Synergistic Ammonium (Hypo)Iodite/Imine Catalysis for the Asymmetric α-Hydroxylation of β-Ketoesters

Article abstract of DOI:10.1021/acs.orglett.0c02198

The synergistic use of chiral bifunctional ammonium iodide catalysts in combination with simple catalytically relevant aldimines allows for an unprecedented asymmetric α-hydroxylation reaction of β-ketoesters using H2O2. The reaction proceeds via in situ

Full text of DOI:10.1021/acs.orglett.0c02198

This is an open access article published under a Creative Commons Attribution (CC-BY)
License, which permits unrestricted use, distribution and reproduction in any medium,
provided the author and source are cited.
pubs.acs.org/OrgLett
Letter
Synergistic Ammonium (Hypo)Iodite/Imine Catalysis for the
Asymmetric α‑Hydroxylation of β‑Ketoesters
Christopher Mairhofer, Johanna Novacek, and Mario Waser*
Cite This: https://dx.doi.org/10.1021/acs.orglett.0c02198
Read Online
sı
*
Metrics & More
Article Recommendations
Supporting Information
ACCESS
ABSTRACT: The synergistic use of chiral bifunctional ammonium iodide catalysts
in combination with simple catalytically relevant aldimines allows for an
unprecedented asymmetric α-hydroxylation reaction of β-ketoesters using H2O2.
The reaction proceeds via in situ formation of a hypervalent iodine species, which
then reacts with the used aldimine to generate an activated electrophilic oxygen
transfer reagent.
he use of chiral quaternary ammonium salt (R4N+X−) ion
pairing catalysts is one of the most versatile approaches to
Scheme 1. Use of Ammonium Iodides under Oxidative
Conditions, Recent Studies, and Preliminary Results
T
facilitate the noncovalent organocatalytic asymmetric control of
prochiral starting materials, and numerous highly enantiose-
lective (and often easily scalable) applications have been
reported.1,2 Although the significance of the chiral quaternary
ammonium group R4N+ for activation and control of the starting
materials/reagents is well-appreciated, the influence of the
achiral counteranion X− is usually less systematically addressed,
as most scientists rely on the anion originating from the catalyst
synthesis (i.e., Cl− or Br− for the commonly used cinchona- and
Maruoka-type catalysts1−4). It has, however, been well-
demonstrated that sometimes different counteranions can have
a remarkable influence on catalyst performance and selectiv-
ity.1,5−8 This effect becomes even more relevant when reactions
are carried out under oxidative conditions, where anions like Br−
or especially I− may easily be oxidized to hypervalent halogen
species X(O)n . The resulting (in situ formed) R4N+X(O)n
−
−
species, such as iodide-based ones (Scheme 1A), show
interesting and unique catalytic properties, merging the potential
of (asymmetric) quaternary ammonium salt catalysis1,2 and
hypervalent iodine catalysis.9
Although this powerful combination is more commonly
documented for achiral ammonium iodides (and bromides to a
lesser extent),9,10 the catalytic utilization of in situ formed chiral
quaternary ammonium (hypo)iodite or iodate species R4N+I-
(O)n− has so far been reported sparingly, with a handful of highly
impressive (intramolecular) examples by Ishihara’s group mainly
(Scheme 1B).11,12
Over the past years, our group has had a strong focus on the
development and use of asymmetric (bifunctional) ammonium
salt catalysts.8,13 In 2016, we reported the asymmetric bifunc-
tional ammonium iodide A1-catalyzed α-hydroxylation of β-
ketoesters 1 using oxaziridines 2 as the O-transfer reagents
(Scheme 1C).8 Despite the high selectivities that were obtained
hereby, combined with an efficient kinetic resolution of the
oxaziridines,8 we recently looked for strategies avoiding the need
