Indanol-Based Chiral Organoiodine Catalysts for Enantioselective Hydrative Dearomatization

Article abstract of DOI:10.1002/anie.201803889

Rapid development in the last decade has rendered chiral organoiodine(I/III) catalysis a reliable methodology in asymmetric catalysis. However, due to the severely limited numbers of effective organoiodine catalysts, many reactions still give low to modes

Full text of DOI:10.1002/anie.201803889

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: Indanol-based Chiral Organoiodine Catalyst for Enantioselective
Hydrative Dearomatization
Authors: Takuya Hashimoto, Yuto Shimazaki, Yamato Omatsu, and
Keiji Maruoka
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201803889
Angew. Chem. 10.1002/ange.201803889
Link to VoR: http://dx.doi.org/10.1002/anie.201803889
http://dx.doi.org/10.1002/ange.201803889

10.1002/anie.201803889
Angewandte Chemie International Edition
COMMUNICATION
Indanol-based Chiral Organoiodine Catalyst for Enantioselective
Hydrative Dearomatization
Takuya Hashimoto,*[a,b,c] Yuto Shimazaki,[a] Yamato Omatsu,[a] and Keiji Maruoka*[a,d]
Abstract: Rapid development in the last decade rendered chiral
organoiodine(I/III) catalysis a reliable methodology in asymmetric
catalysis. However, due to the severely limited numbers of effective
organoiodine catalysts, many reactions are still practiced with low to
modest enantioselectivities. We report herein a solution to this issue
by the introduction of a pivotal indanol scaffold to the catalyst design.
Our catalyst architecture exhibits the advantage of a high modularity
and thereby expedites catalyst optimization. The catalyst was
optimized for the challenging and highly sought-after hydrative
dearomatization of 2-substituted phenols at the 4-position.
However, they are mostly conducted by the use of a
stoichiometric amount of achiral reagent like PhI(OAc)2. While
chiral organoiodine-catalyzed hydrative dearomatization will
certainly be the solution as presented by Harned and Muñiz,[13]
the enantioselectivities remained poor to modest in both cases.
It is assumed that the remote prochiral center, which is five
bonds away from the organoiodine moiety, and the use of water
as small nucleophile render the chirality transfer from the
catalyst to the substrate difficult.[14]
Our study unveiled an indanol-based chiral organoiodine
catalyst which performs the hydrative dearomatization of
phenols to p-quinols in up to 84% ee. Taking advantage of our
indanol scaffold, equipped with two hydroxy groups, the chiral
structure was strategically diversified to expedite the
Organoiodine compounds exert a unique catalytic property
based on its iodine(I/III) cycle in the presence of a stoichiometric
amount of oxidant. This organoiodine catalysis has recently
attracted considerable attention in synthetic organic chemistry
optimization process. In
a
broader context of chiral
organoiodine(I/III) catalysis, this report demonstrates the first
chiral catalyst which achieves good enantioselectivities in an
intermolecular dearomatization.[17]
as
a
way to implement oxidation reactions with low
environmental impact.[1] The current emphasis on this area has
been driven by emergence of effective chiral organoiodine
catalysts which paved the way for highly enantioselective
transformations (Fig. 1a).[2-5] These chiral catalysts have already
found application in a variety of reactions by other researchers,
giving enantioenriched products accessible only by the use of
organoiodine catalysis.[6] However, chiral organoiodine catalyst
which surpasses the selectivities achievable by these leading
catalysts is virtually non-existent,[7] and many organoiodine-
catalyzed reactions are still performed with unsatisfactory level
of selectivities.[7,8] As a solution to overcome this limitation, we
became interested to apply our chiral indanol scaffold, which
demonstrated outstanding selectivities in our studies on a thiyl
radical and a electrophilic selenium catalyst,[9] to design a new
chiral organoiodine catalyst (Fig. 1b).[10]
As a proof of concept, we surmised that the enantiocontrol of
the hydrative dearomatization of phenols at the para-position, to
give p-quinols, would be particularly challenging and rewarding
(Fig. 1c).[11-14] Such organoiodine(III)-mediated oxidative
dearomatizations of phenols are a common strategy in natural
product synthesis, practiced for more than two decades.[15,16]
Figure 1. a) Representative chiral organoiodine catalysts, b) Indanol-based
chiral organoiodine catalyst, c) para-Hydrative dearomatization of phenols.
