Asymmetric Cycloetherification by Bifunctional Organocatalyst

Article abstract of DOI:10.1055/s-0036-1591592

Attempts to obtain enantiomerically enriched tetrahydrofuran derivatives via an intramolecular oxy -Michael addition reaction of ?-hydroxyenone is discussed. Despite previous difficulties associated with the asymmetric induction of this reaction, which can proceed even without a catalyst, a highly efficient asymmetric induction was realized using a bifunctional organocatalyst derived from a cinchona alkaloid. The reaction could be extended to ζ-hydroxyenone to yield an optically active tetrahydropyran derivative with a high ee. In these reactions, it is important for the gentle acidic and basic sites in the bifunctional organocatalyst to be arranged properly within the molecular skeleton of the catalyst. The high performance asymmetric induction relied on the affinity of the catalyst for the substrate, which played an important role. A disubstituted tetrahydropyran synthesis could be effectively performed via kinetic resolution using ζ-hydroxyenone containing a secondary alcohol moiety using a chiral phosphoric acid catalyst.

Full text of DOI:10.1055/s-0036-1591592

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2018, 50, A–K
feature
A
en
K. Asano, S. Matsubara
Feature
Synthesis
Asymmetric Cycloetherification by Bifunctional Organocatalyst
Keisuke Asano*
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2-
9
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Formation of
Chiral Conformer
Seijiro Matsubara*
0
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8-
4
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4-
5
7
4
O
Molecular
Conjugate
Asymmetric
Cycloetherification
O
H
LA
Department of Material Chemistry, Graduate School of Engineer-
ing, Kyoto University, Kyotodaigaku-Katsura, Nishkyo,
615-8510 Kyoto, Japan
LB
Chiral Bifunctional
Organocatalyst
matsubara.seijiro.2@kyoto-u.ac.jp
R’
*
R
O
R
Published as part of the Special Section on the 26th French–Japanese
R
O
O
Symposium on Medicinal and Fine Chemistry
*
*
*
O
O
O
R = aryl, alkyl
7 examples
97–99% yield
85–95% ee
R = Ph
90%
R, R' = aryl, aryl; aryl, alkyl
7 examples
51–63% conversion
dr up to 50:1; ee up to 96%
Received: 17.04.2018
Accepted: 27.04.2018
Published online: 26.06.2018
DOI: 10.1055/s-0036-1591592; Art ID: ss-2018-z0259-fa
can be used to achieve more elaborate selectivities. Recent-
ly, organocatalysts without any metal have been actively
studied. A major feature of organocatalysts is the ease with
which multiple active sites may be positioned within a sin-
gle molecule, despite providing opposite properties, for ex-
ample, acidic and basic sites.2,3 In other words, the asym-
metric arrangement of sites within a molecule can realize
effective asymmetric induction and efficiently facilitate a
reaction by recognizing the specific conformation of the
substrate.
We studied the synthesis of the optically active tetrahy-
drofurans and tetrahydropyrans using a bifunctional or-
ganocatalyst4 that is obtained readily from the cinchona al-
kaloid.5 The asymmetric intramolecular oxy-Michael addi-
tion reaction of ε-hydroxyenone is a direct synthetic
method that gives an optically active tetrahydrofuran ring,
a substructure of many useful bioactive compounds.6 Sev-
eral reports have also described other catalytic methods.7 In
general, a discrimination of routes to form each enantiomer
is subtle, when the activation energy is quite small. This
tetrahydrofuran formation proceeds via entropically and
enthalpically favorable 5-exo-trigonal intramolecular cy-
clization. We had focused on specific interactions between
a catalyst and the substrate, which can induce this 5-exo-
trigonal cyclization and also contain some crucial role for
distinguishing the enantioface. In this sense, the use of a bi-
functional organocatalyst possessing weak acidic and basic
sites might be ideal for controlling this asymmetric cycliza-
tion reaction.8 Because both interactions are indispensable
for promoting the reaction, the substrate could be convert-
ed into the corresponding cyclized product via a molecular
conjugate through them, in which the substrate assumes a
specific chiral conformation (Scheme 1).9
Abstract Attempts to obtain enantiomerically enriched tetrahydrofu-
ran derivatives via an intramolecular oxy-Michael addition reaction of
ε-hydroxyenone is discussed. Despite previous difficulties associated
with the asymmetric induction of this reaction, which can proceed even
without a catalyst, a highly efficient asymmetric induction was realized
using a bifunctional organocatalyst derived from a cinchona alkaloid.
The reaction could be extended to ζ-hydroxyenone to yield an optically
active tetrahydropyran derivative with a high ee. In these reactions, it is
important for the gentle acidic and basic sites in the bifunctional or-
ganocatalyst to be arranged properly within the molecular skeleton of
the catalyst. The high performance asymmetric induction relied on the
affinity of the catalyst for the substrate, which played an important
role. A disubstituted tetrahydropyran synthesis could be effectively per-
formed via kinetic resolution using ζ-hydroxyenone containing a sec-
ondary alcohol moiety using a chiral phosphoric acid catalyst.
Key words organocatalyst, bifunctional catalyst, asymmetric synthe-
sis, oxy-Michael reaction, tetrahydrofuran, tetrahydropyran, kinetic res-
olution
Catalysts play an important role in synthesizing organic
compounds, and a variety of compounds ranging from the
smallest proton to very high molecular weight peptides are
used for this purpose.1 While stabilizing the rate-determin-
ing transition state to accelerate the reaction is the funda-
mental role of catalysts, catalysts improve the selectivity of
the desired reaction. Catalysts that incorporate a variety of
functions require artful design. Metal-centered catalysts,
which have been studied broadly and deeply, exhibit selec-
tivities that depend on the metal’s inherent properties. Cer-
tain ligand combinations convey appropriate steric and
electronic functions that enable highly selective reactions.
Additives to a ligand-coordinated metal-centered catalyst
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–K

B
K. Asano, S. Matsubara
Feature
Synthesis
quinidine, and 3b, derived from cinchonine, gave the R-
form of 2a. The catalyst 3c, derived from quinine, and 3d,
derived from cinchonidine, gave (S)-2a enantioselectively.
Among these catalysts, 3a and 3c in cyclopentyl methyl
ether (CPME) quantitatively gave both enantiomers of 2a at
over 95% ee (Table 1, entries 5 and 8). CPME, a poorly basic
ether, was suitable as a solvent for these reactions.10
Based on the reaction conditions reported in Table 1,
several substrates were examined to obtain optically active
THF derivatives (Table 2). Even if the substituent R in the
enone moiety in 1 was a benzene ring substituted with an
electron-donating/-withdrawing group (Table 2, entries 2–
5), a bulky 2-naphthyl (entry 6) or alkyl group (entry 7), the
cyclization reaction proceeded in high yield and with high
enantioselectivity.
HO
R
O
5-exo-trig
R
*
O
O
2
1
LB* H O
R
HO
R
Cyclization
without
Asymmetric Induction
LA*
O
O
Chiral Base Catalyzed
Chiral Acid Catalyzed
R
Fomation of Chiral
Conformer
O
Molecular
Conjugate
Asymmetric
Cycloetherification
O
H
LA
LB
Chiral
Bifunctional
Olganocatalyst
This method was applied to ζ-hydroxyenone 4, as
shown in Equation 1, to obtain an optically active tetrahy-
dropyran derivative 5 with high ee. The reaction progressed
as described in the case of tetrahydrofuran, shown above.
Scheme 1 Strategy for achieving the catalytic asymmetric cycloetheri-
fication of 1 to form tetrahydrofuran 2 using a bifunctional organocata-
lyst
catalyst 3a
(5.0 mol%)
Table 1 shows the results of the intramolecular oxy-
Michael addition of ε-hydroxyenone 1a using the typical
thiourea-amine bifunctional organocatalyst 3 derived from
the cinchona alkaloid. All reactions starting from ε-hy-
droxyenone 1a were examined at 25 °C over 24 hours in the
presence of various solvents. The catalyst 3a, derived from
Ph HO
Ph
O
CPME
25 °C, 24 h
O
O
4
5 (90%, 91% ee)
Equation 1 Asymmetric cycloetherification of 4 into tetrahydropyran
5 via the bifunctional organocatalyst 3a
Biographical Sketches
Keisuke Asano was born in
1984 and raised in Kobe. He
completed his Ph.D. at Kyoto
University (Japan) in 2012 un-
der the supervision of Professor
Seijiro Matsubara. He was ap-
pointed as an Assistant Profes-
sor at Kyoto University in 2012
and joined the group of Profes-
sor Jun-ichi Yoshida before mov-
ing back to the group of
Professor Seijiro Matsubara in
2013. He received the 30th
Inoue Research Award for Young
Scientists (2014), the Eisai
Award in Synthetic Organic
Chemistry, Japan (2014), and
was a Special Young Lecturer in
the 95th CSJ Annual Meeting
(2015).
Seijiro Matsubara was born
in 1959 and raised in Kobe. He
was educated in chemistry at
Kyoto University (Japan), com-
pleting his Ph.D. in 1986 with
Professors Hitosi Nozaki and
Kiitiro Utimoto, and at the Uni-
versité de Lausanne (Switzer-
land) where he was a Ph.D.
course student with Professor
Manfred Schlosser. He was ap-
pointed as an Assistant Profes-
sor at Kyoto University in 1986.