for the oxaziridine synthesis. Inspired by results by the Ooi
group, who reported the catalytic asymmetric synthesis of
enantioenriched oxaziridines from imines 4 via a Payne-type
oxidation (Scheme 1D),14−17 we thought about developing a
process where oxaziridines 2 would be generated in situ starting
Received: July 3, 2020
https://dx.doi.org/10.1021/acs.orglett.0c02198
© XXXX American Chemical Society
Org. Lett. XXXX, XXX, XXX−XXX
A

Organic Letters
pubs.acs.org/OrgLett
Letter
a
Table 1. Screening of Reagents and Reaction Conditions
b
c
entry
A
4 (equiv)
H2O2 (equiv)
additive (equiv)
solvent
yield (%)
er
1
2
3
4
5
6
7
8
A1
A1
A1
A1
A1
A1
A1
A1
A1
A1
A1
A1
A1
A2
A3
1
1
1
2
2
1
1
1
1
1
1
1
1
1
1
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
CH2Cl2
MTBE
MTBE
MTBE
MTBE
22
34
47
72
75
89
82
57
90
<50
60
96
98/88
97
21
58:42
60:40
81:19
90:10
93:7
CCl3CN (1)
CCl3CN (1)
CCl3CN (2)
4a (1)
4a (2)
4a (2)
4a (1)
4a (0.5)
4a (0.2)
4b (1)
4c (1)
4a (1)
4a (1)
4a (1)
4a (1)
4a (1)
94:6
93:7
70:30
92:8
64:36
87:13
95:5
96.5:3.5
95:5
51:49
9
d
10
11
12
13
14
15
e
f
a
b
c
All reactions were run for 20 h at 0 °C using 0.1 mmol 1a (0.02 M) and 5 mol % of A unless otherwise stated. Isolated yields. Determined by
HPLC using a chiral stationary phase. Absolute configuration of the major S-enantiomer (with R,R-catalysts) was assigned by comparison of
retention time and optical rotation as described previously.8 Limited conversion of 1a because of rapid imine hydrolysis. 0.01 M with respect to
d
e
f
1a. Using 1 mmol 1a (er = 96.5:3.5).
fromimines 4and may then be utilized for the α-hydroxylation of
1.17
Based on these initial experiments, which suggest a rather
unique α-hydroxylation mechanism involving the synergistic
combination of chiral ammonium iodides and imines under
oxidative conditions, we then investigated this (to the best of our
knowledge, unprecedented) catalysis concept further (Table 1
gives an illustrative overview of the most significant results of a
detailed screening).20
Very interestingly, during our initial experiments, we made
some rather unexpected observations (see Scheme 1E for a first
summary and Table 1 for more details). Whereas the A1-
catalyzed α-hydroxylation of the parent ketoester 1a with H2O2
alone18 as well as in combination with CCl3CN19 yielded small
amounts of product 3a with low selectivities only (entries 1 and
2), the use of an equimolar mixture of H2O2, CCl3CN, and
aldimine 4a had a beneficial effect (giving 3a with er = 81:19;
entry 3). This initial result could be improved (er = 90:10) by
increasing the excess of the reagents (entry 4) and in this case
also the formation of slightly enantioenriched oxaziridine 2 (er =
63:35) was observed. Very surprisingly, however, when carrying
out the reaction in the presence of the aldimine 4a and H2O2
only, product 3a was obtained with an even higher
enantioselectivity of 93:7 (entry 5).
It is well-known that chiral iminium salts or imines can
undergo in situ oxidations to oxaziridinium salts or oxaziridines,
which may then be utilized for asymmetric epoxidation or
sulfoxidation reactions.21,22 Quite contrary, however, no
oxaziridine formation was observed under our conditions
when using ammonium iodide catalyst A1, imine 4a, and
H2O2 (this was regularly checked during all further optimiza-
tion). This observation rules out a mechanism proceeding via
(our initially targeted) in situ formation of 2 as the active O-
transfer reagent. In addition, these reported iminium-salt-
catalyzed oxidations mainly used non-oxidizable counter-
anions,21 which is in sharp contrast to our reaction where the
presence of an oxidizable anion is crucial (vide infra).
