Ruthenium-NHC-catalyzed asymmetric hydrogenation of flavones and chromones: General access to enantiomerically enriched flavanones, flavanols, chromanones, and chromanols

Article abstract of DOI:10.1002/anie.201302573

Two to four! Readily available flavones and chromones were efficiently converted into four valuable chiral classes of O-heterocycles - flavanones, chromanones, flavanols, and chromanols - by means of an enantioselective Ru/NHC-catalyzed hydrogenation process (see scheme; NHC=N-heterocyclic carbene, PCC=pyridinium chlorochromate). Copyright

Full text of DOI:10.1002/anie.201302573

.
Angewandte
Communications
DOI: 10.1002/anie.201302573
Asymmetric Hydrogenation
Ruthenium–NHC-Catalyzed Asymmetric Hydrogenation of Flavones
and Chromones: General Access to Enantiomerically Enriched
Flavanones, Flavanols, Chromanones, and Chromanols**
Dongbing Zhao, Bernhard Beiring, and Frank Glorius*
Dedicated to Professor Ryoji Noyori on the occasion of his 75th birthday
Flavanoids and chromanoids including flavanones, flava-
nols, chromanones, and chromanols are a large family of
well-known natural products (Scheme 1).[1,2] These natural
products have been shown to exhibit a wide range of
biological activities including anticancer, antitumor, anti-
bacterial, antimicrobial, antioxidant, estrogenic, and anti-
estrogenic properties. Additionally, these chiral flavanoids
and chromanoids could readily be utilized in the synthesis
of many benzopyran-containing natural products by es-
tablished reaction pathways (Scheme 1).[3]
Although there are numerous reports on the synthesis
of flavanones, flavanols, chromanones, and chromanols,
only few stereoselective methods have been devised to
access enantiomerically enriched products.[4] In fact, to the
best of our knowledge, so far no transition-metal-catalyzed
method has been reported for the highly enantioselective
synthesis of 2-substituted flavanols and chromanols despite
their importance.[2e,5] Owing to minimal negative environ-
mental impact, high atom economy, and operational
simplicity, the transition-metal-catalyzed asymmetric
hydrogenation has long held a respected position both in
Scheme 1. Representative structures of biologically active flavanoid and
chromanoid natural products.
academia and in industry for the preparation of optically
active compounds.[6,7] However, even though the enantio-
selective hydrogenation of natural and commercial chro-
mones and flavones seems to be one of the most straightfor-
ward ways to synthesize flavanones, flavanols, chromanones,
and chromanols, the asymmetric catalytic hydrogenation of
chromones[8] and flavones remains largely unexplored.[9] It
would be highly desirable to develop a general, efficient
catalytic system for the asymmetric hydrogenation of these
heterocycles.
During the course of our investigation into the asymmet-
ric hydrogenation of (hetero)arenes, we found that the
combination of ruthenium(II) and several NHCs (NHC =
N-heterocyclic carbene) led to the formation of highly
active and enantioselective catalysts for the hydrogenation
of quinoxalines, benzofurans, and (benzo)thiophenes.[7n,o,10] In
light of the high level of reactivity and enantioselectivity of
our Ru–NHC catalyst, we rationalized that chromones and
flavones could be hydrogenated directly to flavanols and
chromanols in a stereoselective manner. Further we could
easily obtain the enantiomerically enriched flavanones and
chromanones by a simple and selective subsequent oxida-
tion.[11] Herein we report the first asymmetric hydrogenation
of chromones and flavones using a chiral NHC–Ru complex.
This direct and general route is capable of accessing
biologically active enantiomerically enriched flavanoids and
chromanoids comprising all the above-mentioned structures:
flavanones, flavanols, chromanones, and chromanols
(Scheme 2).
[*] Dr. D. Zhao, B. Beiring, Prof. Dr. F. Glorius
Westfꢀlische Wilhelms-Universitꢀt Mꢁnster
Organisch-Chemisches Institut
Corrensstrasse 40, 48149 Mꢁnster (Germany)
E-mail: glorius@uni-muenster.de
Homepage: http://www.uni-muenster.de/Chemie.oc/glorius/
index.html
[**] We thank Dr. Nuria Ortega for stimulating discussions. This work
was supported by the European Research Council under the
European Community’s Seventh Framework Program (FP7 2007–
2013)/ERC grant agreement no. 25936 and the Alexander von
Humboldt Foundation (D.Z.). The research of F.G. was supported
by the Alfried Krupp Prize for Young University Teachers of the
Alfried Krupp von Bohlen und Halbach Foundation. We also thank
BASF (Prof. Dr. Klaus Ditrich) for the donation of valuable chiral
amines (ChiPros). NHC=N-heterocyclic carbene.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201302573.
