Synthesis of Supramolecular Iridium Catalysts and Their Use in Enantioselective Visible-Light-Induced Reactions

Article abstract of DOI:10.1055/s-0035-1561378

Iridium complexes were prepared which are covalently linked via a bipyridine ligand to a chiral octahydro-1H-4,7-methanoisoindol-1-one skeleton. The skeleton allows for two-point hydrogen bonding to prochiral lactams, which can be processed in iridium-catalyzed photochemical reactions. Attempts to use the iridium complexes in reactions, which typically involve photoinduced electron transfer, failed to provide the desired enantioselectivity. If employed as triplet sensitizers the complexes showed an improved performance and moderate enantioselectivities (up to 29% ee) were achieved in a photochemical epoxide rearrangement.

Full text of DOI:10.1055/s-0035-1561378

SYNLETT
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
©
Georg Thieme Verlag Stuttgart · New York
2016, 27, A–E
A
cluster
Synlett
A. Böhm, T. Bach
Cluster
Synthesis of Supramolecular Iridium Catalysts and Their Use in
Enantioselective Visible-Light-Induced Reactions
Alexander Böhm
Thorsten Bach*
MeO
O
5
mol%
N
N
O
Department Chemie and Catalysis Research Center (CRC),
Technische Universität München, 85747 Garching, Germany
thorsten.bach@ch.tum.de
Ir [(df)(CF3)2ppy]2
N
hν
H
(λ = 419 nm)
75 °C
CH2Cl2)
O
hydrogen
bonding
−
(
O
NH
MeO
O
N
H
H
93% (29% ee)
PF6
Received: 21.12.2015
Accepted after revision: 20.01.2016
Published online: 24.02.2016
an iridium complex with a stereogenic metal center can
serve both purposes, that is, it enabled a photoredox pro-
cess and provided high enantioface differentation.5
,6
DOI: 10.1055/s-0035-1561378; Art ID: st-2015-d0989-c
In our group, we have been working on chiral supramo-
lecular catalysts, in which the metal center is spatially sep-
arated from a chiral entity which in turns allows for coordi-
Abstract Iridium complexes were prepared which are covalently
linked via a bipyridine ligand to a chiral octahydro-1H-4,7-methanoiso-
indol-1-one skeleton. The skeleton allows for two-point hydrogen
bonding to prochiral lactams, which can be processed in iridium-cata-
lyzed photochemical reactions. Attempts to use the iridium complexes
in reactions, which typically involve photoinduced electron transfer,
failed to provide the desired enantioselectivity. If employed as triplet
sensitizers the complexes showed an improved performance and mod-
erate enantioselectivities (up to 29% ee) were achieved in a photo-
chemical epoxide rearrangement.
7
nation of the substrate by hydrogen bonding (structure A,
8
Figure 1). The concept requires a chiral ligand that binds to
the metal and simultaneously features a lactam unit to fa-
9
cilitate hydrogen bonding. Alkyne 1a serves as useful start-
ing material to construct these ligands because the alkyne
part can be readily coupled to compounds, which in turn
enable metal coordination. Given our interest in the enantio-
Key words catalysis, enantioselectivity, iridium, photochemistry
10
selective catalysis of photochemical reactions, we have re-
cently commenced to prepare supramolecular iridium cata-
lysts from 1a, which could be potentially used for enanti-
oselective photochemical reactions. Our preliminary results
are disclosed in this communication.