After postdoctoral research with
Professor Barry M. Trost at Stan-
ford University (USA) in 1988–
1989, he became an Associate
Professor at Kyoto University in
1995. In 2006, he became a Full
Professor at Kyoto University.
He received The 3rd Inoue Re-
search Award for Young Scien-
tists (1987), the Incentive
Award in Synthetic Organic
Chemistry, Japan (1998), the
Asian Core Program Lectureship
Award, Korea and Malaysia
(2014), and The 34th Chemical
Society of Japan Award for Cre-
ative Work (2017).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–K

C
K. Asano, S. Matsubara
Feature
Synthesis
Table 1 Optimizing the Conditions of the Asymmetric Cycloetherification of 1a by the Bifunctional Organocatalyst 3a
catalyst
(3.0 mol%)
3
HO
Ph
O
Ph
solvent
25 °C, 24 h
O
O
1a
(R)-2a
Entry
Catalyst 3
Solvent
CH2Cl2
Yield (%)b
ee (%)
1
3a
3a
3a
3a
3a
3a
3b
3c
3d
99
97
73
99
99
95
99
99
99
92
94
2
benzene
THF
3
90
4
Et2O
94
5
CPME
CPME
CPME
CPME
CPME
95
6c
7
96
89
8d
9d
–96
–94
ArHN
S
ArHN
H
H
H
H
N
N
OMe
N
H
H
N
S
N
N
H
N
N
H
N
H
H
NH
NH
N
OMe
3a
S
S
ArHN
3d
Ar: 3,5-(CF3)2C6H3
ArHN
3b
3c
a Reaction conditions: Substrate 1a (0.25 mmol) and the catalyst 3 (0.0075 mmol) in solvent (0.5 mL).
b Isolated yields.
c Catalyst 3a used: 1.0 mol%.
d (S)-2a was formed enantioselectively.
and carbonyl groups. Each interaction is not strong enough
for reaction activation, and the reaction is initiated only
once both interactions form cooperatively. The substrate
and catalyst must form an advantageous conjugate in the
transition state. Formation of the conjugate increases the
possibility of kinetically resolving the chiral substrate.11,12
As shown in Table 3, the reaction of the racemic (E)-7-
hydroxy-1,7-diphenylhept-2-en-1-one [(rac)-6a] was per-
formed at 0 °C using the bifunctional aminothiourea cata-
lysts 3a–d. The observed selectivity factors were not satis-
factory (Table 3, entries 1–4). We next focused on the chiral
phosphoric acid catalysts 3e–h.13,14 These catalysts possess
both acidic and basic sites, allowing for the multipoint rec-
ognition of substrates via hydrogen bonding. Other sterical-
ly bulky substituents near the catalytic sites play a crucial
role for the recognition of a substrate. In this context, we
envisioned that these chiral phosphoric acid catalysts
would be suitable for the kinetic resolution strategy (en-
tries 5–8). In fact, the phosphoric acid catalyst 3e per-
formed significantly better than the aminothiourea cata-
lysts 3a–d (entry 5). Dichloromethane, diethyl ether, or eth-
yl acetate solvents were examined but were found to
produce low s-factors compare to the reaction in toluene
(entries 9–11). Although the stereoselectivity was not im-
proved by performing the reaction at –20 °C in toluene (en-
try 12), the use of molecular sieves (MS) 4A as an additive
Table 2 Preparation of the Tetrahydrofurans via Asymmetric Cyclo-
etherification of 1 by Bifunctional Organocatalyst 3aa
catalyst 3a
(3.0 mol%)
HO
R
O
R
CPME
25 °C, 24 h
O
O
1
(R)-2
Entry
R
(R)-2 Yield (%)b
ee (%)
1
2
3
4
5
6
7c
Ph
1a
1b
1c
1d
1e
1f
99
99
93
99
99
98
97
(R)-2a
95
94
85
93
92
91
90
p-MeOC6H4
p-F3CC6H4
p-MeC6H4
p-BrC6H4
(R)-2b
(R)-2c
(R)-2d
(R)-2e
(R)-2f
(R)-2g
2-naphthyl
PhCH2CH2
1g
a Reaction conditions: Substrate 1 (0.25 mmol) and 3a (0.0075 mmol) in
CPME (0.5 mL).
b Isolated yields.
c Reaction time: 120 h.
In these intramolecular cyclization reactions, the amine
and thiourea groups in catalyst 3 play important roles in the
asymmetric induction by interacting favorably with the
acidic and basic sites of the substrate, that is, the hydroxyl
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–K

D
K. Asano, S. Matsubara
Feature
Synthesis
Table 3 Asymmetric Cycloetherification of (rac)-6a via Kinetic Resolutiona
Ph
Ph
Ph
O
Ph
O
Ph
+
catalyst
3
O
O
Ph HO
7a
7’a
Ph
O
+
(rac)-6a
Ph HO
O
(R)-6a
Entry
3 (mol%)
Solvent
Temp (°C)
Time (h)
Conv. (%)
7a/7′a (% ee)
(R)-6a (% ee)
sb
1
2
3a (30)
3b (30)
3c (30)
3d (30)
3e (1.0)
3f (0.1)
3g (1.0)
3h (1.0)
3e (1.0)
3e (1.0)
3e (5.0)
3e (1.0)
3e (1.0)
3e (5.0)
CPME (0.5 M)
CPME (0.5 M)
CPME (0.5 M)
CPME (0.5 M)
25
25
25
25
0
48
48
48
48
2
58
55
68
63
55
43
28
47
60
9.6
31
44
44
51
4.3/1 (70, 28)
5.3/1 (71, 27)
2.1/1 (–69, –7)
3.0/1 ( –72, 0)
16/1 (80, 80)
24/1 (4, 0)
72
69
–93
–91
85
3
6.5
7.0
8.0
3
4
10
15
1.1
4.7
14
5
toluene (0.01 M)
toluene (0.01 M)
toluene (0.01 M)
toluene (0.01 M)
CH2Cl2 (0.01 M)
Et2O (0.01 M)
6
0
15
24
9
7
0
24/1 (62, 31)
13/1 (86, 68)
16/1 (51, 67)
6.7/1 (55, 9)
13/1 (66, 39)
19/1 (87, 61)
19/1 (88, 79)
24/1 (89, 87)
23
66
66
5
8
0
9
0
2.5
24
24
12
2
4.9
2.9
4.9
10
11
12
13
14
0
EtOAc (0.01 M)
toluene (0.01 M)
0
26
62
62
85
–20
–20
–40
16
toluene (0.01 M + MS 4A)
toluene (0.01 M + MS 4A)
16
27
4
CF3
CF3
iPr
iPr
iPr
iPr
iPr
iPr
iPr
iPr
iPr
O
O
O
O
O
O
O
O
O
O
O
O
P
P
P
P
OH
OH
OH
OH
iPr
iPr
iPr
CF3
CF3
iPr
iPr
iPr
3e
iPr
iPr
3h
iPr
3f
3g
a Substrate (rac)-6a (0.15 mmol) was used.
b Selectivity factors (s) were calculated from the conversion (%) and ee values of the recovered (R)-6a. See ref. 11: s = kfast/kslow = ln[(1 – Conv%/100)(1 – (R)-
6a%ee/100)]/ln[(1 – Conv%/100)(1 + (R)-6a%ee/100)].
was found to dramatically accelerate the reaction (entry
13). In the presence of MS 4A, the reaction could be per-
formed even at –40 °C, and the s-factor was significantly
improved (entry 14).
With the conditions optimized, several substrates were
examined as shown in Table 4. Although the substrate bear-
ing a p-methoxyphenyl group in R2 gave the corresponding
products in a poor stereoselectivity (Table 4, entry 1), an
electron-deficient aryl carbinol 6c and the huge aryl carbi-
nols 6d, 6e were converted into the optically active 7 with
high selectivities (entries 2–4). The alkyl carbinol 6f (R1 =
n-C4H9) also gave the disubstituted THP with reasonable se-
lectivity (entry 5). The methoxy and trifluoromethyl groups
on the aryl enone did not affect the selectivity (entries 6, 7).
As shown in equation 2, the asymmetric cyclization of 8
using 3e as the catalyst gave 9 in 95% ee at 48% conversion.
The catalyst-controlled cyclization induced chirality at the
bond-forming β-position; the intermediary formed chair-
like conformation of 8 dominated the kinetic resolution.
Within the obtained product 9, the two large substituents,
were arranged in a cis-configuration, which allow them to
take equatorial positions.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–K

E
K. Asano, S. Matsubara
Feature
Synthesis
C6D6 as a solvent, C6D6 was used as an internal standard (δ = 128.06).
1H NMR data are reported as follows: chemical shift, multiplicity
(standard abbreviations), coupling constants (Hz), integration.
19F NMR spectra were measured on a Varian Mercury 200 (19F, 188
MHz) spectrometer with C6F6 as an internal standard (δ = 0). GC-MS
analyses and high-resolution mass spectra were obtained with a Jeol
JMS-700 spectrometer by electron ionization at 70 eV. High-perfor-
mance liquid chromatography (HPLC) was performed with a Shimadzu
Prominence apparatus. IR spectra were determined on a Shimadzu IR
Affinity-1 spectrophotometer. Melting points were determined using
a Yanako MP-500D apparatus. Optical rotations were measured on a
Horiba SEPA-200 polarimeter. TLC analyses were performed by means
of Merck Kieselgel 60 F254 (0.25 mm) Plates. Visualization was accom-
plished with UV light (254 nm) and/or such as an aqueous alkaline
KMnO4 solution followed by heating. Flash column chromatography
was carried out using Kanto Chemical silica gel (spherical, 40–50 μm).
