Synergistic Catalysis of Ionic Br?nsted Acid and Photosensitizer for a Redox Neutral Asymmetric α-Coupling of N-Arylaminomethanes with Aldimines

Article abstract of DOI:10.1021/jacs.5b09329

A redox neutral, highly enantioselective coupling between N-arylaminomethanes and N-sulfonyl aldimines was developed by harnessing the efficient catalysis of P-spiro chiral arylaminophosphonium barfate and a transition-metal photosensitizer under visible

Full text of DOI:10.1021/jacs.5b09329

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Communication
Synergistic Catalysis of Ionic Brønsted Acid and Photosensitizer for a Redox
Neutral Asymmetric #-Coupling of N-Arylaminomethanes with Aldimines
Daisuke Uraguchi, Natsuko Kinoshita, Tomohito Kizu, and Takashi Ooi
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.5b09329 • Publication Date (Web): 11 Oct 2015
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Synergistic Catalysis of Ionic Brønsted Acid and Photosensitizer for a
Redox Neutral Asymmetric α‐Coupling of N‐Arylaminomethanes
with Aldimines
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Daisuke Uraguchi,† Natsuko Kinoshita,† Tomohito Kizu,† and Takashi Ooi*,†,‡
†Institute of Transformative Bio-Molecules (WPI-ITbM) and Department of Applied Chemistry, Graduate School of
Engineering, Nagoya University, Nagoya 464-8602, Japan.
‡CREST, Japan Science and Technology Agency (JST), Nagoya University, Nagoya 464-8602, Japan.
Supporting Information Placeholder
ABSTRACT: A redox neutral, highly enantioselective coupling
Ar
between N-arylaminomethanes and N-sulfonyl aldimines was
H
N
H
N
1a: Ar = Ph
developed by harnessing the efficient catalysis of P-spiro chiral
arylaminophosphonium barfate and transition metal
P
1b: Ar = 2-PhC6H4
1c: Ar = 2-Ph-4-CF3C6H3
a
N
H
N
H
photosensitizer under visible light irradiation. This mode of
synergistic catalysis provides a powerful strategy for controlling
the bond-forming processes of reactive radical intermediates.
Ar
BArF
1·HBArF
Figure 1. P-Spiro Chiral Arylaminophosphonium Barfates 1.
BArF = [3,5-(CF3)2C6H3]4B
narguably, radical-based transformations are fundamental
Isynthetic tools, which are often compatible with various
functional groups and have immense potential to enable
unconventional bond cleavages and constructions.1 Accordingly,
numerous efforts have been devoted to the development of
synthetically useful and selective radical reactions.2,3 In particular,
significant advances have been made in the arena of photoredox
catalysis, providing a number of otherwise unachievable modes of
molecular transformations.4,5 However, precise absolute
stereocontrol in light-driven photochemical reactions still
unknown carbon-carbon bond-forming reaction as a platform for
substantiating our hypothesis. From this standpoint, we adopted
N-sulfonyl imines 2 [Ered = –1.45 V vs. a saturated calomel
electrode (SCE) for 2a] as the precursors of anion-radicals with a
prospective affinity to the hydrogen-bond donor catalyst and
envisioned their enantioselective coupling with the aminomethyl
radical
generated
from
N,N-diphenylaminomethane
(Ph2NMe).18,11c A catalytic cycle we postulated based on the use
of an Ir(II) species as a strong reductant [EII→III = –1.40 V vs.
SCE for IrII(ppy)2(bpy)]19,20 for the generation of an anion-radical
from 2 is illustrated in Figure 2. Initially, Ir(III) complexes such
as [Ir(ppy)2(bpy)]BArF (3a) are reversibly promoted to their
excited state, [*Ir(ppy)2(bpy)]BArF, under visible light irradiation.
