85 (t, J =
1
3
1
F
37.9, 135.2 (JC-F = 10.6 Hz), 133.7, 128.9, 128.5, 124.5 (JC- 7.3 Hz, 3H); C NMR (CDCl
= 3.9 Hz), 116.8 (JC-F = 6.7 Hz), 116.3, 114.4 (JC-F = 18.3 137.9, 133.7, 129.0, 128.4, 127.8, 118.7, 105.3, 63.4, 59.4,
3
, 100 MHz): δ 139.9, 139.2,
+
Hz), 112.9 (JC-F = 3.9 Hz), 59.5, 49.8, 21.4; HRMS (ESI) 34.1, 27.8, 22.1, 13.8; HRMS (ESI) m/z: [M+H] Calcd for
+
m/z: [M+H] Calcd for C17
20.1123.
H
19FNO
2
S 320.1121, Found
17 23 2 2
C H N O S 319.1480, Found 319.1482.
3
(
E)-1-(1-(Phenylsulfonyl)undec-2-en-4-yl)-1H-pyrazole
(
E)-1-(5-(Phenylsulfonyl)pent-3-en-2-yl)-1,2,3,4-
(6c). Compound 6c was synthesized from 1H-pyrazole (2a,
tetrahydroquinoline (3m). Compound 3m was synthesized 20.4 mg, 0.300 mmol) and (((1E,3E)-undeca-1,3-dien-1-
from 1,2,3,4-tetrahydroquinoline (2m, 37.7 μL, 0.300 yl)sulfonyl)benzene (5c, 105 mg, 0.360 mmol) in 82% yield
mmol) and (((1E,3E)-penta-1,3-dien-1-yl)sulfonyl)benzene (88.7 mg, 0.246 mmol) as an ivory solid. The crude product
(
1, 75.0 mg, 0.360 mmol) in 96% yield (98.0 mg, 0.287 was purified using silica gel column chromatography
mmol) as light yellow oil. The crude product was purified (EtOAc:hexanes = 1:1). mp 54-55 °C; IR (neat): 3109 (w),
using silica gel column chromatography (EtOAc:hexanes = 2924 (w), 1443 (w), 1396 (w), 1304 (s), 1142 (s), 1088 (s),
-
1 1
1
(
3
:1). IR (neat): 2908 (w), 2808 (w), 1450 (w), 1304 (s), 1142 972 (m), 895 (w), 741 (s) cm ; H NMR (CDCl , 400 MHz):
-1 1
3
s), 1080 (m), 910 (m), 741 (s) cm ; H NMR (CDCl , 400 δ 7.79 (d, J = 7.3 Hz, 2H), 7.63 (t, J = 7.3 Hz, 1H), 7.52-7.48
MHz): δ 7.87 (d, J = 7.3 Hz, 2H), 7.63 (t, J = 7.8 Hz, 1H), (m, 3H), 7.29 (s, 1H), 6.23 (s, 1H), 5.74 (dd, J = 15.6, 6.9
7
5
1
2
.54-7.50 (m, 2H), 7.13-7.05 (m, 3H), 6.98-6.96 (m, 1H), Hz, 1H), 5.49 (dt, J = 15.6, 7.3 Hz, 1H), 4.63 (q, J = 6.9 Hz,
.64-5.55 (m, 2H), 3.89-3.80 (m, 2H), 3.62 (d, J = 15.0 Hz, 1H), 3.77 (d, J = 7.3 Hz, 2H), 1.97-1.87 (m, 1H), 1.76-1.69
H), 3.53 (d, J = 15.0 Hz, 1H), 3.12 (quint, J = 6.4 Hz, 1H), (m, 1H), 1.29-1.21 (m, 8H), 1.16-1.03 (m, 2H), 0.86 (t, J =
13
3
.85-2.73 (m, 2H), 2.66 (dt, J = 11.6, 5.5 Hz, 1H), 2.49 (dt, 6.9 Hz, 3H); C NMR (CDCl , 100 MHz): δ 139.9, 139.2,
13
J = 11.6, 5.9 Hz, 1H), 1.14 (d, J = 6.4 Hz, 3H); C NMR 137.9, 133.7, 129.0, 128.4, 127.8, 118.6, 105.3, 63.4, 59.4,
(
3
CDCl , 100 MHz): δ 142.9, 138.1, 134.5, 134.1, 133.6,
8
This article is protected by copyright. All rights reserved.

Advanced Synthesis & Catalysis
10.1002/adsc.201901299
+
3
4.4, 31.6, 29.0, 25.7, 22.5, 14.0; HRMS (ESI) m/z: [M+H]
3.39 (t, J = 6.4 Hz 2H), 1.99-1.89 (m, 1H), 1.78-1.69 (m,
Calcd for C20 S 361.1950, Found 361.1950.
H
29
N
2
O
2
1H), 1.60-1.52 (m, 2H), 1.30-1.21 (m, 1H), 1.19-1.10 (m,
1
3
1
1
1
3
H); C NMR (CDCl , 100 MHz): δ 139.7, 139.2, 138.4,
37.9, 133.7, 129.0, 128.3, 128.3, 127.9, 127.6, 127.5, 118.8,
(
E)-1-(7-Methyl-1-(phenylsulfonyl)oct-2-en-4-yl)-1H-
05.3, 72.8, 69.8, 63.3, 59.3, 34.2, 29.1, 22.5; HRMS (ESI)
pyrazole (6d). Compound 6d was synthesized from 1H-
pyrazole (2a, 20.4 mg, 0.300 mmol) and (((1E,3E)-7-
methylocta-1,3-dien-1-yl)sulfonyl)benzene (5d, 95.2 mg,
+
m/z: [M+H] Calcd for C24
H
29
N
2
O
3
S 425.1899, Found
4
25.1898.