Optimization was carried out with the parent bis-CF3-phenyl-
containing bifunctional catalyst system A1,23 but other (less
selective) catalysts were tested, as well.20 After our first hit (entry
5), we found that a lower imine and H2O2 amount resulted in a
slightly more selective and higher-yielding product formation
(entry 6; loweryields with excessH2O2 can be explained by faster
imine hydrolysis and decarboxylation of 1). Based on the fact
that the α-hydroxylation in the presence of imine 4a proceeded
much more selectively and higher-yielding than in its absence
(entry 1 vs 6) and the observation that we could recover
significant quantities of 4a after the reaction (plus the
corresponding aldehyde hydrolysis product), we speculated
that imine 4a serves as a catalytic shuttle in the enantioselective
hydroxylation process. To substantiate this assumption, we
lowered the imine content and were glad to see that, even with
half an equivalent of imine 4a, the outcome is more or less the
same (entry 7). Unfortunately, a further reduction to “truly”
catalytic quantities suffered from the notable background
hydrolysis of 4a under the reaction conditions (entry 8), but in
general, the catalytic role of the imine was confirmed. We next
varied theimines 4(see entries 9and10for two examplesandthe
Supporting Information for further details)20 and found that the
imine nature has a strong impact on the selectivity and thus plays
B
https://dx.doi.org/10.1021/acs.orglett.0c02198
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
a fundamental role in the stereodetermining step (again no in
situ formed oxaziridines 2 were observed in any of these
experiments). Other N-protecting groups turned out to be not
well-suited,20 and we thus used 4a for our further testing. Among
different solvents, dry MTBE was the best (entry 12), and
analogously to our previous oxaziridine report,8 higher dilutions
were slightly beneficial (entry 13), which can be rationalized by
the aggregation tendency of the catalysts at higher concen-
trations.8 We also investigated the influence of catalyst loading
and reaction temperature, but no further improvement was
possible.20 The optimized conditions turned out to be rather
robust, allowing for the same selectivity and high yield on a 1
mmol 1a scale, as well (entry 13). Other oxidants were tested, as
well, but neither of them matched the performance of H2O2.20
Finally, testing different catalyst counteranions showed that
oxidizable anions are absolutely crucial (entries 13−15).
Whereas bromide catalyst A2 performed almost as good as
iodide A1 (entries 13 and 14), non-oxidizable anions did not
allow for any noteworthy catalysis (entry 15 shows one example,
but others were tested with the same outcome).
experiments in the presence of radical scavengers such as
2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) or dibutylhy-
droxytoluene (BHT) point toward a radical-free pathway, as
neither of these two additives influenced the reaction.
Concerning the oxidation of I−, higher oxidation states like
−
−
IO3 or even IO4 can most likely be ruled out under these
neutral conditions.24 Among the lower oxidation state species
(I2, I3 , IO−, and IO2 ), our observations suggest that I2 itself is
not the catalytically relevant species, as I2 in combination with 4a
did not allow for any α-hydroxylation, whereas addition of H2O2
to this mixture allowed for product formation. Investigations by
Ishihara and others clearly showed that IO− is most likely the
catalytically relevant species for quaternary ammonium iodides
under oxidative conditions.10,11 Formation of hypoiodite may
also explain why this reaction proceeds well under base-free
oxidative conditions when I− is present: HIO has a pKa of 10.4,25
and thus IO− may not only be relevant for the oxidation but also
can play a role in the deprotonation of β-ketoesters 1.26 It should,
−
−
−
however, be noted that the formation and catalytic activity of I3
or even the unstable IO2− cannot yet be perfectly ruled out; for
example, some experiments with stoichiometric or catalytic
amounts of Bu4NI3 or in situ formed Bu4NIO11 in the presence
of H2O2 and 4a gave formation of racemic 3a, and in situ
formation of IO2− may also be possible under these conditions.27
Accordingly, a plausible and very general mechanistic scenario
is shown in Scheme 2B. H2O2 first oxidizes the ammonium
iodide to a hypervalent species I. This species then reacts with
the imine 4 to a yet unknown O-transfer species such as
compounds II (other options are feasible, as well!). The catalyst
then controls the enantioselective reaction of this species, with
the β-ketoester 1 giving 3 combined with a release of the imine 4
again. In addition, the reduced catalyst species Ired will be
reoxidized with H2O2 again, closing the proposed catalytic cycle.
With an optimized procedure for the asymmetric α-
hydroxylation of the parent substrate 1a at hand, we next
investigated the application scope of this protocol (Scheme 3).
Testing different ester groups first, we noticed that bulky esters
As mentioned before, other catalysts were less selective and
less active.20 Especially noteworthy are the results obtained with
Maruoka’s ammonium salts B4 and achiral PTCs (Scheme 2A).
