Silver-Catalyzed Enantioselective Sulfimidation Mediated by Hydrogen Bonding Interactions

Article abstract of DOI:10.1002/anie.202016561

An enantioselective sulfimidation of 3-thiosubstituted 2-quinolones and 2-pyridones was achieved with a stoichiometric nitrene source (PhI=NNs) and a silver-based catalyst system. Key to the success of the reaction is the use of a chiral phenanthroline ligand with a hydrogen bonding site. The enantioselectivity does not depend on the size of the two substituents at the sulfur atom but only on the binding properties of the heterocyclic lactams. A total of 21 chiral sulfimides were obtained in high yields (44–99 %) and with significant enantiomeric excess (70–99 % ee). The sulfimidation proceeds with high site-selectivity and can also be employed for the kinetic resolution of chiral sulfoxides. Mechanistic evidence suggests the intermediacy of a heteroleptic silver complex, in which the silver atom is bound to one molecule of the chiral ligand and one molecule of an achiral 1,10-phenanthroline. Support for the suggested reaction course was obtained by ESI mass spectrometry, DFT calculations, and a Hammett analysis.

Full text of DOI:10.1002/anie.202016561

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International Edition:
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Asymmetric Catalysis
Hot Paper
Silver-Catalyzed Enantioselective Sulfimidation Mediated by
Hydrogen Bonding Interactions
Rajasekar Reddy Annapureddy+, Finn Burg+, Johannes Gramüller, Tino P. Golub,
Christian Merten, Stefan M. Huber, and Thorsten Bach*
Abstract: An enantioselective sulfimidation of 3-thiosubstitut-
ed 2-quinolones and 2-pyridones was achieved with a stoichio-
Their chemistry has attracted significant attention and has
been studied for decades.[1] A key structural feature of
sulfimides is the fact that they display a significant barrier to
pyramidal inversion at the sulfur atom. As a consequence,
sulfimides exist at ambient temperature as pairs of separable
enantiomers provided that the two carbon substituents are
different. The stereospecific oxidation of sulfimides to
sulfoximines is feasible and enables access to another class
of chiral sulfur compounds with intriguing properties.[2] Given
the large interest in the synthesis of enantiopure compounds,
enantioselective approaches to sulfimides have been inves-
tigated and the most frequently chosen route to chiral
sulfimides rests on a nitrene transfer reaction to thioethers
(sulfides).[3] Sulfimidation reactions have been mainly per-
formed with N-carboxylated and N-sulfonylated nitrene
precursors. The resulting N-sulfonylated sulfimides I and N-
alkoxycarbonylated sulfimides II represent typical products
and enantioselective imidation reactions have been devel-
oped based on copper,[4] manganese,[5] ruthenium,[6,7] and
iron[8] as catalytically active metal centers (Scheme 1). The
selectivity rests on the differentiation between the two
enantiotopic lone pairs at the sulfur atom of sulfides. The
exposure of the electron pair in turn depends for most
catalytic enantioselective processes on the size difference of
the substituents R. The best enantiomeric excess (ee) is
typically achieved if this size difference is significant with one
group being small (RS) and one being large (RL). However, if
the steric demand of the substituents is similar, a low
asymmetric induction is observed, for example, for diaryl-
sulfides.
=
metric nitrene source (PhI NNs) and a silver-based catalyst
system. Key to the success of the reaction is the use of a chiral
phenanthroline ligand with a hydrogen bonding site. The
enantioselectivity does not depend on the size of the two
substituents at the sulfur atom but only on the binding
properties of the heterocyclic lactams. A total of 21 chiral
sulfimides were obtained in high yields (44–99%) and with
significant enantiomeric excess (70–99% ee). The sulfimida-
tion proceeds with high site-selectivity and can also be
employed for the kinetic resolution of chiral sulfoxides.
Mechanistic evidence suggests the intermediacy of a hetero-
leptic silver complex, in which the silver atom is bound to one
molecule of the chiral ligand and one molecule of an achiral
1,10-phenanthroline. Support for the suggested reaction course
was obtained by ESI mass spectrometry, DFT calculations, and
a Hammett analysis.
Introduction
Sulfur compounds with two carbon–sulfur single bonds
and an additional ylide-type sulfur double bond to a nitrogen
substituent are called sulfimides. Alternatively, the compound
class has been referred to as sulfilimines or iminosulfuraes.
