Iridium-Catalyzed Intramolecular Oxidative Cyclization of Alkenyl Amides and Alkenoic Acids

Article abstract of DOI:10.1055/s-0036-1588435

An iridium/dppf complex efficiently catalyzed the oxidative cyclization of N sulfonyl alkenyl amides and alkenoic acids. Electron deficiena?t alkenes were effective as sacrificial hydrogen acceptors. High selectivity of the oxidative cyclization over the

Full text of DOI:10.1055/s-0036-1588435

SYNTHESIS
0
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1
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1
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X
© Georg Thieme Verlag Stuttgart · New York
2017, 49, A–K
special topic
A
en
M. Nagamoto et al.
Special Topic
Synthesis
Iridium-Catalyzed Intramolecular Oxidative Cyclization of Alkenyl
Amides and Alkenoic Acids
Midori Nagamoto
Takahiro Nishimura*1
Hideki Yorimitsu
[IrCl(coe)2]2/dppf
NaI
methyl vinyl ketone
O
XH
O
O
X
X
0
0
0
0
0-
0
0
2
7-
0
3
2
8-
6
1
3
Y
Y
+
Y
toluene, 100 °C
X = O, NSO2R
Y = CR2, NR
up to 95% yield
up to >99:1
Department of Chemistry, Graduate School of Science,
Kyoto University, Sakyo, Kyoto 606-8502, Japan
tnishi@sci.osaka-cu.ac.jp
Published as part of the Special Topic Modern Cyclization
Strategies in Synthesis
Received: 31.03.2017
Accepted after revision: 02.05.2017
Published online: 13.06.2017
Recently we studied iridium-catalyzed hydrofunction-
alization reactions of alkenes such as asymmetric cycliza-
tion of alkenoic acids and N-sulfonyl alkenyl amides leading
to chiral γ-lactones and γ-lactams.9 Although iridium com-
plexes have emerged as effective catalysts for hydrofunc-
tionalization of alkenes,10 there have been only few reports
on oxidative functionalization with heteroatom nucleop-
hiles. Hartwig and co-workers reported iridium-catalyzed
amination and etherification of aliphatic alkenes, where ox-
idative functionalization was competitive with hydrofunc-
tionalization.10e,f Herein, we report the iridium-catalyzed
intramolecular oxidative functionalization of alkenes with
N-sulfonyl amides and carboxylic acids.
DOI: 10.1055/s-0036-1588435; Art ID: ss-2017-c0211-st
Abstract An iridium/dppf complex efficiently catalyzed the oxidative
cyclization of N-sulfonyl alkenyl amides and alkenoic acids. Electron-
deficient alkenes were effective as sacrificial hydrogen acceptors. High
selectivity of the oxidative cyclization over the competing addition re-
action has been realized by the use of NaI as an additive.
Key words iridium, oxidative functionalization, alkenes, amides, car-
boxylic acids
Direct functionalization of readily available alkenes has
attracted considerable attention from the aspect of atom
and step economy. Additions of heteroatom nucleophiles to
alkenes2 are an important class of transformations as they
afford highly valuable building blocks such as enamines and
vinyl ethers as a result of oxidative functionalization,3–7 or
alkylamines and ethers as a consequence of the formal ad-
dition of heteroatom–hydrogen bond.8 Late transition-met-
al catalysts have contributed much to the development of
efficient protocols for oxidative functionalization.3–6 In par-
ticular, there have been numerous reports on palladium ca-
talysis: Wacker-type oxidation,2a,b,e,3 which involves β-hy-
dride elimination as a key step, has been successfully ex-
tended to oxidative functionalization of alkenes with
various nucleophiles to form carbon–heteroatom bonds.
Rhodium complexes have also been studied as versatile cat-
alysts for functionalization of alkenes.4 Jiménez, Pérez-Tor-
rente, and co-workers reported that cationic rhodium com-
plexes containing flexible hemilabile phosphine ligands ex-
hibit high catalytic activity toward anti-Markovnikov
oxidative amination.4d–f Copper-catalyzed oxidative amina-
tion reactions via radical mechanism have also been report-
ed.5
Treatment of N-tosyl-2,2-diphenyl-4-pentenamide (1a)
in the presence of [IrCl(coe)2]2 (5 mol% of Ir, coe = cyclooc-
tene) and a bisphosphine ligand (5 mol%) in toluene at 100
°C for 3 hours gave the corresponding cyclization products
as a mixture of oxidative amination product 2a and hy-
droamination product 3a, along with 4a formed by hydro-
genation of 1a (Table 1). The reaction in the presence of an
iridium/dppe complex gave hydroamination product 3a
predominantly in low yield (Table 1, entry 1). Dppb and
dppf complexes exhibited higher catalytic activity toward
cyclization and increased the ratio of oxidative amination
product 2a to 28% and 45%, respectively (entries 2 and 3).
By using xantphos, the selectivity of 2a was improved but
the yield of cyclization products was only 12% (entry 4).
Norbornene (A1) and 3,3-dimethylbut-1-ene (A2) were in-
effective to decrease the undesirable formation of 4a, al-
though they have been used as sacrificial hydrogen accep-
tors for several iridium-catalyzed dehydrogenative func-
tionalization reactions (entries 5 and 6).11 In contrast,
electron-deficient alkenes such as ethyl acrylate (A3) and
methyl vinyl ketone (MVK, A4) successfully suppressed the
formation of 4a (entries 7 and 8). Surprisingly, the reaction
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–K

B
M. Nagamoto et al.
Special Topic
Synthesis
in the presence of NaI (50 mol%) dramatically improved the
selectivity of 2a by up to 97% (entry 9). KI and n-Bu4NI had
little effect on the selectivity (entries 10 and 11).
Table 2 Oxidative Cyclization of Alkenyl Amidesa
[IrCl(coe)2]2 (5 mol% Ir)
dppf (5 mol%)
Ts
Ts
NaI (50 mol%)
MVK (3 equiv)
O
NHTs
O
O
N
N
Table 1 Screening Conditionsa
R1
R2
+
R1
R2
R1
toluene, 100 °C, 3 h
R2
1
2
3
[IrCl(coe)2]2
(5 mol% Ir)
ligand (5 mol%)
Ts
N
Ts
N
O
NHTs
O
O
Ts
O
Ts
O
N
N
+
Ph
Ph
Ph
Ph
Ph
Ph
R1
R2
toluene
100 °C, 3 h
1a
2a
3a
2'
2h'
R1, R2
Yield (%) 2 + 3 2/3
PPh2
PPh2
Entry
Ph2P
PPh2
Fe
n
R1 = R2 = 4-MeOC6H4 (1b)
R1 = R2 = 4-ClC6H4 (1c)
R1 = R2 = n-hexyl (1d)
R1 = R2 = benzyl (1e)
R1 = R2 = –(CH2)5– (1f)
R1 = R2 = Me (1g)
89
92
81
89
72
81
27
83
95
91/9
O
1
dppe (n = 2)
dppb (n = 4)
PPh2
PPh2
2b
3b
4
95/5
>99/1
97/3
dppf
xantphos
O
NHTs
Ph
Ph
CO2Et
A3
O
A4
5c
6c
7f
8
99/1d
97/3e
92/8g
98/2
4a
A1
A2
R1 = R2 = H (1h)
Entry Ligand
Hydrogen
acceptor
Additive Yield (%) 2a/3a
2a + 3a
Yield
(%) 4a
R1 = Ph, R2 = cinnamyl (1i)
R1 = R2 = Ph (1j)
9h
97/3
1
2
dppe
dppb
dppf
–
–
15
66
62
12
70
68
88
66
3/97
0
17
24
5
a Reaction conditions: 1 (0.20 mmol), [IrCl(coe)2]2 (5 mol% Ir), dppf (5
mol%), MVK (3 equiv), and NaI (50 mol%) in toluene (0.80 mL) at 100 °C for
–
–
28/72
45/55
73/27
53/47
51/49
70/30
82/18
3
–
–
3 h.
b At 80 °C for 6 h.
4
xantphos
dppf
–
–
c Ethyl vinyl ketone instead of MVK in p-xylene at 120 °C for 12 h.
d 2f/2f′ = 23:77.
5
A1
A2
A3
A4
A4
A4
A4
–
18
21
0
e 2g/2g′ = 24:76.
6
dppf
–
f Ethyl vinyl ketone instead of MVK in p-xylene at 135 °C for 12 h.
g 2h/2h′ = 0:100.
7
dppf
–
h N-Mesylamide instead of N-tosylamide.
8
dppf
–
0
9
dppf
NaI
99 (92)b 97/3
0
clization products in 95% yield with 97% selectivity of 2j
(entry 9).
10
11
dppf
KI
54
83
86/14
88/12
0
dppf
n-Bu4NI
0
Allylamines can be transformed into imidazolidinone
derivatives by a one-pot operation. Treatment of allyl-
amines with tosyl isocyanate gave the corresponding N-al-
lyl-N′-tosylureas, which were subjected to the present cata-
lytic conditions without purification to give the cyclization
products. It was found that allylic substituents had a signif-
icant effect on the selectivity of the reaction (Table 3). The
reaction of an alkenyl urea generated from allylamine (5a)
gave the cyclization product in moderate yield with 96% se-
lectivity of 7a (Table 3, entry 1). However, the reaction of
allylamine 5b bearing a methyl group at the allylic position
gave the cyclization product as a mixture of 7b and 8b in a
ratio of 12:88 (entry 2). A sterically bulky cyclohexyl group
in 5c completely suppressed the formation of 7c and the
hydroamination product 8c was obtained in high yield (en-
try 3). These results indicate that β-hydride elimination
leading to the oxidative cyclization product is inhibited by
the steric repulsion between the allylic substituents and
the iridium center.
a Reaction conditions: 1a (0.10 mmol), [IrCl(coe)2]2 (5 mol% Ir), ligand (5
mol%), hydrogen acceptor (3 equiv), and additive (50 mol%) in toluene
(0.40 mL) at 100 °C for 3 h.
b Isolated yield in parentheses.