0
.360 mmol) in 89% yield (89.0 mg, 0.268 mmol) as an
ivory solid. The crude product was purified using silica gel (E)-1-(1-((tert-Butyldimethylsilyl)oxy)-6-
column chromatography (EtOAc:hexanes = 1:1). mp 53- (phenylsulfonyl)hex-4-en-3-yl)-1H-pyrazole
(6h).
5
4 °C; IR (neat): 3101 (w), 2955 (w), 1443 (w), 1304 (s), Compound 6h was synthesized from 1H-pyrazole (2a, 20.4
-
1
242 (w), 1142 (s), 1088 (m), 1057 (w), 972 (m), 741 (s) cm
mg, 0.300 mmol) and tert-butyldimethyl(((3E,5E)-6-
, 400 MHz): δ 7.79 (d, J = 7.3 Hz, 2H), (phenylsulfonyl)hexa-3,5-dien-1-yl)oxy)silane (5h, 127 mg,
.62 (t, J = 7.3 Hz, 1H), 7.52-7.48 (m, 3H), 7.28 (d, J = 1.8 0.360 mmol) in 77% yield (97.0 mg, 0.231 mmol) as yellow
1
1
;
H NMR (CDCl
3
7
Hz, 1H), 6.22 (t, J = 1.8 Hz, 1H), 5.74 (dd, J = 15.6, 6.9 Hz, oil. The crude product was purified using silica gel column
1
3
1
1
H), 5.48 (dt, J = 15.6, 7.3 Hz, 1H), 4.59 (q, J = 6.9 Hz, 1H), chromatography (EtOAc:hexanes = 1:1). IR (neat): 2955
.77 (d, J = 7.3 Hz, 2H), 1.96-1.86 (m, 1H), 1.77-1.68 (m, (w), 2862 (w), 1466 (w), 1396 (w), 1311 (m), 1250 (m),
-
1 1
H), 1.54-1.44 (m, 1H), 1.10-1.01 (m, 1H), 0.97-0.88 (m, 1142 (m), 1068 (s), 833 (s), 779 (s), 741 (s) cm ; H NMR
13
3
H), 0.83 (d, J = 6.4 Hz, 3H), 0.82 (d, J = 6.4 Hz, 3H); C (CDCl , 400 MHz): δ 7.78 (d, J = 7.3 Hz, 2H), 7.61 (t, J =
NMR (CDCl
3
, 100 MHz): δ 139.9, 139.2, 137.9, 133.7, 7.8 Hz, 1H), 7.51-7.47 (m, 3H), 7.31 (d, J = 1.8 Hz, 1H),
1
2
C
29.0, 128.3, 127.7, 118.7, 105.2, 63.7, 59.3, 34.7, 32.3, 27.6, 6.22 (s, 1H), 5.77 (dd, J = 15.6, 6.9 Hz, 1H), 5.47 (dt, J =
+
2.4, 22.3; HRMS (ESI) m/z: [M+H] Calcd for 15.6, 7.4 Hz, 1H), 4.93 (q, J = 6.5 Hz, 1H), 3.75 (d, J = 7.4
18
H
25
N
2
O
2
S 333.1637, Found 333.1639.
Hz, 2H), 3.51 (dt, J = 10.3, 4.9 Hz, 1H), 3.29-3.23 (m, 1H),
2
3
1
5
.19-2.11 (m, 1H), 1.95-1.87 (m, 1H), 0.87 (s, 9H), -0.01 (s,
13
3
H), -0.03 (s, 3H); C NMR (CDCl , 100 MHz): δ 139.9,
(
E)-1-(7-Phenyl-1-(phenylsulfonyl)hept-2-en-4-yl)-1H-
39.5, 137.9, 133.7, 129.0, 128.9, 128.4, 118.4, 105.0, 59.5,
pyrazole (6e). Compound 6e was synthesized from 1H-
pyrazole (2a, 20.4 mg, 0.300 mmol) and (((1E,3E)-7-
phenylhepta-1,3-dien-1-yl)sulfonyl)benzene (5e, 112.0 mg,
+
9.4, 58.5, 37.0, 25.8, 18.1, -5.6,; HRMS (ESI) m/z: [M+H]
Calcd for C21
H
33
N
2
O
3
SSi 421.1981, Found 421.1980.
0
.360 mmol) in 86% yield (98.0 mg, 0.258 mmol) as an
ivory solid. The crude product was purified using silica gel (E)-1-(8-((tert-Butyldimethylsilyl)oxy)-1-
column chromatography (EtOAc:hexanes = 1:1). mp 78- (phenylsulfonyl)oct-2-en-4-yl)-1H-pyrazole
(6i).