[*] Dr. R. R. Annapureddy,[+] Dr. F. Burg,[+] Prof. Dr. T. Bach
Department Chemie and Catalysis Research Center (CRC)
Technische Universität München
Lichtenbergstraß e 4, 85747 Garching (Germany)
E-mail: thorsten.bach@ch.tum.de
Homepage: http://www.oc1.ch.tum.de/home en/
M. Sc. J. Gramüller
Faculty of Chemistry and Pharmacy
Institute of Organic Chemistry, University of Regensburg
Universitätsstraß e 31, 93040 Regensburg (Germany)
M. Sc. T. P. Golub, Prof. Dr. C. Merten, Prof. Dr. S. M. Huber
Ruhr-Universität Bochum
Faculty for Chemistry and Biochemistry
Universitätsstraß e 150, 44801 Bochum (Germany)
[+] These authors contributed equally to this work.
Supporting information and the ORCID identification number(s) for
the author(s) of this article can be found under:
https://doi.org/10.1002/anie.202016561.
ꢀ 2021 The Authors. Angewandte Chemie International Edition
published by Wiley-VCH GmbH. This is an open access article under
the terms of the Creative Commons Attribution Non-Commercial
License, which permits use, distribution and reproduction in any
medium, provided the original work is properly cited and is not used
for commercial purposes.
Scheme 1. Top: Products I and II of previously reported enantioselec-
tive sulfimidation reactions obtained by metal catalysis (catalytically
active metal and ee given). Bottom: Attempted enantioselective
sulfimidation of substrates III to sulfimides IV with N-sulfonylated
phenyliminoiodinanes and a chiral silver catalyst.
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In the present study we have approached the topic of
lectivity. We employed Ag(PF6) as the source of the catalyti-
enantioselective sulfimidation by using a yet unexplored
catalytically active metal (silver). Even more importantly, we
combined the metal with a ligand that pre-coordinates to
lactam substrates III by hydrogen bonding and thus displays
one of the two enantiotopic lone pairs to the reactive nitrogen
center. As a result, products of type IV have become readily
available in high optical purity. The scope and the mechanism
of the reaction have been studied and the results of our
experiments are presented in this research article.
cally active metal center (10 mol%) and added 1,10-phenan-
throline (10 mol%) as an achiral ligand. The chiral ligand was
used in 12 mol% and N-(p-nitrophenylsulfonyl)iminophenyl-
=
iodinane (PhI NNs) was employed as the nitrene precursor
and dichloromethane as the solvent. The first set of reactions
(Scheme 3) was performed with 3-phenylthio-2-quinolone
(3a). While all ligands 1 facilitated a complete conversion
within 16 hours and yields varied only marginally (92–98%),
the enantioselectivity in the formation of sulfimide 4a was
most pronounced with catalysts 1a (97% ee) and 1c (96%
ee). Although we had anticipated the reaction to be enantio-
selective, the high selectivity achieved in the reaction came as
a very pleasant surprise. In the amination reactions,[11]
enantioselectivities exceeding 90% ee could only been
achieved with cyclic substrates in which free rotations were
completely restricted.
With 3-phenylthio-2-pyridone (5a) a reactivity difference
was notable for the three ligands and the yields of the
respective sulfimide 6a were only moderate when ligands 1b
and 1c were used. The by far best result was recorded for
ligand 1a. Not only did the ligand provide the highest yield
(70%), but it also facilitated the formation of product 6a with
the highest enantioselectivity (92% ee). Also, for the 2-
pyridones the degree of selectivity was remarkable given the
flexibility of the substrate (see the Supporting Information for
further details and other substrates).
Results and Discussion
Ligand synthesis and preliminary studies. The develop-
ment of chiral ligands with a lactam hydrogen bonding site
continues to be a research focus of our group.[9] The goal is to
achieve not only an improved site-selectivity in a given
transition-metal catalyzed reaction[10] but also to induce
a significant enantioselectivity. In a recent contribution,[11]
we prepared chiral phenanthroline ligands 1 which are based
on the readily available octahydro-1H-4,7-methanoisoindol-
1-one skeleton.[12] Their synthesis can be achieved by Sono-
gashira cross-coupling of known alkyne 2[13] with the respec-
tive bromo-substituted phenanthroline (Scheme 2). Ligand
1a was successfully employed in an enantioselective Ag-
À
catalyzed amination of C H bonds which was assumed to
occur by an enantioselective nitrene insertion[14] at the
hydrogen-bonded substrate. Although silver catalysis has
been shown to be a viable approach for the amination[15,16]
and aziridination[15,17] of organic substrates it has not been
extensively applied to sulfides. Bolm and co-workers found
that silver nitrate acts in combination with an achiral
terpyridine ligand as a catalyst to mediate the imidation of
sulfoxides to generate sulfoximines.[18,19] Two sulfimides were
obtained in high yields (77% and 83%) albeit in racemic
form.