[a]
Prof. Dr. Takuya Hashimoto, Yuto Shimazaki, Yamato Omatsu, Prof.
Dr. Keiji Maruoka
Department of Chemistry, Graduate School of Science, Kyoto
University
Sakyo, Kyoto, 606-8502 (Japan)
Armed with a chromatography-free, scalable synthesis of
enantiopure indanol 4,[9a,18] we set up the synthesis of a indanol-
based organoiodine catalyst library (Scheme 1). The hydroxy
group-directed lithiation was carried out to install the iodo moiety
at the 7-position, giving organoiodine 5. By attaching different
substituents to the hydroxy moiety this intermediate can be
derivatized to a variety of chiral organoiodine catalysts 1.
Furthermore, compound 1 can be demethylated by treatment
with a thiolate, allowing us to modify the phenol moiety of 6 and
hence to fine tune the properties of organoiodine catalysts 2.
E-mail: takuya.hash@chiba-u.jp; maruoka@kuchem.kyoto-u.ac.jp
Department of Chemistry, Graduate School of Science, Chiba
University
1-33, Yayoi, Inage, Chiba, 263-8522 (Japan)
Chiba Iodine Resource Innovation Center
1-33, Yayoi, Inage, Chiba, 263-8522 (Japan)
School of Chemical Engineering and Light Industry
Guangdong University of Technology
[b]
[c]
[d]
Panyu District, Guangzhou, 510006 (China)
Supporting information for this article is given via a link at the end of
the document.
This article is protected by copyright. All rights reserved.

10.1002/anie.201803889
Angewandte Chemie International Edition
COMMUNICATION
Ishihara’s report,[5b] attachment of 2,6-disubstituted anilines
further improved the selectivity to more than 80% ee (entries 15-
17). By fixing the catalyst to 3c, the reaction conditions were
fine-tuned, resulting in the use of butanone/H2O solvent system
at 0 °C (entry 18). Under these conditions, p-quinol 8a was
obtained in 54% yield and 82% ee. It is noted that no
racemization of the product was observed in the reaction and
the absolute configuration of 8a was confirmed by X-ray
crystallographic analysis.[20]
Table 1. Catalyst optimization.[a]
Scheme 1. Modular synthesis of indanol-based chiral organoiodine catalysts.
a) BuLi, ether, rt, then I2, THF, –78 °C, 47% yield (87% brsm); b) t-C12H25SH,
NaH, DMF, 130 °C, 86% yield (R = benzyl).
By the use of this strategy, we could diversify the indanol
scaffold 5 rapidly and created a library containing more than 80
chiral organoiodine catalysts, with which the hydrative
dearomatization was optimized (Table 1). 2-Bromo-4-
methylphenol 7a was chosen as model substrate with respect to
the synthetic utility of the bromo moiety for further
functionalization and the poor selectivities achieved in previous
studies (around 40% ee).[13] Taking the aforementioned
derivatization strategy for the catalyst into account, we split the
catalyst optimization into three consecutive rounds. The first
round of optimization was commenced with organoiodines 1,
synthesized by the attachment of alkyl, aryl, acyl and silyl groups
on the C1-alcohol moiety of indanol 5. In the initial screening,
benzyl substitution stood out with which the dearomatized
product could be obtained with 50% ee (entries 1-4). At this
stage, solvents and reaction conditions were examined,
revealing the use of a 2:1 mixture of acetone/H2O at 10 °C as
optimal to give 8a with 59% ee (entries 5-7). Encouraged by the
observed enantioselectivity, comparable to the highest reported
entry
Ar*I
solvent
°C
% yield[b]
% ee[c]
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1d
1d
1a
2a
2b
2c
2d
2e
2f
acetone/H2O = 9/1
rt
rt
rt
rt
rt
rt
10
10
10
10
10
10
10
10
10
10
10
0
49
36
3
51
31
5
73
63
10
46
66
68
49
55
65
46
55
54[e]
50
37
32
4
CH3CN/H2O = 9/1
DMF/H2O = 9/1
acetone/H2O = 2/1
30
68
59
57
37
52
41
70
73
74
77
81
75
82
selectivity,[13]
we
further
screened
other
C1-alcohol
functionalities for catalyst 1 in expectation to attain a higher
selectivity. However, even after thorough investigations, the ee
remained in the range of 40-60% in all cases (see Supporting
Information).