Unless otherwise noted, commercially available reagents were used
without purification. The chiral phosphoric acids 3e–f are commer-
cially available.
Ph
Ph
Ph
Me catalyst 3e
Me
Me
(10 mol%)
Ph HO
Ph HO
Ph
O
toluene, MS 4A
–40 ° C, 24 h
48% conv
O
O
O
(R)-8 84% ee
(rac)-8
9 (95% ee, 25:1 dr)
s = 54
Equation 2 Asymmetric cycloetherification of the tertiary alcohol
(rac)-8 via kinetic resolution
In summary, the asymmetric intramolecular Michael
addition of hydroxyenone by a bifunctional organocatalyst
was shown to be useful as a method for synthesizing opti-
cally active THF and THP derivatives. The reaction proceeds
via formation of a molecular conjugate consisting of the
substrate and the catalyst. In this conjugate, two acid-base
interactions and the affinity of the preferable chiral con-
former of the substrate with the organocatalyst’s molecular
skeleton assist the selective formation of the corresponding
enantiomer of the product. This control enables the trans-
formation of secondary ζ-hydroxyenones into THP deriva-
tives via kinetic resolution.
Asymmetric Synthesis of 2-Substituted Tetrahydrofurans 2; Gen-
eral Procedure
To a 5 mL vial were added ε-hydroxy-α,β-unsaturated ketone 1 (0.25
mmol), cyclopentyl methyl ether (0.5 mL), and quinidine-derived bi-
functional catalyst 3a (0.0075 mmol) sequentially. The mixture was
stirred in an oil bath maintained at 25 °C for 24 h. The mixture was
diluted with hexane/EtOAc (1:1 v/v), passed through a short silica gel
column to remove 3a, and concentrated in vacuo. Purification of the
1H and 13C NMR spectra were taken on a Varian Unity Inova 500 (1H,
500 MHz; 13C, 125.7 MHz) spectrometer using TMS as an internal
standard for 1H NMR (δ = 0) and CDCl3 as an internal standard for
13C NMR (δ = 77.0). When a 13C NMR spectrum was measured using
Table 4 Substrate Scope of the Asymmetric Cycloetherification of (rac)-6 via Kinetic Resolutiona
R2
R2
R1
O
R1
O
R2
+
catalyst 3e
R1 HO
O
O
7
7’
R2
toluene, MS 4A
O
+
(rac)-6
R1 HO
O
(R)-6
Entry
R1, R2 (rac)-6
3e
(mol%)
Time (h)
Temp
(°C)
Conv
(%)
7/7′
(% ee)
(R)-6
(% ee)
s
1
2
3
4
5
6
7
Ph, p-MeOC6H4 (6b)
Ph, p-F3CC6H4 (6c)
Ph, 9-anthracenyl (6d)
Ph, 4-pyrenyl (6e)
Ph, n-C4H9 (6f)
5
5
1
1
5
5
5
36
4
–40
–40
0
63
52
49
58
53
52
57
4.3/1 (58, 96)
16/1 (90, 90)
50/1 (90, 83)
17/1 (79, 71)
14/1 (82, 84)
19/1 (90, 85)
12/1 (86, 88)
50
87
84
98
81
89
97
1.8
26
2
39
26
15
30
26
1
0
2.5
4
–40
–40
–40
p-MeOC6H4 Ph, (6g)
p-F3CC6H4, Ph (6h)
7
O
Ph
HO
O
Ph
HO
(rac)-6d
(rac)-6e
a Substrate (rac)-6 (0.15 mmol) was used. See experimental section.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–K

F
K. Asano, S. Matsubara
Feature
Synthesis
mixture by flash silica gel column chromatography using hexane/EtO-
Ac (3:1 v/v) as an eluent afforded the corresponding 2-substituted tet-
rahydrofuran 2.
19F NMR (CDCl3): δ = 98.0.
HRMS: m/z calcd for C13H13F3O2 (M+): 258.0868; found: 258.0863.
(R)-1-(4-Methylphenyl)-2-(tetrahydrofuran-2-yl)ethanone (2d)
(R)-1-Phenyl-2-(tetrahydrofuran-2-yl)ethanone (2a)
[CAS Reg. No. 1337999-54-8]
[CAS Reg. No. 1337999-50-4]
Yield: 50.5 mg (99%); 93% ee; colorless oil; Rf = 0.29 (hexane/EtOAc
3:1); [α]D23 –1.7 (c 5.75, CH2Cl2).
Yield: 47.0 mg (99%); 95% ee; colorless oil; Rf = 0.26 (hexane/EtOAc
3:1); [α]D23 –3.5 (c 4.98, CH2Cl2).
HPLC: Daicel Chiralcel OD-H; hexane/i-PrOH (99:1), flow rate = 0.5
mL/min, λ = 254 nm, 40 °C; tR = 29.7 min (minor), tR = 31.9 min (ma-
jor).
HPLC: Daicel Chiralcel OD-H; hexane/i-PrOH (99.9:0.1), flow rate =
5.0 mL/min, λ = 254 nm, 40 °C); tR = 15.4 min (minor), tR = 17.1 min
(major).
IR (neat): 3584, 2970, 2870, 2360, 1681, 1607, 1574, 1449, 1408,
IR (neat): 3351, 2973, 2873, 1682, 1598, 1581, 1449, 1382, 1300,
1380, 1301, 1221, 1206, 1181, 1067, 1013, 844, 807, 761, 464 cm–1
.
1280, 1210, 1181, 1067, 1002, 928, 754, 691, 498 cm–1
.
1H NMR (CDCl3): δ = 7.86 (d, J = 8.0 Hz, 2 H), 7.25 (d, J = 8.0 Hz, 2 H),
4.39 (dddd, J = 7.0, 6.5, 6.5, 6.0 Hz, 1 H), 3.89 (m, 1 H), 3.75 (m, 1 H),
3.37 (dd, J = 16.0, 5.0 Hz, 1 H), 3.03 (dd, J = 16.0, 7.0 Hz, 1 H), 2.41 (s, 3
H), 2.19 (m, 1 H), 1.92 (m, 2 H), 1.56 (m, 1 H).
13C NMR (CDCl3): δ = 198.0, 143.9, 134.7, 129.2, 128.3, 75.5, 67.8, 44.6,
31.6, 25.7, 21.6.
1H NMR (CDCl3): δ = 7.97 (m, 2 H), 7.56 (m, 1 H), 7.46 (m, 2 H), 4.41
(dddd, J = 7.0, 6.5, 6.5, 6.0 Hz, 1 H), 3.89 (ddd, J = 8.5, 7.0, 6.5 Hz, 1 H),
3.75 (m, 1 H), 3.40 (dd, J = 16.0, 6.0 Hz, 1 H), 3.06 (dd, J = 16.0, 6.5 Hz,
1 H), 2.20 (m, 1 H), 1.93 (m, 2 H), 1.57 (m, 1 H).
13C NMR (CDCl3): δ = 198.4, 137.1, 133.1, 128.6, 128.2, 75.4, 67.8, 44.7,
31.6, 25.6. HRMS: m/z calcd for C12H15O2 [M + H]+: 191.1072; found:
191.1067.
HRMS: m/z calcd for C13H16O2 (M+): 204.1150; found: 204.1154.
(R)-1-(4-Bromophenyl)-2-(tetrahydrofuran-2-yl)ethanone (2e)
(R)-1-(4-Methoxyphenyl)-2-(tetrahydrofuran-2-yl)ethanone (2b)
[CAS Reg. No. 1337999-55-9]
[CAS Reg. No. 1337999-51-5]
Yield: 66.8 mg (99%); 92% ee; white solid; mp 59.2–59.5 °C; Rf = 0.29
(hexane/EtOAc 3:1); [α]D28 –6.7 (c 6.39, CH2Cl2).
Yield: 54.0 mg (99%); 94% ee; colorless oil; Rf = 0.15 (hexane/EtOAc
3:1); [α]D23 –2.5 (c 4.02, CH2Cl2).
HPLC: Daicel Chiralcel OD-H; hexane/i-PrOH (99:1), flow rate = 2.0
mL/min, λ = 254 nm, 40 °C; tR = 7.9 min (minor), tR = 9.1 min (major).
HPLC: Daicel Chiralcel OD-H; hexane/i-PrOH (99.9:0.1), flow rate =
5.0 mL/min, λ = 254 nm, 40 °C); tR = 34.1 min (minor), tR = 41.1 min
(major).
IR (KBr): 3459, 2928, 2878, 2366, 1679, 1587, 1485, 1397, 1343, 1301,
1209, 1179, 1062, 991, 814, 791, 668, 574 cm–1
.
IR (neat): 3474, 2957, 2872, 2360, 1677, 1601, 1576, 1510, 1458,
1H NMR (CDCl3): δ = 7.83 (m, 2 H), 7.60 (m, 2 H), 4.38 (dddd, J = 7.0,
6.5, 6.5, 6.0 Hz, 1 H), 3.88 (ddd, J = 8.0, 7.0, 6.5 Hz, 1 H), 3.75 (ddd, J =
8.0, 7.5, 7.0 Hz, 1 H), 3.33 (dd, J = 16.0, 6.0 Hz, 1 H), 3.02 (dd, J = 16.0,
6.5 Hz, 1 H), 2.19 (m, 1 H), 1.93 (m, 2 H), 1.56 (m, 1 H).
1419, 1381, 1309, 1261, 1216, 1170, 1066, 1030, 990, 847, 488 cm–1
.