The results obtained for the iridium-catalyzed oxidative
cyclization of N-sulfonyl alkenyl amides are summarized in
Table 2. Amides 1b–e bearing aryl, n-hexyl, and benzyl
groups participated in the reaction to give 2b–e in high
yields with high selectivity (Table 2, entries 1–4). The reac-
tions of 1f and 1g bearing sterically less bulky cyclic pen-
tamethylene and dimethyl groups proceeded at 120 °C to
give the corresponding cyclization products in good yields
(entries 5 and 6). Unsubstituted pentenamide 1h partici-
pated in the reaction at 135 °C to give 2h′ in 27% yield (en-
try 7). In the reaction of amide 1i, which bears both a ter-
minal- and an internal alkene moiety, cyclization occurred
only at the terminal alkene (entry 8). Not only N-tosyl-
amides but also N-mesylamide 1j reacted to give the cy-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–K

C
M. Nagamoto et al.
Special Topic
Synthesis
Table 3 Cyclization of Alkenyl Ureas in Situ Generated from Allyl-
Table 4 Oxidative Cyclization of Alkenoic Acidsa
aminesa
[IrCl(coe)2]2 (5 mol% Ir)
dppf (5 mol%)
O
NHTs
R
O
OH
R3
O
O
O
O
NaI (50 mol%)
MVK (3 equiv)
BnHN
TsNCO (1.05 equiv)
CH2Cl2, r.t., 2 h
R1
R2
BnN
+
R1
R2
R1
R
R2
toluene, 100 °C, 3 h
R3
R3
5
6
9
10
11
[IrCl(coe)2]2 (5 mol% Ir)
dppf (5 mol%)
Entry R1–R3
Yield (%)
10 + 11
10/11
Ts
O
Ts
N
Ts
N
O
O
+
N
NaI (50 mol%)
MVK (3 equiv)
+
BnN
BnN
BnN
1
R1 = R2 = Ph, R3 = H (9a)
95
95
93
90
90
83
59
91
84
97/3
98/2
99/1
98/2
98/2
99/1
>99/1
99/1
90/10
toluene, 100 °C, 3 h
R
R
R
7
8
7'
2
R1 = R2 = 4-MeC6H4, R3 = H (9b)
R1 = R2 = 4-MeOC6H4, R3 = H (9c)
R1 = R2 = 4-FC6H4, R3 = H (9d)
R1 = R2 = 4-ClC6H4, R3 = H (9e)
R1 = R2 = Bn, R3 = H (9f)
3
Entry
R
Yield (%) 7 + 8
7/8
4
1
2
3
H (5a)
66
78
86
96/4b
12/88
<1/99
5b
6
Me (5b)
Cy (5c)
7c
8
R1 = R2 = Me, R3 = H (9g)
a Reaction conditions for urea formation: 5 (0.20 mmol) and TsNCO (0.21
mmol) in CH2Cl2 (0.50 mL) at r.t. for 2 h. Reaction conditions for iridium-
catalyzed cyclization: [IrCl(coe)2]2 (5 mol% Ir), dppf (5 mol%), MVK (3
equiv), and NaI (50 mol%) in toluene (0.80 mL) at 100 °C for 3 h.
b 7a/7a′ = 10/90.
R1 = Ph, R2 = cinnamyl, R3 = H (9h)
R1 = R2 = Ph, R3 = Me (9i)
9
a Reaction conditions: 9 (0.20 mmol), [IrCl(coe)2]2 (5 mol% Ir), dppf (5
mol%), MVK (3 equiv), and NaI (50 mol%) in toluene (0.80 mL) at 100 °C for
3 h.
The same catalyst system can also be applied to the cy-
clization of alkenoic acids leading to γ-lactones (Table 4).
The reactions of alkenoic acids 9a–e bearing electron-rich
and electron-poor aryl groups gave the cyclization products
in high yields with over 97% selectivity of 10a–e (Table 4,
entries 1–5). Alkyl-substituted alkenoic acids 9f and 9g also
participated in the reaction to give 10f and 10g, respective-
ly, with high selectivity (entries 6 and 7). The internal
alkene moiety in 9h did not participate in the reaction (en-
try 8). A methyl group at β-position in 9i slightly decreased
the selectivity of oxidative cyclization (entry 9).
Hartwig and co-workers reported an iridium-catalyzed
addition of benzamides to alkenes,10e where it was pro-
posed that the reaction proceeds via N–H oxidative addi-
tion and alkene insertion into the Ir–N bond of the resulting
amidoiridium(III) species. The formation of a hydridoiridi-
um(III) carboxylate via oxidative addition of carboxylic acid
was also confirmed by Mashima and co-workers.12 Thus,
the present reaction might involve oxidative addition of
acidic N–H and O–H bonds as the first step. A stoichiomet-
ric reaction of [IrCl(coe)2]2, dppf, and 1h in benzene-d6 at
room temperature resulted in the formation of hydridoirid-
ium(III) complexes as a mixture of five isomers. These hy-
dridoiridium(III) species showed double doublet or virtual
triplet peaks at δ = –22.4, –23.7, –27.4, –27.7, and –29.5 in
the 1H NMR spectra, which were assigned to the hydrides at
the cis-position to two phosphorous atoms.
b For 12 h.
c Ethyl vinyl ketone instead of MVK in p-xylene at 135 °C for 12 h.
alkyliridium(I) species D, which undergoes β-hydride elim-
ination to give oxidative cyclization product 2a and hydrid-
oiridium(I) species E. The reaction of E with methyl vinyl
ketone in the presence of HX gives ethyl methyl ketone and
regenerates the iridium catalyst A. An alternative pathway
involves β-hydride elimination from intermediate C to give
iridium(III) dihydride F, and elimination of HX generates E
which reacts with MVK. The inefficiency of norbornene and
3,3-dimethylbut-1-ene as hydrogen acceptors implies that
the iridium(III) dihydride species is not likely to be directly
involved in the hydrogenation of sacrificial alkenes.11 In-
stead, the hydrogen transfer would proceed via conjugate
addition of the iridium(I) hydride to electron-deficient
alkenes and sequential protonation. The key role of sodium
iodide might be the halide exchange on the iridium to facil-
itate the elimination of HX to give the iridium(I) species.
To gain further insight into the reaction mechanism, the
effect of counterions of the iridium catalyst was investigat-
ed. By using [IrI(cod)]2 as a catalyst precursor, the reaction
of 1a in the absence of NaI gave the cyclization products in
85% yield with 84% selectivity of 2a. In contrast, the reac-
tion in the presence of NaI (50 mol%) increased the selectiv-
ity of 2a to 96% (Scheme 2a). These results indicate that the
excess amount of iodide is essential for the high selectivity
of 2. The reaction of 1a was also conducted in the presence
of [Ir(OH)(cod)]2 as a catalyst precursor, which is expected
to react with 1a to form an amidoiridium(I) species G
(Scheme 2b). The cyclization products were not obtained in
the absence of NaI. This result implies that alkene insertion
A plausible catalytic cycle of the present reaction is
shown in Scheme 1. Oxidative addition of amide 1a to the
iridium/dppf complex A generates hydridoiridium(III) spe-
cies B, and alkene insertion into the Ir–N bond generates al-
kylhydridoiridium(III) species C.13 One possible pathway
involves elimination of HX from the intermediate C to form
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–K

D
M. Nagamoto et al.
Special Topic
Synthesis
1
for H and 100 MHz for 13C). Chemical shifts are reported in δ (ppm)
referenced to the residual peaks of CDCl3 (δ 7.26) for 1H NMR, and
CDCl3 (δ 77.00) for 13C NMR. High-resolution mass spectra were ob-
tained with a Bruker micrOTOF spectrometer. Preparative TLC was
performed with Silica Gel 60 PF254 (Merck).
O
O
NHTs
Ph2C
1a
[Ir]X
MVK, HX
A
15
Iridium complexes, [IrCl(coe)2]2,14 [IrI(cod)]2,13 and [Ir(OH)(cod)]2
[Ir]H
[Ir] = Ir(dppf)
X = I or Cl
X
Ts
Ts
O
were prepared according to the reported procedures. Compounds 1a
(CAS: 1799905-43-3), 1f (CAS: 1310538-68-1), 1g (CAS: 1310538-67-
0), 1h (CAS: 413188-48-4), and 1j (CAS: 1993425-86-7) were pre-
pared from the corresponding carboxylic acids according to the re-
ported procedure.16 Allyl amines 5b (CAS: 37857-30-0) and 5c (CAS:
1826073-73-7) were prepared according to the reported procedure.17
Compounds 9a (CAS: 6966-03-6), 9b (CAS: 138952-03-1), 9c (CAS:
1803403-23-7), 9d (CAS: 1397711-73-7), 9e (CAS: 1803403-24-8), 9f
(CAS: 1803403-25-9), 9g (CAS: 16386-93-9), and 9i (CAS: 175879-
58-0) were prepared according to the reported procedures.18,19
N
O
N
[Ir]
E
H
Ph2C
Ph2C
2a
HX
[Ir]
X
B
H
[Ir]
H
Ts
N
2a
O
F
Ph2C
X
D
Ts
O
[Ir]
H
N
Ph2C
HX
C
Ts
O
N-Sulfonyl Alkenyl Amides 1; General Procedure16
N
Ph2C
To a solution of alkenoic acid 9 (1.0 equiv) in THF (0.33 M) was added
p-toluenesulfonyl isocyanate (1.0 equiv), and the mixture was stirred
at r.t. for 10 min. To the solution was added Et3N (1.0 equiv) and the
mixture was stirred at r.t. for 6 h. Aq HCl was added to the mixture,
and the resulting mixture was extracted with EtOAc (3 ×). The com-
bined organic layers were washed with brine, dried (Na2SO4), filtered,
and concentrated on a rotary evaporator. The residue was subjected
to short column chromatography on silica gel with EtOAc/hexane
(1/2) as eluent and recrystallized from EtOAc and hexane to give 1.
