Iridium-Catalyzed Asymmetric Hydroarylation of Chromene Derivatives with Aromatic Ketones: Enantioselective Synthesis of 2-Arylchromanes

Article abstract of DOI:10.1002/adsc.201801664

Catalytic asymmetric hydroarylation of 2H-chromenes with aromatic ketones was realized by use of a cationic iridium/chiral phosphine complex. The reaction proceeded via olefin isomerization, followed by enantioselective hydroarylation, thus giving 2-arylchromanes in high yields with high enantioselectivity. (Figure presented.).

Full text of DOI:10.1002/adsc.201801664

Title: Iridium-Catalyzed Asymmetric Hydroarylation of Chromene
Derivatives with Aromatic Ketones: Enantioselective Synthesis of
2-Arylchromanes
Authors: Kana Sakamoto and Takahiro Nishimura
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Link to VoR: http://dx.doi.org/10.1002/adsc.201801664

10.1002/adsc.201801664
Advanced Synthesis & Catalysis
Very Important Publication
UPDATE
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Iridium-Catalyzed Asymmetric Hydroarylation of Chromene
Derivatives with Aromatic Ketones: Enantioselective Synthesis
of 2-Arylchromanes
Kana Sakamoto and Takahiro Nishimura*
Department of Chemistry, Graduate School of Science, Osaka City University, Sumiyoshi, Osaka 558-8585, Japan
Phone: +81-6-6605-2880 Email: tnishi@sci.osaka-cu.ac.jp
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
we focused on the enantioselective synthesis of a
chromenes with aromatic ketones was realized by use of a variety of 2-arylchromane derivatives.[10] Here we
Abstract. Catalytic asymmetric hydroarylation of 2H-
cationic iridium/chiral phosphine complex. The reaction
proceeded via olefin isomerization, followed by
report
iridium-catalyzed
enantioselective
hydroarylation[11,12] of readily available 2H-
chromenes[13] with aromatic ketones involving olefin
isomerization (Scheme 1). The reaction gave 2-
arylchromanes in high yields with high
enantioselectivity.
enantioselective
hydroarylation,
thus
giving
2-
arylchromanes in high yields with high enantioselectivity.
Keywords: Iridium; C–H activation; Chromanes; Ketones;
Asymmetric synthesis
This work
R
R
O
O
O
chiral Ir+ catalyst
Ar
O
+
Ar
Ar’
The chromane (benzodihydropyran) skeleton is a
privileged scaffold found in natural products and drag
candidates representing bioactivities such as
antioxidant, antitumor, and antibacterial properties.[1]
Of the chromane derivatives, flavans, which include a
2-phenyl-3,4-dihydro-2H-chromene skeleton, are
widely distributed in plants and also exhibit a wide
variety of bioactivities. In order to investigate their
pharmacological properties, the asymmetric synthesis
of 2-arylchromanes has been developed. There have
been several reports on the asymmetric synthesis of
flavans;[2] a) cyclization of chiral haloalkyl ortho-
bromophenyl ethers via C–C bond formation,[3] b)
intramolecular C–O bond formation of chiral
alcohols,[4] c) ring-closing metathesis of chiral
alkenyl ortho-vinylphenyl ether followed by
hydrogenation,[5] d) cyclization of chiral epoxides,[6]
e) enantioselective intramolecular oxysulfenylation
and oxyselenenylation of ortho-alkenylphenols,[7] and
f) enantioselective hydrogenation of 2-aryl-4H-
chromenes.[8]
Recently, we reported the regio- and
enantioselective hydroarylation of alkenyl ethers
catalyzed by an Ir/chiral bisphosphine complex.[9a]
The reaction involves directed ortho-C–H activation
of aromatic compounds such as 2-phenylpyridine
derivatives and the regioselective hydroarylation of
1-alkenyl ethers isomerized from alkenyl ethers such
as allyl and homoallyl ethers. Consequently, the aryl
groups are selectively installed at the α-carbon atom
of the alkoxy group. Based on our previous studies,
*
Ar’
via
O
O
isomerization
Scheme 1. Ir-Catalyzed Asymmetric Hydroarylation of
Chromenes.
Treatment of p-methoxyacetophenone (1a) with
1.5 equivalents of 2H-chromene (2a) in the presence
of [IrCl(cod)]2 (5 mol% of Ir), (R)-binap[14] (6 mol%),
and NaBArF (10 mol%, ArF = 3,5-(CF3)2C6H3) in
4
toluene at 80 ºC for 18 h gave the addition product
3aa in 88% yield with 84% ee (Table 1, entry 1).