1H NMR (CDCl3): δ = 7.95 (m, 2 H), 6.93 (m, 2 H), 4.38 (dddd, J = 7.0,
6.5, 6.5, 6.0 Hz, 1 H), 3.89 (m, 1 H), 3.86 (s, 3 H), 3.74 (m, 1 H), 3.35
(dd, J = 16.0, 6.0 Hz, 1 H), 3.00 (dd, J = 16.0, 7.0 Hz, 1 H), 2.18 (m, 1 H),
1.92 (m, 2 H), 1.56 (m, 1 H).
13C NMR (CDCl3): δ = 197.4, 135.8, 131.9, 129.8, 128.3, 75.3, 67.9, 44.6,
31.6, 25.6.
13C NMR (CDCl3): δ = 196.9, 163.5, 130.5, 130.3, 113.7, 75.6, 67.8, 55.4,
HRMS: m/z calcd for C12H14BrO2 [M + H]+: 269.0177; found: 269.0172.
44.3, 31.6, 25.6.
HRMS: m/z calcd for C13H17O3 [M + H]+: 221.1178; found: 221.1172.
(R)-1-(Naphthalen-2-yl)-2-(tetrahydrofuran-2-yl)ethanone (2f)
[CAS Reg. No. 1337999-53-7]
(R)-2-(Tetrahydrofuran-2-yl)-1-[4-(trifluoromethyl)phenyl]etha-
none (2c)
Yield: 58.8 mg (98%); 91% ee; colorless oil; Rf = 0.27 (hexane/EtOAc
3:1); [α]D23 –0.3 (c 7.36, CH2Cl2).
[CAS Reg. No. 1337999-52-6]
HPLC: Daicel Chiralcel OD-H; hexane/i-PrOH (99:1), flow rate = 2.0
mL/min; λ = 254 nm, 40 °C; tR = 14.2 min (major), tR = 15.8 min (mi-
nor).
Reaction was run on 0.125 mmol scale; yield: 60.0 mg (93%); 85% ee;
white solid; mp 82.0–82.3 °C; Rf = 0.30 (hexane/EtOAc 3:1); [α]D
–7.1 (c 3.18, CH2Cl2).
23
IR (neat): 3058, 2971, 2871, 2368, 1681, 1628, 1597, 1469, 1385,
1359, 1297, 1279, 1210, 1186, 1126, 1065, 1026, 991, 943, 918, 865,
HPLC: Daicel Chiralcel OD-H; hexane/i-PrOH (99:1), flow rate = 1.0
mL/min, λ = 254 nm, 40 °C; tR = 11.8 min (minor), tR = 13.6 min (ma-
jor).
820, 754, 464 cm–1
.
1H NMR (CDCl3): δ = 8.49 (s, 1 H), 8.04 (d, J = 9.0 Hz, 1 H), 7.97 (d, J =
8.0 Hz, 1 H), 7.90 (d, J = 9.0 Hz, 1 H), 7.88 (d, J = 8.5 Hz, 1 H), 7.60 (dd,
J = 8.0, 7.0 Hz, 1 H), 7.56 (dd, J = 8.5, 7.0 Hz), 4.47 (dddd, J = 7.0, 6.5,
6.5, 6.0 Hz, 1 H), 3.92 (m, 1 H), 3.78 (m, 1 H), 3.54 (dd, J = 16.0, 6.0 Hz,
1 H), 3.19 (dd, J = 16.0, 6.5 Hz, 1 H), 2.23 (m, 1 H), 1.95 (m, 2 H), 1.63
(m, 1 H).
13C NMR (CDCl3): δ = 198.3, 135.6, 134.5, 132.5, 130.0, 129.6, 128.5,
128.4, 127.8, 126.7, 123.9, 75.6, 67.9, 44.8, 31.7, 25.7.
HRMS: m/z calcd for C16H16O2 (M+): 240.1150; found: 240.1144.
IR (KBr): 3428, 2987, 2881, 2366, 1685, 1513, 1411, 1387, 1330, 1209,
1159, 1127, 1110, 1060, 1017, 995, 830, 760, 687, 607, 511 cm–1
.
1H NMR (CDCl3): δ = 8.07 (d, J = 8.0 Hz, 2 H), 7.73 (d, J = 8.0 Hz, 2 H),
4.40 (dddd, J = 7.0, 6.5, 6.5, 6.0 Hz, 1 H), 3.89 (ddd, J = 8.5, 7.0, 6.5 Hz, 1
H), 3.76 (m, 1 H), 3.39 (dd, J = 16.0, 6.5 Hz, 1 H), 3.08 (dd, J = 16.0, 6.0
Hz, 1 H), 2.21 (m, 1 H), 1.94 (m, 2 H), 1.58 (m, 1 H).
13C NMR (CDCl3): δ = 197.5, 139.7, 134.4 (q, J = 32.7 Hz), 128.5, 125.6
(q, J = 3.8 Hz), 123.6 (q, J = 272.6 Hz), 75.2, 67.9, 44.9, 31.6, 25.6.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–K

G
K. Asano, S. Matsubara
Feature
Synthesis
(R)-4-Phenyl-1-(tetrahydrofuran-2-yl)butan-2-one (2g)
(R,E)-7-Hydroxy-1,7-diphenylhept-2-en-1-one (6a)
[CAS Reg. No. 1337999-56-0]
[CAS Reg. No. 2087909-34-8]
Yield: 52.9 mg (97%); 90% ee; colorless oil; Rf = 0.33 (hexane/EtOAc
3:1); [α]D28 –4.8 (c 6.14, CH2Cl2).
White solid; yield: 49% (calcd by conversion; isolated: 16.8 mg); mp
42.8–43.3 °C; Rf = 0.25 (hexane/EtOAc 3:1); [α]D +15.4 (c 0.56,
18
CH2Cl2) [for (R)-6a, 85% ee].
HPLC: Daicel Chiralcel OD-H; hexane/i-PrOH (99:1), flow rate = 2.0
mL/min, λ = 254 nm, 40 °C; tR = 10.6 min (major), tR = 15.5 min (mi-
nor).
HPLC: Daicel Chiralpak IB-H; hexane/i-PrOH (90.0:10.0), flow rate =
2.0 mL/min, λ = 254 nm, 40 °C; tR = 6.6 min (minor), tR = 13.3 min
(major).
IR (neat): 3027, 2955, 2870, 1713, 1604, 1498, 1453, 1409, 1383,
1296, 1182, 1126, 1056, 1017, 919, 749, 700, 492 cm–1
.
IR (KBr): 3509, 2950, 2929, 2909, 2883, 2360, 1962, 1895, 1813, 1663,
1609, 1578, 1491, 1447, 1417, 1336, 1297, 1256, 1232, 1216, 1174,
1062, 1038, 1025, 1001, 987, 936, 869, 847, 811, 759, 720, 700, 688
1H NMR (CDCl3): δ = 7.27 (m, 2 H), 7.18 (m, 3 H), 4.21 (m, 1 H), 3.84
(ddd, J = 8.5, 7.0, 7.0 Hz, 1 H), 3.71 (ddd, J = 8.5, 7.0, 7.0 Hz, 1 H), 2.90
(t, J = 8.0 Hz, 2 H), 2.79 (m, 2 H), 2.72 (dd, J = 16.0, 7.0 Hz, 1 H), 2.51
(dd, J = 16.0, 6.0 Hz, 1 H), 2.07 (m, 1 H), 1.88 (m, 2 H), 1.44 (m, 1 H).
13C NMR (CDCl3): δ = 208.3, 141.1, 128.5, 128.3, 126.0, 75.1, 67.8, 48.9,
45.0, 31.5, 29.5, 25.5.
cm–1
.
1H NMR (C6D6): δ = 7.87 (m, 2 H), 7.20–7.02 (m, 9 H), 6.63 (dt, J = 15.0,
1.5 Hz, 1 H), 4.28 (m, 1 H), 1.85 (m, 2 H), 1.58 (m, 1 H), 1.46 (m, 1 H),
1.38 (m, 1 H), 1.26 (d, J = 3.5 Hz, 1 H), 1.23 (m, 1 H).
13C NMR (C6D6): δ = 189.5, 149.0, 145.7, 138.7, 132.4, 128.8, 128.65,
128.59, 127.6, 126.1, 126.0, 74.1, 39.1, 32.7, 24.6.
HRMS: m/z calcd for C14H18O2 (M+): 218.1307; found: 218.1304.
HRMS: m/z calcd for C19H21O2 [M + H]+: 281.1536; found: 281.1532.
(R)-1-Phenyl-2-(tetrahydro-2H-pyran-2-yl)ethanone (5)
[CAS Reg. No. 1337999-57-1]
(R,E)-7-Hydroxy-7-(4-methoxyphenyl)-1-phenylhept-2-en-1-one
To a 5 mL vial, ζ-hydroxy-α,β-unsaturated ketone 4 (0.15 mmol), cy-
clopentyl methyl ether (0.3 mL), and quinidine-derived bifunctional
catalyst 3a (0.0075 mmol) were added sequentially. The mixture was
stirred in an oil bath maintained at 25 °C for 24 h. The mixture was
subsequently diluted with hexane/EtOAc (1:1 v/v), passed through a
short silica gel pad to remove 3a, and concentrated in vacuo. Purifica-
tion of the residue by flash silica gel column chromatography using
hexane/EtOAc (3:1 v/v) as an eluent afforded tetrahydropyran 5;
yield: 27.6 mg (90%); 91% ee; colorless oil; Rf = 0.45 (hexane/EtOAc
3:1); [α]D26 +16.8 (c 2.53, CH2Cl2).