In recent years, the catalysis of photochemical reactions
by ruthenium and iridium complexes has received enor-
1,2
mous attention from synthetic organic chemists. A major
benefit of their use rests on the fact that they allow reac-
tions to be performed with visible light, which had previ-
ously required UV irradiation. In addition, the low catalyst
loading and the robustness of the catalysts make rutheni-
um and iridium complexes attractive for large-scale appli-
cations. Although photoinduced electron transfer (PET) has
so far been the most frequently invoked mode of action for
these catalysts (photoredox catalysis), recent work has es-
tablished that their relatively high triplet energy also allows
for catalysis by triplet energy transfer (sensitization).3
In many photochemical reactions, stereogenic centers
are created. In any instance, in which a prochiral substrate
is converted into a chiral product, it is desirable to control
the absolute configuration of the product by a chiral cata-
lyst. In the past, a photoredox catalyst had been mostly
combined with a second chiral catalyst to achieve enantio-
H
catalytic acitivity
*R
M
O
O
substrate orientation
by hydrogen bond
NH
NH
A
1a
Figure 1 Concept of enantioselective supramolecular catalysts of type
A (M = metal) and structure of chiral ligand precursor 1a with an octa-
hydro-1H-4,7-methanoisoindol-1-one skeleton (R*)
Since many photoactive iridium complexes exhibit at
least one 2,2′-bipyridine ligand, it was attempted to link
11
alkyne 1a to 5-bromo-2,2′-bipyridine (Br-bpy) by Sono-
gashira cross-coupling.1
2–14
The reactions were performed
in parallel with tert-butylacetylene (1b), the products of
which were meant to mimic the scalar properties of the
chiral ligands (Scheme 1). Cross-coupling reactions pro-
ceeded smoothly and delivered the desired alkynylated bi-
4
selectivity. Recently, Meggers and co-workers showed that
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E

B
Synlett
A. Böhm, T. Bach
Cluster
pyridines 2 in high yields. The triple bond could be readily
reduced to the respective single bond by hydrogenation de-
livering bipyridines 3. In product 3a, the bipyridine is
linked to the octahydro-1H-4,7-methanoisoindol-1-one
fragment via an ethano bridge.
therefore not attempted to separate the diastereoisomers
nor to resolve the antipodes of racemic complexes 4b and
5b.
Conceptually, it was envisaged that the iridium catalyst
would, upon excitation and oxidative quenching, generate
an iridium(II) species which would act as a reductant.
Prochiral halides seemed therefore suited as test substrates,
which would generate a radical upon reduction and car-
bon–halogen bond cleavage.17 Since we expected an inter-
molecular reduction of the prochiral radical center to occur
slowly, we searched for substrates which would rather un-
dergo a fast intramolecular C–C bond formation. Indeed,
previous work had revealed that two-point hydrogen bond-
ing generates kinetically labile complexes with other lact-
ams the lifetime of which is in the range of 10–100 ns. Bro-
mides rac-6 were readily accessible from N-tert-butoxycar-
5
mol% Pd(PPh3)2Cl2
1
0 mol% CuI, Et3N
50 °C (THF)
N
N
R
H
+
Br
1
1
a R = R*
b R = Bu
70%
98%
t
H2
1
0 mol% Pd/C
N
N
N
N
(
MeOH)
R
R
2
a
88%
95%
3a
3b
2b
18
bonyl(Boc)-protected piperidinone
by a sequence of
Scheme 1 Synthesis of bipyridine ligands 2 and 3 from alkynes 1 and
acylation,19 deprotection, and α-bromination (see Support-
ing Information).20 In the presence of iridium complex rac-
7 and Hantzsch ester 8, photochemical reactions revealed,
however, that neither one of the substrates underwent cy-
clization. Hydrodebromination was instead observed, and
products 9 were isolated in high yields. Experiments with
chiral iridium complexes confirmed our suspicion that the
hydrodebromination reaction was not enantioselective, and
products related to rac-9 were all found to be racemic
(Scheme 2).