9
10
11
12
13
14
15
16
17
18[d]
We then turned our attention to the second round of the
catalyst optimization using C1-benzyloxy 6 (Scheme 1, R =
benzyl) as template. This time, the phenolic OH group at the 6-
position was modified. After screening of achiral substituents
which ended in vain (entries 8-10, see also SI), we turned our
focus to a chiral lactate moiety introduced by Fujita et al. in their
development of chiral organoiodine(III) reagents.[19] Examination
of both enantiomers of methyl lactate revealed that one isomer
(2d) lowered the ee by 18% and the other (2e) improved the ee
by 11% (entries 12 and 13). It is of note that the chirality of the
lactate is crucial as catalysts bearing achiral glycolate
(CH2CO2Me) or 2-methyllactate (CMe2CO2Me) had no effect on
the selectivity, respectively (see, SI). Further improvement of the
enantioselectivity was observed by the incorporation of N-phenyl
lactamide as the supporting chiral entity (2f, entry 13).[5]
3a
3b
3c
3d
3c
butanone/H2O = 2/1
[a] Reaction conditions: 7a (0.165 mmol), mCPBA (0.363 mmol), and Ar*−I
(0.017 mmol) in solvent (1 mL). [b] NMR yield. [c] Ee determined by chiral
HPLC analysis. [d] Performed on 0.1 mmol scale. [e] Isolated yield.
With the optimized catalyst and reaction conditions in hand,
we then examined the substrate scope, initially focusing on the
2-substituent of phenols (Table 2). The optimized reaction
conditions were applicable to 2-chloro-4-methylphenol with the
same level of enantioselectivity (8b). Interestingly, the
enantioselectivity was maintained even with 2-fluoro-4-
methylphenol (8c), implying that the catalyst recognizes the
electronic bias of the phenol ring. In these two cases, catalyst 3d,
The last optimization round was focused on the amide N-
substituent of organoiodines 3 (entries 14-17). Consistent with
This article is protected by copyright. All rights reserved.

10.1002/anie.201803889
Angewandte Chemie International Edition
COMMUNICATION
bearing a N-4-methyl-(2,6-diphenyl)phenyl group, gave a slightly
higher ee. As for hetero-functionalities, a tosyloxy group was
tolerated albeit with lower enantioselectivity (8d). 2-TMS
substrate was converted to p-quinol 8e with 72% ee.
both cases, the enantioselectivities were unaffected by the
additional substituent, giving 10e and 10f in good yields and
enantioselectivities.
It
is
expected
that
subsequent
debromination of these products would give access to 3,4-
disubstituted p-quinols which are valuable intermediates in
natural product synthesis,[15c,d,f,h] but still hard to synthesize with
state-of-the-art asymmetric catalysis.[13a,21]
Our focus then shifted to different carbon-substituents
attached to the phenol ring. It was revealed that p-quinols 8f-h
bearing a alkynyl, siloxymethyl or amide functionality were
obtained with 70-81% ee by conducting the reaction in either
acetonitrile/H2O or butanone/H2O. The use of 5-methylsalicylate
(7, R1 = CO2Me) resulted in an over-oxidation of the product by
mCPBA (data not shown). The Weinreb amide, a useful
synthetic handle, could be also incorporated into p-quinol 8i with
good enantioselectivity, although the reaction yield still needs to
be improved.
Table 3. 2-Bromophenols substrate scope.
Table 2. 4-Methylphenols substrate scope.
[a] Reaction conditions: 9 (0.10 mmol), mCPBA (0.22 mmol), and 3c (0.01
mmol) in butanone/H2O (2/1, 0.6 mL). [b] Isolated yield. [c] Ee determined by
chiral HPLC analysis.