Before applying the imidation by a nosyl-protected nitro-
gen to a larger array of substrates two other iminophenylio-
dinanes were probed as reagents for a possible nitrene
transfer. The related para-toluenesulfonyl (tosyl, Ts) reagent
gave product 7 in a much lower enantioselectivity of only
Our initial experiments aimed to identify the ligand best
suited for a defined prochiral sulfide. Although pre-coordi-
nation by a given lactam to any of the three ligands 1 can be
assumed, the trajectory of the nitrene transfer was expected
to be different resulting in varying reactivity and enantiose-
Scheme 3. Evaluation of the regioisomeric chiral phenanthroline li-
gands 1 in the enantioselective Ag-catalyzed sulfimidation of represen-
tative 3-substituted 2-quinolone 3a and 2-pyridone 5a (phen=1,10-
phenanthroline).
Scheme 2. Structure of isomeric phenanthroline ligands 1 which are
available from enantiopure alkyne 2 by Sonogashira cross-coupling
with the respective bromo-substituted phenanthroline. The potential
two-point hydrogen bonding site is marked in blue.
Scheme 4. Enantioselective Ag-catalyzed sulfimidation of compound
3a with different N-protected nitrene sources to give products 7 and 8.
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48% ee (Scheme 4). The electronically different trichloroe-
thoxysulfonyl (Tces)-substituted reagent, however, displayed
a similar degree of reactivity and selectivity as the nosyl-based
reagent. Product 8 was obtained in 94% yield and with 90%
ee. The latter result bears some synthetic relevance since
removal of the Tces group can be performed under conditions
that are orthogonal to those employed for the Ns group.[20]
Scope and site-selectivity. The imidation of 3-thiosubsti-
tuted 2-quinolone 3a suggested that various sulfides with
a similar structure could be converted into the respective
sulfimides irrespective of the nature of the thio substituent.
Accordingly, 2-quinolones 3 were prepared and subjected to
a nitrene transfer reaction, both racemic[21] and enantioselec-
tive. Several aryl groups were introduced as group R in
substrates 3 and the reaction turned out to be robust towards
the electronic (products 4b–4 f) and the steric situation
(products 4g–4i). If the opposite enantiomer ent-1a of ligand
1a was employed in the reactions, the ee remained identical
but the opposite sulfimide enantiomer was produced. The
reactions of 3a in the presence of ent-1a for example
delivered ent-4a on a scale of 0.4 mmol. For reasons of
availability the absolute configuration of the sulfimides was
representatively determined for dextrorotatory product ent-
4a. Comparison of experimental and calculated vibrational
circular dichroism (VCD) spectra allowed the assignment
with high fidelity (see the SI for details).[22,23] The (R)-
configuration was assigned to compound ent-4a, its enantio-
mer 4a is (S)-configured. The assignment of the configuration
for all other products which were obtained with 1a and which
were consistently levorotatory was based on analogy.
ations (Scheme 5). Interestingly, also a methyl group could be
used as group R and 3-methylthio-2-quinolone (3j) gave
sulfimide 4j in 98% yield and 96% ee. However, if the size of
the alkyl group increases, the enantioselectivity drops. With
R = isopropyl (substrate 3k) and R = cyclohexyl (substrate
3l) the enantioselectivity remained moderate (70–73% ee).
In a second set of experiments, the scope of the
sulfimidation was explored with 3-thiosubstituted 2-pyridones
5 (Scheme 6). The conditions remained unchanged as com-
pared to 3 and a clean transfer of the nitrogen fragment from
=
PhI NNs to the sulfides was observed. If there was no
additional substituent X in the pyridones, the enantioselec-
tivities were in all cases higher than 83% ee (products 6a–6g).