(6b)
[CAS Reg. No. 2087909-35-9]
White solid; yield: 37% (calcd by conversion; isolated: 14.4 mg); mp
89.0–89.5 °C; Rf = 0.17 (hexane/EtOAc 3:1); [α]D18 +8.0 (c 0.46, CH2Cl2)
[for (R)-6b, 50% ee].
HPLC: Daicel Chiralpak IB-H; hexane/i-PrOH (87.5:12.5), flow rate =
2.0 mL/min, λ = 254 nm, 40 °C; tR = 7.3 min (minor), tR = 10.4 min
(major).
IR (KBr): 3490, 3063, 3005, 2960, 2926, 2906, 2864, 2838, 2054, 1983,
1894, 1833, 1773, 1654, 1594, 1576, 1511, 1462, 1404, 1339, 1300,
1249, 1217, 1170, 1061, 1033, 988, 936, 874, 843, 831, 773, 725, 692
HPLC; Daicel Chiralcel OD-H; hexane/i-PrOH (99:1), flow rate = 2.0
mL/min, λ = 254 nm, 40 °C; tR = 6.1 min (minor), tR = 8.0 min (major).
IR (neat): 3060, 2936, 2849, 1686, 1597, 1581, 1449, 1379, 1357,
1325, 1292, 1273, 1208, 1194, 1175, 1088, 1045, 1003, 971, 904, 810,
cm–1
.
1H NMR (C6D6): δ = 7.90 (m, 2 H), 7.16–7.05 (m, 6 H), 6.82 (m, 2 H),
6.68 (dt, J = 15.5, 1.5 Hz, 1 H), 4.33 (m, 1 H), 3.33 (s, 3 H), 1.92 (m, 2 H),
1.66 (m, 1 H), 1.53 (m, 1 H), 1.44 (m, 1 H), 1.282 (m, 1 H), 1.281 (d, J =
3.5 Hz, 1 H).
13C NMR (C6D6): δ = 189.5, 159.6, 149.0, 138.7, 137.7, 132.4, 128.8,
128.6, 127.4, 126.0, 114.1, 73.8, 54.8, 39.2, 32.7, 24.7.
777, 751, 692, 661, 471 cm–1
.
1H NMR (CDCl3): δ = 7.97 (m, 2 H), 7.56 (m, 1 H), 7.46 (m, 2 H), 3.96
(m, 2 H), 3.48 (m, 1 H), 3.29 (dd, J = 16.0, 6.5 Hz, 1 H), 2.92 (dd, J =
16.0, 5.5 Hz, 1 H), 1.84 (m, 1 H), 1.75 (m, 1 H), 1.57 (m, 2 H), 1.52 (m, 1
H), 1.36 (m, 1 H).
13C NMR (CDCl3): δ = 198.4, 137.4, 133.0, 128.5, 128.3, 74.4, 68.7, 45.4,
32.0, 25.9, 23.4.
HRMS: m/z calcd for C20H23O3 [M + H]+: 311.1642; found: 311.1632.
HRMS: m/z calcd for C13H17O2 [M + H]+: 205.1229; found: 205.1227.
(R,E)-7-Hydroxy-1-phenyl-7-[4-(trifluoromethyl)phenyl]hept-2-
en-1-one (6c)
Kinetic Resolution of 6 and 8; General Procedure
[CAS Reg. No. 2087909-36-0]
A solution of 3e (5.6 mg, 0.0075 mmol) in anhyd toluene (1 mL) was
added to a mixture of (rac)-6 (0.15 mmol), anhyd toluene (14 mL),
and MS 4A (300 mg) at –40 °C. The resulting mixture was stirred at
the same temperature. When the approximate conversion was 50%
(monitored via TLC), the mixture was quenched with a drop of Et3N,
passed through a short silica gel column with hexane/Et2O (1:2 v/v)
to remove 3e, and concentrated in vacuo. Purification of the residue
by flash silica gel column chromatography using hexane/Et2O (1:1
v/v) as an eluent afforded the corresponding cycloether product 7 and
unreacted starting material 6. The recovered 6, after the kinetic reso-
lution in the reaction using 3e, contained the R-isomer as a major
component. For (rac)-8, the same procedure was applied. Conversions
in Tables 3 and 4 and Equation 2 were calculated based on the ob-
tained ee values. See ref. 11.
White solid; yield: 48% (calcd by conversion; isolated: 20.9 mg); mp
53.0–53.5 °C; Rf = 0.22 (hexane/EtOAc 3:1); [α]D +12.4 (c 0.29,
CH2Cl2); [for (R)-6c, 87% ee].
18
HPLC: Daicel Chiralpak IB-H; hexane/i-PrOH (90.0:10.0), flow rate =
2.0 mL/min, λ = 254 nm, 40 °C; tR = 6.0 min (minor), tR = 11.6 min
(major).
IR (KBr): 3459, 2918, 2864, 1929, 1655, 1601, 1575, 1450, 1411, 1330,
1312, 1225, 1168, 1154, 1113, 1070, 1011, 903, 870, 828, 774, 718,
688 cm–1
.
1H NMR (C6D6): δ = 7.90 (m, 2 H), 7.38 (d, J = 8.5 Hz, 2 H), 7.13–7.03
(m, 6 H), 6.70 (dt, J = 15.5, 1.5 Hz, 1 H), 4.20 (m, 1 H), 1.90 (m, 2 H),
1.57 (br s, 1 H), 1.45 (m, 1 H), 1.39–1.32 (m, 2 H), 1.23 (m, 1 H).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–K

H
K. Asano, S. Matsubara
Feature
Synthesis
13C NMR (C6D6): δ = 189.5, 149.6, 148.7, 138.5, 132.6, 129.5 (q, J = 32.6
Hz), 128.8, 128.7, 126.3, 126.1, 125.5 (q, J = 3.9 Hz), 125.1 (q, J = 271.3
Hz), 73.3, 38.9, 32.6, 24.4.
1H NMR (C6D6): δ = 7.94 (m, 2 H), 7.18–7.07 (m, 4 H), 6.76 (dt, J = 15.5,
1.5 Hz, 1 H), 3.29 (br s, 1 H), 1.97 (m, 2 H), 1.44 (m, 1 H), 1.36–1.16 (m,
10 H), 0.90 (t, J = 7.0 Hz, 3 H).
19F NMR (C6D6): δ = 100.8.
13C NMR (C6D6): δ = 189.5, 149.1, 138.6, 132.4, 128.8, 128.6, 126.0,
71.2, 37.7, 37.2, 32.8, 28.2, 24.5, 23.1, 14.3.
HRMS: m/z calcd for C17H25O2 [M + H]+: 261.1849; found: 261.1840.
HRMS: m/z calcd for C20H20F3O2 [M + H]+: 349.1410; found: 349.1399.
(R,E)-7-(Anthracen-9-yl)-7-hydroxy-1-phenylhept-2-en-1-one (6d)
[CAS Reg. No. 2087909-37-1]
(R,E)-7-Hydroxy-1-(4-methoxyphenyl)-7-phenylhept-2-en-1-one
(6g)
Yellow solid; yield: 51% (calcd by conversion; isolated: 24.5 mg); mp
[CAS Reg. No. 2087909-40-6]
18
145.0–145.5 °C; Rf = 0.36 (hexane/EtOAc 3:1); [α]D –13.6 (c 0.95,
CH2Cl2) [for (R)-6d, 84% ee].
Pale yellow oil; yield: 48% (calcd by conversion; isolated 19.1 mg); Rf =
0.16 (hexane/EtOAc 3:1); [α]D18 +13.9 (c 0.72, CH2Cl2) [for (R)-6g, 89%
HPLC: Daicel Chiralpak IB-H; hexane/i-PrOH (80.0:20.0), flow rate =
2.0 mL/min, λ = 254 nm, 40 °C; tR = 5.9 min (minor), tR = 9.0 min (ma-
jor).
ee].
HPLC: Daicel Chiralpak IB-H; hexane/i-PrOH (80.0:20.0), flow rate =
2.0 mL/min, λ = 254 nm, 40 °C; tR = 5.0 min (minor), tR = 7.0 min (ma-
jor).
IR (KBr): 3497, 3446, 3057, 2933, 2861, 2363, 1654, 1610, 1577, 1523,
1459, 1447, 1347, 1299, 1284, 1232, 1212, 1182, 1158, 1056, 1020,
975, 921, 890, 872, 844, 792, 772, 736, 698, 662 cm–1
.
IR (neat): 3445, 3061, 3028, 2937, 2861, 1665, 1609, 1575, 1511,
1494, 1455, 1419, 1345, 1307, 1260, 1235, 1172, 1114, 1063, 1027,
1H NMR (C6D6): δ = 8.75 (br, 2 H), 8.18 (s, 1 H), 7.87–7.83 (m, 4 H),
7.33 (m, 2 H), 7.27 (m, 2 H), 7.13 (m, 1 H), 7.06 (m, 2 H), 7.02 (dt, J =
15.5, 7.0 Hz, 1 H), 6.61 (dt, J = 15.5, 1.5 Hz, 1 H), 5.85 (m, 1 H), 2.32 (m,
1 H), 1.95–1.82 (m, 3 H), 1.63 (m, 1 H), 1.58 (br s, 1 H), 1.28 (m, 1 H).
13C NMR (C6D6): δ = 189.4, 148.9, 138.6, 136.0, 132.3, 129.8, 129.6,
128.8, 128.6, 128.3, 126.0, 125.6, 125.0, 70.7, 37.4, 32.6, 30.0, 25.6.