5
-bromo-2,2′-bipyridine (Br-bpy)
Regarding the nature of the iridium catalyst, it seemed
best to prepare a catalyst, which could be simultaneously
used for photoredox reactions and for sensitized transfor-
mations. In order to mimic the common catalyst [4,4′-
bis(tert-butyl)-2,2′-bipyridine]bis{3,5-difluoro-2-[5-(tri-
fluoromethyl)-2-pyridinyl]phenyl} iridium(III) hexafluoro-
phosphate it was attempted to prepare related catalysts,
in which the 4,4′-bis(tert-butyl)-2,2′-bipyridine unit was
replaced by bipyridines 2 or 3. Introduction of an iridium
metal with two 3,5-difluoro-2-[5-(trifluoromethyl)-2-pyr-
idinyl]phenyl [(df)(CF ) ppy] ligands was accomplished by heat-
15
hν (λ = 419 nm)
2.5 mol% [Ir((df)(CF3)ppy)2bpy]PF6 (rac-7)
3
2
Ph
15
O
O
O
O
ing bipyridines 2 or 3 with complex {Ir[(df)(CF ) ppy] Cl}
3
2
2
2
Br
H
EtOOC
COOEt
in ethylene glycol at 150 °C.16 Anion exchange was subse-
quently performed with an aqueous NH PF solution and
R1
O
NH
R1
O
NH
N
4
6
H
8
r.t. (CH Cl )
2
2
delivered the metal complexes 4 and 5 in the yields given in
Figure 2. Since the iridium atom in the complexes is stereo-
genic, compounds 4a and 5a were obtained as mixtures of
inseparable diastereoisomers (diastereomeric ratio dr =
rac-6
rac-9
O
O
O
O
O
O
O
H
H
H
O
50:50). The chirality of the iridium center should not influ-
O
NH
O
NH
NH
ence the hydrogen bonding event at the chiral lactam entity
which is decisive for the enantioface differentiation. It was
rac-9a (81%)
rac-9b (84%)
rac-9c (63%)
Scheme 2 Attempted iridium-catalyzed cyclization reactions of sub-
strates rac-6 led exclusively to debrominated products rac-9
F
F
F F
F
F
F
F
Contrary to substrates 6, the alkenoyl-substituted 3-
bromopiperidone rac-10 was found to be susceptible to a
cyclization reaction. The reaction delivered product 12 and
its enantiomer ent-12 as single diastereoisomers and it was
studied whether the cyclization could be rendered enantio-
selective upon catalysis by complexes 4a and 5a (Table 1).
Iridium catalyst 4a showed essentially no enantioselectivi-
ty at ambient temperature (Table 1, entry 1). The reaction
temperature was lowered to favor hydrogen bonding (Table
+
III
+III
N
Ir
N
N
Ir
N
F3C
N
N
CF3
PF6
F3C
N
N
CF3
PF6
R
R
4a
(81%)a
rac-4b (90%)
R = R*
5a
rac-5b (79%)
(93%)a
t
R = Bu
Figure 2 Structure of iridium catalysts 4a, rac-4b, 5a, and rac-5b.
Due to the stereogenic iridium atom, complexes 4a and 5a were ob-
tained as a 50:50 mixture of diastereoisomers
a
1, entries 2, 3). Disappointingly, cyclization became disfa-
vored and the debrominated product rac-11 was the only
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E

C
Synlett
A. Böhm, T. Bach
Cluster
isolable material. It was tested, whether the iridium cataly-
sis was required, which proved to be the case (Table 1, entry
let sensitization by iridium catalysts. Indeed, catalyst rac-7
was found to promote the desired rearrangement reaction
upon irradiation at λ = 419 nm (Table 2, entry 1). Catalysts
4).
4a and rac-4b showed an inferior catalytic activity and the
Table 1 Light-Induced Debromination and Cyclization of Alkenoyl-
Substituted 3-Bromopiperidone rac-10 Catalyzed by Chiral Iridium
Complexes 4a and 5a
conversion remained low even after a reaction time of 21
hours at –75 °C (Table 2, entries 2, 3).
Table 2 Photochemical Rearrangement of Epoxide rac-13 to 3-
Acetylindolin-2-ones 14 and ent-14 Catalyzed by Various Iridium Cata-
lysts
hν (λ = 419 nm)
O
O
2.5 mol% Ir cat.
X
8
, T (CH2Cl2)
NH
NH
rac-11
X = H)
+
+
ent-12
(
hν (λ = 419 nm)
O
O
O
5
mol% Ir cat.
T (CH2Cl2)
rac-10 (X = Br)
12
MeO
O
MeO
O
O
+
ent-14
N
N
Entry
Ir cat.