7
1
9 °C; IR (neat): 3109 (w), 2970 (w), 1589 (w), 1497 (w), Compound 6i was synthesized from 1H-pyrazole (2a, 20.4
450 (w), 1304 (s), 1142 (s), 1088 (m), 972 (s), 895 (m), 741 mg, 0.300 mmol) and tert-butyldimethyl(((5E,7E)-8-
-
1 1
(
s) cm ; H NMR (CDCl
3
, 400 MHz): δ 7.77 (d, J = 7.3 Hz, (phenylsulfonyl)octa-5,7-dien-1-yl)oxy)silane (5i, 137 mg,
H), 7.59 (t, J = 7.8 Hz, 1H), 7.50 (s, 1H), 7.47-7.43 (m, 2H), 0.360 mmol) in 81% yield (109 mg, 0.243 mmol) as yellow
.31-7.27 (m, 3H), 7.20 (t, J = 7.3 Hz, 1H), 7.13 (d, J = 7.3 oil. The crude product was purified using silica gel column
2
7
Hz, 2H), 6.24 (s, 1H), 5.73 (dd, J = 15.6, 6.9 Hz, 1H), 5.49 chromatography (EtOAc:hexanes = 1:1). IR (neat): 2947
(
dt, J = 15.6, 7.3 Hz, 1H), 4.65 (q, J = 6.9 Hz, 1H), 3.77 (d, (w), 2862 (w), 1450 (w), 1396 (w), 1311 (m), 1257 (m),
-1
J = 7.3 Hz, 2H), 2.85 (t, J = 7.5 Hz, 2H), 2.03-1.93 (m, 1H), 1142 (m), 1095 (s), 972 (w), 841 (s), 771 (s), 741 (s) cm ;
1
3
1
1
1
1
2
3
.81-1.73 (m, 1H), 1.56-1.36 (m, 2H); C NMR (CDCl
3
,
3
H NMR (CDCl , 400 MHz): δ 7.78 (d, J = 7.3 Hz, 2H),
00 MHz): δ 141.5, 139.6, 139.2, 137.8, 133.7, 129.0, 128.3, 7.62 (t, J = 7.8 Hz, 1H), 7.51-7.47 (m, 3H), 7.27 (s, 1H), 6.21
28.3, 127.8, 125.9, 118.9, 105.3, 63.3, 59.3, 35.2, 33.8, (s, 1H), 5.73 (dd, J = 15.6, 6.9 Hz, 1H), 5.48 (dt, J = 15.6,
+
7.4; HRMS (ESI) m/z: [M+H] Calcd for C22
H
25
N
2
O
2
S
7.4 Hz, 1H), 4.63 (q, J = 6.9 Hz, 1H), 3.76 (d, J = 7.4 Hz,
2H), 3.53 (t, J = 6.4 Hz, 2H), 1.99-1.90 (m, 1H), 1.77-1.71
81.1637, Found 381.1636.
(
m, 1H), 1.50-1.42 (m, 2H), 1.24-1.16 (m, 1H), 1.14-1.09 (m,
13
1
3
H), 0.85 (s, 9H), 0.00 (s, 6H); C NMR (CDCl , 100
(
E)-1-(9-Chloro-1-(phenylsulfonyl)non-2-en-4-yl)-1H-
MHz): δ 139.8, 139.2, 138.0, 133.7, 129.0, 128.4, 127.8,
pyrazole (6f). Compound 6f was synthesized from 1H-
pyrazole (2a, 20.4 mg, 0.300 mmol) and (((1E,3E)-9-
chloronona-1,3-dien-1-yl)sulfonyl)benzene (5f, 108 mg,
1
5
4
18.7, 105.3, 63.4, 62.6, 59.4, 34.2, 32.1, 25.9, 22.1, 18.2, -
+
37 2 3
.4; HRMS (ESI) m/z: [M+H] Calcd for C23H N O SSi
49.2294, Found 449.2294.
0
.360 mmol) in 83% yield (91.4mg, 0.249 mmol) as light
yellow oil. The crude product was purified using silica gel
column chromatography (EtOAc:hexanes = 1:1). IR (neat): 1-((2E,7Z)-1-(Phenylsulfonyl)deca-2,7-dien-4-yl)-1H-
2
1
4
1
1
924 (w), 2870 (w), 1512 (w), 1443 (w), 1396 (w), 1311 (s), pyrazole (6j). Compound 6j was synthesized from 1H-
-1 1
142 (s), 1088 (m), 972 (m), 733 (s) cm ; H NMR (CDCl
3
,
pyrazole (2a, 20.4 mg, 0.300 mmol) and (((1E,3E,7Z)-deca-
00 MHz): δ 7.79 (d, J = 7.3 Hz, 2H), 7.62 (t, J = 7.8 Hz, 1,3,7-trien-1-yl)sulfonyl)benzene (5j, 99.5 mg, 0.360 mmol)
H), 7.52-7.48 (m, 3H), 7.28 (d, J = 1.4 Hz, 1H), 6.23 (s, in 75% yield (77.6 mg, 0.225 mmol) as yellow oil. The crude
H), 5.75 (dd, J = 15.6, 6.9 Hz, 1H), 5.50 (dt, J = 15.6, 7.4 product was purified using silica gel column
Hz, 1H), 4.64 (q, J = 6.9 Hz, 1H), 3.77 (d, J = 7.4 Hz, 2H), chromatography (EtOAc:hexanes = 1:1). IR (neat): 2962
3
3
.47 (t, J = 6.6 Hz, 2H), 2.00-1.91 (m, 1H), 1.78-1.66 (m, (w), 2870 (w), 1450 (w), 1404 (w), 1311 (s), 1142 (s), 1088
-1 1
H), 1.47-1.32 (m, 2H), 1.22-1.15 (m, 1H), 1.13-1.06 (m), 972 (m), 741 (s) cm ; H NMR (CDCl
3
, 400 MHz): δ
, 100 MHz): δ 139.6, 139.2, 138.0, 7.77 (d, J = 7.8 Hz, 2H), 7.60 (t, J = 7.2 Hz, 1H), 7.50-7.46
33.7, 129.1, 128.3, 127.8, 118.8, 105.3, 63.2, 59.3, 44.7, (m, 3H), 7.27 (s, 1H), 6.22 (s, 1H), 5.73 (dd, J = 15.6, 6.9
13
(
m,1H); C NMR (CDCl
3
1
3
C
+
4.2, 32.1, 26.2, 24.9; HRMS (ESI) m/z: [M+H] Calcd for Hz, 1H), 5.46 (dt, J = 15.6, 7.5 Hz, 1H), 5.40-5.34 (m, 1H),
18
H
2
24ClN O
2
S 367.1247, Found 367.1247.
