Palladium-Catalyzed Allylic Amination of Homoallylic Alcohols with Amines via Carbon-Carbon Bond Cleavage

Article abstract of DOI:10.1055/s-0034-1380418

An efficient approach for palladium(II) acetate catalyzed allylic amination of homoallylic alcohols with various amines via sequential retro-allylation and amination was developed, which afforded the corresponding allylic amines in up to 98% yield.

Full text of DOI:10.1055/s-0034-1380418

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2015, 47, 2931–2936
2931
special topic
G.-J. Sun et al.
Special Topic
Synthesis
Palladium-Catalyzed Allylic Amination of Homoallylic Alcohols
with Amines via Carbon–Carbon Bond Cleavage
Gui-Jun Suna,b
Yong Wangb
Qiang Kang*b
Pd(OAc)2 (10 mol%)
dppb (12 mol%)
Cs2CO3 (120 mol%)
OH
Ts
R3 NHTs
+
N
R1
R3
R2
H2O (300 mol%)
ODCB, 100 °C
a College of Chemistry and Chemical Engineering, Fuzhou University,
Fuzhou, Fujian 350108, P. R. of China
b Key Laboratory of Coal to Ethylene Glycol and Its Related Technology,
Fujian Institute of Research on the Structure of Matter, Chinese
Academy of Sciences, Fuzhou, Fujian 350002, P. R. of China
kangq@fjirsm.ac.cn
up to 98% yield
17 examples
R1 = Ph
2 = Ph, Me
C(sp3)–C(sp3) bond cleavage
C–N bond formation
R
Received: 22.03.2015
Accepted after revision: 13.04.2015
Published online: 26.05.2015
lyzed, selective carbon–carbon bond cleavage of tertiary
homoallylic alcohols and sequential amination with amines
as nucleophiles in the presence of a stoichiometric amount
of water as additive.
DOI: 10.1055/s-0034-1380418; Art ID: ss-2015-c0189-st
Abstract An efficient approach for palladium(II) acetate catalyzed al-
lylic amination of homoallylic alcohols with various amines via sequen-
tial retro-allylation and amination was developed, which afforded the
corresponding allylic amines in up to 98% yield.
At the outset of our investigation, we studied the reac-
tion of 2-phenylpent-4-en-2-ol (1a) with 4-methyl-N-(4-
methylphenyl)benzenesulfonamide (2a) under our previ-
ously optimized reaction conditions for palladium-cata-
lyzed allylic esterification [Pd(OAc)2 (10 mol%), Ag2CO3 (1.4
equiv), 1,2-dichlorobenzene (ODCB), 100 °C];10 however,
the desired product was not observed under these reaction
conditions. Interestingly, on replacement of the silver car-
bonate by 1.5 equivalents of cesium carbonate, the reaction
went smoothly to afford the desired amination product 3a
in 36% NMR yield after 48 hours (Table 1, entry 1). Inspired
by this promising result, other bases (such as K3PO4, CsF
and DBU) were screened and it was concluded that cesium
carbonate is the best choice (Table 1, entries 2–4). In an in-
triguing observation, we found that the reaction gave a
trace amount of product 3a when it was carried out under
anhydrous conditions (employing anhydrous Cs2CO3); how-
ever, on addition of 1.5 equivalents of water to the con-
trolled anhydrous reaction, the yield of product 3a could be
improved to 34%. As ligands can markedly influence transi-
tion-metal-catalyzed reactions, we sought to explore the
effect of ligands on this reaction. For that purpose, we test-
ed several ligands (10 mol%) in the pilot reaction (Table 1,
entries 5–11). To our pleasure, addition of some specific li-
gands, such as L1, L3 (Figure 1) and 1,4-bis(diphenylphos-
phino)butane (dppb), to the reaction system significantly
improved the yield of 3a (Table 1, entries 8, 10 and 11). The
optimum result was achieved with the bidentate ligand
dppb, which led to the formation of product 3a in 90% yield
(Table 1, entry 11). Even more satisfactorily, the reaction
time was also significantly reduced to 24 hours on addition
of an increased amount of dppb (12 mol%), along with 93%
Key words C–C bond activation, allylic amination, homoallylic alco-
hols, palladium, allylic amines
Transition-metal-catalyzed activation of unstrained car-
bon–carbon bonds is a highly challenging research topic in
organic synthesis that has received massive attention in re-
cent years.1 Compared to the relatively easy formation of
carbon(sp)–metal2 and carbon(sp2)–metal3 species through
β-carbon eliminations from tertiary alcohols, the formation
of carbon(sp3)–metal species in unstrained molecules usu-
ally proceeds through retro-allylation of homoallylic alco-
hols involving a six-membered transition state.4 Kondo’s
group reported the first ruthenium-catalyzed retro-allyla-
tion of tertiary homoallylic alcohols via selective cleavage
of a carbon–carbon bond.5 Based on this pioneering report,
Oshima and co-workers demonstrated that the in situ gen-
erated α-allylmetal species (from such retro-allylations)
were suitable for coupling reactions with aryl halides,6 Boc-
protected allyl alcohols,7 aldehydes8 and imines.8d More re-
cently, Waibel and Cramer also reported palladium-cata-
lyzed ring-opening reactions of norbornene-derived tertia-
ry alcohols to access highly substituted acylcyclohexenes,
quinolines and tetrahydroquinolines.9 However, reactions
of such allylmetal species derived from such retro-allyla-
tions of homoallylic alcohols with other nucleophiles have
rarely been reported.10 As part of our ongoing program on
the transition-metal-catalyzed activation of unstrained car-
bon–carbon bonds, herein we disclose a palladium(II)-cata-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 2931–2936

2932
G.-J. Sun et al.