8454
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2013, 52, 8454 –8458

Angewandte
Chemie
to be an excellent ligand and the mixture of hexane/toluene
(2:1) was clearly the best choice of solvent for inducing
enantioselectivity and increasing the reactivity (Table 1,
entries 3–9). Generally, we found that lower temperature
and higher hydrogen pressure improved the diastereomeric
ratio. Finally, we could obtain a good diastereomeric ratio
(5:1) and excellent enantioselectivity at 58C under 120 bar of
H2 with 5 mol% of catalyst (Table 1, entry 9). Furthermore,
the ratio could be elevated to 9:1 after recrystallization. By
comparison of the NMR spectrum of 2a with known
compounds, the main product was determined to be cis-
configured.
With optimized conditions in hand, we tested a variety of
2-substituted flavones and chromones to gain insight into the
versatility of our catalytic system (Scheme 3). Fortunately, for
most of the 2-alkyl-substituted chromones including many
with primary and secondary alkyl chains, the reaction
proceeds with full conversion, moderate to good diastereo-
selectivity, and high enantioselectivity for the major product
(Scheme 3, 1a–i). We noticed that the diastereomeric ratio
decreased slightly when the length or substitution of the chain
was increased, while full conversion to the desired product
was maintained. Furthermore, we studied the influence of the
substitution on the carbocyclic ring of the chromone (1h, 1i).
In these cases good diastereoselectivity and high enantiose-
lectivity were observed, as well. Changing the position of the
substituent to position 3 (1q) led to
Scheme 2. Hydrogenation of chromones and flavones to optically
active flavanones, flavanols, chromanones, and chromanols.
We commenced our study with the hydrogenation of 2-
methyl-4H-chromen-4-one (1a) to optimize the reaction
conditions. Fortunately, when we applied our Ru catalyst
formed from ICy·HCl (3a; ICy = N,N’-dicyclohexylimidazol-
2-ylidene) for the hydrogenation of 1a, we exclusively
obtained the corresponding 2-methyl-4H-chroman-4-ol (2a)
with a d.r. of 1:1 (Table 1, entry 1). Encouraged by this result,
we tested whether our previously developed chiral ruthe-
nium–NHC complex, formed from the imidazolinium salt 3b,
could control the diastereoselectivity and enantioselectivity in
the hydrogenation of 1a. When we submitted 1a to the
hydrogenation process at 80 bar of H2 and 608C, the desired
product 2a was formed with full conversion, low diastereo-
selectivity (d.r. = 1.2:1), and good enantioselectivity (for the
major product, e.r. = 93:7) (Table 1, entry 2). We subse-
quently screened a variety of NHC ligands, solvents, pres-
sures, and temperatures. NHC ligand derived from 3b proved
a drop in enantioselectivity but full
conversion and higher diastereose-
Table 1: Optimization of the reaction conditions for the asymmetric hydrogenation of 2-methyl-4H-
chromen-4-one (1a).[a]
lectivity (8.3:1) than with the regio-
isomer 1a. Our method could also
be applied in the hydrogenation of
thiochromenone (2r).
When 2-substituted flavones
were employed as substrates, we
surprisingly found that only small
amounts of the desired hydrogen-
ated products were formed under
the above-mentioned conditions.
Fortunately, the hydrogenation of
flavone 1j proceeded smoothly with
full conversion and good enantiose-
lectivity to give the flavanol 2j
when the reaction was conducted
with 10 mol% of catalyst at room
Entry
L
T [8C]
p(H2) [bar]
Solv.
d.r.[b]
e.r.[c]
Yield[d] [%]
1
2
3
4
5
6
7
3a
3b
3b
3c
3d
3b
3b
3b
3b
60
60
25
25
25
25
25
5
80
80
80
80
80
80
120
120
120
tol.
tol.
tol.
tol.