5.24-5.18 (m, 1H), 4.65 (q, J = 6.9 Hz, 1H), 3.75 (d, J = 7.5
Hz, 2H), 2.06-1.95 (m, 1H), 1.91-1.81 (m, 4H), 1.78-1.70 (m,
1
3
1
3
H), 0.89 (t, J = 7.5 Hz, 3H); C NMR (CDCl , 100 MHz):
(
1
E)-1-(8-(Benzyloxy)-1-(phenylsulfonyl)oct-2-en-4-yl)-
H-pyrazole (6g). Compound 6g was synthesized from 1H-
pyrazole (2a, 20.4 mg, 0.300 mmol) and (((1E,3E)-8-
δ 139.8, 139.2, 137.9, 133.7, 133.2, 129.0, 128.3, 128.0,
26.7, 118.6, 105.2, 62.5, 59.3, 34.2, 23.1, 20.3, 14.1;
1
+
HRMS (ESI) m/z: [M+H] Calcd for
45.1637, Found 345.1639.
19 25 2 2
C H N O S
(
benzyloxy)octa-1,3-dien-1-yl)sulfonyl)benzene (5g, 128
3
mg, 0.360 mmol) in 85% yield (108 mg, 0.254mmol) as light
yellow oil. The crude product was purified using silica gel
column chromatography (EtOAc:hexanes = 1:1). IR (neat): (E)-1-(1-(Phenylsulfonyl)trideca-2,12-dien-4-yl)-1H-
2
1
947 (w), 2854 (w), 1450 (w), 1396 (w), 1304 (m), 1142 (m), pyrazole (6k). Compound 6k was synthesized from 1H-
-1 1
3
088 (m), 972 (w), 733 (s) cm ; H NMR (CDCl , 400 pyrazole (2a, 20.4 mg, 0.300 mmol) and (((1E,3E)-
MHz): δ 7.76 (d, J = 7.8 Hz, 2H), 7.57 (t, J = 7.3 Hz, 1H), tetradeca-1,3,13-trien-1-yl)sulfonyl)benzene (5k, 120 mg,
7
.48-7.44 (m, 3H), 7.34-7.24 (m, 6H), 6.21 (s, 1H), 5.71 (dd, 0.360 mmol) in 75% yield (90.0 mg, 0.225 mmol) as ivory
J = 15.6, 6.9 Hz, 1H), 5.46 (dt, J = 15.6, 7.4 Hz, 1H), 4.62 solid. The crude product was purified using silica gel column
(
q, J = 7.2 Hz, 1H), 4.44 (s, 2H), 3.74 (d, J = 7.4 Hz, 2H), chromatography (EtOAc:hexanes = 1:1). mp 41-42 °C; IR
9
This article is protected by copyright. All rights reserved.

Advanced Synthesis & Catalysis
10.1002/adsc.201901299
(
neat): 3109 (w), 3078 (w), 2916 (m), 1643 (w), 1443 (w), the mixture was washed with EtOAc (3 × 1 mL). The organic
1
7
396 (w), 1304 (s), 1142 (s), 1088 (m), 972 (m), 910 (m), layers were dried over MgSO
4
, filtered and concentrated.
3
, 400 MHz): δ 7.79 (d, J = 7.3 The crude product was purified using silica gel column
-
1 1
41 (s) cm ; H NMR (CDCl
Hz, 2H), 7.62 (t, J = 7.8 Hz, 1H), 7.52-7.48 (m, 3H), 7.28 (s, chromatography (EtOAc:hexanes = 1:20), affording desired
1
H), 6.23 (s, 1H), 5.85-5.71 (m, 2H), 5.49 (dt, J = 15.2, 7.3 product 9 (53.0 mg, 0.141 mmol, 71%) as a light-yellow oil.