Special Topic
Synthesis
Table 1 Optimization of the Reaction Conditionsa
Pd(OAc)2 (10 mol%)
L (10 mol%)
base (1.5 equiv)
OH
Ts
NHTs
N
+
Ph
H2O (150 mol%)
solvent (2 mL)
100 °C, 48 h
2a
1a
3a
Entry
Base
Cs2CO3
Ligand
Solvent
Yieldb (%) of 3a
1c
2c
3c
4c
5
–
ODCB
ODCB
ODCB
ODCB
ODCB
ODCB
ODCB
ODCB
ODCB
ODCB
ODCB
toluene
DMSO
PhCl
36
K3PO4
–
10
CsF
–
23
DBU
–
8
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Ph3P
Cy3P
dppf
L1
45
6
15
7
trace
66
8
9
L2d
14
10
11
12
13
14
15
16
17
L3e
58
dppb
dppb
dppb
dppb
dppb
dppbf
dppbf
90
15
19
44
dioxane
ODCB
ODCB
n.d.
93 (93)g
99 (98)g
h
a Reaction conditions: 1a (0.6 mmol), 2a (0.2 mmol), Pd(OAc)2 (10 mol%), anhydrous Cs2CO3 (1.5 equiv), ligand (10 mol%), H2O (0.3 mmol), solvent (2 mL), 48 h.
b 1H NMR yield using DCE as internal standard.
c Reaction conditions: 1a (0.6 mmol), 2a (0.2 mmol), Pd(OAc)2 (10 mol%), base (1.5 equiv), 1,2-dichlorobenzene (ODCB, 2 mL), 48 h.
d L2 (24 mol%) was employed.
e L3 (20 mol%) was employed.
f dppb (12 mol%) was employed.
g Isolated yield in parenthesis.
h Cs2CO3 (1.2 equiv) was employed.
isolated yield (Table 1, entry 16). The yield of 3a could be
improved further by reducing the amount of cesium car-
bonate to 1.2 equivalents (Table 1, entry 17). Then, we in-
vestigated various solvents including toluene, dimethyl
sulfoxide, chlorobenzene and dioxane in an attempt to opti-
mize the reaction conditions further; all of these tested sol-
vents were found to be less efficient than ODCB (Table 1,
entries 12–15). This interesting observation led us to test
the controlled anhydrous reaction in the presence of differ-
ent amounts of water. Thus, the controlled anhydrous reac-
t-Bu
t-Bu
P(t-Bu)2
O
i-Pr
i-Pr
t-Bu
P
N+
N
O
O
–
BF4
L1
i-Pr
t-Bu
t-Bu
t-Bu
L2
L3
Figure 1
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 2931–2936

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G.-J. Sun et al.
Special Topic
Synthesis
Table 2 Substrate Scope of Homoallylic Alcohols 1a
Pd(OAc)2 (10 mol%)
dppb (12 mol%)
Cs2CO3 (120 mol%)
OH
Ts
NHTs
N
+
R1
R2
H2O (300 mol%)
ODCB (2 mL)
100 °C, 24 h
1
2a
3a
Entry
R1
Ph
R2
1
Yieldb (%) of 3a
1
2
3
4
5
Me
Ph
H
1a
1b
1c
1d
1e
98
90
35
41
46
Ph
2,4-(MeO)2C6H3
2,4-(MeO)2C6H3
i-Pr
Me
i-Pr
a Reaction conditions: 1 (0.6 mmol), 2a (0.2 mmol), Pd(OAc)2 (0.02 mmol), Cs2CO3 (0.24 mmol), dppb (0.024 mmol), H2O (0.6 mmol), 1,2-dichlorobenzene
(ODCB, 2 mL).
b Isolated yield.