The aryl group was selectively installed into the 2-
position of the chromane core.
Higher
enantioselectivity (89% ee) was obtained with a
bulkier ligand, (R)-DM-binap (entry 2), while the use
of (R)-Tol-binap was less effective in terms of both
the reactivity and enantioselectivity (entry 3). (R)-
Binap*[15] having 3,5-dimethyl-4-methoxy groups on
the phosphorous atom showed a nearly identical
enantioselectivity to that obtained with (R)-DM-binap
(entry 4). (S)-Segphos[16] showed similar reactivity to
binap (entry 5) and the use of the bulkier ligand, (R)-
DM-segphos, improved the enantioselectivity to 89%
ee (entry 6). However, the use of a much bulkier
ligand (R)-DTBM-segphos gave no addition product
1
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10.1002/adsc.201801664
Advanced Synthesis & Catalysis
3aa (entry 7). MeObiphep[17] ligands were also
effective in inducing the high enantioselectivity
(entries 8 and 9). In contrast, the use of Josiphos,[18]
dipamp,[19] and QuinoxP*[20] inhibited the reaction
(entries 10–12). 1,5-Cyclooctadiene (cod) did not
work as a ligand in the present reaction (entry 13).
yields. In particular, the reactions of the ketones with
electron-donating groups (1a–c,h) at the para- and
ortho-position showed the high enantioselectivity. A
tetraphenylethenyl group, which has aggregation-
induced emission character,[21] can also be
enantioselectively introduced into the chromane
skeleton giving 3fa in 95% yield with 81% ee by
using (R)-binap.[22] In addition to acetophenones, 2-
acetylthiophene (1i), ethyl phenyl ketone (1j), and
isopropyl phenyl ketone (1k) were also suitable for
this reaction and gave 3ia, 3ja, and 3ka, respectively,
Table 1. Ligand Screening[a]
O
O
[IrCl(cod)]2 (5 mol% Ir)
MeO
with good enantioselectivity.
The reaction of
O
ligand (6 mol%)
1a
+
MeO
substituted benzophenone 1l also took place using
(R)-binap to give 3la in 97% yield, albeit with the
modest enantioselectivity (53% ee). Tetralone 1m,
chromanone 1n, and chromone 1o also reacted with
2a to give the corresponding chromanes 3ma–oa in
good yields with high enantioselectivity.
NaBArF4 (10 mol%)
*
O
toluene
3aa
80 ºC, 18 h
2a
O
O
R
R
PAr2
PAr2
PAr2
PAr2
MeO
MeO
PAr2
PAr2
[IrCl(cod)]2 (5 mol% Ir)
O
(R)-DM-segphos (6 mol%)
NaBArF4 (10 mol%)
O
O
O
Ar
Ar
O
1
toluene, 80 ºC, 48 h
+
(R)-binap (Ar = Ph)
(R)-segphos (Ar = Ph)
(R)-MeObiphep (R = Ph)
2a
(R)-3,5-xylyl-MeObiphep
(Ar = 3,5-Me2C6H3)
(R)-DM-binap
(Ar = 3,5-Me2C6H3)
(R)-DM-segphos
(Ar = 3,5-Me2C6H3)
3
R =
OMe (3aa)
Me (3ba)
86%, 91% ee
(R)-tol-binap
(Ar = 4-MeC6H4)
(R)-DTBM-segphos
85%, 87% ee
79%, 94% ee
71%, 83% ee
91%, 81% ee
95%, 81% ee[a]
O
O
(Ar = 3,5-(t-Bu)2-4-MeOC6H2)
NMe2 (3ca)
Cl (3da)
(R)-binap*
(Ar = 4-MeO-3,5-Me2C6H2)
R
Ar Ph
P
t-Bu Me
F (3ea)
Ph2C=CPh (3fa)
PCy2
N
N
P
Ph2P
Fe
OMe
Me
P
Me
P
O
O
S
O
O
O
Ph Ar
Ar = 2-MeO-C6H4
Me
t-Bu
Josiphos
O
(R,R)-QuinoxP*
Entry Ligand
Yield [%][b]
Ee [%][c]
3ga: 76%, 77% ee
3ha: 76%, 87% ee
3ia: 66%, 75% ee[b]
1
2
3
4
5
6
7
8
9
(R)-binap
88
86
49
94
94