Temp (°C) rac-11 (%)a
12/ent-12 (%)a ee (%)b
H
H
–c
rac-13
14
1
2
3
4
5
6
7
8
4a
4a
4a
–
30
0
26
–c
–c
–c
42
7
2
31
41
–c
–
Time (h)a
14/ent-14 (%)b ee (%)c
Entry
Ir cat.
Temp (°C)
–75
30
–
1
2
3
4
5
6
rac-7
rac-4b
4a
30
–75
–75
–75
–75
30
2
89
21
21
94
93
88
–
–
21
21
2.5
2.5
2.5
–
5a
5a
5a
5a
30
–c
<2
9
19
–
0
24
48
51
rac-5b
5a
–25
–75
–c
–c
–
29
23
–
5a
a
Yield of isolated products after chromatographic purification.
The enantiomeric excess was calculated from the ratio of enantiomers
12/ent-12) as determined by chiral HPLC analysis.
No significant amounts of the respective products were isolated.
b
a
b
c
Reaction time at the indicated temperature.
Yield of isolated products after chromatographic purification.
The enantiomeric excess was calculated from the ratio of enantiomers
(
c
(
14/ent-14) as determined by chiral GLC analysis.
Catalyst 5a showed an improved performance com-
The lack of activity observed for catalysts 4 is likely as-
pared to 4a and its use resulted in a moderate yield of prod-
ucts 12/ent-12 at ambient temperature (Table 1, entry 5). A
temperature decrease, however, led again to a preferred hy-
drodebromination reaction (Table 1, entries 6–8). Minor
amounts of cyclization product could be isolated if the reac-
tion was run at 0 °C (Table 1, entry 5) and a minimal enan-
tiomeric excess was detectable. Given the fact that supra-
molecular catalysts with an octahydro-1H-4,7-methanoiso-
indol-1-one binding site had previously shown high
sociated with their lower triplet energy compared to rac-7,
which in turn could be due to the alkynyl substituent at the
bipyridine ligand. The respective catalysts 5 with an ethano
group bridging the ligand to the hydrogen-bonding device
turned out to be more efficient catalysts (Table 2, entries 4–
6). Conversion was complete after 150 minutes and yields
were high. With catalyst 5a, the enantiomeric excess in fa-
vor of product 14 was determined as 29% ee at –75 °C and
as 23% ee at 30 °C.24
The absolute configuration of the enantiomers 14 and
ent-14 was known from our previous work, which was per-
formed with chiral xanthone catalyst 15 (Figure 3). With
this catalyst, product ent-14 was obtained in 88% yield and
with 20% ee if the reaction was performed at λ = 366 nm
8,9
enantioselectivity in dichloromethane,
we wondered
whether there might be intrinsically an issue with applying
the concept of Figure 1 to photoredox catalysis. Indeed, it
has been shown that several of these reactions do not pro-
ceed via closed catalytic cycles but rather as radical chain
21
reactions. In such a scenario, chiral catalysts such as 4a
and 5a cannot exert any enantioface differentiation because
the substrate does not have to be in proximity to the iridi-
um center for electron transfer.
and at –65 °C in a mixture of trifluorotoluene (PhCF ) and
3
meta-hexafluoroxylene.23 The absolute configuration was
in line with a presumed association of the oxindole at the
lactam binding site of the catalyst and an intramolecular
methyl attack from the Re face at the prostereogenic center
at carbon atom C3 of biradical intermediate 16. In analogy,
the outcome of the reaction rac-13 → 14 can be explained
by intermediate complex 5a·16 in which the methyl group
migrates from the more accessible Si face to the prostereo-
genic carbon atom C3.