In conclusion, we developed the first chiral organoiodine
catalyst which performs the intermolecular hydrative
dearomatization of phenols to give p-quinols with good
enantioselectivities. The key to success was the use of a readily
available enantiopure indanol scaffold, allowing for rapid catalyst
evolution and the creation of a library containing more than 80
organoiodine catalysts. With respect to the fact that selectivities
of many organoiodine-catalyzed reactions still lag behind today’s
standards in asymmetric catalysis, our approach will find a way
to provide a solution to this flourishing field.
[a] Reaction conditions: 7 (0.10 mmol), mCPBA (0.22 mmol), and 3c (0.01
mmol) in butanone/H2O (2/1, 0.6 mL). [b] Isolated yield. [c] Ee determined by
chiral HPLC analysis. [d] Performed with 3d (0.01 mmol). [e] Performed in
CH3CN/H2O (2/1, 1.0 mL). [f] Performed in CH3CN/CHCl3/H2O (7/1/2, 1.0 mL).
Acknowledgements
T.H. thanks JSPS KAKENHI Grant Number JP16H01021 in
Precisely Designed Catalysts with Customized Scaffolding. K.M.
thanks JSPS KAKENHI Grant Number JP26220803.
As the next step, we turned our attention to the 4-alkyl
substituent of 2-bromophenols 9 (Table 3). An ethyl group
instead of a methyl group at the 4-position had no negative
effect on the enantioselectivity (10a). To examine the pendant
functional group tolerance, we then examined substrates
bearing acyl, ester, and ether moieties at the end of the alkyl
chain. While these functionalities were tolerated, the reactions
gave a variable level of enantioselectivities (10b-10d).
Keywords: asymmetric catalysis • iodine • dearomatization
[1]
[2]
a) A. Yoshimura, V. V. Zhdankin, Chem. Rev. 2016, 116, 3328−3345;
b) F. V. Singh, T. Wirth, Chem. Asian J. 2014, 9, 950−971. c) M. Ochiai,
K. Miyamoto, Eur. J. Org. Chem. 2008, 4229-4239.
a) M. Fujita, Tetrahedron Lett. 2017, 58, 4409-4419; b) M. Fujita, J.
Synth. Org. Chem. Jpn. 2016, 74, 233-242; c) F. Berthiol, Synthesis
2015, 47, 587-603; d) A. Parra, S. Reboredo, Chem. Eur. J. 2013, 19,
Finally, 4,5-disubstituted 2-bromophenols were briefly
examined, using 5-fluoro and 5-methyl substituted phenols. In
This article is protected by copyright. All rights reserved.

10.1002/anie.201803889
Angewandte Chemie International Edition
COMMUNICATION
17244−17260; e) H. Liang, M. A. Ciufolini, Angew. Chem. Int. Ed. 2011,
50, 11849-11851; Angew. Chem. 2011, 123, 12051–12053; f) R. M.
Romero, T. H. Woste, K. Muñiz, Chem. Asian J. 2014, 9, 972-983.
Guilbault, B. Basdevant, V. Wanie, C. Y. Legault, J. Org.
Chem. 2012, 77, 11283-11295; m) A. A. Guilbault, C. Y. Legault, ACS
Catal. 2012, 2, 219-222; n) J. Yu, J. Cui, X. S. Hou, S. S. Liu, W. C.
Gao, S. Jiang, J. Tian, C. Zhang, Tetrahedron: Asymmetry 2011, 22,
2039-2055.
[3]
For early works on asymmetric organoiodine catalysis, see: a) R. D.
Richardson, T. K. Page, S. Altermann, S. M. Paradine, A. N. French, T.
Wirth, Synlett 2007, 538-542; b) S. M. Altermann, R. D. Richardson, T.
K. Page, R. K. Schmidt, E. Holland, U. Mohammed, S. M. Paradine, A.
N. French, C. Richter, A. M. Bahar, B. Witulski, T. Wirth, Eur. J. Org.
Chem. 2008, 5315-5328.
[8]
[9]
a) S. M. Banik, K. M. Mennie, E. N. Jacobsen, J. Am. Chem. Soc. 2017,
139, 9152-9155; b) S. E. Wang, Q. Q. He, R. H. Fan, Org.