88
0
84
89
68
87
84
89
–
R
(R)-DM-binap
(R)-Tol-binap
(R)-binap*
(R)-segphos
(R)-DM-segphos
(R)-DTBM-segphos
(R)-MeObiphep
(R)-3,5-Xylyl-
MeObiphep
Josiphos
O
O
Et,H (3ja)
84%, 80% ee
63%, 88% ee
97%, 53% ee[c]
R,R' =
i-Pr,H (3ka)
3,5-Me2C6H3,MeO (3la)
R'
O
O
94
91
85
88
O
O
O
O
O
O
O
10
11
12
13
0
0
0
0
–
–
–
–
(R,R)-dipamp
(R,R)-QuinoxP*
–
3na: 96%, 90% ee[b,c] 3oa: 66%, 82% ee[b,c]
3ma: 68%, 90% ee
Scheme 2. Ir-Catalyzed Asymmetric Hydroarylation of
2H-Chromene. Reaction conditions: 1 (0.20 mmol), 2a
(0.30 mmol), [IrCl(cod)]2 (5 mol% of Ir), (R)-DM-segphos
[a] Reaction conditions: 1a (0.10 mmol), 2a (0.15 mmol),
[IrCl(cod)]2 (5 mol% of Ir), ligand (6 mol%), and NaBArF
4
[b]
(10 mol%) in toluene (0.2 mL) at 80 ºC for 18 h.
(6 mol%), and NaBArF (10 mol%) in toluene (0.4 mL) at
4
Determined by 1H NMR. [c]Determined by HPLC analysis
with a chiral stationary phase column: Chiralcel OD-H.
80 °C for 48 h. [a](R)-Binap was used instead of (R)-DM-
segphos. [b]10 mol% of Ir was used. [c](R)-DM-Binap was
used instead of (R)-DM-segphos.
Scheme 2 summarizes the results obtained for the
hydroarylation of 2H-chromene (2a) with several
aromatic ketones using the Ir/(R)-DM-segphos (or
DM-binap) catalyst. The reaction of substituted
acetophenones proceeded enantioselectively to give
the corresponding 2-arylchromanes 3aa–ha in good
This iridium-catalyzed reaction can also be applied
to several substituted chromene derivatives (Scheme
3). Thus, chromene derivatives substituted with
electron-withdrawing (F, Cl, Br) and -donating
groups (Me, MeO) (2b–g) are all good substrates to
2
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10.1002/adsc.201801664
Advanced Synthesis & Catalysis
give the corresponding products in good yield with
high enantioselectivity. It should be noted that in all
cases the aryl groups were selectively installed into
the 2-position of the chromane derivatives. Benzo-
1,4-dioxene 2h also underwent the hydroarylation
with 1a to give the addition product 3ah in 89% yield
with 70% ee.
conditions. Unfortunately, however, seven- and
eight-membered 2i and 2j were unreactive with
aromatic ketones mainly because of the slow
isomerization of the alkene moiety.[23] Nevertheless,
it was found that 2-phenylpyridine (1q) reacted with
2i and 2j to give 2-arylated products 3qi and 3qj,
respectively, in modest yields with good
enantioselectivity (Scheme 5).
[IrCl(cod)]2
1a
O
(5 mol% Ir)
+
(R)-DM-segphos
(6 mol%)
Ar
O
O
Ir+/(R)-DM-segphos
N
NaBArF4 (10 mol%)
N
O
(5 mol% Ir)
O
toluene, 80 ºC, 48 h
+
X
MeO
Ar
3
X
toluene, 80 ºC, 48 h
2
2i
Ar
O
Ar
O
(1.5 equiv.)
3qi: 54%, 82% ee
1q
1q
X
Br
F (3ab)
X =
85%, 84% ee
73%, 88% ee
Ir+/(R)-DM-segphos
O
Cl (3ac)
OMe (3ad)
3ae: 77%, 94% ee
N
O
(10 mol% Ir)
70%, 84% ee
X
+
toluene, 80 ºC, 72 h
Ar
O
O
Ar
O
(1.5 equiv.)
2j
3qj: 47%, 86% ee
X = F (3af)
Me (3ag)
3ah: 89%, 70% ee
97%, 92% ee
99%, 98% ee
Scheme 5. Asymmetric Hydroarylation of 7 and 8-
Membered Cyclic Alkenes.
Scheme 3. Ir-Catalyzed Asymmetric Hydroarylation of
Chromenes.