Scheme 2. Influence of Ammonium Salt Properties and
Proposed Mechanistic Scenario
a
Scheme 3. Application Scope
In contrast to ammonium bromide A2 (entry 14, Table 1), the
commercially available ammonium bromide B2 was found to be
catalytically relatively incompetent, whereas the analogous
ammonium iodide B1 (derivatives thereof were used by Ishihara
in their oxidative approaches11,12) allowed for some product
formation, albeit with low enantioselectivity (Scheme 2A).
Using tetrabutylammonium iodide (C1, TBAI) or bromide (C2,
TBAB) as achiral PTCs, the conversion was also measurably
slower compared to that with catalysts A. This striking difference
between catalyst class A and ammonium salts B or C most likely
can be attributed to the H-bonding motif of catalysts A, but the
exact mode of activation remains yet speculative.
Nevertheless, all of our observations clearly substantiate a
mechanism where oxidation of the counteranion (i.e., iodide)
and formation of an activated O-transfer agent by reaction of the
oxidized halide species with the imine occurs. Control
a
b
All reactions were carried out using 0.1 mmol β-ketoester 1.20 Fast
c
decarboxylation of the ester under the reaction conditions. Limited
conversion of around 50% after 20 h.
C
https://dx.doi.org/10.1021/acs.orglett.0c02198
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
(i.e., tBu-based ones) are clearly better suited for high
enantioselectivities than Me- or Bn-esters (compare products
3a−e). Varying the aryl substituents of indanone-based t-Bu
esters next, we found that a broad variety of groups in the 4-, 5-,
or 6-position are equally well-tolerated (see products 3f−p). In
contrast, however, substituents in the 7-position (products 3q
and 3r) had a detrimental effect on the selectivity. This is in sharp
contrast to our recent oxaziridine-mediated protocol where
these substrates performed well,8 demonstrating the obviously
different transition state scenarios of these two mechanistically
complementary approaches. Finally, tetralone-based β-ketoest-
ers could also be α-hydroxylated under the standard conditions,
but unfortunately their reactivity was found to be lower
(incomplete conversion after 20 h), and the obtained
selectivities were clearly less satisfactory as compared to the
indanone-based ones (see products 3s−u).
Summing our investigations up, we found that the synergistic
catalyst combination of chiral bifunctional ammonium iodides
with simple aldimines allows for the enantioselective α-
hydroxylation of β-ketoesters using H2O2. The reaction most
presumably proceeds via an in situ generated hypervalent iodine
species which then forms the activated O-transfer agent by
reaction with the used imine shuttle. Control experiments
underline the necessity of iodide as an oxidizable counteranion,
and it was also shown that the bifunctional nature of the catalyst
is crucial. The protocol tolerates a variety of differently
functionalized cyclic β-ketoesters. We are currently working on
getting a better mechanistic understanding of this unprece-
dented synergistic catalysis principle and will hopefully be able to
expand this concept to other target reactions soon.
DEDICATION
■
Dedicated to Prof. Karl Grubmayr, who has been an inspiring
(and patient) teacher to all of us, on the occasion of his 70th
birthday.
REFERENCES
■
(1) Selected general reviews on asymmetric ion pairing catalysis:
̀
(a) Briere, J.-F.; Oudeyer, S.; Dalla, V.; Levacher, V. Recent advances in
cooperative ion pairing in asymmetric organocatalysis. Chem. Soc. Rev.
2012, 41, 1696−1707. (b) Shirakawa, S.; Maruoka, K. Recent
Developments in Asymmetric Phase-Transfer Reactions. Angew.
Chem., Int. Ed. 2013, 52, 4312−4348. (c) Brak, K.; Jacobsen, E. N.
Asymmetric Ion-Pairing Catalysis. Angew. Chem., Int. Ed. 2013, 52,
534−561. (d) Tan, J.; Yasuda, N. Contemporary Asymmetric Phase
Transfer Catalysis: Large-Scale Industrial Applications. Org. Process Res.