There is a weak correlation between the selectivity and the
reactivity. The most reactive substrate 5e (vide supra)
delivered most side products and the lowest ee. The high ee
for ortho-tolyl-substituted product 6g was unexpected given
that this substituent had led in the quinolone case (product
4h) to a decreased enantioselectivity. For substrate 5h (X =
methyl), the enantioselectivity of the sulfimidation was high
but the yield suffered, for substrate 5i (X = trifluoromethyl)
the opposite scenario— high yield, diminished ee— applied.
The observed enantiotopos differentiation in the Ag-
catalyzed sulfimidation were in agreement with the previous
hypothesis that the heteroleptic complex 9 was the catalyti-
cally competent species (Figure 1).[11] Upon transfer of the
protected nitrogen fragment from iminophenyliodinane to
the metal center, pre-coordination of a given substrate, for
example, 3a, would allow in the reactive complex 10 only to
display the pro-S electron pair towards the reactive nitrene
As mentioned in the introduction, the most remarkable
feature of the present Ag-catalyzed sulfimidation is the fact
that it is applicable to diaryl sulfides irrespective of the
relative size of the two substituents. As seen for the aryl-
substituted products 4a–4i the results fully met the expect-
Scheme 5. Enantioselective Ag-catalyzed sulfimidation of various 3-
thiosubstituted 2-quinolones 3 employing ligand 1a as the source of
chirality (60 mmol scale, substrate concentration c=10 mM). The
enantiomeric excess (ee) was calculated from the ratio of enantiomers
(4/ent-4) as determined by chiral HPLC analysis.
Scheme 6. Enantioselective Ag-catalyzed sulfimidation of various 3-
thiosubstituted 2-pyridones 5 employing ligand 1a as the source of
chirality (60 mmol scale, substrate concentration c=10 mM). The
enantiomeric excess (ee) was calculated from the ratio of enantiomers
(6/ent-6) as determined by chiral HPLC analysis.
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atoms (Scheme 8). All reactions with this substrate were
performed with a stoichiometric amount of the imidation
reagent to avoid a two-fold imidation. Achiral conditions
which allowed for a relatively clean reaction included the use
of 20 mol% Ag(PF6) and 60 mol% of 1,10-phenanthroline.
After 24 h the conversion was 60% and sulfimidation had
occurred with notable selectivity at the methylthio group in
the periphery of the molecule. The site-selectivity was
determined as r.r. (regioisomeric ratio) = rac-13/rac-4m =
84/16 by 1H NMR spectroscopic analysis of the crude product.
Product rac-13 was isolated in 47% yield. The outcome of the
enantioselective reaction performed with ligand 1a and the
standard catalyst loading was strikingly different. Product 13
could not be detected, and the reaction exclusively occurred
at the internal sulfur atom that is located at position C3 of the
quinolone. The only product was sulfimide 4m which was
isolated in 53% yield (58% conversion) with 97% ee.
The fact that a bound substrate can only display a distinct
lone pair to the catalytically active center (cf. Figure 1) should
result for any substrate with a single reactive center in
a kinetic resolution. Sulfoxides are like sulfimides chiral and
carry a lone pair at the sulfur atom. If subjected to the
conditions of the enantioselective sulfimidation, one sulfoxide
enantiomer should be preferentially processed as its stereo-
genic sulfur atom is properly configured to match the chirality
of the active site within the catalytically active silver complex.
We probed this hypothesis with sulfoxide rac-14 which was
treated with the imidation reagent and the optimized catalyst
mixture (Scheme 9). The resulting sulfoximine 15 was ob-
tained in enantiomerically enriched form while the recovered
sulfoxide also showed some optical purity. Depending on the
equivalents n of the iminophenyliodinane the enantioselec-
tivity could be optimized for the sulfoximine or the sulfoxide.
Although we did not prove the absolute configuration in this
case, it is highly likely that the (R)-enantiomer of sulfoxide 14
is preferentially processed leaving the (S)-enantiomer behind.
Sulfoximine 15 should thus be (R)-configured as shown.
Mechanistic experiments and discussion. Despite the fact
that the synthetic experiments delivered circumstantial evi-
dence (see the SI for further details) for the postulated
mechanism of the enantioselective sulfimidation we attempt-
ed to obtain further data to substantiate the proposed
reaction pathway. A hint for the formation of the postulated
heteroleptic complex 9 was obtained by high resolution
electrospray ion mass spectrometric (ESI-MS) analysis.