As mentioned in the introduction, iridium catalysts can
also be employed for triplet-sensitized photochemical reac-
tions. Based on observations by Zhang and co-workers,22 we
recently studied the reaction of spirooxindole epoxides
such as rac-13 (Table 2) in the presence of chiral triplet sen-
23
sitizers. The same substrate seemed also suitable for trip-
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E

D
Synlett
A. Böhm, T. Bach
Cluster
Primary Data
O
N
H
Ir
for this article are available online at http://www.thieme-con-
nect.com/products/ejournals/journal/10.1055/s-00000083 and can
H
O
O
O
H
O
OMe
N
.
be cited using the following DOI: 10.4125/pd0075th. Pmri aryD atPmri aryD at104.1
2
5
p/
d
0
0
7
5
Pthm.ri ary
D
atZ
a
heln
1
0
1
C
h
e
msytri
N
N
3
O
.
H
O
15
5a⋅16
Figure 3 Structure of chiral xanthone catalyst 15 and proposed struc-
ture of the complex between catalyst 5a and intermediate 16
References and Notes
(
1) (a) Ischay, M. A.; Anzovino, M. E.; Du, J.; Yoon, T. P. J. Am. Chem.
Soc. 2008, 130, 12886. (b) Nicewicz, D. A.; MacMillan, D. W. C.
Science 2008, 322, 77.
It is remarkable that the enantioselectivity induced by
catalyst 5a was higher than for 15. In this regard it should
be noted that the enantioselectivity does not only depend
on the steric bias of the respective catalytic unit (xanthone,
iridium complex) but is also influenced by the rate of disso-
(
2) Recent reviews: (a) Schultz, D. M.; Yoon, T. P. Science 2014, 343,
1239176/1. (b) Xi, Y.; Yi, H.; Lei, A. Org. Biomol. Chem. 2013, 11,
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Ed. 2009, 48, 9785.
1
0c,25
ciation of the intermediate from the complex.
If com-
plex dissociation is more rapid than the selectivity-deter-
mining step of the reaction, the enantiomeric excess will
remain low. Indeed, it had been previously observed that
catalyst 15 can exhibit a high degree of enantioface differ-
entiation (>90% ee) if employed in appropriate reac-
(3) (a) Lu, Z.; Yoon, T. P. Angew. Chem. Int. Ed. 2012, 51, 10329.
(b) Zou, Y.-Q.; Duan, S.-W.; Meng, X.-G.; Hu, X-Q.; Gao, S.; Chen,
J.-R.; Xiao, W.-J. Tetrahedron 2012, 68, 6914. (c) Farney, E. P.;
Yoon, T. P. Angew. Chem. Int. Ed. 2014, 53, 793.
(
4) Recent reviews: (a) Brimioulle, R.; Lenhart, D.; Maturi, M. M.;
Bach, T. Angew. Chem. Int. Ed. 2015, 54, 3872. (b) Meggers, E.
Chem. Commun. 2015, 51, 3290.
10b,,25,26
tions.
Its failure to deliver similar results in the epox-
ide rearrangement had been hypothesized to be due to the
low reaction rate of the rearrangement. The same argument
could hold for catalyst 5a and it could well be possible that
the catalyst shows an improved performance in other reac-
tions. Work in this direction is ongoing.
(5) (a) Huo, H.; Shen, X.; Wang, C.; Zhang, L.; Röse, P.; Chen, L.-A.;
Harms, K.; Marsch, M.; Hilt, G.; Meggers, E. Nature (London,
U.K.) 2014, 515, 100. (b) Huo, H.; Wang, C.; Harms, K.; Meggers,
E. J. Am. Chem. Soc. 2015, 137, 9551. (c) Wang, C.; Qin, J.; Shen,
X.; Riedel, R.; Harms, K.; Meggers, E. Angew. Chem. Int. Ed. 2016,
55, 685.
In summary, chiral iridium complexes 4a and 5a were
readily available by Sonogashira cross-coupling from
known 8-ethynyl-octahydro-1H-4,7-methanoisoindol-1-
one (1a). Reduction of the ethynyl bridge in 4a delivered
the ethano-bridged complex 5a. Both complexes showed
catalytic activity in several photoredox reactions per-
formed with visible light (λ = 419 nm) but failed to induce a
significant enantioselectivity. Complex 5a was found to be
an excellent catalyst to initiate the rearrangement of spiro-
oxindole epoxide rac-13 upon irradiation at λ = 419 nm. Al-
though the induced enantioselectivity was moderate (up to
(
6) For previous work on chiral ruthenium complexes in enantiose-
lective photochemistry, see: (a) Hamada, T.; Ishida, H.; Usui, S.;
Watanabe, Y.; Tsumura, K.; Ohkubo, K. J. Chem. Soc., Chem.