Lett. 2017, 19, 6478-6481.
a) Y. Kawamata, T. Hashimoto, K. Maruoka, J. Am. Chem. Soc. 2016,
138, 5206-5209; b) T. Hashimoto, Y. Kawamata, K. Maruoka, Nat.
Chem. 2014, 6, 702-705.
[4]
[5]
a) T. Dohi, N. Takenaga, T. Nakae, Y. Toyoda, M. Yamasaki, M. Shiro,
H. Fujioka, A. Maruyama, Y. Kita, J. Am. Chem. Soc. 2013, 135, 4558-
4566; b) T. Dohi, A. Maruyama, N. Takenaga, K. Senami, Y.
Minamitsuji, H. Fujioka, S. B. Caemmerer, Y. Kita, Angew. Chem. Int.
Ed. 2008, 47, 3787-3790; Angew. Chem. 2008, 120, 3847-3850.
a) M. Uyanik, T. Yasui, K. Ishihara, J. Org. Chem. 2017, 82, 11946-
11953; b) M. Uyanik, N. Sasakura, M. Mizuno, K. Ishihara, ACS Catal.
2016, 7, 872-876; c) M. Uyanik, T. Yasui, K. Ishihara, Angew. Chem. Int.
Ed. 2013, 52, 9215-9218; Angew. Chem. 2013, 125, 9385–9388; d) M.
Uyanik, K. Ishihara, J. Synth. Org. Chem. Jpn. 2012, 70, 1116-1122; e)
M. Uyanik, T. Yasui, K. Ishihara, Tetrahedron 2010, 66, 5841-5851; f) M.
Uyanik, T. Yasui, K. Ishihara, Angew. Chem. Int. Ed. 2010, 49, 2175-
2177; Angew. Chem. 2010, 122, 2221-2223.
[10] U. H. Hirt, B. Spingler, T. Wirth, J. Org. Chem. 1998, 63, 7674-7679.
[11] A. M. Harned, Tetrahedron Lett. 2014, 55, 4681-4689.
[12] a) T. Yakura, M. Omoto, Chem. Pharm. Bull. 2009, 57, 643-645; b) T.
Yakura, M. Omoto, Y. Yamauchi, Y. Tian, A. Ozono, Tetrahedron 2010,
66, 5833-5840.
[13] a) K. Muñiz, L. Fra, Synthesis, 2017, 49, 2901-2906; b) K. A. Volp, A. M.
Harned, Chem. Commun. 2013, 49, 3001-3003.
[14] A. M. Harned, Org. Biomol. Chem. 2018, DOI: 10.1039/C8OB00463C.
[15] a) T. Hayashi, K. Ohmori, K. Suzuki, Synlett 2016, 27, 2345-2351; b) B.
Hong, C. Li, Z. Wang, J. Chen, H. Li, X. Lei, J. Am. Chem.
Soc. 2015, 137, 11946-11949; c) Z.-G. Feng, W.-J. Bai, T. R. R.
Pettus, Angew. Chem. Int. Ed. 2015, 54, 1864-1867; Angew. Chem.
2015, 127, 1884-1887; d) H. Jo, M. Choi, M. Viji, H. Y. Lee, Y.-S. Kwak,
K. Lee, S. N. Choi, Y.-J. Lee, H. Lee, T. J. Hong, K. M. Lee, J.-K.
Jung, Molecules 2015, 20, 15966-15975; e) K. A. Volp, D. M. Johnson,
A. M. Harned, Org. Lett. 2011, 13, 4486-4489; f) L. Fang, Y. Chen, J.
Huang, L. Liu, J. Quan, C.-c. Li, Z. Yang, J. Org. Chem. 2011, 76,
2479-2487; g) E. D. Coy B, L. E. Cuca S, M. Sefkow, Org. Biomol.
Chem. 2010, 8, 2003-2005; h) X. Li, R. E. Kyne, T. V.
Ovaska, Tetrahedron 2007, 63, 1899-1906; i) Y. Génisson, P. C. Tyler,
R. G. Ball, R. N. Young, J. Am. Chem. Soc. 2001, 123, 11381-11387; j)
Y. Génisson, P. C. Tyler, R. N. Young, J. Am. Chem. Soc. 1994, 116,
759-760.