1:1
–
>99
>99
>99
>99
trace
>99
>99
51%
>99
1.2:1
2.5:1
1.8:1
–
93:7
95.5:4.5
92:8
–
97:3
97:3
98:2
98.5:1.5
tol.
hex.
hex.
hex.
hex./tol.
(2:1)
2.7:1
3.0:1
4.5:1
5:1
8[e]
9[e]
5
(9.3:1)[f]
temperature.
As
shown
in
[a] General conditions: [Ru(cod)(2-methylallyl)2] (0.015 mmol), KOtBu (0.045 mmol), and NHC ligand
(0.03 mmol) were stirred at 708C in toluene or hexane (2 mL) for 16 h, after which the reaction mixture
was added to 1a (0.3 mmol), and hydrogenation was performed under the conditions listed in each case
for 24 h. [b] d.r. was determined by 1H NMR analysis. [c] e.r. given for main product was determined by
HPLC on a chiral stationary phase. [d] Yields pertain to isolated product. [e] The reaction time was
prolonged to 36 h. [f] After recrystallization from n-hexane/iPrOH; tol.=toluene, hex.=hexane.
Scheme 3, under the modified con-
ditions, in most cases, the reaction
of 2-substituted flavones gave the
desired flavanols in high yields and
good enantioselectivity for the cis
product. We found that the reactiv-
ity changes only slightly with the
electronic properties of the sub-
stituents: When the phenyl ring
bears electron-withdrawing groups
or electron-rich groups, such as
fluorine (1m), trifluoromethyl
(1n), and methoxy (1o) in para
Angew. Chem. Int. Ed. 2013, 52, 8454 –8458
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
8455

.
Angewandte
Communications
further transformed into a variety of enantiomerically
enriched flavanones and chromanones in high yields by
simple selective oxidation in the presence of pyridindium
chlorochromate (PCC) without compromising the integrity of
the newly formed stereocenter at C2 (Scheme 4). Because of
the cleanly proceeding hydrogenation process and the high
efficiency of selective oxidation, the enantiomerically
enriched flavanone and chromanone products could be
obtained in analytically pure form by simple filtration. For
example, exposure of 2a to PCC in CH2Cl2 at room temper-
ature affords the corresponding chromanone 4a with an e.r. of
96:4. Although the flavanol and chromanol products are
formed as mixtures of cis and trans diastereomers with our
catalytic system, the oxidation generally delivers highly
enantiomerically enriched flavanones and chromanones
with a variety of aryl/alkyl groups at the C2 position in
excellent yields (Scheme 4, 4a–o). In contrast, the previously
reported nonhydrogenation-based asymmetric route to these
products afforded enantiomerically enriched 2-alkyl chroma-
nones in only low yield if at all.[4f,h,i] By comparison of the
optical rotation data of 4a and 4j with literature data, the
absolute configuration of 4a could be assigned to be R and the
absolute configuration of 4j could be assigned to be S.[4d,e]
Scheme 3. Catalytic asymmetric hydrogenation of chromones and
flavones. General conditions: [Ru(cod)(2-methylallyl)2] (0.015 mmol),
KOtBu (0.045 mmol), and NHC ligand (0.03 mmol) were stirred at
708C in n-hexane (2 mL) for 16 h, after which the reaction mixture was
added to 1 (0.15–0.3 mmol) and toluene (1 mL). Then hydrogenation
was performed under 120–150 bar of H2 at 5–258C for 36 h. For
experimental details see the Supporting Information; d.r. was deter-
mined by 1H NMR analysis; e.r. given for main product was deter-
mined by HPLC on a chiral stationary phase; full conversion was
obtained in all cases, except for 2r (92% conversion). Cy=cyclohexyl.
position, the reaction proceeds smoothly at room temper-
ature, with full conversion and very good enantiomeric ratio.
We also studied the effect of the substitution pattern of the 2-
phenyl ring on the reactivity. The reaction worked nicely for
the 2-(1-naphthyl)- (1k) and 2-(m-tolyl)-substituted flavone
(1l) with full conversion and excellent enantiomeric ratio. It is
worth noting that even though only low to moderate
diastereoselectivity could be obtained, to our knowledge,
this is the first report of asymmetric hydrogenations of
flavones. These enantiomerically enriched, substituted flava-
nols could provide access to many different chiral frameworks
known from natural products.[3]
Scheme 4. Selective oxidation to diverse enantiomerically enriched 2-
substituted flavanones and chromanones. General conditions: step 1,
see Scheme 3. The corresponding flavanols and chromanols 2 were
oxidized by reaction with PCC (3 equiv) at room temperature in CH2Cl2
for 10 min; e.r. was determined by HPLC on a chiral stationary phase;
yields pertain to isolated product.