tion with 3.0 equivalents of water gave the optimum yield
of 3a (99%), while a further increase of water to 5.0 and 10.0
equivalents resulted in a decreased yield, to 87% and 55%,
respectively (see Supporting Information, Table S5). It may
be noted that there have been a number of reports on allylic
substitution reactions with water as reagent, additive or
solvent.11 Although the role of water is not clear, we sup-
pose that water might be involved in solvation which is im-
portant for hydration of the hydroxy group in the homoal-
lylic alcohol for generation of the π-allyl–palladium inter-
mediate.11a
With the optimized reaction conditions in hand
[Pd(OAc)2 (10 mol%), dppb (12 mol%), Cs2CO3 (120 mol%),
H2O (300 mol%), OCDB (2 mL), 100 °C], the generality of the
allylic amination of amine 2a with a variety of homoallylic
alcohols 1 was investigated (Table 2). The reaction of 2a
with 300 mol% of 1,1-diphenylbut-3-en-1-ol (1b) took
place smoothly to afford 3a in satisfactory yield (90%; Table
2, entry 2), while the reaction of 2a with secondary ho-
moallylic alcohol 1c (300 mol%) gave 35% yield (entry 3),
which might be due to β-hydrogen elimination. The reac-
tion of amine 2a with 1d and 1e resulted in 41% and 46%
yield, respectively, under the optimized reaction conditions
(Table 2, entries 4 and 5).
3, entries 6–11). It is worth noting that various functional-
ities, including carbethoxy (3g) and acetamido (3n) groups,
are tolerated under the optimal reaction conditions. Subse-
quently, we turned our attention towards aliphatic amines:
the aliphatic amines with an aromatic group gave the de-
sired products 3m and 3q in moderate to high yield (Table
3, entries 13 and 17), while N-tosyl-N-butylamine could
provide product 3p in only 13% yield (Table 3, entry 16). In-
terestingly, heteroaromatic amines were also tolerated un-
der our optimized reaction conditions; the reaction of N-to-
sylpyridin-2-amine occurred smoothly to afford the corre-
sponding product 3o in moderate yield (39%; Table 3, entry
15).
In conclusion, we have successfully developed a novel
approach towards allylic amination of homoallylic alcohols
with amines via transition-metal-catalyzed carbon–carbon
bond cleavage. Palladium(II) acetate catalyzed allylic ami-
nation of homoallylic alcohols with various amines pro-
ceeds through sequential retro-allylation and amination,
affording the corresponding allylic amines in good yields.
Further studies on the asymmetric synthesis of allylic
amines based on carbon–carbon bond activation are ongo-
ing in our laboratory and the results will be reported in due
course.
Then, we explored the scope of the amine substrates
(Table 3). N-Tosylanilines with alkyl substitution at the
meta and/or para positions of the phenyl ring were well-
tolerated under the optimized reaction conditions to afford
the desired products 3a–c in good to excellent yields (74–
98%; Table 3, entries 1–3). Gratifyingly, the reaction of a ste-
rically hindered ortho-disubstituted aniline also proceeded
smoothly, affording product 3e in 65% yield (Table 3, entry
5). Likewise, aromatic amines with either an electron-rich
or electron-deficient group on the aromatic ring also deliv-
ered the corresponding products 3f–k in good yields (Table
1,2-Dichlorobenzene (ODCB) was distilled from CaH2. Commercially
obtained reagents were used without further purification, unless oth-
erwise noted. Reactions were checked for completion by TLC analysis
and plates were visualized with short-wave UV light (254 nm). The 1H
and 13C NMR spectra were obtained in CDCl3 or DMSO-d6 using a
Bruker Avance III spectrometer at 400 and 100 MHz for 1H and 13C
NMR, respectively. Chemical shifts are reported in parts per million (δ
value) calibrated against the residual solvent peak. Signal patterns are
indicated as follows: s, singlet; d, doublet; t, triplet; q, quartet; m,
multiplet. Coupling constants (J) are given in hertz (Hz). The infrared
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 2931–2936

2934
G.-J. Sun et al.
Special Topic
Synthesis
Table 3 Substrate Scope of the Aminesa
Pd(OAc)2 (10 mol%)
N-Allyl-4-methyl-N-(4-methylphenyl)benzenesulfonamide (3a)12
Yield: 59 mg (98%); pale yellow oil.
1H NMR (400 MHz, CDCl3): δ = 7.52 (d, J = 8.4 Hz, 2 H), 7.27 (d, J = 8.2
Hz, 2 H), 7.10 (d, J = 8.2 Hz, 2 H), 6.94 (d, J = 8.2 Hz, 2 H), 5.81–5.71 (m,
1 H), 5.11–5.05 (m, 2 H), 4.17 (d, J = 6.3 Hz, 2 H), 2.45 (s, 3 H), 2.35 (s,
3 H).
13C NMR (100 MHz, CDCl3): δ = 114.3, 136.7, 135.4, 134.7, 132.0,
128.5, 128.3, 127.7, 126.7, 117.6, 52.6, 20.5, 20.1.
dppb (12 mol%)
Cs2CO3 (120 mol%)
OH
Ts
N
R3 NHTs
+
R1
R3
R2
H2O (300 mol%)
ODCB (2 mL)
100 °C
2
3
1a: R1 = Ph, R2 = Me
1b: R1 = Ph, R2 = Ph
Entry
Alcohol 1
Amine 2 (R3)
Product 3
Yieldb (%) of 3
N-Allyl-N-(4-isopropylphenyl)-4-methylbenzenesulfonamide (3b)
Yield: 49 mg (74%); colorless solid; mp 86–87 °C.