Dev. 2015, 19, 1731−1746. (e) Kaneko, S.; Kumatabara, Y.; Shirakawa,
S. A new generation of chiral phase-transfer catalysts. Org. Biomol. Chem.
2016, 14, 5367−5376. (f) Zong, L.; Tan, C.-H. Phase-Transfer and Ion-
Pairing Catalysis of Pentanidiums and Bisguanidiniums. Acc. Chem. Res.
2017, 50, 842−856. (g) Qian, D.; Sun, J. Recent Progressin Asymmetric
Ion-Pairing Catalysis with Ammonium Salts. Chem. - Eur. J. 2019, 25,
3740−3751. (h) Nakamura, T.; Okuno, K.; Nishiyori, R.; Shirakawa, S.
Hydrogen-Bonding Catalysis of Alkyl-Onium Salts. Chem. - Asian J.
2020, 15, 463−472.
(2) Reviews on bifunctional ammonium salt catalysis: (a) Novacek, J.;
Waser, M. Bifunctional Chiral Quaternary Ammonium Salt Catalysts: A
Rapidly Emerging Class of Powerful Asymmetric Catalysts. M. Eur. J.
Org. Chem. 2013, 2013, 637−648. (b) Wang, H. Chiral Phase-Transfer
Catalysts with Hydrogen Bond: A Powerful Tool in the Asymmetric
Synthesis. Catalysts 2019, 9, 244. (c) Wang, H.; Zheng, C.; Zhao, G.
Bifunctional Ion Pair Catalysts from Chiral α-Amino Acids. Chin. J.
Chem. 2019, 37, 1111−1119.
(3) Seminal studies using cinchona PTCs: (a) Helder, R.; Hummelen,
J. C.; Laane, R. W. P. M.; Wiering, J. S.; Wynberg, H. Catalytic
asymmetric induction in oxidation reactions. The synthesis of optically
active epoxides. Tetrahedron Lett. 1976, 17, 1831−1834. (b) Dolling, U.
H.; Davis, P.; Grabowski, E. J. J. Efficient catalytic asymmetric
alkylations. 1. Enantioselective synthesis of (+)-indacrinone via chiral
phase-transfer catalysis. J. Am. Chem. Soc. 1984, 106, 446−447.
(4) Seminal report on Maruoka-type catalysts: Ooi, T.; Kameda, M.;
Maruoka, K. Molecular Design of a C2-Symmetric Chiral Phase-
Transfer Catalyst for Practical Asymmetric Synthesis of α-Amino Acids.
J. Am. Chem. Soc. 1999, 121, 6519−6520.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c02198.
■
sı
Experimental and analytic details (including copies of
HPLC traces) as well as further details of the screening
and optimization process (PDF)
AUTHOR INFORMATION
Corresponding Author
■
(5) Ooi, T.; Maruoka, K. Asymmetric Organocatalysis of Structurally
Well-Defined Chiral Quaternary Ammonium Fluorides. Acc. Chem. Res.
2004, 37, 526−533.
Mario Waser − Institute of Organic Chemistry, Johannes Kepler
University Linz, 4040 Linz, Austria; orcid.org/0000-0002-
8421-8642; Phone: +4373224685411; Email: mario.waser@
jku.at
(6) (a) Tozawa, T.; Yamane, Y.; Mukaiyama, T. Enantioselective
Synthesis of 3,4-Dihydropyran-2-ones by Chiral Quaternary Ammo-
nium Phenoxide-catalyzed Tandem Michael Addition and Lactoniza-
tion. Chem. Lett. 2006, 35, 56−57. (b) Bernardi, L.; Indrigo, E.;
Pollicino, S.; Ricci, A. Organocatalytic trifluoromethylation of imines
using phase-transfer catalysis with phenoxides. A general platform for
catalytic additions of organosilanes to imines. Chem. Commun. 2012, 48,
1428−1430.
(7) Ohshima, T.; Shibuguchi, T.; Fukuta, Y.; Shibasaki, M. Catalytic
asymmetric phase-transfer reactions using tartrate-derived asymmetric
two-center organocatalysts. Tetrahedron 2004, 60, 7743−7754.
(8) Novacek, J.; Izzo, J. J. A.; Vetticatt, M. J.; Waser, M. Bifunctional
Ammonium Salt Catalyzed Asymmetric α-Hydroxylation of β-
Ketoesters by Simultaneous Resolution of Oxaziridines. Chem. - Eur.