One of the key aspects of the process is that after
hydrogenation, these chiral flavanols and chromanols can be
8456 www.angewandte.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2013, 52, 8454 –8458

Angewandte
Chemie
Science, Hauppauge, 2009; e) N. C. Veitch, R. J. Grayer, Nat.
Prod. Rep. 2011, 28, 1626.
The presented reaction involves the hydrogenation of two
=
=
double bonds, a C C and C O bond. A stepwise hydro-
genation reaction, where the partially reduced substrate
dissociates from the catalyst after the first hydrogenation
step, could proceed via intermediates A or B (Scheme 5).
[2] a) I. M. Chandler, C. R. Mclntyre, T. J. Simpson, J. Chem. Soc.
Perkin Trans. 1 1992, 2285; b) K. Picker, E. Ritchie, W. C. Taylor,
Aust. J. Chem. 1976, 29, 2023; c) R. F. Bosch, R. Gaspo, A. E.
Busch, H. J. Lang, G.-R. Li, S. Nattel, Cardiovasc. Res. 1998, 38,
441; d) A. Maiti, M. Cuendet, V. L. Croy, D. C. Endringer, J. M.
Pezzuto, M. Cushman, J. Med. Chem. 2007, 50, 2799; e) Z. Zhao,
J. Ruan, J. Jin, J. Zou, D. Zhou, W. Fang, F. Zeng, J. Nat. Prod.
2006, 69, 265; f) U. Albrecht, M. Lalk, P. Langer, Bioorg. Med.
Chem. 2005, 13, 1531; g) R. L. Farmer, M. M. Biddle, A. E.
Nibbs, X. Huang, R. C. Bergan, K. A. Scheidt, ACS Med. Chem.
Lett. 2010, 1, 400.
[3] a) T. Todoroki, A. Saito, A. Tanaka, Biosci. Biotechnol. Bio-
chem. 2002, 66, 1772; b) A. L. Tçkꢀs, Liebigs Ann. Chem. 1989,
89; c) B. R. Brown, S. Guffogg, M. L. Kahn, J. W. Smart, I. A.
Stuart, J. Chem. Soc. Perkin Trans. 1 1983, 1825; d) Q. Wang, X.
She, X. Ren, J. Ma, X. Pan, Tetrahedron: Asymmetry 2004, 15, 29.
[4] For some selected reviews and examples on preparing enantio-
merically enriched flavanones and chromanones, see: a) A. E.
Nibbs, K. A. Scheidt, Eur. J. Org. Chem. 2012, 449; b) J. P. J.
Marais, D. Ferreira, D. Slade, Phytochemistry 2005, 66, 2145;
c) S. Ramadas, G. L. D. Krupadanam, Tetrahedron: Asymmetry
2004, 15, 3381; d) M. M. Biddle, M. Lin, K. A. Scheidt, J. Am.
Chem. Soc. 2007, 129, 3830; e) L. Wang, X. Liu, Z. Dong, X. Fu,
X. Feng, Angew. Chem. 2008, 120, 8798; Angew. Chem. Int. Ed.
2008, 47, 8670; f) J. Chen, J. Chen, F. Lang, X. Zhang, L. Cun, J.
Zhu, J. Deng, J. Liao, J. Am. Chem. Soc. 2010, 132, 4552; g) S. T.
Saengchantara, T. W. Wallace, J. Chem. Soc. Chem. Commun.
1986, 1592; h) J. C. Holder, A. N. Marziale, M. Gatti, B. Mao,
B. M. Stoltz, Chem. Eur. J. 2013, 19, 74; i) T. Korenaga, K.
Hayashi, Y. Akaki, R. Maenishi, T. Sakai, Org. Lett. 2011, 13,
2022.
[5] a) Z. Zhao, J. Jin, J. Ruan, C. Zhu, C. Lin, W. Fang, Y. Cai, J. Nat.