[Ir]X
3a
Scheme 1 Plausible catalytic cycle
into Ir(I)–N bond does not take place13 and that the amid-
oiridium(I) is inactive toward oxidative addition of another
molecule of 1a to form hydridoiridium(III) species. The
presence of NaI (50 mol%) prompted the reaction to give the
cyclization products in 81% yield with 94% selectivity of 2a.
This is presumably because the catalytically active iodoirid-
ium(I) species was generated from the amidoiridium(I) in
the presence of excess NaI.
2,2-Bis(4-methoxyphenyl)-N-tosylpent-4-enamide (1b)
This compound was prepared from 2,2-bis(4-methoxyphenyl)pent-4-
enoic acid (9c, CAS: 1803403-23-7) according to the general proce-
dure; yield: 885.4 mg (1.90 mmol, 95%); white solid.
1H NMR (CDCl3): δ = 7.79 (br s, 1 H), 7.75 (d, J = 8.2 Hz, 2 H), 7.28 (d, J =
8.2 Hz, 2 H), 7.04 (d, J = 8.9 Hz, 4 H), 6.81 (d, J = 8.9 Hz, 4 H), 5.51 (ddt,
J = 16.9, 10.4, 7.0 Hz, 1 H), 4.88 (d, J = 10.4 Hz, 1 H), 4.86 (d, J = 16.9 Hz,
1 H), 3.81 (s, 6 H), 2.99 (d, J = 7.0 Hz, 2 H), 2.45 (s, 3 H).
13C NMR (CDCl3): δ = 171.9, 158.8, 144.9, 135.1, 133.6, 132.2, 129.9,
129.4, 128.4, 118.8, 114.0, 60.2, 55.3, 42.9, 21.7.
(a)
[IrI(cod)]2 (5 mol% Ir)
dppf (5 mol%), MVK (3 equiv)
1a
1a
2a + 3a
toluene, 100 °C, 3 h
without NaI: 85% (2a/3a = 84:16)
with NaI (50 mol%): 95% (2a/3a = 96:4)
(b)
Ts
HRMS (APCI): m/z [M + H]+ calcd for C26H28NO5S: 466.1683; found:
466.1702.
[Ir(OH)(cod)]2 (5 mol% Ir)
dppf (5 mol%), MVK (3 equiv)
O
N
[Ir]
2a + 3a
Ph2C
toluene, 100 °C, 3 h
without NaI: 0%
G
2,2-Bis(4-chlorophenyl)-N-tosylpent-4-enamide (1c)
with NaI (50 mol%): 81% (2a/3a = 94:6)
This compound was prepared from 2,2-bis(4-chlorophenyl)pent-4-
enoic acid (9e, CAS: 1803403-24-8) according to the general proce-
dure; yield: 339.2 mg (0.72 mmol, 72%); white solid.
Scheme 2 Mechanistic studies
1H NMR (CDCl3): δ = 7.80 (br s, 1 H), 7.75 (d, J = 8.1 Hz, 2 H), 7.30 (d, J =
8.1 Hz, 2 H), 7.26 (d, J = 8.1 Hz, 4 H), 7.03 (d, J = 8.1 Hz, 4 H), 5.47 (ddt,
J = 17.3, 10.2, 7.0 Hz, 1 H), 4.95 (d, J = 10.2 Hz, 1 H), 4.91 (d, J = 17.3 Hz,
1 H), 3.01 (d, J = 7.0 Hz, 2 H), 2.46 (s, 3 H).
13C NMR (CDCl3): δ = 170.4, 145.3, 138.3, 134.6, 134.0, 132.4, 130.0,
129.4, 128.9, 128.4, 120.1, 60.6, 42.5, 21.7.
In summary, we have developed the oxidative cycliza-
tion of N-sulfonyl alkenyl amides and alkenoic acids cata-
lyzed by an iridium/dppf complex in the presence of methyl
vinyl ketone and NaI. The efficiency of electron-deficient
alkenes as sacrificial hydrogen acceptors indicates that an
iridium(I) hydride species is involved in the catalytic cycle.
The presence of NaI was found to be important to suppress
the competing addition reaction.
HRMS (APCI): m/z [M + H]+ calcd for C24H2235Cl2NO3S: 474.0692;
found: 474.0675.
2-Allyl-2-hexyl-N-tosyloctanamide (1d)
This compound was prepared from 2-allyl-2-hexyloctanoic acid
(CAS: 1803403-26-0) according to the general procedure; yield: 382.3
mg (0.91 mmol, 91%); white solid.
All anaerobic and moisture-sensitive manipulations were carried out
with standard Schlenk techniques under predried N2. NMR spectra
were recorded on JEOL JNM ECA-600 spectrometer (600 MHz for 1H
and 150 MHz for 13C) and JEOL JNM ECZ-400 spectrometer (400 MHz
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–K

E
M. Nagamoto et al.
Special Topic
Synthesis
1H NMR (CDCl3): δ = 8.16 (br s, 1 H), 7.93 (d, J = 8.1 Hz, 2 H), 7.32 (d, J =
8.1 Hz, 2 H), 5.53 (ddt, J = 17.0, 10.2, 7.3 Hz, 1 H), 5.05–4.99 (m, 2 H),
2.43 (s, 3 H), 2.22 (d, J = 7.3 Hz, 2 H), 1.47–1.41 (m, 2 H), 1.38–1.32 (m,
2 H), 1.26–1.19 (m, 4 H), 1.19–1.13 (m, 8 H), 1.09–1.00 (m, 2 H), 1.00–
0.91 (m, 2 H), 0.86 (t, J = 7.1 Hz, 6 H).
1H NMR (CDCl3): δ = 7.39–7.34 (m, 4 H), 7.31–7.24 (m, 5 H), 7.22–7.18
(m, 1 H), 6.23 (d, J = 14.3 Hz, 1 H), 5.91 (dt, J = 14.3, 7.3 Hz, 1 H), 5.62
(ddt, J = 17.5, 10.1, 7.3 Hz, 1 H), 5.13 (d, J = 17.5 Hz, 1 H), 5.10 (d, J =
10.1 Hz, 1 H), 2.98 (dd, J = 13.9, 7.3 Hz, 1 H), 2.92 (dd, J = 13.9, 7.3 Hz,
1 H), 2.88 (dd, J = 13.9, 7.3 Hz, 1 H), 2.82 (dd, J = 13.9, 7.3 Hz, 1 H).
13C NMR (CDCl3): δ = 174.3, 144.9, 135.5, 132.7, 129.4, 128.5, 119.0,
13C NMR (CDCl3): δ = 180.1, 140.9, 137.3, 133.9, 133.1, 128.54, 128.46,
50.0, 37.4, 35.1, 31.5, 29.6, 23.4, 22.5, 21.6, 14.0.
127.2, 126.5, 126.1, 124.7, 119.0, 53.7, 38.8, 38.0.
HRMS (APCI): m/z [M + H]+ calcd for C24H40NO3S: 422.2723; found:
HRMS (APCI): m/z [M + H]+ calcd for C20H21O2: 293.1536; found:
422.2723.
293.1546.
2,2-Dibenzyl-N-tosylpent-4-enamide (1e)
Ir-Catalyzed Oxidative Cyclization (Tables 1, 2, and 4)
This compound was prepared from 2,2-dibenzylpent-4-enoic acid
(9f, CAS: 1803403-25-9) according to the general procedure; yield:
327.0 mg (0.75 mmol, 75%); white solid.
1H NMR (CDCl3): δ = 7.92 (d, J = 8.2 Hz, 2 H), 7.81 (br s, 1 H), 7.38 (d, J =
8.2 Hz, 2 H), 7.19 (t, J = 7.5 Hz, 2 H), 7.13 (t, J = 7.5 Hz, 4 H), 6.95 (d, J =
7.5 Hz, 4 H), 5.90 (ddt, J = 17.0, 10.6, 6.8 Hz, 1 H), 5.27 (d, J = 10.6 Hz, 1
H), 5.15 (d, J = 17.0 Hz, 1 H), 3.09 (d, J = 14.0 Hz, 2 H), 2.76 (d, J = 14.0
Hz, 2 H), 2.51 (s, 3 H), 2.17 (d, J = 6.8 Hz, 2 H).
Additive (50 mol%), dppf (5 mol%), and [IrCl(coe)2]2 (5 mol% of Ir)
were placed in a Schlenk tube under N2. Toluene (0.25 M) and hydro-
gen acceptor (3.0 equiv) were added and the mixture was stirred at
r.t. for 10 min. N-Sulfonyl alkenyl amide 1 or alkenoic acid 9 (1.0
equiv) was added to the Schlenk tube and the tube was capped with a
glass stopper and heated at 100 °C for 3 h with stirring. The mixture
was passed through a short plug of silica gel with EtOAc as eluent and
concentrated on a rotary evaporator. The residue was subjected to
preparative TLC on silica gel to give the corresponding cyclization
products.
13C NMR (CDCl3): δ = 173.4, 145.0, 135.9, 135.4, 132.4, 130.2, 129.4,
129.0, 128.4, 126.9, 120.4, 52.0, 42.3, 35.6, 21.7.
HRMS (APCI): m/z [M + H]+ calcd for C26H28NO3S: 434.1784; found:
434.1795.
