Formal Enone α-Arylation via I(III)-Mediated Aryl Migration/Elimination

Article abstract of DOI:10.1021/acs.orglett.1c00251

A formal enone α-arylation is described. This metal-free transformation relies on the I(III)-mediated skeletal reorganization of silyl enol ethers and features mild conditions, good yields, and high stereoselectivities for β-substituted enones.

Full text of DOI:10.1021/acs.orglett.1c00251

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Letter
Formal Enone α‑Arylation via I(III)-Mediated Aryl Migration/
Elimination
Bruna S. Martins,† Daniel Kaiser,† Adriano Bauer, Irmgard Tiefenbrunner, and Nuno Maulide*
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ABSTRACT: A formal enone α-arylation is described. This metal-free transformation
relies on the I(III)-mediated skeletal reorganization of silyl enol ethers and features
mild conditions, good yields, and high stereoselectivities for β-substituted enones.
(V),3 iodine(III),4 and arynes5 have emerged in the last years.
Alternative methodologies employing N-alkoxyenamines,6
enolonium equivalents,7 oxy-allyl cations,8 and radical-
mediated arylations9 have also been developed.
he development of novel approaches for the synthesis of
Tα-arylated carbonyl compounds remains a topic of
interest in synthetic chemistry. Whereas classical approaches
rely on transition-metal-catalyzed couplings of carbonyl-
derived enolates with aryl halides or pseudohalides (Scheme
1A),1 complementary transition-metal-free methods based on
electrophilic aromatic derivatives such as sulfur(IV),2 bismuth-
Despite the great progress achieved with transition-metal-
free approaches, limitations in achievable substitution patterns
and low atom economy still remain as drawbacks. In a recently
disclosed elegant contribution by Wengryniuk and coworkers
on the transition-metal-free α-arylation of enones, the direct
C−H α-arylation occurs via the reductive iodonium Claisen
rearrangement of in-situ-generated β-pyridinium silyl enol
ethers (4) and ArI(O2CCF3)2 reagents (Scheme 1B).10
Although this method features high atom economy, com-
parably expedient substrate synthesis, and a broad arene scope,
its modularity is limited by the inevitable presence of an ortho-
iodo substituent and accompanying restrictions in the
substitution pattern of the aromatic in addition to the need
to prepare the iodoarenes.
Scheme 1. (A) Transition-Metal-Catalyzed Approach for α-
Arylation of Carbonyl Compounds, (B) Enone Arylation via
β-Pyridinium Enolonium Species, and (C) This Work:
Enone α-Arylation via Iodine(III)-Mediated Aryl
Migration/Elimination.
As part of our long-standing interest in the rearrangements
of high-energy intermediates, we have established method-
ologies for the iodine(III)-mediated α-arylation11 and α-
cyclopropanation12 of carbonyl compounds through oxidative
C−C bond activation and carbocationic rearrangements,
respectively. Inspired by the outstanding ability of iodine-
(III)13 in promoting oxidative rearrangements,14 we wondered
whether this class of reagents could evoke an intramolecular α-
arylation of enones. Herein we report a practical transition-
metal-free protocol for the formal α-arylation of enones via
iodine(III)-mediated aryl migration/elimination.
Encouraged by our previous work on I(III)-mediated
rearrangements,11,12 we envisioned a process in which
intermediate 9 (Scheme 1C), the product of aryl migration
Received: January 21, 2021
Published: February 26, 2021
© 2021 The Authors. Published by
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https://dx.doi.org/10.1021/acs.orglett.1c00251
Org. Lett. 2021, 23, 2094−2098
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on enolonium species 8, would undergo elimination to form 7.
We therefore started our investigations with the silyl enol ether
6a as a model substrate and TMSOTf (trimethylsilyl
trifluoromethanesulfonate) as the activator for a range of
I(III) reagents (Table 1). The commercially available I(III)
reagent PIDA (diacetoxyiodo)benzene, PhI(OAc)2) gave a
promising 50% yield of the desired α-arylated enone (entry 1).
Increasing the amount of Et3N (required for elimination) from
2 to 4 equiv led to the formation of 7a in 74% yield (entry 2),
and a screening of I(III) reagents revealed PIDA as the
optimum oxidant for this transformation (entries 3−5).
Switching from Et3N to either DIPEA (N,N-diisopropyle-
thylamine) or NaOH did not lead to any improvement (entries
6 and 7); rather, through the presence of 35% β-triflated, α-
arylated ketone, we were able to determine that the observed
process likely proceeds via the capture of 9 by a triflate anion
rather than direct elimination. It is additionally worth
mentioning that during the examination of the conditions
employing PIDA as the I(III) reagent, we observed the
formation of distinct side products (α- and β-acetates),
generated by competitive reactions with intermediates 8 and
