Enantioselective Excited-State Photoreactions Controlled by a Chiral Hydrogen-Bonding Iridium Sensitizer

Article abstract of DOI:10.1021/jacs.7b10586

Stereochemical control of electronically excited states is a long-standing challenge in photochemical synthesis, and few catalytic systems that produce high enantioselectivities in triplet-state photoreactions are known. We report herein an exceptionally effective chiral photocatalyst that recruits prochiral quinolones using a series of hydrogen-bonding and π-π interactions. The organization of these substrates within the chiral environment of the transition-metal photosensitizer leads to efficient Dexter energy transfer and effective stereoinduction. The relative insensitivity of these organometallic chromophores toward ligand modification enables the optimization of this catalyst structure for high enantiomeric excess at catalyst loadings as much as 100-fold lower than the optimal conditions reported for analogous chiral organic photosensitizers.

Full text of DOI:10.1021/jacs.7b10586

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Article
Enantioselective Excited-State Photoreactions Controlled
by a Chiral Hydrogen-Bonding Iridium Sensitizer
Kazimer L Skubi, Jesse B Kidd, Hoimin Jung, Ilia A. Guzei, Mu-Hyun Baik, and Tehshik P. Yoon
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.7b10586 • Publication Date (Web): 31 Oct 2017
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Enantioselective Excited-State Photoreactions Controlled by a Chiral
Hydrogen-Bonding Iridium Sensitizer
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Kazimer L. Skubi,† Jesse B. Kidd,† Hoimin Jung,‡,§ Ilia A. Guzei,† Mu-Hyun Baik,*,‡,§ and Tehshik
P. Yoon*,†
†Department of Chemistry, University of Wisconsin–Madison, 1101 University Avenue, Madison, Wisconsin 53706,
United States
‡Center for Catalytic Hydrocarbon Functionalizations, Institute for Basic Science (IBS), Daejeon 34141, Republic of
Korea
§Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic
of Korea
ABSTRACT: Stereochemical control of electronically excited states is a long-standing challenge in photochemical synthesis,
and few catalytic systems that produce high enantioselectivities in triplet-state photoreactions are known. We report herein
an exceptionally effective chiral photocatalyst that recruits prochiral quinolones using a series of hydrogen-bonding and π–
π interactions. The organization of these substrates within the chiral environment of the transition metal photosensitizer
leads to efficient Dexter energy transfer and effective stereoinduction. The relative insensitivity of these organometallic
chromophores towards ligand modification enables the optimization of this catalyst structure for high enantiomeric excess
(ee) at catalyst loadings as much as 100-fold lower than the optimal conditions reported for analogous chiral organic pho-
tosensitizers.
organic sensitizers, including their long excited-state life-
times, their high intersystem crossing quantum yields, and
their robust chemical stability. Recent investigations have
led to the development of a range of new, highly enanti-
oselective photocatalytic methods.4 Almost all of these new
asymmetric catalytic photochemical transformations,
however, have been photoredox reactions,5 in which the
propensity of photoexcited chromophores to participate in
electron-transfer reactions is exploited to produce radical
or radical ion intermediates. Thus, these reactions can be
characterized as “secondary” photoreactions, in which
bond formation occurs from photogenerated intermedi-
ates in their ground-state electronic configurations, rather
than from excited-state molecules.6
INTRODUCTION
Organic molecules in their electronically excited states
undergo reactions that differ significantly from those of
ground-state, closed-shell intermediates. The distinctive
transformations available via excited-state chemistry have
motivated the development of the field of synthetic photo-
chemistry throughout the past century.1 However, control
over the stereochemistry of excited-state reactions remains
a considerable challenge with few practical solutions, par-
ticularly using modern asymmetric catalytic approaches.2
This difficulty is attributable to the short lifetimes and gen-
erally high reactivity of electronically excited organic inter-
mediates, which challenge the ability of exogenous chiral
catalysts to intercept and to modulate their subsequent re-
actions. Thus, successful strategies for highly enantioselec-
tive photocatalytic reactions have only been reported
within the past decade, and applications of photochemical
reactions to the synthesis of structurally complex, stereo-
chemically well-defined organic molecules have remained
quite limited.