Ir-Catalyzed Oxidative Cyclization of N-Sulfonyl Alkenyl Ureas
Generated in Situ (Table 3)
To a solution of amine 5 (0.20 mmol) in CH2Cl2 (0.50 mL) was added
p-toluenesulfonyl isocyanate (32.1 μL, 0.21 mmol), and the mixture
was stirred at r.t. for 2 h. The solvent was removed under vacuum at
r.t. To the mixture were added NaI (15.0 mg, 50 mol%), dppf (5.5 mg, 5
mol%), [IrCl(coe)2]2 (4.5 mg, 0.010 mmol of Ir), toluene (0.80 mL), and
methyl vinyl ketone (50 μL, 0.60 mmol) under N2. The Schlenk tube
was capped with a glass stopper and heated at 100 °C for 3 h with
stirring. The mixture was passed through a short plug of silica gel
with EtOAc as an eluent and concentrated on a rotary evaporator. The
residue was subjected to preparative TLC on silica gel to give the cor-
responding cyclization products.
(E)-2-Allyl-2,5-diphenyl-N-tosylpent-4-enamide (1i)
This compound was prepared by the reaction of (E)-2-allyl-2,5-di-
phenylpent-4-enoic acid (9h) according to the general procedure;
yield: 341.5 mg (0.77 mmol, 77%); white solid.
1H NMR (CDCl3): δ = 7.82 (d, J = 7.3 Hz, 2 H), 7.69 (br s, 1 H), 7.37–7.30
(m, 3 H), 7.28–7.23 (m, 4 H), 7.19 (t, J = 7.3 Hz, 1 H), 7.13 (d, J = 7.3 Hz,
2 H), 7.11 (d, J = 7.3 Hz, 2 H), 6.29 (d, J = 14.4 Hz, 1 H), 5.64 (dt, J = 14.4,
7.5 Hz, 1 H), 5.42–5.35 (m, 1 H), 5.01 (d, J = 10.2 Hz, 1 H), 5.00 (d, J =
17.0 Hz, 1 H), 2.77 (d, J = 7.5 Hz, 2 H), 2.68 (dd, J = 14.8, 8.0 Hz, 1 H),
2.64 (dd, J = 14.8, 8.0 Hz, 1 H), 2.42 (s, 3 H).
13C NMR (CDCl3): δ = 172.5, 145.0, 139.7, 136.9, 135.3, 134.4, 132.0,
129.4, 129.2, 128.5, 128.4, 128.1, 127.4, 127.0, 126.2, 123.4, 119.7,
55.0, 39.1, 38.3, 21.7.
HRMS (APCI): m/z [M + H]+ calcd for C27H28NO3S: 446.1784; found:
446.1792.
5-Methylene-3,3-diphenyl-1-tosylpyrrolidin-2-one (2a) and 5-
Methyl-3,3-diphenyl-1-tosylpyrrolidin-2-one (3a)
The crude mixture was subjected to preparative TLC on silica gel with
EtOAc/hexane (1/2) to give a mixture of 2a and 3a (97/3) in 92% yield
(37.1 mg, 0.092 mmol).
Alkenoic Acids 9a–h; General Procedure18
Compound 2a
To a solution of i-Pr2NH (2.5 equiv) in THF (4.0 M) at 0 °C was slowly
added n-BuLi (1.63 M in hexane, 2.5 equiv), and the mixture was
stirred at 0 °C for 1 h. To the solution was added the appropriate α,α-
disubstituted acetic acid (1.0 equiv) in THF (0.8 M), and the mixture
was stirred at 45 °C for 1.5 h. Allyl bromide (2.0 equiv) was added to
the solution and the mixture was stirred at 45 °C overnight. H2O was
added to the mixture and the aqueous layer was washed with Et2O.
The aqueous layer was acidified with aq HCl, and the mixture was ex-
tracted with Et2O (3 ×). The combined organic layers were washed
with brine, dried (Na2SO4), filtered, and concentrated on a rotary
evaporator. The solid residue was recrystallized from CHCl3 and hex-
ane to give 9.
Colorless oil.
1H NMR (CDCl3): δ = 7.83 (d, J = 8.2 Hz, 2 H), 7.24 (d, J = 8.2 Hz, 2 H),
7.22–7.19 (m, 6 H), 7.11–7.08 (m, 4 H), 5.58–5.57 (m, 1 H), 4.67–4.66
(m, 1 H), 3.34–3.33 (m, 2 H), 2.43 (s, 3 H).
13C NMR (CDCl3): δ = 174.0, 145.4, 140.7, 138.4, 134.8, 129.4, 128.4,
128.0, 127.5, 127.4, 94.6, 57.2, 42.5, 21.7.
HRMS (APCI): m/z [M + H]+ calcd for C24H22NO3S: 404.1315; found:
404.1309.
Compound 3a (CAS: 2019142-42-6)
Colorless oil.
(E)-2-Allyl-2,5-diphenylpent-4-enoic Acid (9h)
1H NMR (CDCl3): δ = 7.83 (d, J = 8.7 Hz, 2 H), 7.26–7.13 (m, 10 H), 7.07
(d, J = 8.7 Hz, 2 H), 4.29–4.23 (m, 1 H), 3.05 (dd, J = 13.3, 6.8 Hz, 1 H),
2.43 (s, 3 H), 2.41 (dd, J = 13.3, 7.5 Hz, 1 H), 1.52 (d, J = 6.1 Hz, 3 H).
This compound was prepared from (E)-2,5-diphenylpent-4-enoic acid
(CAS: 351207-71-1) according to the general procedure; yield: 649.0
mg (2.2 mmol, 55%); white solid.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–K

F
M. Nagamoto et al.
Special Topic
Synthesis
3,3-Bis(4-methoxyphenyl)-5-methylene-1-tosylpyrrolidin-2-one
(2b) and 3,3-Bis(4-methoxyphenyl)-5-methyl-1-tosylpyrrolidin-2-
one (3b)
3,3-Dihexyl-5-methylene-1-tosylpyrrolidin-2-one (2d)
The crude mixture was subjected to preparative TLC on silica gel with
EtOAc/hexane (1/2) to give 2d in 81% yield (33.9 mg, 0.081 mmol) as a
colorless oil.
1H NMR (CDCl3): δ = 7.93 (d, J = 8.6 Hz, 2 H), 7.31 (d, J = 8.6 Hz, 2 H),
5.50 (d, J = 2.1 Hz, 1 H), 4.53 (d, J = 1.4 Hz, 1 H), 2.52 (s, 2 H), 2.42 (s, 3
H), 1.45–1.33 (m, 4 H), 1.22–1.16 (m, 4 H), 1.15–1.05 (m, 10 H), 0.84
(t, J = 7.5 Hz, 6 H), 0.86–0.78 (m, 2 H).
The crude mixture was subjected to preparative TLC on silica gel with
EtOAc/hexane (1/2) to give a mixture of 2b and 3b (91/9) in 89% yield
(82.8 mg, 0.178 mmol).
Compound 2b
13C NMR (CDCl3): δ = 178.2, 145.2, 139.8, 135.4, 129.4, 128.0, 93.4,
Colorless oil.
1H NMR (CDCl3): δ = 7.80 (d, J = 8.1 Hz, 2 H), 7.22 (d, J = 8.1 Hz, 2 H),
7.00 (d, J = 8.1 Hz, 4 H), 6.72 (d, J = 8.1 Hz, 4 H), 5.56 (d, J = 1.4 Hz, 1 H),
4.64 (d, J = 1.4 Hz, 1 H), 3.76 (s, 6 H), 3.26 (s, 2 H), 2.42 (s, 3 H).
47.3, 37.2, 37.1, 31.5, 29.5, 23.7, 22.4, 21.7, 14.0.
HRMS (APCI): m/z [M + H]+ calcd for C24H38NO3S: 420.2567; found:
420.2563.
13C NMR (CDCl3): δ = 174.4, 158.7, 145.3, 138.6, 134.8, 132.8, 129.4,
128.6, 127.9, 113.8, 94.4, 56.0, 55.2, 42.8, 21.7.
HRMS (APCI): m/z [M + H]+ calcd for C26H26NO5S: 464.1526; found:
3,3-Dibenzyl-5-methylene-1-tosylpyrrolidin-2-one (2e) and 3,3-
Dibenzyl-5-methyl-1-tosylpyrrolidin-2-one (3e)
464.1544.
The crude mixture was subjected to preparative TLC on silica gel with
EtOAc/hexane (1/2) to give a mixture of 2e and 3e (97/3) in 89% yield
(77.2 mg, 0.178 mmol) as colorless oils.
Compound 3b
Colorless oil.
Compound 2e
1H NMR (CDCl3): δ = 7.81 (d, J = 8.1 Hz, 2 H), 7.22 (d, J = 8.1 Hz, 2 H),
7.05 (d, J = 8.9 Hz, 2 H), 6.97 (d, J = 8.9 Hz, 2 H), 6.76 (d, J = 8.9 Hz, 2 H),
6.70 (d, J = 8.9 Hz, 2 H), 4.25–4.19 (m, 1 H), 3.77 (s, 3 H), 3.75 (s, 3 H),
2.97 (dd, J = 13.3, 6.8 Hz, 1 H), 2.42 (s, 3 H), 2.32 (dd, J = 13.3, 7.5 Hz, 1
H), 1.52 (d, J = 6.1 Hz, 3 H).
13C NMR (CDCl3): δ = 174.9, 158.7, 158.4, 144.7, 135.3, 134.4, 132.0,
129.2, 128.8, 128.4, 128.3, 113.8, 113.7, 56.7, 55.2, 53.6, 42.5, 22.0,
21.6.