J. 2016, 22, 17339−17344.
Authors
Christopher Mairhofer − Institute of Organic Chemistry,
Johannes Kepler University Linz, 4040 Linz, Austria
Johanna Novacek − Institute of Organic Chemistry, Johannes
Kepler University Linz, 4040 Linz, Austria
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.0c02198
Notes
(9) Overviews on (asymmetric) catalysis using organo-iodine species
under oxidative conditions: (a) Uyanik, M.; Ishihara, K. Catalysis with
In Situ-Generated(Hypo)iodite Ionsfor Oxidative CouplingReactions.
ChemCatChem 2012, 4, 177−185. (b) Finkbeiner, P.; Nachtsheim, B. J.
Iodine in Modern Oxidation Catalysis. Synthesis 2013, 45, 979−999.
(c) Wu, X.-F.; Gong, J.-L.; Qi, X. A powerful combination: recent
achievements on using TBAI and TBHP as oxidation system. Org.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the Austrian Science Funds (FWF),
Project No. P31784, and the Linz Institute of Technology (LIT),
Project ID LIT-2019-8-SEE-111.
D
https://dx.doi.org/10.1021/acs.orglett.0c02198
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
Biomol. Chem. 2014, 12, 5807−5817. (d) Claraz, A.; Masson, G.
Asymmetric iodine catalysis-mediated enantioselective oxidative trans-
formations. Org. Biomol. Chem. 2018, 16, 5386−5402.
oxaziridination catalyzed by cinchona alkaloid derivatives containing
sulfide. Tetrahedron 2013, 69, 7416−7422.
(17) Direct use of chiral in situ generated electron-deficient
oxaziridines for enantioselective α-hydroxylations of silyl enol ethers:
Tanaka, N.; Tsutsumi, R.; Uraguchi, D.; Ooi, T. N-Sulfonyl a-imino
ester-derived chiral oxaziridines: catalytic asymmetric synthesis and
application as a modular chiral organic oxidant. Chem. Commun. 2017,
53, 6999−7002.
(10) Achiral approaches: (a) Uyanik, M.; Suzuki, D.; Yasui, T.;
Ishihara, K. In Situ Generated (Hypo)Iodite Catalysts for the Direct a-
Oxyacylation of Carbonyl Compounds with Carboxylic Acids. Angew.
Chem., Int. Ed. 2011, 50, 5331−5334. (b) Froehr, T.; Sindlinger, C. P.;
Kloeckner, U.; Finkbeiner, P.; Nachtsheim, B. J. A. Metal-Free
Amination of Benzoxazoles - The First Example of an Iodide-Catalyzed
Oxidative Amination of Heteroarenes. Org. Lett. 2011, 13, 3754−3757.
(c) Ma, L.; Wang, X.; Yu, W.; Han, B. TBAI-catalyzed oxidative
coupling of aminopyridines with β-keto esters and 1,3-diones - synthesis
of imidazo[1,2-a]pyridines. Chem. Commun. 2011, 47, 11333−11335.
(d)Kloeckner, U.; Weckenmann, N. M.; Nachtsheim, B. J. AMetal-Free
Oxidative Amination of Benzoxazoles with Primary Amines and
Ammonia. Synlett 2012, 2012, 97−100. (e) Han, J.-Q.; Zhang, H.-H.;
Xu, P.-F.; Luo, Y.-C. Lewis Acid and (Hypo)iodite Relay Catalysis
Allows a Strategy for the Synthesis of Polysubstituted Azetidines and
Tetrahydroquinolines. Org. Lett. 2016, 18, 5212−5215. (f) Uyanik, M.;
Nishioka, K.; Ishihara, K. Ammonium Hypoiodite-catalyzed Oxidative
Dearomatizative Azidation of Arenols. Chem. Lett. 2019, 48, 353−356.
(11) (a) Uyanik, M.; Okamoto, H.; Yasui, T.; Ishihara, K. Quaternary
Ammonium (Hypo)iodite Catalysis for Enantioselective Oxidative
Cycloetherification. Science 2010, 328, 1376−1379. (b) Uyanik, M.;
Hayashi, H.; Ishihara, K. High-turnover hypoiodite catalysis for
asymmetric synthesis of tocopherols. Science 2014, 345, 291−294.