Deuterium-labeling experiments proved that ortho-
C–H activation of 4-methoxyacetophenone (1a)
occurred in the presence of the cationic iridium
complex.[24] Thus, in the reaction of 1a with
deuterated p-methoxystyrene 6,[25] deuterium was
transferred from 6 to ortho-positions of 1a [Eq. (1)].
The result indicates that the C–H activation of 1a
giving an aryl(hydrido)iridium and reversible
insertion/elimination between the hydridoiridium and
The absolute configuration of the products was
assigned by analogy with (S)-3pa, which was
transformed into the known chiral flavan (Scheme 4).
Thus, treatment of chromane 3pa, which was
obtained by using (R)-DM-segphos, with NaOCl
solution (8 equiv.) and 1 N NaOHaq (6.2 equiv.) in
1,4-dioxane at 75 °C for 12 h gave 4 in 94% yield.
6 occurred.
isomerization of 2H-chromene 2a into 4H-chromene
2a' is presumably promoted by the
aryl(hydrido)iridium. In contrast, as shown in
The result also implies that the
Carboxylic acid
4
was converted into the
corresponding aldehyde, which was then subjected to
deformylation through an Ir catalysis to give flavan 5.
The absolute configuration of 5 was determined to be
25
Equation 2, the cationic iridium complex can also
S-(–) by its specific rotation [[α]D –12 (c = 0.60,
isomerize 2H-chromene 2a into 4H-chromene 2a'.[26]
20
CHCl3) for 79% ee (S); lit. [α]D –10.6 (c = 0.06,
CHCl3) for (S)-5].[3c]
D
[IrCl(cod)]2 (5 mol% Ir)
D
binap (6 mol%)
NaBArF4 (10 mol%)
[IrCl(cod)]2 (5 mol% Ir)
O
D
(R)-DM-segphos
1a
+
(1)
(2)
Ar
O
toluene, 80 ºC, 3 h
MeO
O
(6 mol%)
O
D
D
NaBArF4 (10 mol%)
1.73D/2H
O
6 (5 equiv.)
Ar = 4-MeOC6H4
2a
+
1a-d2: 86%
toluene, 80 ºC, 48 h
(1.5 equiv.)
1p
[IrCl(cod)]2 (5 mol% Ir)
(R)-DM-segphos (6 mol%)
NaBArF4 (10 mol%)
(0.50 mmol)
3pa: 79%, 84% ee
O
OH
1) LiAlH4
2) MnO2
3) [IrCl(cod)]2
PPh3
toluene
NaOClaq
NaOHaq
O
80 ºC, 3 h
2a'
2a:2a' = 47:53
2a
O
O
On the basis of the deuterium-labeling experiments
4: 94%
5: 35% (3 steps), 79% ee (S)
and the recent computational studies on the Ir-
catalyzed hydroarylation,[27] the catalytic cycle of the
present reaction is proposed as illustrated in Scheme
6. Ortho-C–H activation of a cationic iridium A
forms an aryl(hydrido)iridium(I) species B. Species
B undergoes irreversible carbometalation to 4H-
chromene 2a' leading to the alkyliridium intermediate
Scheme 4. Transformation into Flavan.
Six-membered chromene derivatives are good
substrates undergoing the addition of the C–H bond
of aromatic ketones under the present catalytic
3
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10.1002/adsc.201801664
Advanced Synthesis & Catalysis
This work was supported by JSPS KAKENHI Grant Number
JP15H03810.
C, and reductive elimination forming a C–H bond
gives an addition product and regenerates A. The
species B promotes olefin isomerization of 2H-
chromene 2 into 4H-chromene 2a' by reversible
References
alkene insertion via alkyliridium E.
The
isomerization can also be promoted by the cationic
iridium(I) via π-allyl complex F formed by allylic C–
H activation.[26]
[1]a) E. Middleton, Jr., C. Kandaswami, T. C. Theoharides,
Pharmacol. Rev. 2000, 52, 673; b) X. Hu, J.-W. Wu, M.
Wang, M.-H. Yu, Q.-S. Zhao, H.-Y. Wang, A.-J. Hou,
J. Nat. Prod. 2012, 75, 82.
O
3ap
[2] For reviews, see: a) H. C. Shen, Tetrahedron 2009, 65,
3931; b) M. G. Núñez, P. García, R. F. Moro, D. Díez,
Tetrahedron 2010, 66, 2089.