[6]
a) K. M. Mennie, S. M. Banik, E. C. Reichert, E. N. Jacobsen, J. Am.
Chem. Soc. 2018, 140, 4797-4802; b) R. Pluta, P. E. Krach, L. Cavallo,
L. Falivene, M. Rueping, ACS Catal. 2018, 8, 2582-2588; c) C. Gelis, A.
Dumoulin, M. Bekkaye, L. Neuville, G. Masson, Org. Lett. 2017, 19,
278-281; d) N. Jain, S. Xu, M. A. Ciufolini, Chem. Eur. J. 2017, 23,
4542-4546; e) K. Muñiz, L. Barreiro, R. M. Romero, C. Martínez, J. Am.
Chem. Soc. 2017, 139, 4354-4357; f) S. Haubenreisser, T. H. Woste, C.
Martinez, K. Ishihara, K. Muñiz, Angew. Chem. Int. Ed. 2016, 55, 413-
417; Angew. Chem. 2016, 128, 422-426; g) T. H. Wöste, K. Muñiz,
Synthesis 2016, 48, 816-827; h) S. M. Banik, J. W. Medley, E. N.
Jacobsen, Science 2016, 353, 51-54; i) S. M. Banik, J. W. Medley, E. N.
Jacobsen, J. Am. Chem. Soc. 2016, 138, 5000-5003; j) E. M. Woerly, S.
M. Banik, E. N. Jacobsen, J. Am. Chem. Soc. 2016, 138, 13858-13861;
k) I. G. Molnár, R. Gilmour, J. Am. Chem. Soc. 2016, 138, 5004-5007; l)
Y. Cao, X. Zhang, G. Lin, D. Zhang-Negrerie, Y. Du, Org. Lett. 2016, 18,
5580-5583; m) M. Brown, R. Kumar, J. Rehbein, T. Wirth, Chem. Eur.
J. 2016, 22, 4030-4035; n) Y. Feng, R. Huang, L. Hu, Y. Xiong, V.
Coeffard, Synthesis 2016, 48, 2637-2644; o) B. Basdevant, C. Y.
Legault, Org. Lett. 2015, 17, 4918-4921; p) A. Alhalib, S. Kamouka, W.
J. Moran, Org. Lett. 2015, 17, 1453-1456; q) D. Y. Zhang, L. Xu, H. Wu,
L. Z. Gong, Chem. Eur. J. 2015, 21, 10314-10317; r) H. Wu, Y. P. He, L.
Xu, D. Y. Zhang, L. Z. Gong, Angew. Chem. Int. Ed. 2014, 53, 3466-
3469; s) M. Shimogaki, M. Fujita, T. Sugimura, Eur. J. Org. Chem.
2013, 2013, 7128-7138; t) M. Fujita, K. Mori, M. Shimogaki, T.
Sugimura, Org. Lett. 2012, 14, 1294-1297.
[16] For examples of substrate control, see: a) H. H. Dhanjee, Y. Kobayashi,
J. F. Buergler, T. C. McMahon, M. W. Haley, J. M. Howell, K. Fujiwara,
J. L. Wood, J. Am. Chem. Soc. 2017, 139, 14901-14904; b) A.
Kimishima, H. Umihara, A. Mizoguchi, S. Yokoshima, T.
Fukuyama, Org. Lett. 2014, 16, 6244-6247; c) L. H. Mejorado, T. R. R.
Pettus, J. Am. Chem. Soc. 2006, 128, 15625-15631.
[17] For organoiodine(III)-mediated 2-hydroxylative dearomatizations of
phenols, see: a) M. El Assal, P. A. Peixoto, R. Coffinier, T. Garnier, D.
Deffieux, K. Miqueu, J.-M. Sotiropoulos, L. Pouységu, S. Quideau, J.
Org. Chem. 2017, 82, 11816-11828; b) R. Coffinier, M. E. Assal, P. A.
Peixoto, C. Bosset, K. Miqueu, J.-M. Sotiropoulos, L. Pouységu, S.