Scheme 1. Previous Reports of Enantioselective [2+2] Photo-
cycloadditions using Chiral Organic Sensitizers
n
Bach (ref 9)
O
H
1
NH
O
10 mol% 1
S
H
O
N
hn
(>400 nm)
N
N
O
O
H
H
Recently, there has been a renewed interest in photo-
catalytic synthesis centered largely on the remarkable pho-
tochemical properties of visible-light-absorbing transition
92% ee
CF3
n
Sivaguru (ref 10)
F3C
S
H
2+
10 mol% 2
N
N
CF3
metal complexes exemplified by Ru(bpy)3 and Ir(ppy)3.3
H
H
OH
H
O
hn
(350 nm)
Many of the photophysical characteristics of these coordi-
nation compounds compare favorably to those of classical
O
O
O
2
F3C
92% ee
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Fewer strategies are available for controlling the stereo- than the most effective chiral triplet sensitizers described
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chemistry of “primary” photoreactions, which are defined
to date.
as transformations where the bond-forming events arise
directly from electronically excited intermediates.6 To
,7
RESULTS AND DISCUSSION
date, only a handful of systems have been able to deliver
high ee’s in primary photoreactions at reasonably low con-
centrations of chiral catalyst (e.g., >80% ee at <10 mol%).8
Arguably the most well-established of these are chiral hy-
drogen-bonding organic photosensitizers developed by
Bach9 and Sivaguru,10 both of which feature photosensitiz-
ing chromophores functionalized with a hydrogen-bond-
ing moiety that orients a polar, achiral organic substrate
within the stereocontrolling environment of the chiral
photosensitizer (Scheme 1). Notably, the photocatalytic
moieties in both systems are organic chromophores. In the
past five years, several laboratories, including our own,
have studied transition metal photocatalysts as sensitizers
for a variety of triplet-state reactions (e.g., cycloaddi-
Optimization and scope studies. Our preliminary in-
vestigations (Table 1) were based on three central premises.
First, we elected to study 3-alkoxyquinolone 3 as a model
substrate because its triplet energy is computationally es-
timated to be ~55 kcal/mol, easily within a range accessible
using common iridium(III) complexes previously studied
in our laboratory.11a,c,12 It is also similar in structure to the
quinolones and coumarins that are the optimal substrates
for previously reported chiral organic photosensitizers,
which provides an opportunity to directly compare the ef-
fectiveness of these photoacatalysts. Second, iridium(III)
photocatalysts bearing electron-deficient cyclometalated
phenylpyridine ligands can possess quite high-energy tri-
plet excited states. Thus, we adapted the synthetic route
developed by Meggers to prepare enantiopure complexes
of general structure 5 that we hoped would have a triplet
energy sufficient to sensitize 3. Finally, Meggers has re-
ported a range of chiral-at-metal complexes bearing L2 lig-
ands functionalized with Brønsted acidic moieties that
serve as highly effective hydrogen-bonding asymmetric
catalysts in non-photochemical applications. We hoped
that a heterocyclic ligand previously utilized to activate ni-
troalkenes19a,b might similarly be capable of binding 3
within the stereoinducing environment defined by the oc-
tahedral Ir stereocenter. In our initial experiments, irradi-
ation of 3 with blue LEDs in the presence of 1 mol% of Ir
catalyst 5a at –70 °C resulted in the formation of 4 in 49%
ee (Table 1), confirming the validity of our design plan.
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,
tion,5 11 aziridination,12 isomerization,13 cross-coupling,14
and formal C–H amination15). An important feature of this
work is the tunability of the transition metal photocatalyst.