982, 915, 843, 793, 702, 677 cm–1
.
1H NMR (C6D6): δ = 7.97 (m, 2 H), 7.22–7.17 (m, 4 H), 7.14–7.08 (m, 2
H), 6.76 (dt, J = 15.5, 1.5 Hz, 1 H), 6.67 (m, 2 H), 4.32 (m, 1 H), 3.17 (s,
3 H), 1.93 (m, 2 H), 1.63 (m, 1 H), 1.55–1.38 (m, 2 H), 1.34–1.25 (m, 2
H).
13C NMR (C6D6): δ = 187.8, 163.5, 148.0, 145.7, 131.6, 131.1, 128.6,
127.5, 126.2, 125.8, 114.0, 74.2, 54.9, 39.2, 32.7, 24.7.
HRMS: m/z calcd for C27H25O2 [M + H]+: 381.1849; found: 381.1840.
HRMS: m/z calcd for C20H23O3 [M + H]+: 311.1642; found: 311.1642.
(R,E)-7-Hydroxy-1-phenyl-7-(pyren-4-yl)hept-2-en-1-one (6e)
[CAS Reg. No. 2087909-38-2]
(R,E)-7-Hydroxy-7-phenyl-1-[4-(trifluoromethyl)phenyl]hept-2-
en-1-one (6h)
Pale yellow oil; yield: 42% (calcd by conversion; isolated 21.2 mg); Rf =
0.15 (hexane/EtOAc 3:1); [α]D18 +81.0 (c 0.83, CH2Cl2) [for (R)-6e, 98%
[CAS Reg. No. 2087909-41-7]
ee].
White solid; yield: 43% (calcd by conversion; isolated: 18.3 mg); mp
49.0–49.5 °C; Rf = 0.17 (hexane/EtOAc 3:1); [α]D +19.0 (c 0.69,
CH2Cl2) [for (R)-6h, 97% ee].
HPLC: Daicel Chiralpak IB-H; hexane/i-PrOH (85.0:15.0), flow rate =
2.0 mL/min, λ = 254 nm, 40 °C; tR = 10.0 min (minor), tR = 13.6 min
(major).
18
HPLC: Daicel Chiralpak IC-H; hexane/i-PrOH (97.5:2.5), flow rate = 2.0
mL/min, λ = 254 nm, 40 °C; tR = 30.8 min (minor), tR = 35.4 min (ma-
jor).
IR (neat): 3421, 3048, 2944, 2862, 2347, 1669, 1617, 1507, 1448,
1340, 1297, 1224, 1182, 1072, 1018, 978, 848, 760, 719, 693 cm–1
.
1H NMR (C6D6): δ = 8.22 (d, J = 9.5 Hz, 1 H), 8.16 (d, J = 8.0 Hz, 1 H),
8.00–7.91 (m, 4 H), 7.87–7.82 (m, 4 H), 7.78 (m, 1 H), 7.12–7.00 (m, 4
H), 6.66 (dt, J = 15.5, 1.5 Hz, 1 H), 5.36 (m, 1 H), 1.95 (br s, 1 H), 1.91–
1.79 (m, 4 H), 1.56 (m, 1 H), 1.43 (m, 1 H).
IR (KBr): 3483, 2931, 2869, 2363, 1660, 1603, 1577, 1507, 1456, 1411,
1319, 1226, 1169, 1120, 1069, 1015, 838, 798, 767, 746, 700, 659 cm–
1
.
1H NMR (C6D6): δ = 7.60 (d, J = 8.0 Hz, 2 H), 7.25 (d, J = 8.0 Hz, 2 H),
7.21–7.17 (m, 4 H), 7.10 (m, 1 H), 6.98 (dt, J = 15.5, 7.0 Hz, 1 H), 6.47
(dt, J = 15.5, 1.5 Hz, 1 H), 4.31 (m, 1 H), 1.87 (m, 2 H), 1.62 (m, 1 H),
1.54–1.38 (m, 2 H), 1.31–1.22 (m, 2 H).
13C NMR (C6D6): δ = 188.7, 150.3, 145.6, 141.2, 133.5 (q, J = 32.2 Hz),
129.0, 128.6, 127.7, 126.1, 125.7, 125.6 (q, J = 3.9 Hz), 124.5 (q, J =
273.1 Hz), 74.1, 39.1, 32.7, 24.5.
13C NMR (C6D6): δ = 189.4, 148.9, 139.2, 138.5, 132.3, 131.8, 131.1,
130.9, 128.7, 128.5, 128.2, 127.9, 127.84, 127.79, 127.4, 126.1, 126.0,
125.5, 125.34, 125.27, 125.22, 123.7, 122.9, 70.9, 38.8, 32.5, 24.8.
HRMS: m/z calcd for C29H25O2 [M + H]+: 405.1849; found: 405.1836.
(R,E)-7-Hydroxy-1-phenylundec-2-en-1-one (6f)
[CAS Reg. No. 2087909-39-3]
19F NMR (C6D6): δ = 100.1.
HRMS: m/z calcd for C20H20F3O2 [M + H]+: 349.1410; found: 349.1398.
Colorless oil; yield: 47% (calcd by conversion; isolated: 15.6 mg); Rf =
18
0.29 (hexane/EtOAc 3:1); [α]D +2.2 (c 0.58, CH2Cl2) [for (R)-6f, 81%
ee].
1-Phenyl-2-[(2R,6S)-6-phenyltetrahydro-2H-pyran-2-yl]ethan-1-
one (7a)
HPLC: Daicel Chiralpak IB-H; hexane/i-PrOH (98.0:2.0), flow rate = 2.0
mL/min, λ = 254 nm, 40 °C; tR = 14.3 min (minor), tR = 20.6 min (ma-
jor).
[CAS Reg. No. 2087909-42-8]
1
The ratio of diastereomers was determined by H NMR analysis. The
IR (neat): 3422, 3059, 2931, 2869, 1668, 1621, 1579, 1448, 1345,
diastereomers were further separated by flash silica gel column chro-
matography using hexane/EtOAc (10:1 v/v) as an eluent. Conversion:
51% (isolated: 15 mg); dr = 24:1; 89% ee; colorless oil; Rf = 0.62 (hex-
ane/EtOAc 3:1); [α]D18 –33.2 (c 0.53, CH2Cl2).
1296, 1228, 1180, 1128, 1002, 855, 770, 692, 671 cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–K

I
K. Asano, S. Matsubara
Feature
Synthesis
HPLC: Daicel Chiralpak IA; hexane/i-PrOH (99.0:1.0), flow rate = 1.0
mL/min, λ = 254 nm, 40 °C; tR = 9.9 min (minor), tR = 11.9 min (major).
13C NMR (CDCl3): δ = 198.5, 147.0, 137.3, 133.1, 129.2 (q, J = 33.3 Hz),
128.5, 128.3, 125.9, 125.1 (q, J = 3.8 Hz), 126.4 (q, J = 272.6 Hz), 79.0,
75.0, 45.3, 33.3, 31.2, 23.7.
IR (neat): 3356, 3062, 3029, 2936, 2859, 1683, 1597, 1581, 1496,
1449, 1388, 1343, 1308, 1286, 1071, 1045, 1001, 923, 752, 698 cm–1
.
19F NMR (CDCl3): δ = 99.3.
1H NMR (CDCl3): δ = 8.00 (m, 2 H), 7.56 (m, 1 H), 7.46 (m, 2 H), 7.31–
7.27 (m, 4 H), 7.23 (m, 1 H), 4.44 (dd, J = 11.0, 2.0 Hz, 1 H), 4.18 (dddd,
J = 8.0, 6.5, 6.0, 6.0 Hz, 1 H), 3.42 (dd, J = 16.0, 6.0 Hz, 1 H), 3.07 (dd, J =
16.0, 6.5 Hz, 1 H), 1.96 (m, 1 H), 1.89–1.83 (m, 2 H), 1.76 (m, 1 H), 1.52
(m, 1 H), 1.40 (m, 1 H).
13C NMR (CDCl3): δ = 198.6, 143.1, 137.3, 133.0, 128.5, 128.3, 128.2,
127.1, 125.7, 79.8, 75.0, 45.5, 33.2, 31.3, 23.8.
HRMS: m/z calcd for C20H20F3O2 [M + H]+: 349.1410; found: 349.1401.
2-[(2R,6S)-6-(Anthracen-9-yl)tetrahydro-2H-pyran-2-yl]-1-phenyl-
ethan-1-one (7d)
[CAS Reg. No. 2087909-45-1]
1
The ratio of diastereomers was determined by H NMR analysis. The
diastereomers were further separated by flash silica gel column chro-
matography using hexane/EtOAc (10:1 v/v) as an eluent. Conversion:
49% (isolated: 17.9 mg); dr = 50:1; 90% ee; pale yellow solid; mp
50.5–51.0 °C; Rf = 0.63 (hexane/EtOAc 3:1); [α]D18 –42.1 (c 0.68, CH2-
Cl2).