1
2
1a
1a
1a
1b
1a
1a
1a
1a
1b
1b
1b
1a
1b
1a
1a
1a
4-MeC6H4
4-i-PrC6H4
3-MeC6H4
Ph
3a
3b
3c
3d
98
74
83
66
65
69
84
90
71
81
50
70
71
41
39
13c
IR (KBr): 3042, 2961, 2923, 2899, 2866, 1597, 1508, 1442, 1352, 1338,
1289, 1166, 1092, 924, 874, 817, 662 cm–1
.
3
1H NMR (400 MHz, CDCl3): δ = 7.50 (d, J = 8.4 Hz, 2 H), 7.25 (d, J = 8.0
Hz, 2 H), 7.13 (d, J = 8.4 Hz, 2 H), 6.95 (d, J = 8.4 Hz, 2 H), 5.79–5.69 (m,
1 H), 5.11–5.03 (m, 2 H), 4.14 (d, J = 6.0 Hz, 2 H), 2.88 (m, 1 H), 2.43 (s,
3 H), 1.23 (d, J = 6.8 Hz, 6 H).
13C NMR (100 MHz, CDCl3): δ = 146.2, 143.7, 136.3, 134.1, 129.6,
127.3, 127.2, 122.1, 33.5, 31.0, 23.9, 21.6.
4
5
2,4,6-Me3C6H2
4-MeOC6H4
4-EtO2CC6H4
4-FC6H4
3e
3f
6
7
3g
3h
3i
8
HRMS (ESI): m/z [M + H]+ calcd for C19H24O2NS: 330.1522; found:
330.1517.
9
4-ClC6H4
3-ClC6H4
4-F3CC6H4
2-Naph
10
11
12
13
14
15
16
3j
N-Allyl-4-methyl-N-(3-methylphenyl)benzenesulfonamide (3c)
3k
3l
Yield: 50 mg (83%); colorless solid; mp 51–53 °C.
IR (KBr): 3087, 3067, 3037, 2919, 2864, 1607, 1584, 1486, 1453, 1343,
1308, 1287, 1272, 1165, 1092, 1076, 1024, 990, 931, 907, 827, 813,
Bn
3m
3n
3o
3p
693, 662 cm–1
.
4-AcNHC6H4
2-pyridyl
n-Bu
1H NMR (400 MHz, CDCl3): δ = 7.48 (d, J = 8.4 Hz, 2 H), 7.23 (d, J = 8.4
Hz, 2 H), 7.13 (t, J = 7.6 Hz, 1 H), 7.05 (d, J = 7.6 Hz, 1 H), 6.90 (s, 1 H),
6.74 (d, J = 7.6 Hz, 1 H), 5.76–5.67 (m, 1 H), 5.07–5.00 (m, 2 H), 4.13
(d, J = 6.4 Hz, 2 H), 2.40 (s, 3 H), 2.27 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 143.4, 139.1, 138.8, 135.6, 133.0,
17
1a
3q
24
129.9, 129.4, 128.6, 128.5, 127.8, 125.4, 118.6, 53.6, 21.5, 21.3.
HRMS (ESI): m/z [M + H]+ calcd for C17H20O2NS: 302.1209; found:
302.1205.
N
H
a Reaction conditions: 1 (0.6 mmol), 2 (0.2 mmol), Pd(OAc)2 (10 mol%),
Cs2CO3 (120 mol%), dppb (12 mol%), H2O (0.6 mmol), 1,2-dichlorobenzene
(ODCB; 2 mL).
N-Allyl-4-methyl-N-phenylbenzenesulfonamide (3d)
Yield: 38 mg (66%); yellowish solid; mp 62–64 °C.
b Isolated yield.
c NMR yield using DCE as internal standard.
IR (KBr): 3058, 3038, 2981, 2959, 2925, 1645, 1596, 1493, 1451, 1427,
1403, 1346, 1307, 1162, 1108, 1092, 1038, 918, 860, 812, 770, 728,
696 cm–1
.
spectra were recorded on a VERTEX 70 IR spectrometer as KBr pellets,
with absorption reported in cm–1. HRMS data were obtained on a
Thermo Fisher Scientific LTQ FT Ultra system.
1H NMR (400 MHz, CDCl3): δ = 7.48 (d, J = 8.0 Hz, 2 H), 7.31–7.23 (m, 5
H), 7.06–7.02 (m, 2 H), 5.78–5.68 (m, 1 H), 5.09–5.02 (m, 2 H), 4.17 (d,
J = 6.4 Hz, 2 H), 2.43 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 142.3, 138.0, 134.3, 131.7, 128.3,
127.7, 126.7, 126.6, 117.7, 52.4, 20.4.