While the photophysical properties of organic chromo-
phores can often be sensitive to small structural perturba-
tions,16 transition metal photocatalysts have proven to be
substantially more robust towards modification, and a
large family of octahedral ruthenium(II) and iridium(III)
complexes bearing extensively modified ligand sets gener-
ally serve as excellent photocatalysts.17
Most of these Ru and Ir photocatalysts feature helical,
metal-centered chirality, although they are typically uti-
lized in racemic form. We wondered if this intrinsic chiral
information could be exploited to control excited-state
photoreactions. Meggers has designed a family of chiral-at-
metal coordination complexes that provide high ee’s in a
remarkably broad range of transformations.18 These in-
clude non-photochemical reactions in which the chiral
metal complexes serves principally as a chiral structural
scaffold; bidentate L2-type ligands bearing hydrogen-
bonding19 or basic amine moieties20 are introduced as cata-
lytic functional groups. More recently, Meggers has also
shown that Lewis acidic bis(acetonitrile) iridium(III) com-
plexes can be effective enantioselective catalysts for photo-
catalytic reactions.21 In these processes, the metal complex
typically plays a dual role as both a chiral Lewis acid as well
as a photoredox catalyst, which has resulted in the devel-
opment of a range of enantioselective reactions involving
photogenerated radical intermediates. However, the use of
chiral enantiopure organometallic complexes as triplet en-
ergy transfer photocatalysts has not yet been reported.22
Table 1. Effects of Modified Hydrogen-Bonding Ligands
BArF
CF3
F
N
H
1 mol% 5
CH2Cl2, –70 °C
N
O
F
F
Ir
O
N
16 W blue LED
14 h
N
H
O
N
H
O
N
L-5
3a
4a
F
CF3
N
N
N
[Ir]
N
N
N
[Ir]
[Ir]
[Ir]
N
N
O
HN
O
HN
HN
HN
HN
HN
NH2
OH
CF3
Me
5a 98% yield
49% ee
5b 93% yield
5c 24% yield
58% ee
5d 73% yield
Herein, we describe the identification of a novel enanti-
opure iridium complex functionalized with a hydrogen-
bonding domain that can serve as a highly enantioselective
triplet sensitizer. The development of the optimal catalyst
was guided not only by photophysical considerations but
also by a rational study of substrate binding. The catalyst
that emerged from these investigations exploits a unique
dual hydrogen bonding interaction to organize a quino-
lone substrate and is capable of providing high enantiose-
lectivities at loadings as low as 0.1 mol%, significantly lower
47% eea
28% eea
Me
C
N
N
N
N
[Ir]
[Ir]
[Ir]
N
[Ir]
N
N
N
HN
HN
HN
N
SMe
Me
5e 82% yield
5f 91% yield
69% ee
5g 78% yield
1% ee
5h 42% yield
68% ee
69% eea
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Figure 1. A. Binding isotherm obtained by monitoring the pyrazole N–H resonance of catalyst 5f upon addition of varying
concentrations of quinolone 3a. B. Stack plot of 1H NMR spectra depicting changes in the aromatic region of catalyst 5f upon
titration with 3a. C. Heat map showing where the largest changes in NMR chemical shifts are localized on catalyst 5f. D. Opti-
mization of the cyclometalating ligand of the photocatalyst.
a Conducted with Δ-5. The sign of the ee value is corrected
for the absolute stereochemistry of the catalyst.
basic functional group on the substrate, which we pre-
sumed was likely the quinolone carbonyl. In order to better
understand the mode of substrate binding, we carried out
an NMR titration experiment with 3 and (±)-5f. As ex-
pected, the chemical shift associated with the pyrazole N–
H changes significantly as a function of added 3. The re-
sponse fits well to a 1:1 binding model, and from these data
we calculated an association constant of Ka = 560 M–1 (Fig-
ure 1A).