1H NMR (CDCl3): δ = 7.82 (d, J = 8.1 Hz, 2 H), 7.32 (d, J = 8.1 Hz, 2 H),
7.18 (t, J = 7.5 Hz, 2 H), 7.11 (t, J = 7.5 Hz, 4 H), 6.94 (d, J = 7.5 Hz, 4 H),
5.10 (s, 1 H), 4.22 (s, 1 H), 3.08 (d, J = 13.3 Hz, 2 H), 2.63 (d, J = 13.3 Hz,
2 H), 2.50 (s, 2 H), 2.49 (s, 3 H).
13C NMR (CDCl3): δ = 177.0, 145.1, 138.7, 135.7, 135.3, 130.2, 129.4,
128.33, 128.27, 126.8, 94.0, 50.4, 42.6, 34.2, 21.7.
HRMS (APCI): m/z [M + H]+ calcd for C26H26NO3S: 432.1628; found:
432.1635.
HRMS (APCI): m/z [M + H]+ calcd for C26H28NO5S: 466.1683; found:
466.1687.
Compound 3e
1H NMR (CDCl3): δ = 7.87 (d, J = 8.1 Hz, 2 H), 7.34 (d, J = 8.1 Hz, 2 H),
7.24–7.18 (m, 3 H), 7.14 (d, J = 8.1 Hz, 1 H), 7.07 (t, J = 8.1 Hz, 2 H),
7.03 (d, J = 8.1 Hz, 2 H), 6.94 (d, J = 8.1 Hz, 2 H), 3.56–3.49 (m, 1 H),
3.20 (d, J = 13.6 Hz, 1 H), 3.12 (d, J = 13.6 Hz, 1 H), 2.57 (d, J = 10.2 Hz,
1 H), 2.55 (d, J = 10.2 Hz, 1 H), 2.50 (s, 3 H), 2.22 (dd, J = 13.6, 9.5 Hz, 1
H), 1.54 (dd, J = 13.6, 5.4 Hz, 1 H), 0.78 (d, J = 6.1 Hz, 3 H).
13C NMR (CDCl3): δ = 177.5, 144.6, 136.8, 136.3, 136.0, 130.4, 130.2,
129.2, 128.6, 128.4, 128.3, 126.9, 126.8, 53.0, 51.5, 44.8, 44.0, 33.0,
22.2, 21.7.
3,3-Bis(4-chlorophenyl)-5-methylene-1-tosylpyrrolidin-2-one(2c)
and 3,3-Bis(4-chlorophenyl)-5-methyl-1-tosylpyrrolidin-2-one
(3c)
The crude mixture was subjected to preparative TLC on silica gel with
EtOAc/hexane (1/2) to give a mixture of 2c and 3c (95/5) in 92% yield
(87.0 mg, 0.184 mmol).
Compound 2c
Colorless oil.
HRMS (APCI): m/z [M + H]+ calcd for C26H28NO3S: 434.1784; found:
434.1795.
1H NMR (CDCl3): δ = 7.77 (d, J = 8.5 Hz, 2 H), 7.23 (d, J = 8.5 Hz, 2 H),
7.17 (d, J = 8.8 Hz, 4 H), 7.01 (d, J = 8.8 Hz, 4 H), 5.61 (d, J = 1.4 Hz, 1 H),
4.69 (d, J = 1.4 Hz, 1 H), 3.26 (s, 2 H), 2.44 (s, 3 H).
3-Methylene-2-tosyl-2-azaspiro[4.5]decan-1-one (2f), 3-Methyl-2-
tosyl-2-azaspiro[4.5]dec-3-en-1-one (2f′), and 3-Methyl-2-tosyl-2-
azaspiro[4.5]decan-1-one (3f)
13C NMR (CDCl3): δ = 173.3, 145.7, 138.6, 137.8, 134.2, 133.8, 129.4,
128.8, 128.7, 127.9, 95.0, 56.3, 42.1, 21.7.
HRMS (APCI): m/z [M + H]+ calcd for C24H2035Cl2NO3S: 472.0535;
found: 472.0533.
The crude mixture was subjected to preparative TLC on silica gel with
EtOAc/hexane (1/2) to give a mixture of 2f, 2f′, 3f (23/76/1) in 72%
yield (51.7 mg, 0.162 mmol). Compound 2f could not be separated
from compound 2f′.
Compound 3c
Colorless oil.
1H NMR (CDCl3): δ = 7.78 (d, J = 8.8 Hz, 2 H), 7.24–7.20 (m, 4 H), 7.14
(d, J = 8.8 Hz, 2 H), 7.06 (d, J = 8.8 Hz, 2 H), 6.98 (d, J = 8.8 Hz, 2 H),
4.26–4.20 (m, 1 H), 2.99 (dd, J = 13.4, 6.8 Hz, 1 H), 2.44 (s, 3 H), 2.31
(dd, J = 13.4, 7.8 Hz, 1 H), 1.54 (d, J = 5.4 Hz, 3 H).
Compound 2f
Colorles oil.
1H NMR (CDCl3): δ = 7.89 (d, J = 8.1 Hz, 2 H), 7.30 (d, J = 8.1 Hz, 2 H),
5.48 (d, J = 1.4 Hz, 1 H), 4.56 (d, J = 1.4 Hz, 1 H), 2.52 (s, 2 H), 2.41 (s, 3
H), 1.70–1.20 (m, 10 H).
13C NMR (CDCl3): δ = 173.8, 145.2, 140.3, 137.7, 134.7, 133.7, 133.4,
129.3, 129.0, 128.8, 128.7, 128.2, 56.9, 53.6, 41.9, 22.2, 21.7.
HRMS (APCI): m/z [M + H]+ calcd for C24H2235Cl2NO3S: 474.0692;
13C NMR (CDCl3): δ = 178.3, 145.2, 139.2, 135.4, 129.5, 127.8, 94.4,
44.9, 38.2, 32.0, 25.0, 21.6.
found: 474.0707.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–K

G
M. Nagamoto et al.
Special Topic
Synthesis
Compound 2f′
5-Methyl-1-tosyl-1,5-dihydro-2H-pyrrol-2-one (2h′) and 5-Meth-
yl-1-tosylpyrrolidin-2-one (3h)
Colorless oil.
The crude mixture was subjected to preparative TLC on silica gel with
EtOAc/hexane (1/2) to give a mixture of 2h′ and 3h (92/8) in 27% yield
(13.6 mg, 0.054 mmol) as colorless oils.
1H NMR (CDCl3): δ = 7.87 (d, J = 8.1 Hz, 2 H), 7.31 (d, J = 8.1 Hz, 2 H),
5.38 (s, 1 H), 2.42 (s, 3 H), 2.29 (s, 3 H), 1.72–1.52 (m, 4 H), 1.36–1.22
(m, 6 H).
13C NMR (CDCl3): δ = 180.6, 144.8, 137.4, 136.2, 129.6, 127.7, 113.5,
50.0, 32.9, 25.2, 22.0, 21.6, 16.8.
HRMS (APCI): m/z [M + H]+ calcd for C17H22NO3S: 320.1315; found:
320.1305.
Compound 2h′ (CAS: 96013-62-6)
1H NMR (CDCl3): δ = 7.96 (d, J = 8.1 Hz, 2 H), 7.32 (d, J = 8.1 Hz, 2 H),
7.14 (dd, J = 6.0, 1.7 Hz, 1 H), 5.97 (dd, J = 6.0, 1.7 Hz, 1 H), 4.87 (qt, J =
6.3, 1.7 Hz, 1 H), 2.42 (s, 3 H), 1.58 (d, J = 6.3 Hz, 3 H).
Compound 3f
Compound 3h (CAS: 118429-46-2)
Colorless oil.
1H NMR (CDCl3): δ = 7.95 (d, J = 8.2 Hz, 2 H), 7.32 (d, J = 8.2 Hz, 2 H),
4.55–4.50 (m, 1 H), 2.59–2.52 (m, 1 H), 2.43 (s, 3 H), 2.39–2.32 (m, 1
H), 2.31–2.23 (m, 1 H), 1.74–1.69 (m, 1 H), 1.47 (d, J = 6.1 Hz, 3 H).
1H NMR (CDCl3): δ = 7.91 (d, J = 7.8 Hz, 2 H), 7.30 (d, J = 7.8 Hz, 2 H),
4.32–4.26 (m, 1 H), 2.42 (s, 3 H), 2.23 (dd, J = 12.9, 8.2 Hz, 1 H), 1.54
(d, J = 6.1 Hz, 3 H), 1.70–1.52 (m, 5 H), 1.43–1.37 (m, 2 H), 1.29–1.20
(m, 4 H).
3-Cinnamyl-5-methylene-3-phenyl-1-tosylpyrrolidin-2-one (2i)
and 3-Cinnamyl-5-methyl-3-phenyl-1-tosylpyrrolidin-2-one (3i)
13C NMR (CDCl3): δ = 178.6, 144.7, 136.1, 129.4, 128.2, 53.3, 45.5, 38.2,
33.6, 33.0, 25.1, 23.4, 21.7, 21.63, 21.57.
HRMS (APCI): m/z [M + H]+ calcd for C17H24NO3S: 322.1471; found:
322.1478.
The crude mixture was subjected to preparative TLC on silica gel with
EtOAc/hexane (1/2) to give a mixture of 2i and 3i (98/2) in 83% yield
(73.3 mg, 0.166 mmol).
3,3-Dimethyl-5-methylene-1-tosylpyrrolidin-2-one (2g), 3,3,5-
Trimethyl-1-tosyl-1,3-dihydro-2H-pyrrol-2-one (2g′), and 3,3,5-
Trimethyl-1-tosylpyrrolidin-2-one (3g)
Compound 2i
Colorless oil.