(c) Uyanik, M.; Sasakura, N.; Kaneko, E.; Ohori, K.; Ishihara, K. Chiral
Ammonium Hypoiodite-catalyzed Enantioselective Oxidative Dear-
omatization of 1-Naphthols Using Hydrogen Peroxide. Chem. Lett.
2015, 44, 179−181. (d) Uyanik, M.; Hayashi, H.; Iwata, H.; Ishihara, K.
Chiral Ammonium Hypoiodite Salt-catalyzed Enantioselective Oxida-
tive Cycloetherification to 2-Acyl Tetrahydrofurans. Chem. Lett. 2016,
45, 353−355. (e) Uyanik, M.; Kato, T.; Sahara, N.; Katade, O.; Ishihara,
K. High-Performance Ammonium Hypoiodite/Oxone Catalysis for
Enantioselective Oxidative Dearomatization of Arenols. ACS Catal.
2019, 9, 11619−11626.
(18) Recent racemic quaternary ammonium salt/H2O2-mediated
approach: Wang, Y.; Wang, S.; Gao, Q.; Li, L.; Zhi, H.; Zhang, T.;
Zhang, J. Transition-metal, organic solvent and base free α-
hydroxylation of β-keto esters and β-keto amides with peroxides in
water. Tetrahedron 2019, 75, 3856−3863.
(19) Ohmatsu, K.; Ando, Y.; Ooi, T. In Situ Electrophilic Activation of
Hydrogen Peroxide for Catalytic Asymmetric α-Hydroxylation of 3-
Substituted Oxindoles. Synlett 2017, 28, 1291−1294.
(20) Further details and examples can be found in the online
Supporting Information.
(21) Reviews on asymmetric iminium salt catalysts which are in situ
oxidized to chiral oxaziridinium species: (a) Wong, O. A.; Shi, Y.
Organocatalytic Oxidation. Asymmetric Epoxidation of Olefins
Catalyzed by Chiral Ketones and Iminium Salts. Chem. Rev. 2008,
108, 3958−3987. (b) Day, D. P.; Sellars, P. B. Recent Advances in
Iminium-Salt-Catalysed Asymmetric Epoxidation. Eur. J. Org. Chem.
2017, 2017, 1034−1044.
(22) Oxidation reactions where the active oxidant is generated in situ
by oxidation of chiral imines with H2O2 in the absence of any
ammonium iodide catalysts: (a) Page, P. C. B.; Heer, J. P.; Bethell, D.;
Collington, E. W.; Andrews, D. M. A new system for catalytic
asymmetric oxidation of sulfides using a hydrogen peroxide based
reagent. Tetrahedron Lett. 1994, 35, 9629−9632. (b) Page, P. C. B.;
Heer, J. P.; Bethell, D.; Collington, E. W.; Andrews, D. M. Highly
Enantioselective Catalystic Asymmetric Oxidation of Sulfides using
Hydrogen Peroxide. Synlett 1995, 1995, 773−775. (c) Bethell, D.;
Bulman Page, P. C.; Vahedi, H. Catalytic Asymmetric Oxidation of
Sulfides to Sulfoxides Mediated by Chiral 3-Substituted-1,2-benziso-
thiazole 1,1-Dioxides. J. Org. Chem. 2000, 65, 6756−6760.
(23) Recent report on the use of similar catalysts by others: Yasui, M.;
Yamada, A.; Tsukano, C.; Hamza, A.; Papai, I.; Takemoto, Y.
Enantioselective Acetalization via Dynamic Kinetic Resolution for
Synthesis of γ-Alkoxybutenolide by Thiourea−Quaternary Ammonium
Salt Catalysts: Its Application to Strigolactones. Angew. Chem., Int. Ed.
2020, DOI: 10.1002/anie.202002129.
(24) (a) McAlpine, R. K. The rate of oxidation of iodide ion by
hydrogen peroxide. J. Chem. Educ. 1945, 22, 387−390. (b) Schmitz, G.
The oxidation of iodine to iodate by hydrogen peroxide. Phys. Chem.