Next, we interrogated the role the acidic trifluoroa-
cetamide N–H bond plays as a H-bond donor (Table 1). We
replaced the trifluoroacetamide moiety with a variety of
other groups bearing hydrogen bond donors (5b-d), but
surprisingly, there was no clear correlation between pKa
and the ee of the cycloadduct. This suggests that the pres-
ence of this hydrogen bond-donating substituent on the
pyrazole ring is likely not critical for binding the substrate.
Consistent with this hypothesis, an analogue bearing a thi-
oether substituent (5e) incapable of donating a hydrogen
bond provided improved ee. Moreover, a complex featur-
ing an unsubstituted pyridylpyrazole ligand provided both
faster rate and high ee (5f). We found that the pyrazole
moiety is necessary and sufficient for this level of enantio-
control. A complex in which the critical N–H of the pyri-
dylpyrazole ligand is blocked with a methyl group (5g) pro-
vided no enantioinduction. In contrast, the use of a com-
plex bearing a monodentate pyrazole ligand and an ace-
tonitrile ligand (5h) afforded almost the same ee as the op-
timal catalyst with a bidentate pyridylpyrazole ligand, al-
beit with diminished reactivity.
While performing this titration study, we observed that
the chemical shifts of other protons also changed over the
course of the titration (Figure 1B). As expected, the signal
associated with the critical pyrazole N–H enjoyed the larg-
est chemical shift change, but several other signals also
shifted significantly. Moreover, the magnitude of Δδ varied
over a wide range as a function of position. These observa-
tions suggested a strategy for further optimization of the
chiral photocatalyst. We reasoned that large changes in
chemical shift at various positions on the catalyst would
likely correlate to close contacts with the substrate. Thus,
modification at those positions associated with the largest
chemical shift changes might be expected to have a sub-
stantial impact on the enantioselectivity of the catalyst.
These chemical shift changes are graphically summa-
rized in Figure 1C. Several features of this heat map warrant
comment. First, while the pyrazole moiety itself is strongly
affected by association of the substrate, consistent with its
These studies suggested that the acidic N–H bond of the
pyrazole provides a critical interaction with some Lewis
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critical role in binding, its pyridyl substituent is not
Page 4 of 8
H
1 mol% L-6b
CH2Cl2:pentane (1:1)
1
2
3
4
5
6
7
8
strongly impacted. This is consistent with the empirical
observation that a complex lacking the pyridyl group nev-
ertheless provides high ee (Table 1, 5h). Second, most of
the significant changes in chemical shift are localized to
one of the two cyclometalating phenylpyridine ligands; the
other is comparatively unaffected. Moreover, the magni-
tude of the chemical shifts on the cyclometalating phenyl
moiety are generally larger than on the pyridyl group.
Thus, it seems reasonable to suppose that alteration of the
cyclometalating ligands, and specifically the substituents
about the phenyl ring, should have a large impact on the
enantioselectivity of the photocycloaddition.
O
O
O
N
O
N
–78 °C, blue LEDs, 24 h
H
H
3
4
H
H
H
H
Cl
Br
I
O
O
O
O
N
O
N
H
O
N
O
N
O
H
H
H
4a
4b
4cb
>98% yield
90% ee
4d
>98% yield
91% ee
93% yield
90% ee
>98% yield
79% ee
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H
H
H
H
F3C
Me
MeO
O
O
O
O
O
O
O
O
N
H
N
H
N
H
Cl
N
H
4e
97% yield
84% ee
4f
4g
4h
Optimization studies varying the structure of the cy-
clometalating ligands are in good agreement with this ex-
pectation (Figure 1D). Modest changes to the fluorination
pattern on the phenyl group result in large increases in en-
antioselectivity, albeit at the cost of reaction rate. Catalyst
6b, which provides 89% ee in the cycloaddition reaction,
exhibits a substantially larger association constant of Ka =
3000 M–1, suggesting that the stronger interaction between
the catalyst and substrate might be responsible for the
heightened selectivity.