Commun. 1993, 909. (b) Ohkubo, K.; Hamada, T.; Ishida, H.
J. Chem. Soc., Chem. Commun. 1993, 1423.
(7) For recent reviews on supramolecular and substrate-specific
catalysis, see: (a) Dydio, P.; Reek, J. N. H. Chem. Sci. 2014, 5,
2135. (b) Lindbäck, E.; Dawaigher, S.; Wärnmark, K. Chem. Eur. J.
2014, 20, 13432. (c) Raynal, M.; Ballester, P.; Vidal-Ferran, A.;
van Leeuwen, P. W. N. M. Chem. Soc. Rev. 2014, 43, 1660.
(d) Carboni, S.; Gennari, C.; Pignatoro, L.; Piarulli, U. Dalton
Trans. 2011, 40, 4355.
(8) Recent work: (a) Frost, J. R.; Huber, S. M.; Breitenlechner, S.;
Bannwarth, C.; Bach, T. Angew. Chem. Int. Ed. 2015, 54, 691.
29% ee), the catalyst holds promise for further use in trip-
let-sensitized reactions.
(
b) Zhong, F.; Pöthig, A.; Bach, T. Chem. Eur. J. 2015, 21, 10310.
9) Fackler, P.; Berthold, C.; Voss, F.; Bach, T. J. Am. Chem. Soc. 2010,
32, 15911.
(
1
Acknowledgment
(
10) Selected contributions: (a) Bauer, A.; Westkämper, F.; Grimme,
S.; Bach, T. Nature (London, U.K.) 2005, 436, 1139. (b) Müller, C.;
Bauer, A.; Bach, T. Angew. Chem. Int. Ed. 2009, 48, 6640.
This project was supported by the Deutsche Forschungsgemeinschaft
(DFG) in the framework of the DFG Research Training Group ‘Chemi-
(
c) Müller, C.; Bauer, A.; Maturi, M. M.; Cuquerella, M. C.;
Miranda, M. A.; Bach, T. J. Am. Chem. Soc. 2011, 133, 16689.
d) Brimioulle, R.; Bach, T. Science 2013, 342, 840. (e) Alonso, R.;
cal Photocatalysis’ (GRK 1626). A.B. acknowledges fellowship support
by the GRK.
(
Bach, T. Angew. Chem. Int. Ed. 2014, 53, 4368.
(
11) Brotschi, C.; Mathis, G.; Leumann, C. J. Chem. Eur. J. 2005, 11,
Supporting Information
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Supporting information for this article is available online at
(12) (a) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett.
1975, 16, 4467. (b) Sonogashira, K. In Comprehensive Organic
Synthesis; Vol. 3; Trost, B., Ed.; Pergamon Press: Oxford, 1991,
http://dx.doi.org/10.1055/s-0035-1561378.
S
u
p
p
ortioIgnfrm oaitn
S
u
p
p
ortioIgnfrm oaitn
©
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Cluster
5
21–549. (c) Sonogashira, K. In Metal-Catalyzed Cross-Coupling
Reactions; Diederich, F.; Stang, P. J., Eds.; Wiley-VCH: Weinheim,
998, 203–229.
13) Additional reviews: (a) Chinchilla, R.; Nájera, C. Chem. Soc. Rev.
(21) Cismesia, M. A.; Yoon, T. P. Chem. Sci. 2015, 6, 5426.
(22) Wang, L.; Su, Y.; Xu, X.; Zhang, W. Eur. J. Org. Chem. 2012, 6606.
(23) Maturi, M. M.; Pöthig, A.; Bach, T. Aust. J. Chem. 2015, 68, 1682.