Figure 1. Putative heteroleptic silver complex 9 formed from the silver
source, one equivalent of ligand 1a, and one equivalent of 1,10-
phenanthroline and enantioselective nitrene transfer within complex
10: Only the pro-S electron pair at the sulfur atom of substrate 3a is
displayed towards the reactive center.
center. The reaction would consequently lead to the (S)-
configured sulfimides as observed.
The constraints for a nitrene transfer as postulated in
complex 10 stimulated further experiments which aimed to
verify and to exploit the pre-coordination by hydrogen bonds.
A straightforward experiment along these lines involves the
reaction of an N-alkylated substrate that is not competent to
form two hydrogen bonds to complex 9. The experiment was
performed with 2-quinolone 11, the N-methylated derivative
of substrate 3a (Scheme 7). The sulfimidation led to a product
which was completely racemic (product rac-12).
An interesting consequence of the hydrogen bond-medi-
ated sulfimidation relates to the fact that the reaction should
not only proceed with high enantioselectivity but also with
exquisite site-selectivity.[24] This issue was addressed with
substrate 3m that contains two potentially reactive sulfur
Scheme 7. Ag-catalyzed sulfimidation of 2-quinolone 11 under the
conditions previously applied to substrates 3 and 5 (60 mmol scale,
substrate concentration c=10 mM). Within the limits of error, product
12 was formed as the racemate (rac-12).
Scheme 9. Kinetic resolution of sulfoxide rac-14 by the enantioselective
Ag-catalyzed sulfimidation in the presence of chiral ligand 1a. Depen-
dent on the equivalents n of the imidation reagent, product 15 or the
recovered (recd.) substrate 14 can be isolated with high enantiomeric
excess.
Scheme 8. Site-selectivity in the sulfimidation of substrate 3m: The
hydrogen bonding ligand 1a directs the reaction to a defined site
(bottom) while an achiral ligand exerts the opposite site-selectivity
(top).
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Figure 2. ESI mass spectrometric analysis of a mixture obtained by dissolving AgPF6 (3 mmol), 1,10-phenanthroline (phen, 3 mmol), and ligand 1a
(3.6 mmol) in dichloromethane (1 mL). A 0.1 mL aliquot was diluted with 0.9 mL CH2Cl2 before subjecting the mixture to the analysis.
Under conditions that mimicked the composition of the
catalytically active mixture, a sample was subjected to ESI-
MS in the positive detection mode (detection of cationic
species). It was clearly evident from the exact mass analysis
(Figure 2) that the most intense peak at m/z = 640.1254 (m/z
calcd = 640.1261) corresponds to the heteroleptic complex 9
with the formula C35H27AgN5O+ formed from one equivalent
AgPF6, 1,10-phenanthroline and ligand 1a (see the SI for
further details). Likewise, the other two signals at m/z =
467.0411 (m/z calcd = 467.0420) and m/z = 813.2081 (m/z
calcd = 813.2102) could be matched with the formula
C24H16AgN4 and C46H38AgN6O2 . The former mass corre-
lates to the homoleptic silver complex 16 with two 1,10-
phenanthroline ligands while the latter mass can be assigned
to the homoleptic complex 17 of silver and two chiral
phenanthroline ligands 1a.
in Gibbs free energy, in agreement with the experimental
findings. The associated barrier of activation is 83 kJmolÀ1,
which is also in line with a reaction at room temperature.
The more favorable transition state is shown in Figure 3. It
features N···S and Ag···N distances of 1.91 and 2.23 Š,
respectively, and the substrate is also clearly bound via
a two-point hydrogen bonding motif (with O···H distances of
1.86 and 1.90 Š). Each phenanthroline ligand is coordinated
to the Ag center via a shorter bond (2.22 and 2.25 Š,
originating from the nitrogen atoms para to the alkynyl linker
and trans to this one) and a somewhat longer bond (2.34 and
2.55 Š). The C3-S single bond adapts an s-trans orientation,
+
+
Diffusion Ordered Spectroscopy (DOSY) experiments[25]
were performed with AgPF6 and 1,10-phenanthroline in
CD2Cl2 solution and corroborated the existence of homo-
leptic complex 16. Likewise, the homoleptic complex 17 could
be identified when studying AgPF6 and ligand 1a. Experi-
ments with AgPF6, phen, and ligand 1a, remained somewhat
1
inconclusive, however. H-NMR chemical shift data suggest
its formation but the increase in the apparent volume as
measured by the DOSY experiment was lower than expected
(see the SI for further details).