Hz, 1H), 5.01-4.91 (m, 2H), 4.63 (q, J = 6.9 Hz, 1H), 3.77 IR (neat): 3032 (w), 2970 (w), 2847 (w), 1605 (m), 1481 (m),
(
1
1
d, J = 7.3 Hz, 2H), 2.02 (q, J = 6.9 Hz, 2H), 1.97-1.88 (m, 1389 (w), 1257 (m), 1180 (w), 1026 (w), 910 (s), 733 (s),
-
1 1
H), 1.76-1.68 (m, 1H), 1.35 (quint, J = 6.9 Hz, 2H), 1.27- 702 (s) cm ; H NMR (400 MHz, CDCl
3
): δ 7.69-7.61 (m,
4H), 7.55 (d, J = 1.8 Hz, 1H), 7.47-7.43 (m, 4H), 7.42-7.34
, 100 MHz): δ 139.9, 139.2, 139.1, 138.0, (m, 4H), 7.05 (d, J = 7.3 Hz, 1H), 6.91 (t, J = 7.3 Hz, 1H),
33.7, 129.0, 128.4, 127.8, 118.6, 114.1, 105.3, 63.4, 59.4, 6.59 (t, J = 7.3 Hz, 1H), 6.05 (d, J = 7.3 Hz, 1H), 4.76 (q, J
4.4, 33.7, 29.3, 29.2, 29.0, 29.0, 28.8, 25.7; HRMS (ESI) = 6.9 Hz, 1H), 3.53-3.48 (m, 1H), 3.45-3.38 (m, 1H), 2.94
13
.23 (m, 8H), 1.17-1.11 (m, 1H), 1.09-1.05 (m, 1H);
C
NMR (CDCl
3
1
3
+
13
m/z: [M+H] Calcd for C23
H
33
N
2
O
2
S 401.2263, Found (dd, J = 9.6, 6.9 Hz, 2H), 1.41 (d, J = 6.9 Hz, 3H); C NMR
4
01.2262.
(100 MHz, CDCl
3
): δ 150.9, 142.1, 141.2, 140.6, 139.7,
39.5, 130.2, 129.4, 129.2, 128.8, 128.2, 127.3, 127.1, 127.0,
26.0, 124.1, 116.9, 107.5, 51.8, 48.5, 28.2, 16.7; HRMS
1
1
(
E)-1-(1-(Phenylsulfonyl)oct-2-en-7-yn-4-yl)-1H-
+
(
ESI) m/z: [M] Calcd for C28
H
25N 375.1987, Found
pyrazole (6l). Compound 6l was synthesized from 1H-
pyrazole (2a, 20.4 mg, 0.300 mmol) and (((1E,3E)-octa-1,3-
dien-7-yn-1-yl)sulfonyl)benzene (5l, 88.7 mg, 0.360 mmol)
3
75.1989.
in 83% yield (78.0 mg, 0.248 mmol) as yellow oil. The crude 1-(1-([1,1'-Biphenyl]-2-yl)ethyl)indoline (11). Compound
product was purified using silica gel column 11 was synthesized from (E)-1-(5-(phenylsulfonyl)pent-3-
chromatography (EtOAc:hexanes = 1:1). IR (neat): 3279 en-2-yl)indoline (3n, 65.5 mg, 0.200 mmol) and
(
(
(
7
5
1
2
w), 2955 (w), 2353 (w), 2322 (w), 1512 (w), 1443 (w), 1311 cinnamaldehyde 10 (25.2 μL, 0.200 mmol) in 92% yield
-1 1
m), 1142 (s), 1088 (m), 975 (m), 741 (s) cm ; H NMR (55.0 mg, 0.184 mmol) as yellow oil. The crude product was
CDCl , 400 MHz): δ 7.76 (d, J = 7.3 Hz, 2H), 7.59 (t, J = purified using silica gel column chromatography
.8 Hz, 1H), 7.49-7.45 (m, 3H), 7.31 (s, 1H), 6.19 (s, 1H), (EtOAc:hexanes = 1:20). IR (neat): 3047 (w), 2986 (w),
.74 (dd, J = 15.6, 6.9 Hz, 1H), 5.53 (dt, J = 15.6, 7.4 Hz, 1605 (m), 1481 (s), 1389 (w), 1257 (m), 1157 (w), 910 (m),
3
-
1 1
H), 4.85 (q, J = 7.0 Hz, 1H), 3.74 (d, J = 7.4 Hz, 2H), 2.18- 841 (m), 733 (s) cm ; H NMR (CDCl
3
, 400 MHz): δ 7.64-
7.59 (m, 4H), 7.52-7.45 (m, 4H), 7.37 (t, J = 7.3 Hz, 1H),
3
, 100 MHz): δ 139.6, 138.8, 137.8, 133.7, 7.10 (d, J = 6.9 Hz, 1H), 7.04 (t, J = 7.8 Hz, 1H), 6.65 (t, J
13
.11 (m, 1H), 2.08-1.98 (m, 2H), 1.92-1.83 (m, 2H);
C
NMR (CDCl
1
1
3
29.0, 128.7, 128.3, 119.4, 105.2, 82.3, 69.7, 61.5, 59.3, 32.7, = 7.3 Hz, 1H), 6.44 (d, J = 7.8 Hz, 1H), 4.80 (q, J = 6.9 Hz,
+
4.8; HRMS (ESI) m/z: [M+H] Calcd for C17
H
19
N
2
O
2
S
1H), 3.49-3.37 (m, 2H), 3.00 (t, J = 8.5 Hz, 2H), 1.60 (d, J
13
15.1167, Found 315.1165.
= 6.9 Hz, 3H); C NMR (CDCl
3
,100 MHz): δ 151.3, 141.9,
1
1
40.8, 139.8, 130.1, 128.7, 127.5, 127.2, 127.1, 127.0, 124.4,
+
17.0, 107.2, 54.2, 47.9, 28.2, 16.5; HRMS (ESI) m/z: [M]
Experimental procedures for the synthesis of 8, 9 and 11
Calcd for C22
H
21N 299.1674, Found 299.1673.