>98% yield
82% ee
>98% yield
79% ee
>98% yield
77% ee
Me
Me
Me
H
H
H
H
O
O
O
O
N
H
O
N
H
O
N
O
N
H
O
H
Cl
F
4i
4j
4k
86% yield
68% ee
4l
98% yield
20% ee
90% yield
87% ee
82% yield
69% ee
Et
H
H
H
O
O
O
O
O
N
O
H
N
O
Given the sensitivity of hydrogen bonding interactions
to solvent dielectric, we wondered if the substrate–catalyst
interaction might be strengthened by reducing the solvent
4m
Me
4n
>98% yield
3% ee
from (Z)-3m
85% yield
3:1 dr
from (E)-3m
85% yield
3:1 dr
4o
71% yield
3% ee
85% ee/75% ee
80% ee/71% ee
polarity.
Indeed, conducting the reaction in 1:1
CH2Cl2:pentane resulted in an increase in the measured
binding constant to Ka = 19000 M–1 and the formation of
cycloadduct 4 in quantitative yield and 91% ee. Complex
6b is an exceptionally effective asymmetric photocatalyst;
it provides high ee’s at catalyst loadings considerably lower
than the optimal conditions reported for chiral organic
a
b
Isolated yields on 0.25 mmol scale. Reaction conducted
for 48 h.
A brief examination of substrates (Table 2) demonstrates
that structurally related quinolones can also provide excel-
lent yield and high ee in this transformation. Chloro- and
bromo-substituted quinolones behave comparably to the
parent substrate (4b and 4c), while an iodinated substrate
exhibited diminished ee (4d) due to an uncatalyzed back-
ground reaction arising from direct excitation. However,
only trace amounts of de-iodinated product were observed
under our conditions, consistent with the low energy of the
visible light utilized in this procedure. Electron-poor (4e)
and electron-rich (4f, 4g) quinolones also react in high
yields and good enantioselectivities. Substitution of a chlo-
rine at the 8-position of the quinolone (4i) results in a dra-
matic drop to 20% ee, presumably because this large sub-
stituent interferes with the critical hydrogen bonding con-
tact necessary for catalyst binding. In contrast, the smaller
8-fluoroquinolone (4j) exhibits only a slight decrease in en-
antioselectivity compared to 4a. The alkene moiety can
also be modified; substitution on the alkene tether (4k, 4l,
4m) is tolerated, though with somewhat diminished enan-
tioselectivity. Finally, we also tested substrates in which
the amidyl N–H moiety is either blocked with an alkyl sub-
stituent (4n) or replaced by an oxygen that is incapable of
donating a hydrogen bond (4o). In both cases, these sub-
strates give good yields but negligible ee. This suggests that
the quinolone N–H bond plays a critical role in organizing
the substrate relative to the stereodetermining Ir ligand
sphere, but that it is not important for the success of the
sensitized cycloaddition itself.
,
photosensitizers.9 10 As a demonstration of this point, we
conducted a [2+2] cycloaddition using only 0.1 mol% of 6b.
Although this led to the formation of 4 at diminished rate
(38% yield at 24 h), there was negligible effect on enanti-
oselectivity (88% ee). These results underscore the remark-
able photocatalytic properties of this family of Ir(III) pho-
tosensitizers, which generally provide superior reactivity
compared to classical organic sensitizers.
Table 2. Scope and Limitations of Enantioselective [2+2] Pho-
tocycloadditiona
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Figure 3. A. Conceptual illustration of Dexter energy transfer. B. Frontier molecular orbital plots of the triplet excited state Ir-
photocatalyst and the singlet ground state quinolone. (isodensity value: 0.05 au) C. Computationally optimized structures for
hydrogen bonding complexes.