HRMS: m/z calcd for C19H21O2 [M + H]+: 281.1536; found: 281.1532.
2-[(2R,6S)-6-(4-Methoxyphenyl)tetrahydro-2H-pyran-2-yl]-1-
phenylethan-1-one (7b)
[CAS Reg. No. 2087909-43-9]
HPLC: Daicel Chiralpak IB; hexane/i-PrOH (98.0:2.0), flow rate = 2.0
mL/min, λ = 254 nm, 40 °C; tR = 6.9 min (minor), tR = 9.1 min (major).
1
The ratio of diastereomers was determined by H NMR analysis. The
diastereomers were further separated by flash silica gel column chro-
matography using hexane/EtOAc (10:1 v/v) as an eluent. Conversion:
63% (isolated: 18.0 mg); dr = 4.3:1; 58% ee; colorless oil; Rf = 0.44
(hexane/EtOAc 3:1); [α]D18 –22.8 (c 0.83, CH2Cl2).
IR (KBr): 3432, 3052, 2938, 2857, 2363, 1676, 1449, 1345, 1286, 1210,
1197, 1158, 1075, 1057, 1001, 936, 888, 848, 789, 752, 733, 691, 668
cm–1
.
1H NMR (CDCl3): δ = 8.70 (br s, 2 H), 8.38 (s, 1 H), 7.99–7.96 (m, 4 H),
7.51–7.42 (m, 5 H), 7.36 (m, 2 H), 5.97 (dd, J = 12.0, 2.5 Hz, 1 H), 4.36
(dddd, J = 7.5, 7.0, 5.5, 5.0 Hz, 1 H), 3.51 (dd, J = 16.0, 5.5 Hz, 1 H), 3.24
(dd, J = 16.0, 7.0 Hz, 1 H), 2.39 (m, 1 H), 2.14–1.95 (m, 3 H), 1.88 (m, 1
H), 1.75 (m, 1 H).
13C NMR (CDCl3): δ = 198.5, 137.2, 133.5, 133.0, 131.7, 129.2, 129.0,
128.4, 128.3, 127.9, 125.2, 124.6, 78.0, 76.1, 45.6, 31.5, 31.2, 24.4.
IR (neat): 3421, 3061, 2999, 2935, 2858, 1682, 1614, 1581, 1449,
1342, 1304, 1285, 1247, 1207, 1179, 1078, 1036, 1001, 921, 831, 752,
691 cm–1
.
HPLC: Daicel Chiralpak IA; hexane/i-PrOH (99.0:1.0), flow rate = 1.7
mL/min, λ = 254 nm, 40 °C; tR = 11.9 min (minor), tR = 13.5 min (ma-
jor).
1H NMR (CDCl3): δ = 7.99 (m, 2 H), 7.56 (m, 1 H), 7.45 (m, 2 H), 7.23
(m, 2 H), 6.84 (m, 2 H), 4.38 (dd, J = 11.5, 2.0 Hz, 1 H), 4.17 (dddd, J =
8.0, 6.5, 6.5, 5.5 Hz, 1 H), 3.78 (s, 3 H), 3.40 (dd, J = 16.0, 5.5 Hz, 1 H),
3.06 (dd, J = 16.0, 6.5 Hz, 1 H), 1.96 (m, 1 H), 1.85–1.82 (m, 2 H), 1.74
(m, 1 H), 1.53 (m, 1 H), 1.38 (m, 1 H).
13C NMR (CDCl3): δ = 198.5, 158.7, 137.3, 135.3, 133.0, 128.5, 128.3,
127.1, 113.5, 79.4, 74.9, 55.2, 45.5, 33.0, 31.3, 23.8.
HRMS: m/z calcd for C27H25O2 [M + H]+: 381.1849; found: 381.1835.
1-Phenyl-2-[(2R,6S)-6-(pyren-1-yl)tetrahydro-2H-pyran-2-
yl]ethan-1-one (7e)
[CAS Reg. No. 2087909-46-2]
1
The ratio of diastereomers was determined by H NMR analysis. The
diastereomers were further separated by flash silica gel column chro-
matography using hexane/EtOAc (10:1 v/v) as an eluent. Conversion:
58% (isolated: 25.1 mg); dr = 17:1; 79% ee; white solid; mp 124.0–
124.5 °C; Rf = 0.50 (hexane/EtOAc 3:1); [α]D18 +24.6 (c 0.57, CH2Cl2).
HRMS: m/z calcd for C20H23O3 [M + H]+: 311.1642: found: 311.1634.
1-Phenyl-2-{(2R,6S)-6-[4-(trifluoromethyl)phenyl]tetrahydro-2H-
pyran-2-yl}ethan-1-one (7c)
HPLC: Daicel Chiralpak IA; hexane/i-PrOH (98.0:2.0), flow rate = 2.0
mL/min, λ = 254 nm, 40 °C; tR = 9.1 min (minor), tR = 11.2 min (major).
[CAS Reg. No. 2087909-44-0]
1
The ratio of diastereomers was determined by H NMR analysis. The
IR (KBr): 3039, 2934, 2857, 2328, 1685, 1596, 1507, 1449, 1354, 1288,
1209, 1195, 1080, 1051, 1039, 1001, 921, 841, 828, 751, 717, 689 cm–
.
diastereomers were further separated by flash silica gel column chro-
matography using hexane/EtOAc (10:1 v/v) as an eluent. Conversion:
52% (isolated: 20.1 mg); dr = 16:1; 90% ee; white solid; mp 75.0–75.5
°C; Rf = 0.61 (hexane/EtOAc 3:1); [α]D18 –40.2 (c 0.54, CH2Cl2).
1
1H NMR (CDCl3): δ = 8.30 (d, J = 9.5 Hz, 1 H), 8.18–8.15 (m, 2 H), 8.14
(d, J = 2.0 Hz, 2 H), 8.09 (d, J = 9.5 Hz, 1 H), 8.03 (s, 2 H), 8.02–7.97 (m,
3 H), 7.53 (dddd, J = 7.5, 7.5, 1.5, 1.5 Hz, 1 H), 7.45–7.42 (m, 2 H), 5.45
(dd, J = 11.0, 2.0 Hz, 1 H), 4.47 (ddd, J = 6.0, 6.0, 2.0 Hz, 1 H), 3.51 (dd,
J = 16.0, 6.0 Hz, 1 H), 3.17 (dd, J = 16.0, 6.0 Hz, 1 H), 2.17–2.07 (m, 2 H),
2.04–1.95 (m, 2 H), 1.86 (m, 1 H), 1.58 (m, 1 H).
13C NMR (CDCl3): δ = 198.5, 147.0, 137.3, 136.3, 133.0, 131.3, 130.7,
130.5, 128.5, 128.3, 127.6, 127.4, 127.3, 127.0, 125.7, 125.0, 124.91,
124.86, 124.76, 123.3, 123.1, 77.4, 75.4, 45.6, 32.8, 31.5, 24.2.
HPLC: Daicel Chiralpak IA; hexane/i-PrOH (99.5:0.5), flow rate = 2.0
mL/min, λ = 254 nm, 40 °C; tR = 7.7 min (minor), tR = 11.1 min (major).
IR (KBr): 3503, 3043, 2957, 2906, 2862, 2354, 1942, 1683, 1620, 1597,
1582, 1452, 1420, 1394, 1356, 1331, 1208, 1185, 1161, 1118, 1087,
1063, 1001, 924, 846, 818, 790, 757, 691 cm–1
.
1H NMR (CDCl3): δ = 8.00 (m, 2 H), 7.57 (m, 1 H), 7.53 (d, J = 8.0 Hz, 2
H), 7.47 (m, 2 H), 7.38 (m, 2 H), 4.48 (dd, J = 11.5, 1.5 Hz, 1 H), 4.19
(dddd, J = 8.0, 7.0, 6.5, 6.0 Hz, 1 H), 3.42 (dd, J = 16.0, 6.5 Hz, 1 H), 3.05
(dd, J = 16.0, 6.0 Hz, 1 H), 1.98 (m, 1 H), 1.91–1.84 (m, 2 H), 1.78 (m, 1
H), 1.50–1.37 (m, 2 H).
HRMS: m/z calcd for C29H25O2 [M + H]+: 405.1849; found: 405.1834.
2-[(2R,6S)-6-Butyltetrahydro-2H-pyran-2-yl]-1-phenylethan-1-
one (7f)
[CAS Reg. No. 2087909-47-3]
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–K

J
K. Asano, S. Matsubara
Feature
Synthesis
1
The ratio of diastereomers was determined by H NMR analysis. The
diastereomers were further separated by flash silica gel column chro-
matography using hexane/EtOAc (10:1 v/v) as an eluent. Conversion:
53% (isolated: 17.7 mg); dr = 14:1; 82% ee; colorless oil; Rf = 0.72 (hex-
ane/EtOAc 3:1); [α]D18 +10.4 (c 0.45, CH2Cl2).
1H NMR (CDCl3): δ = 8.09 (dd, J = 9.0, 1.0 Hz, 2 H), 7.72 (m, 2 H), 7.28
(m, 2 H), 7.25–7.20 (m, 3 H), 4.41 (dd, J = 11.5, 2.0 Hz, 1 H), 4.16
(dddd, J = 8.5, 7.0, 6.5, 6.0 Hz, 1 H), 3.42 (dd, J = 15.5, 6.5 Hz, 1 H), 3.06
(dd, J = 15.5, 6.0 Hz, 1 H), 1.98 (m, 1 H), 1.89–1.82 (m, 2 H), 1.76 (m, 1
H), 1.51 (m, 1 H), 1.42 (m, 1 H).