Quideau, Org. Lett. 2016, 18, 1120-1123; c) C. Bosset, R. Coffinier, P.
A. Peixoto, M. El Assal, K. Miqueu, J.-M. Sotiropoulos, L. Pouysegu, S.
Quideau, Angew. Chem. Int. Ed. 2014, 53, 9860-9864; Angew. Chem.
2014, 126, 10018–10022; d) S. Quideau, G. Lyvinec, M. Marguerit, K.
Bathany, A. Ozanne-Beaudenon, T. Buffeteau, D. Cavagnat, A.
Chenede, Angew. Chem. Int. Ed. 2009, 48, 4605-4609; Angew. Chem.
2009, 121, 4675–4679; e) J. K. Boppisetti, V. B. Birman, Org.
Lett. 2009, 11, 1221-1223.
[7]
a) Y. Wang, H. Yuan, H. Lu, W.-H. Zheng, Org. Lett. 2018, DOI:
10.1021/acs.orglett.8b00711; b) C. Hempel, C. Maichle-Mossmer, M. A.
Pericas, B. J. Nachtsheim, Adv. Synth. Catal. 2017, 359, 2931-2941; c)
G. Levitre, A. Dumoulin, P. Retailleau, A. Panossian, F. R. Leroux, G.
Masson, J. Org. Chem. 2017, 82, 11877-11883; d) M. Ogasawara, H.
Sasa, H. Hu, Y. Amano, H. Nakajima, N. Takenaga, K. Nakajima, Y.
Kita, T. Takahashi, T. Dohi, Org. Lett. 2017, 19, 4102-4105; e) T. Dohi,
H. Sasa, K. Miyazaki, M. Fujitake, N. Takenaga, Y. Kita, J. Org.
[18] T. Hashimoto, Y. Shimazaki, H. Nagaoka, Y. Kawamata, K. Maruoka,
manuscript in preparation.
[19] M. Fujita, S. Okuno, H. J. Lee, T. Sugimura, T. Okuyama, Tetrahedron
Lett. 2007, 48, 8691-8694.
Chem. 2017, 82,
11954-11960;
f)
M.
Bekkaye,
G.
Masson, Synthesis 2016, 48, 302-312; g)
S. J. Murray, H.
[20] CCDC 1828983 contains the supplementary crystallographic data of 8a.
The data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures.
[21] The dearomatization of 3,4-dimethylphenol under the optimized
reaction conditions gave the corresponding p-quinol in 20% yield and
2% ee.
Ibrahim, Chem. Commun. 2015, 51, 2376-2379; h) P. Mizar, A. Laverny,
M. El-Sherbini, U. Farid, M. Brown, F. Malmedy, T. Wirth, Chem. Eur.
J. 2014, 20, 9910-9913; i) S. Suzuki, T. Kamo, K. Fukushi, T. Hiramatsu,
E. Tokunaga, T. Dohi, Y. Kita, N. Shibata, Chem. Sci. 2014, 5, 2754-
2760; j) S. Brenet, F. Berthiol, J. Einhorn, Eur. J. Org.
Chem. 2013, 2013, 8094-8096; k) M. E. Therien, A. A. Guilbault, C. Y.
Legault, Tetrahedron: Asymmetry 2013, 24, 1193-1197; l) A. A.
This article is protected by copyright. All rights reserved.

10.1002/anie.201803889
Angewandte Chemie International Edition
COMMUNICATION
Entry for the Table of Contents (Please choose one layout)
Layout 2:
COMMUNICATION
Takuya Hashimoto,* Yuto Shimazaki,
Yamato Omatsu, and Keiji Maruoka*
Page No. – Page No.
Indanol-based Chiral Organoiodine
Catalyst for Enantioselective
Hydrative Dearomatization
We report herein the introduction of a pivotal indanol scaffold to a new chiral
organoiodine catalyst design. Our catalyst architecture exhibits the advantage of a
high modularity and thereby expedites catalyst optimization. The catalyst was
optimized for the challenging and highly sought-after para-hydrative
dearomatization of phenols, achieving up to 84% ee.
This article is protected by copyright. All rights reserved.