Mechanistic investigations. The design strategy for
the development of Ir complex 6b was premised upon the
ability of similar octahedral Ir polypyridyl complexes to
catalyze a wide variety of primary photoreactions, includ-
ing cycloadditions, via triplet energy transfer. However, we
also considered several mechanistic alternatives for this re-
action.
in the UV-vis spectrum of the Rh–substrate complex that
is significantly enhanced relative to the sum of the individ-
ual spectra of the catalyst and substrate. We conducted an
analogous UV-vis absorption experiment using Ir catalyst
6 and quinonlone 3 (Figure 2). While there is a subtle bath-
ochromic shift in the absorption spectrum of 6 upon addi-
tion of a 20-fold excess of 3, the effect is comparatively
modest. Moreover, the fact that 6 remains an effective pho-
tocatalyst for cycloaddition of substrates that cannot form
the same hydrogen-bonded complex as 3a (Table 2, 3n and
3o) indicates that pre-association is not critical for photo-
activation to occur, and that a different mechanism is likely
operative.
First, we examined the possibility that the [2+2] cycload-
dition might be initiated by photoinduced electron trans-
fer, rather than energy transfer. Electrochemical studies in
CH2Cl2 indicate a substrate oxidation potential of +1.59 V
and reduction potential of <–1.7 V vs. SCE, both of which
lie well outside the potentials of the photoexcited catalyst
(+1.27 V and –0.78 V, respectively). Thus, photoinduced
electron transfer to or from the photocatalyst is not ther-
modynamically feasible. Second, control experiments indi-
cate that no reaction occurs in the absence of photocatalyst
or in the dark, ruling out alternative mechanisms involving
either direct excitation of 3a or a purely thermal process in
which the iridium catalyst serves as a chiral Brønsted acid.
Finally, Meggers very recently reported that a chiral-at-
metal Rh Lewis acid is capable of catalyzing the [2+2] pho-
tocycloadditions of enones with excellent enantioselectiv-
ity.23 The optimal Rh catalyst for this reaction, however,
was not proposed to behave as a triplet sensitizer. Instead,
Meggers showed that the rhodium center forms an associ-
ation complex with the substrate, in a manner analogous
to the Lewis acid catalyzed photocycloaddition methods
described by Bach.9 The key enabling feature of this reac-
tion is the appearance of a strong, long-wavelength feature
Figure 2. UV-vis absorption spectra for association of
quinolone 3a to catalyst 6b.
Thus, the available experimental evidence suggests that
a Dexter energy transfer mechanism is operative. The
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emission maximum of our catalyst is 480 nm, correspond- that the N–H of the quinolone is necessary to achieve en-
1
2
3
4
5
6
7
8
ing to a triplet energy of 59.6 kcal/mol. We computation-
ally estimated the substrate triplet energy as 55.0 kcal/mol,
which indicates that the state change associated with tri-
plet energy transfer from the photocatalyst to 3 would be
exergonic. Xanthone-sensitized [2+2] cycloadditions of
quinolones have been studied extensively by Bach, who
proposed an analogous mechanism.24 Finally, independent
experiments with stereochemically defined (E)-3m and
(Z)-3m converge to the same diastereomeric ratio, con-
sistent with a stepwise triplet cycloaddition in which bond
rotation occurs faster than radical recombination, rather
than a concerted singlet process.
antioselectivity (cf. 4n, 4o). In contrast, complex B, which
features an analogous hydrogen-bonding pattern but with
the opposite Si face blocked, cannot establish the π–π in-
teraction. Both complexes are calculated to be more stable
than their two non-interacting components; A is located at
–2.1 kcal/mol and B is located at –0.6 kcal/mol, respec-
tively.