Allylic Amines 3a–q; General Procedure
HRMS (ESI): m/z [M + H]+ calcd for C16H18O2NS: 288.1053; found:
288.1056.
To an oven-dried 25-mL Schlenk tube equipped with a stir bar was
added Cs2CO3 (78 mg, 0.24 mmol) in a glovebox. Pd(OAc)2 (4.5 mg,
0.02 mmol) was added along with dppb (11 mg, 0.024 mmol) and an
amine 2 (0.2 mmol) under a nitrogen atmosphere. To this mixture
was added purified water (10.8 μL, 0.6 mmol), followed by a homoal-
lylic alcohol 1 (0.6 mmol) dissolved in 1,2-dichlorobenzene (ODCB, 2
mL). The mixture was stirred at 100 °C until the reaction was com-
pleted. The resulting mixture was then cooled to r.t. and directly puri-
fied by silica gel column chromatography (EtOAc–PE) to afford the al-
lylic amine product 3.
N-Allyl-N-mesityl-4-methylbenzenesulfonamide (3e)
Yield: 43 mg (65%); colorless solid; mp 101–102 °C.
IR (KBr): 2977, 2921, 1596, 1480, 1338, 1304, 1220, 1155, 1138, 1087,
1074, 1006, 940, 856, 817, 712, 698, 663, 611 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.68 (d, J = 8.0 Hz, 2 H), 7.28 (d, J = 8.0
Hz, 2 H), 6.83 (s, 2 H), 5.92–5.82 (m, 1 H), 5.03–4.99 (m, 2 H), 4.09 (d,
J = 7.2 Hz, 2 H), 2.43 (s, 3 H), 2.25 (s, 3 H), 2.01 (s, 6 H).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 2931–2936

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G.-J. Sun et al.
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Synthesis
13C NMR (100 MHz, CDCl3): δ = 143.2, 138.8, 138.4, 137.9, 134.2,
133.3, 129.7, 129.6, 127.4, 118.2, 53.9, 21.6, 21.0, 19.1.
N-Allyl-4-methyl-N-[4-(trifluoromethyl)phenyl]benzenesulfon-
amide (3k)12
HRMS (ESI): m/z [M + H]+ calcd for C19H24O2NS: 330.1522; found:
Yield: 36 mg (50%); yellowish solid.
1H NMR (400 MHz, CDCl3): δ = 7.56 (d, J = 8.4 Hz, 2 H), 7.48 (d, J = 8.0
Hz, 2 H), 7.27 (d, J = 8.0 Hz, 2 H), 7.19 (d, J = 8.4 Hz, 2 H), 5.76–5.66 (m,
1 H), 5.11–5.06 (m, 2 H), 4.20 (d, J = 6.4 Hz, 2 H), 2.43 (s, 3 H).
330.1517.
N-Allyl-N-(4-methoxyphenyl)-4-methylbenzenesulfonamide (3f)12
13C NMR (100 MHz, CDCl3): δ = 142.9, 141.3, 134.9, 131.2, 128.6,
Yield: 44 mg (69%); colorless solid.
1H NMR (400 MHz, CDCl3): δ = 7.48 (d, J = 8.4 Hz, 2 H), 7.23 (d, J = 8.4
Hz, 2 H), 6.91 (d, J = 8.8 Hz, 2 H), 6.77 (d, J = 8.8 Hz, 2 H), 5.77–5.67 (m,
1 H), 5.06–5.01 (m, 2 H), 4.12 (d, J = 6.4 Hz, 2 H), 3.76 (s, 3 H), 2.41 (s,
3 H).
13C NMR (100 MHz, CDCl3): δ = 159.0, 143.4, 135.5, 133.0, 131.6,
130.2, 129.4, 127.8, 118.7, 114.1, 55.4, 53.8, 21.6.
127.6, 126.5, 124.9, 118.3, 52.1, 20.5.
N-Allyl-4-methyl-N-2-naphthylbenzenesulfonamide (3l)
Yield: 47 mg (70%); yellowish solid; mp 86–87 °C.
IR (KBr): 3060, 2986, 2920, 2361, 2341, 1596, 1505, 1431, 1342, 1163,
1130, 1110, 1089, 923, 822, 762, 708, 668 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.82–7.80 (m, 1 H), 7.76–7.72 (m, 2 H),
7.53–7.45 (m, 5 H), 7.23 (d, J = 8.0 Hz, 2 H), 7.16–7.13 (m, 1 H), 5.82–
5.72 (m, 1 H), 5.11–5.00 (m, 2 H), 4.27 (d, J = 6.2 Hz, 2 H), 2.42 (s, 3 H).
Ethyl 4-(N-Allyl-4-methylphenylsulfonamido)benzoate (3g)
Yield: 60 mg (84%); yellowish solid; mp 74–75 °C.