Subsequent reductive quenching of the *Ir(III) species with
Ph2NMe would result in the requisite, electronically neutral Ir(II)
complex and the cation-radical of Ph2NMe accompanying the
negatively charged counterion, BArF–. The resulting Ir(II)
species could transfer an electron to imine 2 to form the
corresponding anion-radical that should be spontaneously paired
with the positively charged Ir(III) complex (Ir-Im).21,22 Ir-Im
would undergo prompt ion exchange with the aminophosphonium
ion 1·H, featuring double hydrogen-bond-donor ability, to afford
a key chiral ion pair P-Im with concomitant regeneration of the
parent photosensitizer. Concurrently with this process, an
aminomethyl radical is formed via deprotonation of the Ph2NMe
cation-radical by a basic species (B).23 Then, a coupling reaction
between the imine anion-radical and the aminomethyl radical
would take place under the guidance of 1·H to enantioselectively
produce the 1,2-diamine derivative 4 as the major product.
constitutes a formidable challenge.6-9
For addressing this
important problem, several dual catalytic systems based on the
combined use of transition metal photosensitizer and
stereocontroller5a,10–13 have been successfully introduced, leading
to the establishment of highly stereoselective protocols for the
assembly of chiral molecules through unique bond formations. In
seeking to make our own contribution in this emerging field, we
became interested in the viability of dictating the selectivity of
ion-radicals, which are always involved in photoredox processes
of organic substrates and are considered to exhibit ambiphilic
character as radicals and ions.14 Specifically, in conjunction with
our research program for developing novel asymmetric ion-pair
catalysis, we hypothesized that the catalytic ion-pairing of a chiral
tetraaminophosphonium ion of type 1·H (Fig. 1) with an anion-
radical would allow this reactive intermediate to engage in
subsequent bond formations with rigorous selectivity control by
the structurally modifiable chiral cation.15–17 As an initial step in
this pursuit, we communicate herein the development of a redox
neutral,
highly
enantioselective
α-coupling
of
N-
arylaminomethanes with N-sulfonyl aldimines under the catalysis
of 1·H and Ir-centered photosensitizer with visible light
irradiation.
In the initial experiments to examine this possibility, achiral
tetraaminophosphonium
barfate,
(4-CF3C6H4NH)4P·BArF
(5·HBArF), was employed as the hydrogen-bond donor. Visible
light irradiation (15 W household white LED lamp) of a toluene
At the outset of our study, we sought to develop a previously
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Table 1. Effect of Each Element of the Synergistic Catalysisa
Ms
HN
1
2
3
4
5
6
7
8
MsHN
Ar'
NHMs
Ar'
Ar'
NMePh
Ms
imine
amine
6
7
Friedel-Crafts
pinacol coupling
Ms
H
N
Ar'
BArF
HN
H
2
N
P
N
NPh2
NPh2
[IrIII
]
Ar'
H
Ms
N
N
N
H
4
H
[IrII]
H
9
Ar'
1·HBArF
Ir-Im
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
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radical
coupling
H
N
H
yield
ee
[IrIII
]
entry hydrogen-bond donor
L (3)b
N
P
N
[ IrIII
]
(%)c (%)e
H
Ms
N
N
H
BArF
BArF
1
2
5·HBArF
5·HBArF
bpy (3a)
21
0
-
-
P-Im Ar'
3
visible
light
none
B·HBArF
3d
5·HBArF
0
-
NPh2
BArF
3a
NPh2
H
B
4
none
6
-
3a
5
5·HBArF
phen (3b)
46
79
7
-
Figure 2. Working hypothesis.