Prod. 2007, 70, 1683; b) L. Dykes, L. W. Rooney, R. D. Waniska,
W. L. Rooney, J. Agric. Food Chem. 2005, 53, 6813; c) F. Spinelli,
J.-B. Speakman, W. Rademacher, H. Halbwirth, K. Stich, G.
Costa, Eur. J. Plant Pathol. 2005, 112, 133; d) C. Pouget, C.
Fagnere, J.-P. Basly, H. Leveque, A.-J. Chuliaa, Tetrahedron
2000, 56, 6047.
[6] For reviews, see: a) T. Imamoto in Hydrogenation (Ed.: I.
Karamꢀ), Intech, Rijeka, 2012, Chap. 1, pp. 3 – 30; b) D.-S.
Wang, Q.-A. Chen, S.-M. Lu, Y.-G. Zhou, Chem. Rev. 2012,
112, 2557; c) J.-H. Xie, S.-F. Zhu, Q.-L. Zhou, Chem. Rev. 2011,
111, 1713; d) D. H. Woodmansee, A. Pfaltz, Chem. Commun.
2011, 47, 7912; e) T. L. Church, P. G. Andersson, Coord. Chem.
Rev. 2008, 252, 513; f) S. J. Roseblade, A. Pfaltz, Acc. Chem. Res.
2007, 40, 1402; g) A. J. Minnaard, B. L. Feringa, L. Lefort, J. G.
de Vries, Acc. Chem. Res. 2007, 40, 1267; h) Handbook of
Homogeneous Hydrogenation (Eds.: J. G. de Vries, C. J. Elsev-
ier), Wiley-VCH, Weinheim, 2007; i) X. Cui, K. Burgess, Chem.
Rev. 2005, 105, 3272; j) F. Glorius, Org. Biomol. Chem. 2005, 3,
4171; k) W. Tang, X. Zhang, Chem. Rev. 2003, 103, 3029; l) W. S.
Knowles, Angew. Chem. 2002, 114, 2096; Angew. Chem. Int. Ed.
2002, 41, 1998; m) R. Noyori, T. Ohkuma, Angew. Chem. 2001,
113, 40; Angew. Chem. Int. Ed. 2001, 40, 40.
Scheme 5. Possible pathways for the hydrogenation of chromones.
Alternatively, a pathway in which the partially reduced
substrate stays coordinated to the ruthenium center until
both hydrogenation steps are completed would directly lead
to the product.
To gain insight into the reaction process, a series of control
experiments were conducted. First we examined the kinetics
of the hydrogenation of 2-methylchromone (1a). The reac-
tions were stopped at different times (0.5, 1, 1.5, 3, 6, 9, 24 h),
and the reaction mixture was analyzed by 1H NMR spectros-
copy. We found that the reaction is quite fast (96%
conversion after 3 h).[12] During the reaction, we never
detected the corresponding intermediate A or intermediate
B. Since it seems that these intermediates do not react faster
than the starting material,[12] the involvement of the free
intermediates as the main pathway is rather unlikely. Instead,
the formation of a metal-bound species, such as a ruthenium
enolate resulting from conjugate addition of a ruthenium
hydride species to the substrate, seems more likely.[13]
In conclusion, we have developed the asymmetric hydro-
genation of 2-substituted flavones and chromones leading to
the formation of enantiomerically enriched flavanones, fla-
vanols, chromanones, and chromanols using a chiral ruthe-
nium–NHC complex. Further studies focusing on catalyst
characterization, mechanistic aspects of this reaction, and
hydrogenation of other challenging substrates are ongoing.
Received: March 27, 2013
Published online: July 1, 2013
[7] For recent examples of enantioselective hydrogenation, see:
a) C. Liu, J.-H. Xie, Y.-L. Li, J.-Q. Chen, Q.-L. Zhou, Angew.
Chem. 2013, 125, 621; Angew. Chem. Int. Ed. 2013, 52, 593; b) S.
Song, S.-F. Zhu, Y.-B. Yu, Q.-L. Zhou, Angew. Chem. 2013, 125,
1596; Angew. Chem. Int. Ed. 2013, 52, 1556; c) R. Kuwano, R.
Morioka, M. Kashiwabara, N. Kameyama, Angew. Chem. 2012,
124, 4212; Angew. Chem. Int. Ed. 2012, 51, 4136; d) X. Wang, Z.