1H NMR (CDCl3): δ = 7.86 (d, J = 7.5 Hz, 2 H), 7.33–7.24 (m, 7 H), 7.23–
7.18 (m, 3 H), 7.13 (d, J = 7.5 Hz, 2 H), 6.31 (d, J = 14.4 Hz, 1 H), 5.75
(dt, J = 14.4, 7.4 Hz, 1 H), 5.52 (d, J = 1.3 Hz, 1 H), 4.62 (d, J = 1.3 Hz, 1
H), 3.07 (d, J = 14.0 Hz, 1 H), 2.99 (d, J = 14.0 Hz, 1 H), 2.77 (dd, J = 13.8,
7.4 Hz, 1 H), 2.71 (dd, J = 13.8, 7.4 Hz, 1 H), 2.39 (s, 3 H).
The crude mixture was subjected to preparative TLC on silica gel with
EtOAc/hexane (1/2) to give a mixture of 2g, 2g′, and 3g (23/74/3) in
81% yield (40.0 mg, 0.144 mmol).
Compound 2g (CAS: 1875033-08-1)
13C NMR (CDCl3): δ = 175.3, 145.3, 139.3, 138.8, 136.7, 135.1, 134.6,
129.4, 128.7, 128.4, 127.9, 127.53, 127.50, 126.2, 126.1, 123.6, 94.7,
52.1, 42.0, 38.4, 21.7.
HRMS (APCI): m/z [M + H]+ calcd for C27H26NO3S: 444.1628; found:
444.1625.
Colorless oil.
1H NMR (CDCl3): δ = 7.92 (d, J = 8.1 Hz, 2 H), 7.33 (d, J = 8.1 Hz, 2 H),
5.52 (d, J = 2.0 Hz, 1 H), 4.58 (d, J = 2.0 Hz, 1 H), 2.47 (s, 2 H), 2.44 (s, 3
H), 1.09 (s, 6 H).
Compound 2g′
Compound 3i
Colorless oil.
Colorless oil; d.r. = 60:40.
1H NMR (CDCl3): δ = 7.87 (d, J = 7.2 Hz, 2 H), 7.32 (d, J = 7.2 Hz, 2 H),
1H NMR (CDCl3): δ = 7.94 [d, J = 8.2 Hz, 2 H (minor)], 7.75 [d, J = 8.2 Hz,
2 H (major)], 7.35–7.15 [m, 10 H (major) + 12 H (minor)], 7.10 [d, J =
8.2 Hz, 2 H (major)], 6.33 [d, J = 14.0 Hz, 1 H (major)], 6.30 [d, J = 14.0
Hz, 1 H (minor)], 5.87 [dt, J = 14.0, 7.6 Hz, 1 H (major)], 5.74 [dt, J =
14.0, 7.6 Hz, 1 H (minor)], 4.42–4.36 [m, 1 H (minor)], 4.11–4.05 [m, 1
H (major)], 2.74–2.62 [m, 3 H (major) + 2 H (minor)], 2.54 [dd, J =
14.0, 8.2 Hz, 1 H (minor)], 2.43 [s, 3 H (minor)], 2.42 [s, 3 H (major)],
2.24 [dd, J = 14.0, 2.7 Hz, 1 H (minor)], 1.90 [dd, J = 13.3. 9.2 Hz, 1 H
(major)], 1.59 [d, J = 6.1 Hz, 3 H (major)], 1.25 [d, J = 6.1 Hz, 3 H (mi-
nor)].
5.07 (s, 1 H), 2.43 (s, 3 H), 2.26 (s, 3 H), 1.07 (s, 6 H).
13C NMR (CDCl3): δ = 181.2, 144.9, 137.0, 136.0, 129.6, 127.7, 116.3,
45.2, 23.7, 21.6, 16.6.
HRMS (APCI): m/z [M + H]+ calcd for C14H18NO3S: 280.1002; found:
280.1005.
Compound 3g
Colorless oil.
1H NMR (CDCl3): δ = 7.92 (d, J = 8.1 Hz, 2 H), 7.31 (d, J = 8.1 Hz, 2 H),
4.33–4.27 (m, 1 H), 2.43 (s, 3 H), 2.13 (dd, J = 12.9, 8.2 Hz, 1 H), 1.55
(dd, J = 12.9, 6.8 Hz, 1 H), 1.55 (d, J = 6.1 Hz, 3 H), 1.14 (s, 3 H), 1.01 (s,
3 H).
13C NMR (CDCl3): δ = 179.0, 144.8, 136.0, 129.4, 128.2, 53.1, 42.2, 41.2,
25.2, 23.0, 21.7.
HRMS (APCI): m/z [M + H]+ calcd for C27H28NO3S: 446.1784; found:
446.1771.
1-Methanesulfonyl-5-methylene-3,3-diphenylpyrrolidin-2-one
(2j) and 1-Methanesulfonyl-5-methyl-3,3-diphenylpyrrolidin-2-
one (3j)
HRMS (APCI): m/z [M + H]+ calcd for C14H20NO3S: 282.1158; found:
282.1172.
The crude mixture was subjected to preparative TLC on silica gel with
EtOAc/hexane (1/2) to give a mixture of 2j and 3j (97/3) in 95% yield
(62.2 mg, 0.190 mmol).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–K

H
M. Nagamoto et al.
Special Topic
Synthesis
Compound 2j
1-Benzyl-5-methyl-4-methylene-3-tosylimidazolidin-2-one (7b)
and 1-Benzyl-trans-4,5-dimethyl-3-tosylimidazolidin-2-one (8b)
Colorless oil.
The crude mixture was subjected to preparative TLC on silica gel with
EtOAc/hexane (1/2) to give a mixture of 7b and 8b (12/88) in 78%
yield (55.5 mg, 0.156 mmol).
1H NMR (CDCl3): δ = 7.36–7.28 (m, 10 H), 5.41 (d, J = 1.7 Hz, 1 H), 4.68
(d, J = 1.7 Hz, 1 H), 3.44 (s, 2 H), 3.29 (s, 3 H).
13C NMR (CDCl3): δ = 175.3, 140.9, 138.0, 128.7, 127.7, 127.5, 95.1,
57.3, 42.8, 41.3.
Compound 7b
HRMS (APCI): m/z [M + H]+ calcd for C18H18NO3S: 328.1002; found:
328.1010.
Colorless oil.
1H NMR (CDCl3): δ = 7.95 (d, J = 8.2 Hz, 2 H), 7.34 (d, J = 8.2 Hz, 2 H),
7.30–7.25 (m, 3 H), 7.12–7.08 (m, 2 H), 5.55 (t, J = 2.2 Hz, 1 H), 4.80 (d,
J = 15.3 Hz, 1 H), 4.42 (t, J = 2.2 Hz, 1 H), 3.97 (d, J = 15.3 Hz, 1 H), 3.94–
3.90 (m, 1 H), 2.46 (s, 3 H), 1.21 (d, J = 6.1 Hz, 3 H).
13C NMR (CDCl3): δ = 152.6, 145.0, 141.1, 135.7, 135.3, 129.6, 128.8,
128.0, 127.94, 127.90, 91.8, 52.9, 44.7, 21.7, 19.7.
Compound 3j (CAS: 1993426-09-7)
Colorless oil.
1H NMR (CDCl3): δ = 7.36–7.31 (m, 8 H), 7.31–7.25 (m, 2 H), 4.31–4.25
(m, 1 H), 3.26 (s, 3 H), 3.13 (dd, J = 13.3, 6.8 Hz, 1 H), 2.56 (dd, J = 13.3,
6.1 Hz, 1 H), 1.43 (d, J = 6.1 Hz, 3 H).
HRMS (APCI): m/z [M + H]+ calcd for C19H21N2O3S: 357.1267; found:
357.1268.
1-Benzyl-4-methylene-3-tosylimidazolidin-2-one (7a), 1-Benzyl-
4-methyl-3-tosyl-1,3-dihydro-2H-imidazol-2-one (7a′), and 1-
Benzyl-4-methyl-3-tosylimidazolidin-2-one (8a)
Compound 8b
Colorless oil.
The crude mixture was subjected to preparative TLC on silica gel with
EtOAc/hexane (1/2) to give a mixture of 7a, 7a′, and 8a (10/86/4) in
66% yield (45.2 mg, 0.132 mmol).
1H NMR (CDCl3): δ = 7.95 (d, J = 7.9 Hz, 2 H), 7.33 (d, J = 7.9 Hz, 2 H),
7.31–7.25 (m, 3 H), 7.16 (d, J = 7.9 Hz, 2 H), 4.72 (d, J = 15.0 Hz, 1 H),
3.92 (d, J = 15.0 Hz, 1 H), 3.83 (qd, J = 6.1, 3.8 Hz, 1 H), 2.99 (qd, J = 6.1,
3.8 Hz, 1 H), 2.44 (s, 3 H), 1.39 (d, J = 6.1 Hz, 3 H), 1.07 (d, J = 6.1 Hz, 3
H).
13C NMR (CDCl3): δ = 153.3, 144.4, 136.3, 135.8, 129.5, 128.7, 128.1,
128.0, 127.8, 58.2, 55.7, 44.9, 21.6, 21.0, 18.1.
Compound 7a
Colorless oil.
1H NMR (CDCl3): δ = 7.96 (d, J = 8.1 Hz, 2 H), 7.34 (d, J = 8.1 Hz, 2 H),
7.32–7.27 (m, 3 H), 7.15–7.12 (m, 2 H), 5.51 (q, J = 2.3 Hz, 1 H), 4.43 (q,
J = 2.3 Hz, 1 H), 4.36 (s, 2 H), 3.81 (t, J = 2.3 Hz, 2 H), 2.45 (s, 3 H).
HRMS (APCI): m/z [M + H]+ calcd for C19H23N2O3S: 359.1424; found:
359.1423.
13C NMR (CDCl3): δ = 153.0, 145.1, 135.6, 134.9, 134.4, 129.6, 128.9,
128.2, 128.1, 127.9, 91.9, 47.3, 47.2, 21.7.
HRMS (APCI): m/z [M + H]+ calcd for C18H19N2O3S: 343.1111; found:
343.1121.