HPLC: Daicel Chiralpak IF; hexane/i-PrOH (99.0:1.0), flow rate = 1.0
mL/min, λ = 254 nm, 40 °C; tR = 7.8 min (minor), tR = 8.6 min (major).
13C NMR (CDCl3): δ = 197.9, 142.9, 140.1, 134.2 (q, J = 32.1 Hz), 128.7,
128.2, 127.2, 125.6, 125.5 (q, J = 3.8 Hz), 123.6 (q, J = 272.6 Hz), 79.8,
75.0, 45.7, 33.1, 31.3, 23.8.
19F NMR (CDCl3): δ = 98.7.
HRMS: m/z calcd for C20H20F3O2 [M + H]+: 349.1410; found: 349.1399.
IR (neat): 3375, 3064, 2933, 2860, 1684, 1598, 1581, 1449, 1373,
1347, 1285, 1210, 1195, 1088, 1074, 1049, 1002, 896, 751, 691, 667
cm–1
.
1H NMR (CDCl3): δ = 7.97 (m, 2 H), 7.55 (m, 1 H), 7.45 (m, 2 H), 3.93
(dddd, J = 9.0, 6.5, 6.5, 6.5 Hz, 1 H), 3.31 (dd, J = 16.0, 6.5 Hz, 1 H), 3.28
(m, 1 H), 2.94 (dd, J = 16.0, 6.5 Hz, 1 H), 1.83 (m, 1 H), 1.74 (m, 1 H),
1.61–1.51 (m, 2 H), 1.45 (m, 1 H), 1.38–1.13 (m, 7 H), 0.83 (t, J = 7.0
Hz, 3 H).
13C NMR (CDCl3): δ = 198.9, 137.4, 132.9, 128.4, 128.3, 78.1, 74.6, 45.6,
36.2, 31.8, 31.4, 27.6, 23.6, 22.7, 14.0.
2-[(2R,6S)-6-Methyl-6-phenyltetrahydro-2H-pyran-2-yl]-1-phenyl-
ethan-1-one (9)
[CAS Reg. No. 2087909-65-5]
1
The ratio of diastereomers was determined by H NMR analysis. The
diastereomers were further separated by flash silica gel column chro-
matography using benzene as an eluent. Conversion: 48% (isolated:
HRMS: m/z calcd for C17H25O2 [M + H]+: 261.1849; found: 261.1841.
18
17.1 mg); dr = 25:1; 95% ee; colorless oil; Rf = 0.53 (benzene); [α]D
–53.9 (c 0.18, CH2Cl2, 90% ee).
1-(4-Methoxyphenyl)-2-[(2R,6S)-6-phenyltetrahydro-2H-pyran-2-
yl]ethan-1-one (7g)
HPLC: Daicel Chiralpak IA; hexane/i-PrOH (99.4:0.6), flow rate = 0.8
mL/min, λ = 254 nm, 40 °C; tR = 11.8 min (minor), tR = 15.8 min (ma-
jor).
[CAS Reg. No. 2087909-48-4]
1
The ratio of diastereomers was determined by H NMR analysis. The
IR (neat): 3087, 3058, 2977, 2936, 2850, 1688, 1598, 1581, 1494,
1370, 1288, 1260, 1202, 1171, 1065, 1030, 993, 962, 898, 763, 715,
diastereomers were further separated by flash silica gel column chro-
matography using hexane/EtOAc (10:1 v/v) as an eluent. Conversion:
52% (isolated: 20.1 mg); dr = 19:1; 90% ee; white solid; mp 88.2–88.7
°C; Rf = 0.51 (hexane/EtOAc 3:1); [α]D18 –13.9 (c 0.74, CH2Cl2).
698, 665 cm–1
.
1H NMR (CDCl3): δ = 8.02 (m, 2 H), 7.58 (m, 1 H), 7.48 (m, 2 H), 7.33
(m, 2 H), 7.25 (m, 2 H), 7.18 (m, 1 H), 4.45 (dddd, J = 7.0, 7.0, 5.5, 5.0
Hz, 1 H), 3.40 (dd, J = 15.5, 7.0 Hz, 1 H), 2.97 (dd, J = 15.5, 5.5 Hz, 1 H),
1.95 (m, 1 H), 1.91–1.78 (m, 3 H), 1.62 (m, 1 H), 1.47 (s, 3 H), 1.32 (m,
1 H).
13C NMR (CDCl3): δ = 199.3, 149.9, 137.6, 132.9, 128.5, 128.4, 127.9,
126.2, 124.1, 75.2, 68.1, 45.8, 35.7, 31.6, 23.1, 20.0.
HPLC: Daicel Chiralpak IA; hexane/i-PrOH (98.5:1.5), flow rate = 2.0
mL/min, λ = 254 nm, 40 °C; tR = 9.1 min (minor), tR = 11.5 min (major).
IR (KBr): 3478, 3028, 2933, 2908, 2874, 2859, 2840, 2369, 1674, 1606,
1576, 1510, 1458, 1415, 1390, 1359, 1343, 1314, 1260, 1217, 1176,
1126, 1085, 1069, 1027, 993, 970, 925, 846, 816, 754, 703 cm–1
.
1H NMR (CDCl3): δ = 7.98 (m, 2 H), 7.31–7.28 (m, 4 H), 7.23 (m, 1 H),
6.93 (m, 2 H), 4.43 (dd, J = 11.5, 2.5 Hz, 1 H), 4.16 (dddd, J = 8.0, 7.0,
6.5, 6.0 Hz, 1 H), 3.87 (s, 3 H), 3.37 (dd, J = 15.5, 6.0 Hz, 1 H), 3.01 (dd,
J = 15.5, 6.5 Hz, 1 H), 1.95 (m, 1 H), 1.89–1.82 (m, 2 H), 1.75 (m, 1 H),
1.51 (m, 1 H), 1.37 (m, 1 H).
HRMS: m/z calcd for C20H23O2 [M + H]+: 295.1693; found: 295.1687.
Funding Information
13C NMR (CDCl3): δ = 197.1, 163.4, 143.1, 130.6, 130.5, 128.1, 127.1,
125.8, 113.6, 79.8, 75.1, 55.4, 45.2, 33.2, 31.4, 23.8.
This work was supported financially by JSPS KAKENHI Grant Number
15H05845, 16K13994, 17K19120, 18K14214, and 18H04258.
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HRMS: m/z calcd for C20H23O3 [M + H]+: 311.1642; found: 311.1633.
Supporting Information
2-[(2R,6S)-6-Phenyltetrahydro-2H-pyran-2-yl]-1-[4-(trifluoro-
methyl)phenyl]ethan-1-one (7h)
Supporting information for this article is available online at
https://doi.org/10.1055/s-0036-1591592. Included are the prepara-
tion of starting substrates (1a–g, 6, and 8) and the derivatization of 2b
[CAS Reg. No. 2087909-49-5]
1
The ratio of diastereomers was determined by H NMR analysis. The
into (R)-2-(tetrahydrofuran-2-yl)ethanol].
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diastereomers were further separated by flash silica gel column chro-
matography using hexane/EtOAc (10:1 v/v) as an eluent. Conversion:
57% (isolated: 25.7 mg); dr = 12:1; 86% ee; colorless oil; Rf = 0.52 (hex-
ane/EtOAc 3:1); [α]D18 –28.8 (c 0.64, CH2Cl2).
References
(1) (a) Knowles, R. R.; Jacobsen, E. N. Proc. Natl. Acad. Sci. U.S.A.
2010, 107, 20678. (b) Zhou, Q.-L. Angew. Chem. Int. Ed. 2016, 55,
5352.
(2) For metallic bifunctional catalysts, see: (a) Sasai, H.; Suzuki, T.;
Itoh, N.; Tanaka, K.; Date, T.; Okamura, K.; Shibasaki, M. J. Am.
Chem. Soc. 1993, 115, 10372. (b) Hamashima, Y.; Sawada, D.;
Kanai, M.; Shibasaki, M. J. Am. Chem. Soc. 1999, 121, 2641.
(c) Trost, B. M.; Ito, H.; Silcoff, E. R. J. Am. Chem. Soc. 2001, 123,
HPLC: Daicel Chiralpak IA; hexane/i-PrOH (99.0:1.0), flow rate = 1.0
mL/min, λ = 254 nm, 40 °C; tR = 9.1 min (minor), tR = 11.3 min (major).
IR (neat): 3369, 3082, 3032, 2938, 2860, 1691, 1582, 1510, 1491,
1452, 1441, 1410, 1325, 1286, 1207, 1169, 1128, 1067, 1045, 1017,
997, 925, 855, 828, 755, 698 cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–K

K
K. Asano, S. Matsubara
Feature
Synthesis
3367. (d) Trost, B. M.; Hirano, K. Angew. Chem. Int. Ed. 2012, 51,
6480. (e) Shibasaki, M.; Kanai, M.; Matsunaga, S.; Kumagai, N.
Acc. Chem. Res. 2009, 42, 1117.
G.; Zhao, G. ACS Catal. 2013, 3, 1356. (e) Kobayashi, Y.;
Taniguchi, Y.; Hayama, N.; Inokuma, T.; Takemoto, Y. Angew.
Chem. Int. Ed. 2013, 52, 11114. (f) Hintermann, L.; Dittmer, C.
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–K