O
Ir
H
A
H
1p
[3] a) K. J. Hodgetts, Tetrahedron Lett. 2001, 42, 3763; b)
K. J. Hodgetts, Tetrahedron 2005, 61, 6860; c) E. T.
Choi, M. H. Lee, Y. Kim, Y. S. Park, Tetrahedron
2008, 64, 1515.
Ir = [Ir(DM-segphos)]+
O
Ir
O
H
Ir
B
O
H
O
Ir
[4] a) B. Xu, J. Xue, J. Zhu, Y. Li, Chem. Lett. 2008, 37,
202; b) Y. Wang, R. Franzén, Synlett 2012, 925.
H
O
O
D
[5] H. He, K.-Y. Ye, Q.-F. Wu, L.-X. Dai, S.-L. You, Adv.
Synth. Catal. 2012, 354, 1084.
C
2a'
[6] J. Chapelat, A. Buss, A. Chougnet, W.-D. Woggon,
O
Org. Lett. 2008, 10, 5123.
H
A or B
O
Ir
Ir
[7]a) S. E. Denmark, D. J. P. Kornfilt, J. Org. Chem. 2017,
82, 3192; b) H. Zhang, S. Lin, E. N. Jacobsen, J. Am.
Chem. Soc. 2014, 136, 16485.
O
2a
O
or
E
F
[8] a) C. Valla, A. Baeza, F. Menges, A. Pfaltz, Synlett
2008, 3167; b) M. Terada, T. Yamanaka, Y. Toda,
Chem. Eur. J. 2013, 19, 13658.
Scheme 5. Plausible Catalytic Cycle.
[9] a) Y. Ebe, M. Onoda, T. Nishimura, H. Yorimitsu,
Angew. Chem., Int. Ed. 2017, 56, 5607; Angew. Chem.
2017, 129, 5699; b) Y. Ebe, T. Nishimura, J. Am. Chem.
Soc. 2015, 137, 5899; c) D. Yamauchi, T. Nishimura, H.
Yorimistu, Chem. Commun. 2017, 53, 2760; d) M.
Hatano, Y. Ebe, T. Nishimura, H. Yorimistu, J. Am.
Chem. Soc. 2016, 138, 4010.
In summary, we have developed asymmetric
hydroarylation of 2H-chromenes with aromatic
ketones by use of a cationic iridium/chiral phosphine
complex.
The reaction proceeded via olefin
followed by enantioselective
isomerization,
hydroarylation, thus giving 2-arylchromanes in high
yields with high enantioselectivity.
[10] One preliminary result of the asymmetric
hydroarylation of 2H-chromene with acetophenone was
reported in 9a.
Experimental Section
For detailed experimental information and the
characterization of compounds, see the supporting
information.
[11] For selected examples of Ir-catalyzed intermolecular
asymmetric hydroarylation, see: a) R. Aufdenblatten, S.
Diezi, A. Togni, Monatsh. Chem. 2000, 131, 1345; b) S.
Pan, N. Ryu, T. Shibata, J. Am. Chem. Soc. 2012, 134,
17474; c) C. S. Sevov, J. F. Hartwig, J. Am. Chem. Soc.
2013, 135, 2116; d) T. Shibata, T. Shizuno, Angew.
Chem., Int. Ed. 2014, 53, 5410; Angew. Chem. 2014,
126, 5514; e) T. Shirai, Y. Yamamoto, Angew. Chem.,
Int. Ed. 2015, 54, 9894; Angew. Chem. 2015, 127,
10032; f) T. Shibata, M. Michino,ꢀ H. Kurita, Y.
Tahara, K. S. Kanyiva, Chem. Eur. J. 2017, 23, 88; g)
S. Grꢀlaud, P. Cooper, L. J. Feron, J. F. Bower, J. Am.
Chem. Soc. 2018, 140, 9351. For selected examples of
Ir-catalyzed intramolecular asymmetric cyclization
involving C–H activation, see: h) D. F. Fernández, M.
Gulías, J. L. Mascareñas, F. López, Angew. Chem. Int.
Ed. 2017, 56, 9541; Angew. Chem. 2017, 129, 9669. i)
T. Shibata, N. Ryu, H. Takano, Adv. Synth. Catal. 2015,
357, 1131.