6
5·HBArF
Me2phen (3c)
-
solution of benzaldehyde-derived N-sulfonyl imine 2a and
Ph2NMe in the presence of 5·HBArF (4 mol%) and the
photosensitizer 3a (1 mol%) led to the formation of diamine 4a in
21% yield (Table 1, entry 1). The photoredox conditions were
crucial for this bond connection, given that 4a could not be
obtained upon conducting the reaction in the absence of the
sensitizer or irradiation.24 Instead, a Friedel-Crafts-type adduct 6a
7
Bu4N·BArF
phosphoric acid
benzoic acid
3,3'-Ph2-BINOL
thiourea
-
3c
3c
3c
3c
3c
3c
3c
3c
3c
3c
3c
8
9
-
9
12
11
21
40
56
59
56
79
89
-
10
11
12
13
14
15
16
17
-
-
1
(Ar' = Ph, Fig. 2) was detected from the H NMR analysis of the
Et3N·HBArF
2,6-lutidine·HBArF
8·HBArF
-
crude aliquots (~12%, entries 2 and 3), suggesting that 5·HBArF
simply acted as a Brønsted acidic activator of 2a. More
importantly, an attempted reaction in the absence of 5·HBArF
gave a pinacol-type coupling product meso-7a (Ar' = Ph, Fig. 2), a
homodimer of 2a, in approximately 30% yield along with a trace
amount of 4a (entry 4). This indicates the participation of the
anion-radical of 2a, and its reactivity seems to be attenuated by
the aminophosphonium ion 5·H.25,26 Because the efficiency of the
one-electron reduction of 2a to the anion-radical would be
associated with the oxidation potential of the transient Ir(II)
species, we pursued the modification of the photosensitizer at this
stage with respect to the structure of the bipyridine ligand. We
found that the Ir(III) complex 3c, bearing neocuproine (2,9-
dimethyl-1,10-phenanthroline, Me2phen), to be an optimal
sensitizer,27 thus allowing the isolation of 4a in 79% yield (entries
5 and 6). These profiles are consistent with the proposed radical
coupling mechanism.25 However, we recognize that the addition
of the aminomethyl radical to the imine 2a coordinated by 5·H,
followed by one-electron reduction of the resulting nitrogen-
centered radical, is also feasible and cannot be ruled out.28,29
-
-
1a·HBArF
1b·HBArF
1c·HBArF
53
89
94
a Unless otherwise indicated, the reactions were performed with
0.20 mmol of 2a and 0.10 mmol of Ph2NMe with a hydrogen-
bond donor (4.0 mol%) and 3 (1.0 mol%) in 0.5 mL of toluene at
ambient temperature for 8 h under argon atmosphere with visible
light irradiation (15 W white LED). b bpy = 2,2'-bipyridine, phen
=
1,10-phenanthroline,
Me2phen
=
2,9-dimethyl-1,10-
phenanthroline. c Isolated yield.
Under dark. e Enantiomeric
d
excesses were determined by chiral stationary phase HPLC.
phenyl)thiourea, one of the weak Brønsted acids, delivered slight
improvement in the reaction profile (entry 11), and a notable
enhancement in the yield of 4a was attained when ionic
triethylammonium and 2,6-lutidinium barfates were applied
(entries 12 and 13). These results demonstrate that exploiting a
positively charged, ionic hydrogen-bond donor is a prerequisite
for the present catalysis to be synergistically operative with the
Ir(III) photosensitizer, and the aminophosphonium ion appeared
to be particularly effective.
The critical importance of the aminophosphonium ion in
facilitating the desired coupling reaction prompted us to probe the
essential elements required for the catalyst to exert effective
performance. The use of tetrabutylammonium salt (Bu4N·BArF),
which lacks hydrogen-bond-donor ability, in place of 5·HBArF
under identical photoredox conditions with 3c mainly yielded
meso-7a. This outcome is similar to that observed in the reaction
conducted without 5·HBArF (entry 4 vs. entry 7).
Encouraged by the comparable activity of the P-spiro-type
aminophosphonium ion 8·H (entry 14), we undertook the absolute
stereocontrol of this new carbon-carbon bond-forming reaction by
combined utilization of chiral aminophosphonium barfate
1a·HBArF and 3c under visible light irradiation. This trial
afforded 4a in good chemical yield with moderate
enantioselectivity (entry 15). The introduction of 2-biphenyl
groups into the 3,3'-positions of one of the two binaphthyl
subunits (1b·HBArF) significantly improved the stereoselectivity
On the other hand, employment of the widely utilized nonionic
Brønsted acids such as 1,1'-binaphthol-derived phosphoric acid
diester, benzoic acid, and the 1,1'-binaphthol derivative as
hydrogen-bond donors turned out to be ineffective for selectively
obtaining 4a, and meso-7a was again isolated as the major product
along with other unidentified side products (entries 8–10).30 It
was of interest that the use of N,N'-bis(3,5- bistrifluoromethyl
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Table 2. Substrate Scope.a
(entry 16). Eventually, rigorous enantiocontrol was achieved with
1c·HBArF, possessing 2-phenyl-4-trifluoromethylphenyl
1
a
substituent, and 4a was obtained in 89% yield with 94% ee (entry
17). The three-dimensional molecular structure of 1c·H was
unambiguously determined by single-crystal X-ray diffraction
analysis, revealing its “R,R,R” configuration, and the pendant 2-
phenyl group of the 3,3'-substituents contributed to the creation of
a cavity over the ionic hydrogen-bonding site (Fig. 3).