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CONCLUSION
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In conclusion, we have developed a highly effective chi-
ral triplet sensitizer that combines the exceptional photo-
chemical properties of transition metal coordination com-
plexes with a hydrogen bonding domain to orient the or-
ganic substrate. Notably, the robust photophysical proper-
ties of iridium(III) polypyridyl complexes enabled consid-
erable optimization of both the cyclometalating and L2 lig-
ands. The flexibility of this strategy led us to discover an
enantioselective catalyst that exploits an unexpected π–π
interaction and unusual N–H to π hydrogen bond, rather
than any direct inner-sphere substrate–catalyst associa-
tion. The optimal complex can be utilized at catalyst load-
ings two orders of magnitude lower than current state of
the art chiral organic photosensitizers. We believe this
constitutes an attractive new approach to stereocontrol in
excited state photoreactions, which have historically
proven to be a formidable synthetic challenge. Further ex-
ploration of these design principles is a continuing theme
of research in our laboratory.
Dexter energy transfer is an electron exchange process
between a triplet-excited donor and a singlet acceptor mol-
ecule, as illustrated in Figure 3A, that can be conceptual-
ized as a combination of two concerted events: (i) The
movement of an electron in the α-HOMO of the excited
donor to the α-LUMO of the acceptor and (ii) the transfer
of an electron from acceptor to the β-LUMO of the donor.
Here, the triplet energy donor is the excited state of the Ir-
catalyst, and the acceptor is the quinolone substrate. For
the Dexter energy transfer to occur effectively, the donor
and acceptor orbitals must show proper overlap, as the
double electron-transfer requires reasonably strong elec-
tronic coupling.
Examining the shapes of the orbitals that will engage in
the exchange process is helpful for obtaining a rough idea
of which portions of the catalyst and substrate must be ar-
ranged in close proximity. The orbital plots in Figure 3B
show that both the α-HOMO and β-LUMO of the excited
state of the Ir-catalyst are localized on the phenylpyri-
dine(ppy) ligand that is cyclometalated to the Ir center.
Since the α-LUMO and β-HOMO of the substrate are also
found in the π-space, a catalyst-substrate geometry that
enables the π-orbitals of the quinolone to sufficiently over-
lap with the π-orbitals of the ppy-ligand is most appropri-
ate. This arrangement requires a coplanar alignment of the
substrate with the ppy-ligand, posing a stringent limitation
on which of the many possible adducts will be competent
in carrying out the Dexter energy transfer, which is pro-
posed to ultimately determine the enantioselectivity.
ASSOCIATED CONTENT
Supporting Information
Experimental procedures, characterization data, crystallo-
graphic data, Cartesian coordinates of all computed structures
and energy components. The Supporting Information is avail-
able free of charge on the ACS Publications website.
AUTHOR INFORMATION
Corresponding Authors
*E-mail: mbaik2805@kaist.ac.kr
*E-mail: tyoon@chem.wisc.edu
The computationally derived encounter complex A (Fig-
ure 3C) successfully predicts the absolute sense of stereoin-
duction in the cycloaddition and exhibits structural fea-
tures consistent with the experimental observations out-
lined above. A strong H-bonding interaction between the
pyrazole and the quinolone carbonyl establishes the main
contact, but an important π–π interaction between the
substrate and cyclometalating ligand is also formed. This
interaction may not only explain the large changes in
chemical shift observed in the NMR titration experiments
but may also be required for efficient coupling between the
triplet excited state of the Ir sensitizer and the π orbital
fragment of the substrate, as described above. Interest-
ingly, there is an unusual N–H-π interaction between the
quinolone amide and the pyrazole group that stabilizes
this conformation and is consistent with the observation
Notes
The authors declare no competing financial interests.
ACKNOWLEDGMENT
We are grateful to the NSF for a research grant (CHE 1665109)
and a fellowship to JBK. MB acknowledges support from the
Institute for Basic Science (IBS-R10-D1) in Korea. Analytical in-
strumentation at UW–Madison is supported in part by the
NIH (S10 OD020022, S10 OD012245) and by a generous gift
from the Paul J. Bender fund. We thank Anastasiya I. Vinkour
for assistance processing crystallographic data.
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CF3
F
N
H
F
N
F
F
Ir
F
O
N
N
N
H
O
H
F
N
chiral
H
organometallic
triplet sensitizer
O
91% ee
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N
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O
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