13C NMR (100 MHz, CDCl3): δ = 143.5, 136.5, 135.5, 133.3, 132.8,
132.5, 129.5, 128.7, 128.0, 127.8, 127.7, 127.6, 126.6, 126.5, 126.4,
118.9, 53.6, 21.6.
HRMS (ESI): m/z [M + H]+ calcd for C20H20O2NS: 338.1209; found:
338.1207.
IR (KBr): 3051, 2090, 1708, 1648, 1604, 1506, 1494, 1468, 1399, 1368,
1352, 1275, 1166, 1110, 1060, 935, 876, 814, 707 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.97 (d, J = 8.4 Hz, 2 H), 7.36 (d, J = 8.4
Hz, 2 H), 7.25 (d, J = 8.4 Hz, 2 H), 7.14 (d, J = 8.8 Hz, 2 H), 5.76–5.66 (m,
1 H), 5.10–5.04 (m, 2 H), 4.40–4.31 (m, 2 H), 4.21 (d, J = 6.0 Hz, 2 H),
2.42 (s, 3 H), 1.38 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 165.9, 143.8, 143.3, 135.0, 132.4,
N-Allyl-N-benzyl-4-methylbenzenesulfonamide (3m)13
130.2, 129.6, 129.4, 128.0, 127.6, 119.2, 61.2, 53.0, 21.6, 14.3.
HRMS (ESI): m/z [M + H]+ calcd for C19H22O4NS: 360.1264; found:
360.1259.
Yield: 43 mg (71%); colorless solid.
1H NMR (400 MHz, CDCl3): δ = 7.69 (d, J = 8.4 Hz, 2 H), 7.28–7.19 (m, 7
H), 5.47–5.37 (m, 1 H), 5.02–4.92 (m, 2 H), 4.34 (s, 2 H), 3.70 (d, J = 6.4
Hz, 2 H), 2.39 (s, 3 H).
N-Allyl-N-(4-fluorophenyl)-4-methylbenzenesulfonamide (3h)12
13C NMR (100 MHz, CDCl3): δ = 142.3, 136.5, 135.0, 131.2, 128.7,
Yield: 55 mg (90%); white solid.
127.5, 126.7, 126.2, 118.3, 49.1, 48.4, 20.5.
1H NMR (400 MHz, CDCl3): δ = 7.48 (d, J = 8.4 Hz, 2 H), 7.26 (d, J = 8.0
Hz, 2 H), 7.01–6.94 (m, 4 H), 5.77–5.67 (m, 1 H), 5.07–5.03 (m, 2 H),
4.14 (d, J = 6.0 Hz, 2 H), 2.43 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 162.0, 159.6, 142.6, 134.2, 133.9,
131.6, 129.7, 126.7, 118.1, 114.9, 114.7, 52.7, 20.5.
N-{4-[Allyl(tosyl)amino]phenyl}acetamide (3n)
Yield: 28 mg (41%); yellowish solid; mp 54–55 °C.
IR (KBr): 3311, 3061, 2922, 1671, 1600, 1536, 1510, 1469, 1408, 1344,
1311, 1161, 1090, 869, 813, 716, 662 cm–1
.
1H NMR (400 MHz, DMSO-d6): δ = 10.02 (s, 1 H), 7.50–7.38 (m, 6 H),
6.94 (d, J = 8.8 Hz, 2 H), 5.71–5.61 (m, 1 H), 5.14–5.02 (m, 2 H), 4.14 (t,
J = 5.6 Hz, 2 H), 2.40 (s, 3 H), 2.03 (s, 3 H).
N-Allyl-N-(4-chlorophenyl)-4-methylbenzenesulfonamide (3i)12
Yield: 46 mg (71%); white powder.
1H NMR (400 MHz, CDCl3): δ = 7.47 (d, J = 8.4 Hz, 2 H), 7.27–7.24 (m, 4
H), 7.00 (d, J = 8.8 Hz, 2 H), 5.75–5.67 (m, 1 H), 5.08–5.04 (m, 2 H),
4.13 (d, J = 6.0 Hz, 2 H), 2.43 (s, 3 H).
13C NMR (100 MHz, DMSO-d6): δ = 168.9, 143.9, 139.0, 135.3, 133.6,
133.5, 130.2, 129.3, 119.4, 119.2, 53.1, 24.4, 21.5.
HRMS (ESI): m/z [M + H]+ calcd for C18H21O3N2S: 345.1267; found:
345.1262.
13C NMR (100 MHz, CDCl3): δ = 143.7, 137.6, 135.1, 133.6, 132.5,
130.1, 129.6, 129.1, 127.7, 119.2, 53.4, 21.6.
N-Allyl-4-methyl-N-(2-pyridyl)benzenesulfonamide (3o)
Yield: 22 mg (39%); yellowish solid; mp 75–77 °C.
N-Allyl-N-(3-chlorophenyl)-4-methylbenzenesulfonamide (3j)
Yield: 52 mg (81%); white powder; mp 76–77 °C.