In order to evaluate a possible transition state that would
be accessible for heteroleptic complex 9 and substrate 3a
upon conversion of 9 to a nitrene complex, we turned to DFT
calculations (M06L[26]-D3[27] def2-TZVP(D),[28] for further
details see SI). Assuming triplet multiplicity, two transition
states leading to product 4a and its enantiomer (ent-4a) were
identified. The former is approx. 26 kJmolÀ1 more favorable
Figure 3. Favorable transition state for the conversion of substrate 3a
to product 4a, according to DFT calculations. Graphics generated with
CYLview20.[30]
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that is, the phenyl group points away from the site of
with reversible coordination of chiral and achiral ligands at
hydrogen bonding (cf. structure 10 in Figure 1). In addition,
the sulfur center to be sulfimidated carries a noticeable
positive charge of + 0.98 according to an NBO[29] analysis. The
less favorable transition state (leading to ent-4a) shares
several structural similarities with the more favorable one, for
example, with respect to the hydrogen bonding motif and the
orientation of the phenanthroline ligands (see the SI for
further information). However, the C3-S single bond is s-cis
oriented and the phenyl group points towards the binding site.
The transition state is overall somewhat later on the reaction
coordinate, with a shorter N···S (1.89 Š) and a longer Ag···N
(2.27 Š) distance. Apart from this, the two most striking
differences are the already mentioned CO-C3-S-CPh dihedral
angle (À448 vs. À1488) and a narrower Ag-N-S angle (1058 vs.
1218).
The DFT calculation suggests that the sulfur atom carries
a partial positive charge in the transition state. A Hammett
analysis of the sulfimidation reaction was performed in order
to interrogate the stereoelectronic situation at the sulfur atom
and to potentially confirm the predicted positive charge
increase (Figure 4). To this end, the six para-substituted 3-
(phenylthio)quinolones 3b–3 f were studied and the relative
rates of the sulfimidation was determined in comparison with
the parent compound 3a. Depending on the substituent X we
see a rate increase for electron donating substituent and a rate
decrease for electron withdrawing groups. The decadic
logarithm of the relative rates kX/kH reveals a good relation
with the tabulated sp values[31] of the substituents X. The slope
of the linear function was determined as 1 = À0.52 (see the SI
for more details) in agreement with a positive charge to be
developed at the reactive center.[32,33]
a cationic metal center. The observed site- and enantioselec-
tivity makes several heterocyclic sulfimides available which
would be difficult to access in enantioselective form by known
methods of asymmetric catalysis. The suggested reaction
mechanism of the nitrene transfer which had been previously
proposed to occur via a nitrene-silver complex with distorted
trigonal bipyramidal coordination[11] has been further corro-
borated and offers a useful model for the design of related
phenanthroline ligands with which more remote positions of
a given substrate can be aminated.
Acknowledgements
Financial support by the Deutsche Forschungsgemeinschaft
(grant Ba 1372/17-2) is gratefully acknowledged. A.R.R.
thanks the Alexander von Humboldt foundation for a re-
search fellowship. J.G. thanks the Fonds der Chemischen
Industrie (KekulØ fellowship). We thank M. Muhr (group of
Prof. R. A. Fischer, TUM) for his help with the ESI-MS
measurements and Prof. R. M. Gschwind (Regensburg) for
helpful discussions. O. Ackermann, F. Pecho, L. Koser, and J.
Kudermann (all at TUM) are acknowledged for their help
with HPLC and GLC analyses. Open access funding enabled
and organized by Projekt DEAL.
Conflict of interest
The authors declare no conflict of interest.
Keywords: asymmetric catalysis ·enantioselectivity ·
hydrogen bonds ·ligand design ·silver
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Figure 4. Hammett analysis performed for substrates 3a–3 f. Condi-
tions: Competing reactions were performed under typical catalytic
conditions with 1 equiv of the respective para-substituted 3-(phenyl-
thio)quinolone 3 and 1 equiv of 3a at ambient temperature (2 equiv
=
PhI NNs). The reaction was stopped after two hours (<25% con-
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Conclusion
In summary, our study has revealed that the directing
power of hydrogen bonding ligands is not only operative in
defined metal complexes but also in an equilibrium scenario
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Manuscript received: December 14, 2020
Accepted manuscript online: January 13, 2021
Version of record online: February 26, 2021
7926 www.angewandte.org ꢀ 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH Angew. Chem. Int. Ed. 2021, 60, 7920 –7926