Han, Z. Wang, K. Ding, Angew. Chem. 2012, 124, 960; Angew.
Chem. Int. Ed. 2012, 51, 936; e) A. Iimuro, K. Yamaji, S.
Kandula, T. Nagano, Y. Kita, K. Mashima, Angew. Chem. 2013,
125, 2100; Angew. Chem. Int. Ed. 2013, 52, 2046; f) Y. Liu, W.
Keywords: asymmetric catalysis · chromanols · hydrogenation ·
N-heterocyclic carbenes · ruthenium
.
[1] a) G. P. Ellis, Chromenes, Chromanones, and Chromones, Wiley,
New York, 1977; b) S. T. Saengchantara, T. W. Wallace, Nat.
Prod. Rep. 1986, 3, 465; c) Ø. M. Andersen, K. R. Markham,
Flavonoids: Chemistry, Biochemistry and Applications, CRC,
Taylor & Francis, Boca Raton, 2006; d) R. B. Keller, Flavonoids:
Biosynthesis, Biological Effects and Dietary Sources, Nova
Angew. Chem. Int. Ed. 2013, 52, 8454 –8458
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
8457

.
Angewandte
Communications
Zhang, Angew. Chem. 2013, 125, 2259; Angew. Chem. Int. Ed.
2013, 52, 2203; g) Z.-S. Ye, R.-N. Guo, X.-F. Cai, M.-W. Chen, L.
Shi, Y.-G. Zhou, Angew. Chem. 2013, 125, 3773; Angew. Chem.
Int. Ed. 2013, 52, 3685; h) G. Liu, X. Liu, Z. Cai, G. Jiao, G. Xu,
W. Tang, Angew. Chem. 2013, 125, 4329; Angew. Chem. Int. Ed.
2013, 52, 4235; i) T. Imamoto, K. Tamura, Z. Zhang, Y. Horiuchi,
M. Sugiya, K. Yoshida, A. Yanagisawa, I. D. Gridnev, J. Am.
Chem. Soc. 2012, 134, 1754; j) K. Dong, Z. Wang, K. Ding, J. Am.
Chem. Soc. 2012, 134, 12474; k) S. Li, K. Huang, B. Cao, J.
Zhang, W. Wu, X. Zhang, Angew. Chem. 2012, 124, 8701; Angew.
Chem. Int. Ed. 2012, 51, 8573; l) D. J. Frank, A. Franzke, A.
Pfaltz, Chem. Eur. J. 2013, 19, 2405; m) T. Zhou, B. Peters, M. F.
Maldonado, T. Govender, P. G. Andersson, J. Am. Chem. Soc.
2012, 134, 13592; n) N. Ortega, S. Urban, B. Beiring, F. Glorius,
Angew. Chem. 2012, 124, 1742; Angew. Chem. Int. Ed. 2012, 51,
1710; o) S. Urban, B. Beiring, N. Ortega, D. Paul, F. Glorius, J.
Am. Chem. Soc. 2012, 134, 15241.
[8] Surprisingly, only two patents describe the asymmetric hydro-
genation of two specific chromones to give chromanones: a) H.
Bokel, R. Mackert, C. Muramann, N. Schweickert, U.S. Patent
66646136 B1, Nov. 11, 2003; b) A. V. Gontcharov, A. A.
Nikitenko, P. Raveendranath, C. Shaw, B. K. Wilk, D. Zhou,
WO 2007/123941 A2, Nov. 1, 2007.
[9] V. Semeniuchenko, T. E. Exnera, V. Khilyab, U. Grotha, Appl.
Organomet. Chem. 2011, 25, 804.
[10] S. Urban, N. Ortega, F. Glorius, Angew. Chem. 2011, 123, 3887;
Angew. Chem. Int. Ed. 2011, 50, 3803.
[11] F. A. Luzzio, Org. React. 1998, 53, 1 – 221.
[12] For the detailed experiments, see the Supporting Information.
[13] a) Y. Tsuchiya, Y. Hamashima, M. Sodeoka, Org. Lett. 2006, 8,
4851; b) R. R. Huddleston, M. J. Krische, Org. Lett. 2003, 5,
1143; c) C. J. Scheuermann nꢀe Taylor, C. Jaeckel, Adv. Synth.
Catal. 2008, 350, 2708.
8458
www.angewandte.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2013, 52, 8454 –8458