IR (KBr): 3092, 3056, 2920, 2853, 1633, 1599, 1555, 1503, 1456, 1370,
1353, 1283, 1266, 1167, 1137, 1084, 972, 914, 827, 766, 660 cm–1
.
IR (KBr): 3075, 2979, 2921, 1586, 1492, 1472, 1420, 1163, 1092, 1071,
1013, 930, 889, 804, 702, 682, 668 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.83 (d, J = 8.0 Hz, 2 H), 7.71–7.68 (m, 1
H), 7.50–7.47 (m, 2 H), 7.23 (d, J = 8.0 Hz, 2 H), 6.54–6.51 (m, 1 H),
6.01–5.92 (m, 1 H), 5.31–5.28 (m, 2 H), 4.77 (d, J = 6.0 Hz, 2 H), 2.38 (s,
3 H).
1H NMR (400 MHz, CDCl3): δ = 7.49 (d, J = 8.4 Hz, 2 H), 7.28–7.20 (m, 4
H), 7.05–7.04 (m, 1 H), 7.00–6.94 (m, 1 H), 5.76–5.66 (m, 1 H), 5.10–
5.06 (m, 2 H), 4.14 (d, J = 6.3 Hz, 2 H), 2.43 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 143.9, 140.4, 135.1, 134.3, 132.5,
13C NMR (100 MHz, CDCl3): δ = 155.5, 141.7, 140.8, 140.1, 138.2,
129.8, 129.6, 129.0, 128.1, 127.8, 127.0, 119.3, 53.5, 21.6.
131.1, 129.1, 126.4, 120.0, 118.3, 110.8, 54.9, 21.5.
HRMS (ESI): m/z [M + H]+ calcd for C16H17O2NClS: 322.0663; found:
HRMS (ESI): m/z [M + H]+ calcd for C15H17O2N2S: 289.1005; found:
322.0658.
289.1000.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 2931–2936

2936
G.-J. Sun et al.
Special Topic
Synthesis
N-Allyl-N-[2-(1H-indol-3-yl)ethyl]-4-methylbenzenesulfonamide
(3) (a) Terao, Y.; Wakui, H.; Satoh, T.; Miura, M.; Nomura, M. J. Am.
Chem. Soc. 2001, 123, 10407. (b) Terao, Y.; Wakui, H.; Nomoto,
M.; Satoh, T.; Miura, M.; Nomura, M. J. Org. Chem. 2003, 68,
5236.
(4) (a) Yorimitsu, H.; Oshima, K. Bull. Chem. Soc. Jpn. 2009, 82, 778.
(b) Ruhland, K. Eur. J. Org. Chem. 2012, 2683.
(5) Kondo, T.; Kodoi, K.; Nishinaga, E.; Okada, T.; Morisaki, Y.;
Watanabe, Y.; Mitsudo, T. J. Am. Chem. Soc. 1998, 120, 5587.
(6) (a) Hayashi, S.; Hirano, K.; Yorimitsu, H.; Oshima, K. J. Am. Chem.
Soc. 2006, 128, 2210. (b) Iwasaki, M.; Hayashi, S.; Hirano, K.;
Yorimitsu, H.; Oshima, K. J. Am. Chem. Soc. 2007, 129, 4463.
(c) Iwasaki, K.; Hayashi, S.; Hirano, K.; Yorimitsu, H.; Oshima, K.
Tetrahedron 2007, 63, 5200. (d) Iwasaki, M.; Yorimitsu, H.;
Oshima, K. Bull. Chem. Soc. Jpn. 2009, 82, 249. (e) Hayashi, S.;
Hirano, K.; Yorimitsu, H.; Oshima, K. J. Am. Chem. Soc. 2007, 129,
12650. (f) Wakabayashi, R.; Fujino, D.; Hayashi, S.; Yorimitsu, H.;
Oshima, K. J. Org. Chem. 2010, 75, 4337.
(3q)14
Yield: 17 mg (24%); white solid.
1H NMR (400 MHz, CDCl3): δ = 8.00 (s, 1 H), 7.70 (d, J = 8.0 Hz, 2 H),
7.54 (d, J = 8.0 Hz, 1 H), 7.35 (d, J = 8.0 Hz, 1 H), 7.26 (d, J = 5.6 Hz, 2 H),
7.18 (t, J = 8.0 Hz, 1 H), 7.10 (t, J = 8.0 Hz, 1 H), 7.00 (d, J = 2.0 Hz, 1 H),
5.72–5.62 (m, 1 H), 5.20–5.14 (m, 2 H), 3.85 (d, J = 6.4 Hz, 2 H), 3.43–
3.39 (m, 2 H), 3.04–3.00 (m, 2 H), 2.40 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 143.2, 137.2, 136.2, 133.4, 129.7,
127.3, 127.2, 122.1, 119.4, 118.9, 118.7, 112.7, 111.2, 51.1, 47.9, 25.1,
21.5.