Chem. Phys. 2001, 3, 4741−4746.
(25) Bichsel, Y.; von Gunten, U. Hypoiodous acid: Kinetics of the
buffer-catalyzed disproportionation. Water Res. 2000, 34, 3197−3203.
(26) Data on acidity and nucleophilicity of β-ketoesters: (a) Cram, D.
J. Fundamentals of Carbanion Chemistry; Academic Press: NewYork,
1965; pp 8−20. (b) Corral-Bautista, F.; Mayr, H. Quantification of the
Nucleophilic Reactivities of Cyclic β-Keto Ester Anions. Eur. J. Org.
Chem. 2015, 2015, 7594−7601.
(12) Uyanik, M.; Nishioka, K.; Kondo, R.; Ishihara, K. Chemoselective
oxidative generation of ortho-quinone methides and tandem trans-
formations. Nat. Chem. 2020, 12, 353−362.
(13) Examples on catalyst development: (a) Gratzer, K.; Waser, M.
Investigations Concerning the Syntheses of TADDOL-Derived
Secondary Amines and Their Use to Access Novel Chiral Organo-
catalysts. Synthesis 2012, 44, 3661−3670. (b) Tiffner, M.; Novacek, J.;
Busillo, A.; Gratzer, K.; Massa, A.; Waser, M. Design of Chiral Urea-
Quaternary Ammonium Salt Hybrid Catalysts for Asymmetric
Reactions of Glycine Schiff Bases. RSC Adv. 2015, 5, 78941−78949.
̈
(c) Schorgenhumer, J.; Otte, S.; Haider, V.; Novacek, J.; Waser, M. A
flexible strategy for the synthesis of bifunctional 6’-(thio)-urea
containing Cinchona alkaloid ammonium salts. Tetrahedron 2019,
130816.
(14) (a) Uraguchi, D.; Tsutsumi, R.; Ooi, T. Catalytic Asymmetric
Oxidation of N-Sulfonyl Imines with Hydrogen Peroxide−Trichlor-
oacetonitrile System. J. Am. Chem. Soc. 2013, 135, 8161−8164.
(b) Tsutsumi, R.; Kim, S.; Uraguchi, D.; Ooi, T. The Practical
Preparation of Chiral N-Sulfonyl Oxaziridines via Catalytic Asymmetric
Payne Oxidation. Synthesis 2014, 46, 871−878. (c) Uraguchi, D.;
Tsutsumi, R.; Ooi, T. Catalytic asymmetric Payne oxidation under the
catalysis of P-spiro chiral triaminoiminophosphorane: application to the
synthesis of N-sulfonyl oxaziridines. Tetrahedron 2014, 70, 1691−1701.
(15) Reviews on oxaziridines: (a) Williamson, K. S.; Michaelis, D. J.;
Yoon, T. P. Advances in the chemistry of oxaziridines. Chem. Rev. 2014,
114, 8016−8036. (b) Ren, Q.; Yang, W.; Lan, Y.; Qin, X.; He, Y.; Yuan,
L. Recent Advances in the Catalytic Asymmetric Reactions of
Oxaziridines. Molecules 2018, 23, 2656.
(27) (a) Wren, J. C.; Paquette, J.; Sunder, S.; Ford, B. L. Iodine
chemistry in the + 1 oxidation state. II. A Raman and uv−visible
spectroscopic study of the disproportionation of hypoiodite in basic
solutions. Can. J. Chem. 1986, 64, 2284−2296. (b) Zhu, C.; Wei, Y. An
Inorganic Iodine-Catalyzed Oxidative System for the Synthesis of
Benzimidazoles Using Hydrogen Peroxide under Ambient Conditions.
ChemSusChem 2011, 4, 1082−1086.
(16) Related organocatalytic asymmetric oxaziridine formations:
(a) Lykke, L.; Rodriguez-Escrich, C.; Jørgensen, K. A. Catalytic
enantioselective oxaziridination. J. Am. Chem. Soc. 2011, 133, 14932−
14935. (b) Zhang, T.; He, W.; Zhao, X.; Jin, Y. Asymmetric
E
https://dx.doi.org/10.1021/acs.orglett.0c02198
Org. Lett. XXXX, XXX, XXX−XXX