2
-((E)-3-(Indolin-1-yl)but-1-en-1-yl)-3-
phenylcyclopropyl)(phenyl)methanone (8). To a solution
of compound 3n (65.5 mg, 0.200 mmol) in THF (2 mL) was
added NaH (60% in mineral oil, 20.0 mg, 0.500 mmol) at
room temperature. And then a solution of trans-chalcone (7,
Acknowledgements
This research was supported by the Basic Science Research
Program through the National Research Foundation of Korea
4
1.7 mg, 0.200 mmol) in THF (2 mL) was added to the
reaction mixture. The reaction was heated at 70 °C and
stirred for 3 h. After that time, the mixture was allowed to
cool to room temperature, quenched with water (3 mL) and
washed with EtOAc (3 x 2 mL). The organic layers were
(
NRF) (NRF-2017R1A2B4008310). This work was also partially
supported by the Bio & Medical Technology Development
Program of the National Research Foundation (NRF) and was
funded by the Korean government (MSIP&MOHW) (NRF-
4
dried over MgSO , filtered and concentrated. The crude
2
015M3A9E6029594) and by the Research Grant from
product was purified using silica gel column
chromatography (EtOAc:hexanes = 1:20), affording desired
product 8 (65.0 mg, 0.165 mmol, 83%) as a yellow oil. IR
Kwangwoon University in 2019.
(
neat): 3055 (w), 2986 (w), 2839 (w), 1736 (m), 1666 (m),
1
8
605 (m), 1489 (w), 1257 (m), 1018 (w), 972 (w), 910 (m),
References
-1 1
3
72 (w), 733 (s), 702 (s) cm ; H NMR (400 MHz, CDCl ),
a 1:1 mixture of diastereomers: δ 8.08 (d, J = 7.3 Hz, 2H),
8
4
4
.03 (d, J = 7.3 Hz, 2H), 7.64-7.59 (m, 2H), 7.55-7.49 (m, [1] a) A. Ricci, Amino Group Chemistry: From Synthesis to
H), 7.37-7.33 (m, 4H), 7.30-7.27 (m, 6H), 7.07-6.99 (m,
the Life Sciences, 1st ed., Wiley-VCH, Weinheim, 2007;
b) R. Hili, A. K. Yudin, Nat. Chem. Biol. 2006, 2, 284–
H), 6.64 (t, J = 7.3 Hz, 1H), 6.63 (t, J = 7.3 Hz, 1H), 6.40
(
d, J = 7.8 Hz, 1H), 6.31 (d, J = 7.8 Hz, 1H), 5.82 (dd, J =
2
87; c) M. C. Bagley, J. W. Dale, E. A. Merritt, X. Xiong,
1
5.6, 5.9 Hz, 1H), 5.75 (dd, J = 15.3, 5.7 Hz, 1H), 5.22-5.15
(
m, 2H), 4.11 (quint, J = 6.5 Hz, 2H), 3.34-3.11 (m, 8H),
Chem. Rev. 2005, 105, 685–714.
2
6
.94-2.83 (m, 4H), 2.69-2.62 (m, 2H), 1.19 (t, J = 7.1 Hz,
13
H); C NMR (100 MHz, CDCl
3
), a 1:1 mixture of [2] For representative reviews, see: a) J. Gmach, Ł.
diastereomers: δ 198.0, 151.0, 150.9, 137.7, 136.4, 133.0,
Joachimiak, K. M. Błażewska, Synthesis 2016, 48,
681–2704; b) M. Sánchez-Roselló, J. L. Aceña, A.
1
1
1
3
32.9, 132.9, 132.4, 130.3, 130.1, 129.1, 129.1, 128.6, 128.6,
28.3, 128.1, 127.9, 127.8, 127.0, 127.0, 126.7, 124.4, 124.3,
17.1, 117.0, 107.6, 107.5, 52.0, 51.9, 46.9, 46.7, 34.8, 34.6,
2
Simón-Fuentes, C. del-Pozo, Chem. Soc. Rev. 2014, 43,
7430–7453; c) Z. Amara, J. Caron, D. Joseph, Nat. Prod.
Rep. 2013, 30, 1211–1225; d) J. Wang, P. Li, P. Y. Choy,
A. S. C. Chan, F. Y. Kwong, ChemCatChem 2012, 4,
4.6, 34.4, 32.2, 31.8, 28.1, 28.0, 16.7, 16.1; HRMS (ESI)
+
m/z: [M+H] Calcd for C28
H
28NO 394.2171, Found
3
94.2172.
9
17–925; e) A. Y. Rulev, Russ. Chem. Rev. 2011, 80,
1
-(1-([1,1':3',1''-Terphenyl]-4'-yl)ethyl)indoline
(9).
Allylic sulfone 3n (65.5 mg, 0.200 mmol), trans-chalcone
197–218; f) P. R. Krishna, A. Sreeshailam, R. Srinivas,
Tetrahedron 2009, 65, 9657–9672; g) D. Enders, C.
Wang, J. X. Liebich, Chem. -Eur. J. 2009, 15, 11058–
(
7, 41.7 mg, 0.200 mmol), NaOH (32.0 mg, 0.800 mmol),
and PEG 2000 (160 mg, 0.0800 mmol) were added to a vial
(
4 mL), which was sealed with a cap (phenolic open-top cap
1
1076; h) J. L. Vicario, D. Badía, L. Carrillo, Synthesis
with gray PTFE/silicone). The reaction mixture was heated
at 70 °C. After stirring for 1 h, the reaction was quenched by
2007, 2007, 2065–2092; i) J. L. Vicario, D. Badía, L.