2
3
4
5
6
7
8
9
yield ee
(%)b (%)c
85 97
entry
Ar' (2)
R, R'
prod
1
2
3
4
5
6
7
8
4-MeC6H4 (2b)
4-FC6H4 (2c)
Ph, Ph
Ph, Ph
4b
4c
4d
4e
4f
90 91
85 91
72 96
75 90
75 85
77 94
64 94
60 95
82 93
83 91
4-ClC6H4 (2d)
4-MeSC6H4 (2e)
3-MeC6H4 (2f)
3-MeOC6H4 (2g)
2-MeC6H4 (2h)
2-Naphthyl (2i)
Ph, Ph
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
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Ph, Ph
Ph, Ph
Ph, Ph
4g
4h
4i
Ph, Ph
Ph, Ph
9d 3-Thiophenyl (2j)
Ph, Ph
4j
Figure 3. ORTEP diagram of 1c·HCl.
Chloride ion,
10
11
12
13
14
15
16
Ph (2a)
Ph (2a)
2-Naphthyl, Ph
3-MeC6H4, Ph
4k
4l
calculated hydrogen atoms, and solvent molecules (methanol)
are omitted for clarity. Gray: carbon, purple: phosphorus,
blue: nitrogen, green: fluorine.
Ph (2a)
4-MeC6H4, 4-ClC6H4 85 89
4m
4n
4o
4p
4q
Ph (2a)
4-BrC6H4, 4-BrC6H4 63 92
With the optimized catalyst combination in hand, the generality
Ph (2a)
iPr, Ph
iPr, Ph
nHex, Ph
73 91
83 94
65 91
of this asymmetric coupling protocol was explored.
As
summarized in Table 2, the reaction proceeded smoothly with a
wide range of aromatic N-sulfonyl imines, irrespective of their
electronic properties and substitution patterns, to give 1,2-diamine
derivatives 4 with excellent enantioselectivities (entries 1–7). The
absolute configuration of 4b was assigned to be “R” based on the
single-crystal X-ray diffraction analysis (See SI). This system
also tolerated fused aromatic and heteroaromatic imines, although
a certain decrease in the chemical yield was observed (entries 8
and 9). In contrast, aliphatic imines with a lower reduction
potential (Ered) remained intact under the present catalysis. With
respect to the aminomethane component, significant variation in
the substituents (R, R') was possible with a comparable degree of
reactivity and stereoselectivity (entries 10–16). Notably, not only
various N,N-diarylaminomethanes but also N-alkyl derivatives
appeared to be good candidates for coupling partners and
consistently reacted via the generation of the corresponding
aminomethyl radicals. It is worth adding that the α-coupling did
not occur in the reaction with N,N-diphenylaminoethane.
4-MeC6H4 (2b)
4-MeC6H4 (2b)
a Unless otherwise noted, reactions were performed with 0.20
mmol of 2 and 0.10 mmol of RR'NMe with 1c·HBArF (4.0
mol%) and 3c (1.0 mol%) in 0.5 mL of toluene under argon
b
atmosphere with visible light irradiation (15 W white LED).
Isolated yield. c Enantiomeric excesses were determined by chiral
stationary phase HPLC. Absolute configuration of 4b was
d
determined by X-ray crystallographic analysis.
2.0 mL of
toluene was used as solvent. Reaction time was 34 hours.