General procedure for Ir-catalyzed asymmetric
hydroarylation of 2H-chromene: [IrCl(cod)]2 (3.4 mg,
0.0050 mmol, 5 mol% of Ir), (R)-DM-segphos (8.7 mg,
0.0012 mmol, 6 mol%), NaBArF (18.4 mg calculated as
4
the dihydrate, 0.020 mmol, 10 mol%), and toluene (0.4
mL) were placed in a Schlenk tube under N2, and the
mixture was stirred at room temperature for 10 min. Then,
aromatic ketone 1 (0.20 mmol) and chromene 2 (0.30
mmol) were added to the tube successively, and the
mixture was stirred at 80 ºC for 48 h. The mixture was
passed through a short column of alumina with CH2Cl2 as
an eluent, and the solvent was removed on a rotary
evaporator. The residue was subjected to preparative TLC
on silica gel eluted with EtOAc/hexane (1:3–1:10) to give
3.
Acknowledgements
4
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10.1002/adsc.201801664
Advanced Synthesis & Catalysis
[12] For reviews of the asymmetric reactions involving C–
H activation, see: a) C. G. Newton, S.-G. Wang, C. C.
Oliveira, N. Cramer, Chem. Rev. 2017, 117, 8908; b) C.
Zheng, S.-L. You, RSC Adv. 2014, 4, 6173; c) J.
Wencel-Delord, F. Colobert, Chem. Eur. J. 2013, 19,
14010; d) S. Pan, T. Shibata, ACS Catal. 2013, 3, 704;
e) R. Giri, B.-F.ꢀ Shi, K. M. Engle, N. Maugel, J.-Q.
Yu, Chem. Soc. Rev. 2009, 38,ꢀ 3242.
[19] B. D. Vineyard, W. S. Knowles, M. J. Sabacky, G. L.
Bachman, D. J. Weinkauff, J. Am. Chem. Soc. 1977, 99,
5946.
[20] T. Imamoto, K. Sugita, K. Yoshida, J. Am. Chem. Soc.
2005, 127, 11934.
[21] R. T. K. Kwok, C. W. T. Leung, J. W. Y. Lam, B. Z.
Tang, Chem. Soc. Rev. 2015, 44, 4228.
[13] a) R. C. Larock, L. Wei, T. R. Hightower, Synlett
1998, 522; b) I. N. Lykakis, C. Efe, C. Gryparis, M.
Stratakis, Eur. J. Org. Chem. 2011, 2334.
[22] The use of (R)-DM-segphos or (R)-DM-binap
resulted in the formation of a low yield of 3fa.
[23] Isomerization of 2j did not proceed at all under the
same condition as Scheme 2 used binap as a ligand,
regardless of the presence or absence of 1a.
[14] H. Takaya, K. Mashima, K. Koyano, M. Yagi, H.
Kumobayashi, T. Taketomi, S. Akutagawa, R. Noyori,
J. Org. Chem. 1986, 51, 629.
[24] K. Tsuchikama, M. Kasagawa, Y. Hashimoto, K.
[15] T. Senda, M. Ogasawara, T. Hayashi, J. Org. Chem.
2001, 66, 6852.
Endo, T. Shibata, J. Orgnomet. Chem. 2008, 693, 3939.
[25] M. Hatano, T. Nishimura, H. Yorimitsu, Org. Lett.
2016, 18, 3674.
[16] T. Saito, T. Yokozawa, T. Ishizaki, T. Moroi, N. Sayo,
T. Miura, H. Kumobayashi, Adv. Synth. Catal. 2001,
343, 264.
[26] D. Baudry, M. Ephritikhine, H. Felkin, J. Chem. Soc.,
Chem. Commun. 1978, 694.
[17] R. Schmid, J. Foricher, M. Cereghetti, P. Schönholzer,
[27] M. Zhang, L. Hu, Y. Lang, Y. Chao, G. Huang, J.
Org. Chem. 2018, 83, 2937.
Helv. Chim. Acta 1991, 74, 370.
[18] A. Togni, C. Breutel, A. Schnyder, F. Spindler, H.
Landert, A. Tijani, J. Am. Chem. Soc. 1994, 116, 4062.
5
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10.1002/adsc.201801664
Advanced Synthesis & Catalysis
UPDATE
Iridium-Catalyzed Asymmetric Hydroarylation of
Chromene Derivatives with Aromatic Ketones:
Enantioselective Synthesis of 2-Arylchromanes
R
H
R
O
O
+
chiral Ir+
O
O
Ar
Ar’
Ar
*
Adv. Synth. Catal. Year, Volume, Page – Page
Ar’
via
O
O
up to 98% ee
isomerization
Kana Sakamoto and Takahiro Nishimura*
6
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