4
adding a saturated aqueous solution of NH Cl (2 mL), and
1
0
This article is protected by copyright. All rights reserved.

Advanced Synthesis & Catalysis
10.1002/adsc.201901299
Carrillo, J. Etxebarria, E. Reyes, N. Ruiz, Org. Prep. [10] S. Park, S. Kang, Y. Lee, Adv. Synth. Catal. 2019, 361,
Proced. Int. 2005, 37, 513–538. 1071–1083.
[
3] T. G. Back, M. Parvez, J. E. Wulff, J. Org. Chem. 2003, [11] For representative reviews of NHC-copper complexes
6
8, 2223–2233.
in catalysis, see: a) F. Lazreg, F. Nahra, C. S. J. Cazin,
Coord. Chem. Rev. 2015, 293-294, 48–79; b) J. D.
Egbert, C. S. J. Cazin, S. P. Nolan, Catal. Sci. Technol.
[
4] a) M. Yamazaki, S. K. Guha, Y. Ukaji, K. Inomata, Bull.
Chem. Soc. Jpn. 2008, 81, 740–753; b) M. Yamazaki, S.
K. Guha, Y. Ukaji, K. Inomata, Chem. Lett. 2006, 35,
2
013, 3, 912–926; c) S. Díez-González, N. Marion, S. P.
Nolan, Chem. Rev. 2009, 109, 3612–3676; d) S. Díez-
González, S. P. Nolan, Synlett 2007, 2158–2167.
5
14–515; c) T. Cuvigny, C. H. du Penhoat, M. Julia,
Tetrahedron 1986, 42, 5321–5328.
[
12] Y. Kim, Y. Kim, M. Y. Hur, E. Lee, J. Organomet.
Chem. 2016, 820, 1–7.
[
[
5] a) K. S. Halskov, T. Naicker, M. E. Jensen, K. A.
Jørgensen, Chem. Commun. 2013, 49, 6382–6384; b) Q.-
Y. Dou, Y.-Q. Tu, Y. Zhang, J.-M. Tian, F.-M. Zhang, [13] For understanding mechanism of aza-Michael addition
S.-H. Wang, Adv. Synth. Catal. 2016, 358, 874–879.
of arylamines using an NHC-copper complex, see: a) L.
A. Goj, E. D. Blue, C. Munro-Leighton, T. B. Gunnoe, J.
L. Petersen, Inorg. Chem. 2005, 44, 8647–8649; b)
References [9b] and [9f].
6] For representative reviews of 1,6-conjugate addition of
carbon-based nucleophiles, see: a) P. Chauhan, U. Kaya,
D. Enders, Adv. Synth. Catal. 2017, 359, 888–912; b) T.
E. Schmid, S. Drissi-Amraoui, C. Crévisy, O. Baslé, M. [14] The amination reaction of 3a with 2a provided the
Mauduit, Beilstein J. Org. Chem. 2015, 11, 2418–2434;
c) A. G. Csákÿ, G. de la Herrán, M. C. Murcia, Chem.
Soc. Rev. 2010, 39, 4080–4102; For recent examples of
conjugate addition of boron-based nucleophiles to dienes,
see: d) T. Jia, M. J. Smith, A. P. Pulis, G. J. P. Perry, D.
J. Procter, ACS Catal. 2019, 9, 6744−6750; e) X. Li, F.
Meng, S. Torker, Y. Shi, A. H. Hoveyda, Angew. Chem.,
Int. Ed. 2016, 55, 9997−10002; f) L. Jiang, P. Cao, M.
Wang, B. Chen, B. Wang, J. Liao, Angew. Chem., Int. Ed.
desired product 4d in 75% yield in the presence of 7.5
mol % IPrCuCl and 7 mol % KOt-Bu at 70 °C.
[
15] When allylic sulfone 3a was treated with 7.5 mol %
SIPrCuCl and 7 mol % KOt-Bu in the absence of
pyrazole, vinyl sulfone product 4c was not observed. It
was postulated that pyrazole was required for
isomerization of 3a to 4c, although vinyl sulfone
1
intermediate 4c could not be detected by H NMR
analysis during the catalytic reaction of 3a with pyrazole.
2
016, 55, 13854−13858; For recent examples of
conjugate addition of silicon-based nucleophiles to [16] For representative reviews, see: a) M. Faisal, A. Saeed,
dienes, see: g) T. Ahmad, Q. Li, S.-Q. Qiu, J.-L. Xu, Y.-
H. Xu, T.-P. Loh, Org. Biomol. Chem. 2019, 17, 6122–
S. Hussain, P. Dar, F. A. Larik, J. Chem. Sci. 2019, 131,
70; b) K. Karrouchi, S. Radi, Y. Ramli, J. Taoufik, Y. N.
Mabkhot, F. A. Al-aizari, M. Ansar, Molecules 2018, 23,
134–209; c) A. Ansari, A. Ali, M. Asif, Shamsuzzaman,
New J. Chem. 2017, 41, 16–41; d) M. J. Naim, O. Alam,
F. Nawaz, M. J. Alam, P. Alam, J. Pharm. Bioallied Sci.
6
126; h) K.-s. Lee, H. Wu, F. Haeffner, A. H. Hoveyda,
Organometallics 2012, 31, 7823−7826.