1-Benzyl-trans-5-cyclohexyl-4-methyl-3-tosylimidazolidin-2-one
(8c)
The crude mixture was subjected to preparative TLC on silica gel with
EtOAc/hexane (1/3) to give a mixture of 8c in 86% yield (73.4 mg,
0.172 mmol) as a colorless oil.
1H NMR (CDCl3): δ = 7.96 (d, J = 8.2 Hz, 2 H), 7.34–7.26 (m, 5 H), 7.19
(d, J = 8.2 Hz, 2 H), 4.82 (d, J = 14.9 Hz, 1 H), 4.09 (qd, J = 6.4, 2.9 Hz, 1
H), 3.86 (d, J = 14.9 Hz, 1 H), 2.79 (t, J = 2.9 Hz, 1 H), 2.43 (s, 3 H), 1.74
(br d, J = 12.9 Hz, 1 H), 1.68–1.58 (m, 2 H), 1.53–1.47 (m, 1 H), 1.33 (br
d, J = 13.3 Hz, 1 H), 1.30 (d, J = 6.4 Hz, 3 H), 1.24 (br d, J = 13.3 Hz, 1 H),
1.21–1.12 (m, 1 H), 1.11–1.03 (m, 1 H), 1.03–0.93 (m, 2 H), 0.72–0.64
(m, 1 H).
Compound 7a′
Colorless oil.
1H NMR (CDCl3): δ = 7.99 (d, J = 8.1 Hz, 2 H), 7.34 (d, J = 8.1 Hz, 2 H),
7.32–7.27 (m, 3 H), 7.14 (d, J = 8.1 Hz, 2 H), 5.80 (s, 1 H), 4.58 (s, 2 H),
2.44 (s, 3 H), 2.26 (s, 3 H).
13C NMR (CDCl3): δ = 150.9, 145.3, 135.6, 135.5, 129.7, 128.8, 128.13,
128.08, 128.0, 119.0, 110.1, 46.8, 21.7, 13.3.
HRMS (APCI): m/z [M + H]+ calcd for C18H19N2O3S: 343.1111; found:
343.1112.
13C NMR (CDCl3): δ = 153.3, 144.4, 136.7, 135.9, 129.4, 128.7, 128.09,
128.07, 127.8, 64.0, 51.7, 45.2, 38.3, 28.0, 26.2, 26.1, 25.6, 24.9, 23.2,
21.6.
Compound 8a
HRMS (APCI): m/z [M + H]+ calcd for C24H31N2O3S: 427.2050; found:
Colorless oil.
427.2039.
1H NMR (CDCl3): δ = 7.96 (d, J = 8.1 Hz, 2 H), 7.33 (d, J = 8.1 Hz, 2 H),
7.31–7.26 (m, 3 H), 7.13 (d, J = 8.1 Hz, 2 H), 4.34 (dd, J = 14.7 Hz, 1 H),
4.37–4.31 (m, 1 H), 4.27 (d, J = 14.7 Hz, 1 H), 3.40 (t, J = 9.1 Hz, 1 H),
2.79 (dd, J = 9.1, 4.1 Hz, 1 H), 2.44 (s, 3 H), 1.44 (d, J = 6.1 Hz, 3 H).
5-Methylene-3,3-diphenyldihydrofuran-2(3H)-one (10a) and 5-
Methyl-3,3-diphenyldihydrofuran-2(3H)-one (11a)
The crude mixture was subjected to preparative TLC on silica gel with
EtOAc/hexane (1/4) to give a mixture of 10a and 11a (97/3) in 95%
yield (43.9 mg, 0.190 mmol).
13C NMR (CDCl3): δ = 153.8, 144.4, 136.4, 135.4, 129.4, 128.7, 128.2,
128.1, 127.9, 50.4, 49.1, 47.6, 21.9, 21.6.
HRMS (APCI): m/z [M + H]+ calcd for C18H21N2O3S: 345.1267; found:
345.1284.
Compound 10a (CAS: 137415-99-7)
Colorless oil.
1H NMR (CDCl3): δ = 7.36–7.33 (m, 8 H), 7.32–7.28 (m, 2 H), 4.82–4.80
(m, 1 H), 4.44–4.42 (m, 1 H), 3.57 (t, J = 1.7 Hz, 2 H).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–K

I
M. Nagamoto et al.
Special Topic
Synthesis
Compound 11a (CAS: 1729-20-0)
3,3-Bis(4-fluorophenyl)-5-methylenedihydrofuran-2(3H)-one
(10d) and 3,3-Bis(4-fluorophenyl)-5-methyldihydrofuran-2(3H)-
one (11d)
Colorless oil.
1H NMR (CDCl3): δ = 7.38–7.21 (m, 10 H), 4.51–4.45 (m, 1 H), 3.06 (dd,
J = 12.9, 4.8 Hz, 1 H), 2.59 (dd, J = 12.9, 10.2 Hz, 1 H), 1.46 (d, J = 6.1 Hz,
3 H).
The crude mixture was subjected to preparative TLC on silica gel with
EtOAc/hexane (1/4) to give a mixture of 10d and 11d (98/2) in 90%
yield (26.1 mg, 0.090 mmol).
3,3-Bis(4-methylphenyl)-5-methylenedihydrofuran-2(3H)-one
(10b) and 3,3-Bis(4-methylphenyl)-5-methyldihydrofuran-2(3H)-
one (11b)
Compound 10d
Colorless oil.
The crude mixture was subjected to preparative TLC on silica gel with
EtOAc/hexane (1/4) to give a mixture of 10b and 11b (98/2) in 95%
yield (52.9 mg, 0.190 mmol).
1H NMR (CDCl3): δ = 7.29 (dd, J = 8.9, 4.8 Hz, 4 H), 7.04 (t, J = 8.9 Hz, 4
H), 4.84–4.82 (m, 1 H), 4.47–4.46 (m, 1 H), 3.52 (s, 2 H).
13C NMR (CDCl3): δ = 174.9, 162.2 (d, JF,C = 248 Hz), 152.2, 136.4 (d,
JF,C = 3 Hz), 129.1 (d, JF,C = 9 Hz), 115.7 (d, JF,C = 22 Hz), 89.9, 56.1, 41.8.
Compound 10b
HRMS (APCI): m/z [M + H]+ calcd for C17H13F2O2: 287.0878; found:
287.0891.
Colorless oil.
1H NMR (CDCl3): δ = 7.21 (d, J = 8.1 Hz, 4 H), 7.14 (d, J = 8.1 Hz, 4 H),
4.79–4.77 (m, 1 H), 4.41–4.40 (m, 1 H), 3.53 (s, 2 H), 2.33 (s, 6 H).
Compound 11d [CAS: 1803403-18-0 for (R)-11d]
13C NMR (CDCl3): δ = 175.4, 152.9, 138.0, 137.4, 129.4, 127.2, 89.2,
Colorless oil.
56.6, 41.8, 21.0.
1H NMR (CDCl3): δ = 7.33–7.29 (m, 2 H), 7.28–7.24 (m, 2 H), 7.04 (t, J =
8.7 Hz, 2 H), 6.99 (t, J = 8.7 Hz, 2 H), 4.49–4.43 (m, 1 H), 3.01 (dd, J =
12.9, 4.8 Hz, 1 H), 2.53 (dd, J = 12.9, 10.2 Hz, 1 H), 1.46 (d, J = 6.1 Hz, 3
H).
HRMS (APCI): m/z [M + H]+ calcd for C19H19O2: 279.1380; found:
279.1392.
Compound 11b [CAS: 1803403-16-8 for (R)-11b]
3,3-Bis(4-chlorophenyl)-5-methylenedihydrofuran-2(3H)-one
(10e) and 3,3-Bis(4-chlorophenyl)-5-methyldihydrofuran-2(3H)-
one (11e)
Colorless oil.
1H NMR (CDCl3): δ = 7.25 (d, J = 8.1 Hz, 2 H), 7.19 (d, J = 8.1 Hz, 2 H),
7.16 (d, J = 8.1 Hz, 2 H), 7.11 (d, J = 8.1 Hz, 2 H), 4.50–4.44 (m, 1 H),
3.02 (dd, J = 12.9, 4.8 Hz, 1 H), 2.55 (dd, J = 12.9, 10.2 Hz, 1 H), 2.34 (s,
3 H), 2.31 (s, 3 H), 1.46 (d, J = 6.1 Hz, 3 H).
The crude mixture was subjected to preparative TLC on silica gel with
EtOAc/hexane (1/4) to give a mixture of 10e and 11e (98/2) in 90%
yield (57.7 mg, 0.180 mmol).
3,3-Bis(4-methoxyphenyl)-5-methylenedihydrofuran-2(3H)-one
(10c) and 3,3-Bis(4-methoxyphenyl)-5-methyldihydrofuran-
2(3H)-one (11c)
Compound 10e
Colorless oil.
The crude mixture was subjected to preparative TLC on silica gel with
EtOAc/hexane (1/3) to give a mixture of 10c and 11c (99/1) in 93%
yield (58.0 mg, 0.186 mmol).
1H NMR (CDCl3): δ = 7.33 (d, J = 8.1 Hz, 4 H), 7.25 (d, J = 8.1 Hz, 4 H),
4.84 (q, J = 1.7 Hz, 1 H), 4.47 (q, J = 1.7 Hz, 1 H), 3.51 (t, J = 1.7 Hz, 2 H).
13C NMR (CDCl3): δ = 174.4, 152.0, 138.9, 134.1, 129.0, 128.7, 90.1,
56.3, 41.4.
Compound 10c
HRMS (APCI): m/z [M + H]+ calcd for C17H1335Cl2O2: 319.0287; found:
319.0286.
Colorless oil.
1H NMR (CDCl3): δ = 7.24 (d, J = 8.9 Hz, 4 H), 6.86 (d, J = 8.9 Hz, 4 H),
4.79–4.78 (m, 1 H), 4.42–4.41 (m, 1 H), 3.79 (s, 6 H), 3.50 (s, 2 H).