Acknowledgment
We thank the National Natural Science Foundation of China
(21302183) and the Strategic Priority Research Program of the Chi-
nese Academy of Sciences (Grant No. XDA09030102) for financial
support.
(7) Sumida, Y.; Hayashi, S.; Hirano, K.; Yorimitsu, H.; Oshima, K.
Org. Lett. 2008, 10, 1629.
(8) (a) Takada, Y.; Hayashi, S.; Hirano, K.; Yorimitsu, H.; Oshima, K.
Org. Lett. 2006, 8, 2515. (b) Sumida, Y.; Takada, Y.; Hayashi, S.;
Hirano, K.; Yorimitsu, H.; Oshima, K. Chem. Asian J. 2008, 3, 119.
(c) Jang, M.; Hayashi, S.; Hirano, K.; Yorimitsu, H.; Oshima, K.
Tetrahedron Lett. 2007, 48, 4003. (d) Sai, M.; Yorimitsu, H.;
Oshima, K. Angew. Chem. Int. Ed. 2011, 50, 3294.
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0034-1380418.
S
u
p
p
ortiInfogrmoaitn
S
u
p
p
ortioInfgrmoaitn
(9) Waibel, M.; Cramer, N. Angew. Chem. Int. Ed. 2010, 49, 4455.
(10) Wang, Y.; Kang, Q. Org. Lett. 2014, 16, 4190.
(11) (a) Kinoshita, H.; Shinokubo, H.; Oshima, K. Org. Lett. 2004, 6,
4085. (b) Uozumi, Y.; Tanaka, H.; Shibatomi, K. Org. Lett. 2004, 6,
281. (c) Uozumi, Y.; Suzuka, T. J. Org. Chem. 2006, 71, 8644.
(d) Nishikata, T.; Lipshutz, B. H. Org. Lett. 2009, 11, 2377.
(e) Moser, R.; Nishikata, T.; Lipshutz, B. H. Org. Lett. 2010, 12,
28. (f) Xiong, T.; Li, Y.; Mao, L. J.; Zhang, Q. Chem. Commun. 2012,
48, 2246. (g) Nishikata, T.; Lipshutz, B. H. J. Am. Chem. Soc. 2009,
131, 12103. (h) Baig, R. B. N.; Varma, R. S. Ind. Eng. Chem. Res.
2014, 53, 18625. (i) Ueda, M.; Hartwig, J. F. Org. Lett. 2010, 12,
92. (j) You, S.-L.; Hou, X.-L.; Dai, L.-X.; Yu, Y.-H.; Xia, W. J. Org.
Chem. 2002, 67, 4684. (k) Gärtner, M.; Mader, S.; Seehafer, K.;
Helmchen, G. J. Am. Chem. Soc. 2011, 133, 2072.
(12) Metayer, B.; Mingot, A.; Vullo, D.; Supuran, C. T.; Thibaudeau, S.
Chem. Commun. 2013, 49, 6015.
(13) Dong, X.; Sang, R.; Wang, Q.; Tang, X. Y.; Shi, M. Chem. Eur. J.
2013, 19, 16910.
(14) Zhang, D. H.; Tang, X. Y.; Wei, Y.; Shi, M. Chem. Eur. J. 2013, 19,
13668.
References
(1) For recent reviews, see: (a) Jones, W. D. Nature 1993, 364, 676.
(b) Rybtchinski, B.; Milstein, D. Angew. Chem. Int. Ed. 1999, 38,
870. (c) van der Boom, M. E.; Milstein, D. Chem. Rev. 2003, 103,
1759. (d) Jun, C. H. Chem. Soc. Rev. 2004, 33, 610. (e) Necas, D.;
Kotora, M. Curr. Org. Chem. 2007, 11, 1566. (f) Seiser, T.; Cramer,
N. Org. Biomol. Chem. 2009, 7, 2835. (g) Bonesi, S. M.; Fagnoni,
M. Chem. Eur. J. 2010, 16, 13572. (h) Murakami, M.; Matsuda, T.
Chem. Commun. 2011, 47, 1100. (i) Aïssa, C. Synthesis 2011,
3389. (j) Dong, G. Synlett 2013, 24, 1. (k) Dermenci, A.; Coe, J.
W.; Dong, G. Org. Chem. Front. 2014, 1, 567. (l) Liu, H.; Feng, M.
H.; Jiang, X. F. Chem. Asian J. 2014, 9, 3360. (m) Chen, F.; Wang,
T.; Jiao, N. Chem. Rev. 2014, 114, 8613. (n) Marek, I.; Masarwa,
A.; Delaye, P.-O.; Leibeling, M. Angew. Chem. Int. Ed. 2015, 54,
414.
(2) (a) Chow, H.-F.; Wan, C.-W.; Low, K.-H.; Yeung, Y.-Y. J. Org.
Chem. 2001, 66, 1910. (b) Nishimura, T.; Araki, H.; Maeda, Y.;
Uemura, S. Org. Lett. 2003, 5, 2997.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 2931–2936