[
[
7] a) A.‐ N. R. Alba, X. Companyó, R. Rios, Chem. Soc.
Rev. 2010, 39, 2018– 2033; b) A. EI-Awa, M. N. Noshi,
X. M. du Jourdin, P. L. Fuchs, Chem. Rev. 2009, 109,
2
016, 8, 2–17; e) A. Schmidt, A. Dreger, Curr. Org.
Chem. 2011, 15, 1423–1463.
2
315–2349; c) A. Hassner, E. Ghera, T. Yechezkel, V.
Kleiman, T. Balasubramanian, D. Ostercamp, Pure Appl. [17] The structure of 4-methylimidazole product 3h was
Chem. 2000, 72, 1671–1683; d) C. Nájera, M. Yus,
Tetrahedron 1999, 55, 10547–10658.
confirmed by 2D NMR (NOESY) experiment.
[
18] a) D. C. M. Albanese, S. Brunialti, D. Destro, Catalysts
2016, 6, 142; b) M.-Y. Chang, C.-K. Chan, S.-Y. Lin,
M.-H. Wu, Tetrahedron 2013, 69, 10036–10044; c) M.-
Y. Chang, C.-K. Chan, S.-Y. Lin, M.-H. Wu,
Tetrahedron 2013, 69, 9616–9624; d) M.-Y. Chang, C.-
K. Chan, M.-H. Wu, Tetrahedron 2013, 69, 7916–7924.
8] a) C. Pabba, B. T. Gregg, D. B. Kitchen, Z. Jia Chen, A.
Judkins, Bioorg. Med. Chem. Lett. 2011, 21, 324–328; b)
F. Reck, F. Zhou, M. Girardot, G. Kern, C. J. Eyermann,
N. J. Hales, R. R. Ramsay, M. B. Gravestock, J. Med.
Chem. 2005, 48, 499–506; c) H. G. F. Richter, P.
Angehrn, C. Hubschwerlen, M. Kania, M. G. P. Page, J.-
L. Specklin, F. K. Winkler, J. Med. Chem. 1996, 39,
[
[
19] The stereochemistry of the cyclopropane ring was
suggested based on the structure by analysis of X-ray
crystallography in Reference [18b] and was confirmed
by 2D NMR (NOESY) experiment.
3
712–3722.
[
9] a) S. Kang, S. Park, K.-s. Kim, C. Song, Y. Lee, J. Org.
Chem. 2018, 83, 2694−2705; b) S. Kim, S. Kang, G. Kim,
Y. Lee, J. Org. Chem. 2016, 81, 4048–4057; c) S. Kang,
H. Yoon, Y. Lee, Chem. Lett. 2016, 45, 1356–1358; d) S.
Yamazaki, M. Yamamoto, A. Sumi, Tetrahedron 2007,
20] For synthesis of IPrCuCl, see: a) W.-J. Yoo, T. V. Q.
Nguyen, S. Kobayashi, Angew. Chem., Int. Ed. 2014, 53,
1
0213–10217; For synthesis of SIPrCuCl, see: b) L. Goj,
E. D. Blue, S. A. Delp, T. B. Gunnoe, T. R. Cundari, A.
6
3, 2320–2327; e) M. L. Kantam, B. Neelima, C. V.
Reddy, R. Chakravarti, Ind. Eng. Chem. Res. 2007, 46,
614–8619; f) C. Munro-Leighton, S. A. Delp, E. D.
Blue, T. B. Gunnoe, Organometallics 2007, 26, 1483–
493; g) C. Munro-Leighton, E. D. Blue, T. B. Gunnoe,
J. Am. Chem. Soc. 2006, 128, 1446–1447.
W. Pierpont, J. L. Petersen, P. D. Boyle, Inorg. Chem.
2
006, 45, 9032–9045; For synthesis of IMesCuCl, see:
c) W. Xie, S. Chang, Angew. Chem., Int. Ed. 2016, 55,
876–1880; For synthesis of SIMesCuCl, see: d) S. M.
Opalka, J. K. Park, A. R. Longstreet, D. T. McQuade,
8
1
1
1
1
This article is protected by copyright. All rights reserved.

Advanced Synthesis & Catalysis
10.1002/adsc.201901299
Org. Lett. 2013, 15, 996–999; For synthesis of TripPy-
IPrCuCl, see: e) Reference [12].
[
[
21] a) S. H. Hwang, M. J. Kurth, Tetrahedron Lett. 2002,
4
2
3, 53–56; b) D. Zhao, F. Lied, F. Glorius, Chem. Sci.
014, 5, 2869–2873.
22] T. Hata, T. Nakada, Y. T. Oh, N. Hirone, H. Urabe, Adv.
Synth. Catal. 2013, 355, 1736–1740.
1
2
This article is protected by copyright. All rights reserved.

Advanced Synthesis & Catalysis
10.1002/adsc.201901299
FULL PAPER
Copper-Catalyzed Regio- and Stereoselective 1,6-
Conjugate Addition of Aza-Heterocycles to 1-
Sulfonyl-1,3-dienes
Adv. Synth. Catal. Year, Volume, Page – Page
Subin Park, Hanseul Lee and Yunmi Lee*
1
3
This article is protected by copyright. All rights reserved.