(24) Experimental Procedure for the Enantioselective Rearrange-
ment of rac-13
1
(
2
011, 40, 5084. (b) Chinchilla, R.; Nájera, C. Chem. Rev. 2007,
1
07, 874.
To a solution of 10.0 mg (46.0 μmol, 1.0 equiv) 5-methoxy-3′,3′-
23
(
14) For related Sonogashira cross-coupling reactions, see: (a) Voss,
F.; Bach, T. Synlett 2010, 1493. (b) Voss, F.; Vogt, F.; Herdtweck,
E.; Bach, T. Synthesis 2011, 961.
15) Lowry, M. S.; Goldsmith, J. I.; Slinker, J. D.; Rohl, R.; Pascal, R. A.;
Malliaras, G. G.; Bernhard, S. Chem. Mater. 2005, 17, 5712.
16) Slinker, J. D.; Gorodetsky, A. A.; Lowry, M. S.; Wang, J.; Parker, S.;
Rohl, R.; Bernhard, S.; Malliaras, G. G. J. Am. Chem. Soc. 2004,
dimethylspiro[indoline-3,2′-oxiran]-2-one (rac-13) in 4.6 mL
degassed CH Cl , 2.72 mg (2.3 μmmol, 0.05 equiv), Ir cat. 5a was
2
2
added, and the reaction mixture was irradiated for 2.5 h at
–75 °C. After evaporation of the solvent, the crude product was
(
purified by column chromatography (SiO , 2.5 × 4 cm, pentane–
2
(
EtOAc = 2:1 → 1:1) to obtain 9.3 mg (93%, 29% ee) (S)-3-acetyl-
23
1
5-methoxy-3-methylindolin-2-one (14) as a colorless solid. H
1
26, 2763.
NMR (360 MHz, CDCl , 300 K): δ = 7.79 (br s, 1 H, NH), 6.87 (d,
3
3
3
4
(
17) (a) Narayanam, J. M. R.; Tucker, J. W.; Stephenson, C. R. J. J. Am.
Chem. Soc. 2009, 131, 8756. (b) Tucker, J. W.; Nguyen, J. D.;
Narayanam, J. M. R.; Krabbe, S. W.; Stephenson, C. R. J. Chem.
Commun. 2010, 46, 4985.
J = 8.4 Hz, 1 H, C7H), 6.82 (dd, J = 8.4 Hz, J = 2.5 Hz, 1 H, C6H),
4
6.73 (d, J = 2.5 Hz, 1 H, C4H), 3.77 (s, 3 H, OCH ), 2.05 (s, 3 H,
3
13
COCH ), 1.59 (s, 3 H, CH ) ppm. C NMR (125 MHz, CDCl , 300
3
3
3
K): δ = 200.9 (s, COCH ), 177.6 (s, C2), 156.4 (s, C5), 134.0 (s,
3
(18) Flynn, D. L.; Zelle, R. E.; Grieco, P. A. J. Org. Chem. 1983, 48, 2424.
(19) Heller, S. T.; Natarajan, S. R. Org. Lett. 2006, 8, 2675.
(20) Sevenard, D. V.; Vorobyev, M.; Sosnovskikh, V. Y.; Wessel, H.;
Kazakova, O.; Vogel, V.; Shevchenko, N. E.; Nenajdenko, V. G.;
Lork, E.; Röschenthaler, G.-V. Tetrahedron 2009, 65, 7538.
C7a), 131.4 (s, C3a), 114.2 (d, C6), 110.7 (d, C7), 110.6 (d, C4),
62.9 (s, C3), 55.9 (q, OCH ), 26.2 (q, COCH ), 19.1 (q, CH ) ppm.
3
3
3
(25) Maturi, M. M.; Wenninger, M.; Alonso, R.; Bauer, A.; Pöthig, A.;
Riedle, E.; Bach, T. Chem. Eur. J. 2013, 19, 7461.
(26) Maturi, M. M.; Bach, T. Angew. Chem. Int. Ed. 2014, 53, 7661.
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E