In conclusion, we have demonstrated the remarkable
effectiveness of the synergistic catalysis of chiral
arylaminophosphonium ions 1·H and Ir(III) photosensitizer 3 for
achieving a redox neutral, highly enantioselective α-coupling of
N-arylaminomethanes with N-sulfonyl imines 2 under visible light
irradiation. This study may have significant implications on the
catalytic control of ion-radicals, and we believe that a judicious
combination of chiral ionic Brønsted acid and photoredox
catalysis offers a new opportunity for the development of an array
of photoinduced stereoselective radical transformations.
The immediate utility of this asymmetric direct coupling
between aminomethanes and imines was highlighted by the rapid
construction of chiral benzopiperazine frameworks, which are
core structures of potent pharmaceutical motifs, such as active
cholesteryl ester transfer protein inhibitors.31 For instance, the
reaction of 2b and N-2-bromophenyl-N-phenylaminomethane
under standard conditions produced the corresponding 1,2-
diamine 4r in 77% yield with 98% ee. The subsequent palladium-
catalyzed intramolecular amination furnished the desired chiral
benzopiperazine 9 as shown in Scheme 1.
ASSOCIATED CONTENT
Supporting Information
Experimental procedures and characterizations of compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
Scheme 1. Preparation of Chiral Benzopiperazine 9.
AUTHOR INFORMATION
Corresponding Author
tooi@apchem.nagoya-u.ac.jp
Notes
The authors declare no competing financial interests.
ACKNOWLEDGMENT
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reaction with aminoalkyl radicals: (c) Ruiz Espelt, L.; McPherson, I. S.;
Wiensch, E. M.; Yoon, T. P. J. Am. Chem. Soc. 2015, 137, 2452.
Financial support was provided by CREST-JST, a Grant-in-Aid
for Scientific Research on Innovative Areas “Advanced Molecular
Transformations by Organocatalysts” from MEXT, IGER
Program in Nagoya University, Grants of JSPS for Scientific
Research, and the Asahi Glass Foundation. N.K. and T.K.
acknowledge JSPS for financial support.
1
2
3
4
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Tellis, J. C.; Primer, D. N.; Molander, G. A.; Kozlowski, M. C. J. Am.
Chem. Soc. 2015, 137, 4896.
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(21) While we presumed the electron transfer to free imine 2a followed by
the ion exchange with the hydrogen-bond donor catalyst 1·HBArF,
intervention of the proton-coupled electron-transfer (PCET) in forming the
key chiral ion pair P-Im cannot be rigorously excluded because most of
1·H would interact with 2a.11a However, we confirmed that the quenching
rate of an excited Ir(ppy)3 derivative with 2a was not enhanced upon
addition of 8·HBArF. For details, see SI.
(6) For reviews on enantioselective reactions under photo-irradiation, see:
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(22) Yayla, H. G.; Knowles, R. R. Synlett 2014, 25, 2819.
(23) As previously seen in the literatures,18 an actual species that functions
as a base is uncertain and therefore it is not specified in the catalytic cycle.
We anticipate that N,N-diphenylaminomethane itself, anion-radical of 2,
and/or conjugate base of 1·H could play this role.
(7) For selected examples of the pioneering studies from the Bach group
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Bach, T.; Bergmann, H.; Grosch, B.; Harms, K. J. Am. Chem. Soc. 2002,
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(24) We also confirmed that the product formation occurred only during
the period of constant irradiation. See “light/dark” experiment in SI.
(8) For recent seminal study on the development of chiral sensitizers for
asymmetric photoredox reactions, see: (a) Huo, H.; Shen, X.; Wang, C.;
Zhang, L.; Röse, P.; Chen, L.-A.; Harms, K.; Marsch, M.; Hilt, G.;
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(26) Without such effect, we speculate that the coupling of the anion-
radical Ir-Im with the aminomethyl radical might be inherently
unfavorable. In addition, considering the level of enantioselectivity
observed in this study, ion-exchange between Ir-Im and 1·HBArF would
be fast enough to minimize the intervention of this racemic pathway.
(9) For selected examples with chiral amine catalysts, see: (a) Nagib, D.
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