Compound 11e [CAS: 1803403-19-1 for (R)-11e]
13C NMR (CDCl3): δ = 175.7, 158.9, 152.9, 133.1, 128.4, 114.0, 89.2,
White solid.
56.0, 55.3, 42.0.
1H NMR (CDCl3): δ = 7.32 (d, J = 8.8 Hz, 2 H), 7.29–7.22 (m, 6 H), 4.49–
4.43 (m, 1 H), 2.99 (dd, J = 12.9, 4.8 Hz, 1 H), 2.53 (dd, J = 12.9, 10.9 Hz,
1 H), 1.46 (d, J = 6.1 Hz, 3 H).
HRMS (APCI): m/z [M + H]+ calcd for C19H19O4: 311.1278; found:
311.1287.
Compound 11c [CAS: 1803403-17-9 for (R)-11c]
3,3-Dibenzyl-5-methylenedihydrofuran-2(3H)-one (10f) and 3,3-
Dibenzyl-5-methyldihydrofuran-2(3H)-one (11f)
Colorless oil.
The crude mixture was subjected to preparative TLC on silica gel with
EtOAc/hexane (1/4) to give a mixture of 10f and 11f (99/1) in 83%
yield (46.8 mg, 0.166 mmol).
1H NMR (CDCl3): δ = 7.26 (d, J = 8.9 Hz, 2 H), 7.19 (d, J = 8.9 Hz, 2 H),
6.86 (d, J = 8.9 Hz, 2 H), 6.82 (d, J = 8.9 Hz, 2 H), 4.48–4.42 (m, 1 H),
3.78 (s, 3 H), 3.76 (s, 3 H), 2.99 (dd, J = 12.9, 4.8 Hz, 1 H), 2.51 (dd, J =
12.9, 10.2 Hz, 1 H), 1.44 (d, J = 6.1 Hz, 3 H).
Compound 10f
Colorless oil.
1H NMR (CDCl3): δ = 7.31–7.24 (m, 6 H), 7.17 (d, J = 8.1 Hz, 4 H), 4.34
(q, J = 1.7 Hz, 1 H), 3.94–3.92 (m, 1 H), 3.21 (d, J = 13.5 Hz, 2 H), 2.81
(d, J = 13.5 Hz, 2 H), 2.71 (t, J = 1.7 Hz, 2 H).
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Synthesis
13C NMR (CDCl3): δ = 178.5, 153.1, 135.7, 130.3, 128.5, 127.2, 88.3,
Compound 10i
51.1, 42.9, 32.9.
White solid.
HRMS (APCI): m/z [M + H]+ calcd for C19H19O2: 279.1380; found:
279.1390.
1H NMR (CDCl3): δ = 7.50 (d, J = 8.2 Hz, 2 H), 7.41–7.32 (m, 3 H), 7.30–
7.24 (m, 3 H), 6.99–6.94 (m, 2 H), 4.86 (t, J = 2.4 Hz, 1 H), 4.38 (t, J = 2.4
Hz, 1 H), 3.93 (qt, J = 6.8, 2.4 Hz, 1 H), 0.97 (d, J = 6.8 Hz, 3 H).
Compound 11f [CAS: 1803403-20-4 for (R)-11f]
13C NMR (CDCl3): δ = 175.1, 158.6, 139.1, 138.8, 128.4, 128.2, 127.8,
Colorless oil.
127.4, 88.9, 60.4, 41.8, 14.0.
1H NMR (CDCl3): δ = 7.31–7.17 (m, 10 H), 3.41–3.35 (m, 1 H), 3.27 (d,
J = 13.5 Hz, 1 H), 3.16 (d, J = 13.5 Hz, 1 H), 2.77 (d, J = 13.2 Hz, 1 H),
2.71 (d, J = 13.2 Hz, 1 H), 2.17 (dd, J = 13.2, 7.1 Hz, 1 H), 1.77 (dd, J =
13.2, 9.2 Hz, 1 H), 0.84 (d, J = 6.8 Hz, 3 H).
HRMS (ESI): m/z [M + Na]+ calcd for C18H16O2Na: 287.1048; found:
287.1039.
Compound 11i
Colorless oil.
3,3-Dimethyl-5-methylenedihydrofuran-2(3H)-one (10g) (CAS:
1H NMR (CDCl3): δ = 7.45–7.41 (m, 2 H), 7.39–7.34 (m, 2 H), 7.33–7.25
(m, 4 H), 6.97–6.93 (m, 2 H), 4.14–4.06 (m, 1 H), 3.04–2.95 (m, 1 H),
1.49 (d, J = 6.0 Hz, 3 H), 0.90 (d, J = 6.0 Hz, 3 H).
13C NMR (CDCl3): δ = 177.7, 140.2, 138.7, 129.1–127.2 (br), 78.4, 61.3,
45.4 (br), 18.0 (br), 11.9.
86972-24-9)
The crude mixture was subjected to column chromatography on silica
gel with Et2O/pentane (1:4) to give a mixture of 10g in 59% yield (22.5
mg, 0.177 mmol) as a colorless oil.
1H NMR (CDCl3): δ = 4.75 (d, J = 1.9 Hz, 1 H), 4.32 (d, J = 1.9 Hz, 1 H),
2.69 (t, J = 1.9 Hz, 2 H), 1.30 (s, 6 H).
HRMS (ESI): m/z [M + Na]+ calcd for C18H18O2Na: 289.1205; found:
289.1214.
3-Cinnamyl-5-methylene-3-phenyldihydrofuran-2(3H)-one (10h)
and 3-Cinnamyl-5-methyl-3-phenyldihydrofuran-2(3H)-one (11h)
Stoichiometric Reaction of 1h with [IrCl(coe)2]2/dppf
Dppf (11.0 mg, 0.020 mmol) and [IrCl(coe)2]2 (5.1 mg, 0.020 mmol Ir)
were placed in a Schlenk tube under N2. C6D6 (0.60 mL) was added to
the Schlenk tube and the mixture was stirred at r.t. for 15 min. Com-
pound 1h and 1,4-dimethoxybenzene (3.3 mg, 0.024 mmol as an in-
ternal standard) were added to the Schlenk tube and the mixture was
stirred at r.t. for 30 min. The resulting solution was transferred to an
NMR tube capped with a rubber septum by use of a syringe pump.
The signal of the hydride was observed at δ = –29.5 (t, JP,H = 22 Hz), –
27.7 (dd, JP,H = 27, 16 Hz), –27.4 (dd, JP,H = 29, 18 Hz), –23.7 (t, JP,H = 20
Hz), and –22.4 (t, JP,H = 22 Hz). The yield of the iridium hydride com-
plex was estimated to be 3%, 23%, 9%, 10%, and 6%, respectively.
The crude mixture was subjected to preparative TLC on silica gel with
EtOAc/hexane (1/4) to give a mixture of 10h and 11h (99/1) in 91%
yield (53.1 mg, 0.182 mmol).
Compound 10h
Colorless oil.
1H NMR (CDCl3): δ = 7.50 (d, J = 7.8 Hz, 2 H), 7.40 (t, J = 7.8 Hz, 2 H),
7.32 (t, J = 7.8 Hz, 1 H), 7.30–7.27 (m, 4 H), 7.25–7.21 (m, 1 H), 6.48 (d,
J = 14.4 Hz, 1 H), 6.00 (dt, J = 14.4, 7.5 Hz, 1 H), 4.76 (d, J = 1.9 Hz, 1 H),
4.36 (J = 1.9 Hz, 1 H), 3.25 (dt, J = 16.0, 1.9 Hz, 1 H), 3.21 (dt, J = 16.0,
1.9 Hz, 1 H), 2.91 (dd, J = 13.5, 7.5 Hz, 1 H), 2.88 (dd, J = 13.5, 7.5 Hz, 1
H).
13C NMR (CDCl3): δ = 176.4, 153.1, 139.2, 136.7, 135.1, 128.9, 128.5,
127.7, 127.6, 126.3, 126.1, 123.4, 89.2, 52.3, 42.7, 37.4.
HRMS (APCI): m/z [M + H]+ calcd for C20H19O2: 291.1380; found:
291.1381.
Funding Information
Japan Society for the Promotion of Science, Grant / Award Number:
'JP15H03810'.
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Acknowledgment
Colorless oil; d.r. = 70:30.
This work was supported by JSPS KAKENHI Grant Number
JP15H03810. M.N. thanks the JSPS for a Research Fellowship for Young
Scientists.
1H NMR (CDCl3): δ = 7.56 [d, J = 7.5 Hz, 2 H (minor)], 7.45 [d, J = 7.5 Hz,
2 H (major)], 7.40–7.20 [m, 8 H (major) + 8 H (minor)], 6.45 [d, J = 16.3
Hz, 1 H (major)], 6.42 [d, J = 16.3 Hz, 1 H (minor)], 6.07–5.97 [m, 1 H
(major) + 1 H (minor)], 4.68–4.62 [m, 1 H (minor)], 4.41–4.35 [m, 1 H
(major)], 2.86–2.72 [m, 3 H (major) + 3 H (minor)], 2.32 [dd, J = 13.2,
7.8 Hz, 1 H (minor)], 2.12 [t, J = 12.2 Hz, 1 H (major)], 1.40 [d, J = 6.1
Hz, 3 H (major)], 1.34 [d, J = 6.1 Hz, 3 H (minor)].
Supporting Information
Supporting information for this article is available online at
HRMS (APCI): m/z [M + H]+ calcd for C20H21O2: 293.1542; found:
https://doi.org/10.1055/s-0036-1588435.
S
u
p
p
o
nrtogI
f
rmoaitn
S
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p
ortiInfogrmoaitn
293.1550.
References
4-Methyl-5-methylene-3,3-diphenyldihydrofuran-2(3H)-one (10i)
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K
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Special Topic
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