9.11,12,15 Attempting to avoid the formation of these by-
products, we increased the amount of the activator TMSOTf,
which led to an improved isolated yield (82%) of the α-
arylated enone 7a (entry 8).
a
Table 1. Optimization of the Reaction Conditions
b
g
entry
I(III) reagent
TMSOTf (equiv)
base
yield (%)
c
1
2
3
4
5
6
7
8
PhI(OAc)2
PhI(OAc)2
PhIO
PhI(OPiv)2
PhI(OCOCF3)2
PhI(OAc)2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.4
Et3N
50
74
70
56
24
38
12
d
d
d
d
Et3N
Et3N
Et3N
Et3N
de
,
DIPEA
f
PhI(OAc)2
PhI(OAc)2
NaOH
d
h
With the optimized conditions in hand, we investigated the
impact of electronics and sterics on the employed silyl enol
ethers (Scheme 2). We first evaluated different substituents on
the benzoyl moiety (Scheme 2a). Electron-donating, -with-
drawing, and -neutral groups were all well tolerated, and the
products 7a−j were obtained in good yields regardless of the
position of the substituent. Furthermore, a silyl enol ether
Et3N
82
a
All screening was performed on 0.2 mmol of 6a (1 equiv) in 2 mL of
b
c
d
e
DCM (0.1 M). 1.2 equiv. 2 equiv. 4 equiv. Alongside 35% β-
f
g
h
trifate. 1 M, 4 equiv. NMR yields. Isolated yield. TMSOTf =
trimethylsilyl trifluoromethanesulfonate. DIPEA = N,N-diisopropyle-
thylamine. DCM = dichloromethane.
a
Scheme 2. Scope of I(III)-Mediated α-Arylation of Enones
a
b
All yields refer to pure, isolated products, unless otherwise stated. NMR yields were determined using mesitylene as an internal standard.
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bearing a disubstituted aromatic ring was also susceptible to
rearrangement in high yield (7i). Substrates bearing more
elaborate aromatic rings such as 2-naphthyl (7k) and 1,3-
benzodioxol-5-yl (7l) were also successfully transformed, as
was 2-thienoyl-derived substrate (7m). In addition, an alkyl α-
arylated enone 7n and an enal 7o were formed in 86 and 60%
yield, respectively.16
Next, we evaluated the migration of substituted aryl groups.
The rearrangement of an o-tolyl moiety afforded the product
7p in 57% yield, whereas the migration of a m-fluoro derivative
provided the enone 7q in 51% yield. Additionally, the
migration of a disubstituted aromatic group was accomplished
effectively, yielding enone 7r in 65%. Unfortunately, the shift
of an electron-poor aryl group such as p-CF3C6H4 proved
fruitless as a consequence of its diminished migratory ability.
Instead, we obtained the corresponding β-arylated, α,β-
unsaturated ketone as a major product under standard
conditions.
Interestingly, we found that substrates with fused rings
underwent I(III)-mediated aryl migration/ring expansion/
elimination, leading to α-arylated enones 7t and 7u in high
yields (Scheme 2b). Gratifyingly, the formal α-arylation of β-
substituted enones proceeded readily, giving the desired
products 7v and 7w in excellent yields and with excellent
stereoselectivities. (See the Supporting Information for a
rationalization of this selectivity.) It is worth highlighting that
the product 7w proved more reactive to aryl migration/
elimination than to a competitive intramolecular Friedel−
Crafts reaction. In the case of an iso-propyl-substituted silyl
enol ether (6x), we found that 2,3-dihydrofuran 7x was formed
in 62% yield (Scheme 3a). We presume that this heterocycle
was generated through a phenyl migration/Wagner−Meerwein
rearrangement/cyclization sequence.
To explore the synthetic utility of the new method, we chose
product 7a for further derivatization (Scheme 3b). Scale up (5
mmol) of its preparation could be achieved without a
significant decrease in yield. The enone 7a subsequently
readily underwent Nazarov cyclization or a (3 + 2)-
cycloaddition reaction. The synthesis of 2-phenyl-1-indanone
(10) was accomplished in 59% yield, whereas the cyclo-
addition of 7a with N-phenyl-C-phenyl nitrone furnished the
desired isoxazolidine 11 in an excellent yield of 97%.
In summary, we have developed a skeletal rearrangement-
based methodology for the α-arylation of enones. The use of
I(III) to mediate the aryl migration/elimination enabled the
formation of a series of α-arylated enones in good yields under
mild conditions. Furthermore, we demonstrated that our
method is suitable for substrates bearing fused rings,
promoting aryl migration/ring expansion/elimination, as well
as for β-substituted silyl enol ethers, giving high yields and
excellent stereoselectivities.
ASSOCIATED CONTENT
* Supporting Information
■
sı
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.1c00251.
Experimental procedures, 1H and 13C NMR spectra, and
characterization data of compounds (PDF)
AUTHOR INFORMATION
Corresponding Author
■
Nuno Maulide − University of Vienna, Institute of Organic
Chemistry, 1090 Vienna, Austria; orcid.org/0000-0003-
3643-0718; Email: nuno.maulide@univie.ac.at
Authors
Bruna S. Martins − University of Vienna, Institute of Organic
Chemistry, 1090 Vienna, Austria; orcid.org/0000-0001-
9143-4434
Daniel Kaiser − University of Vienna, Institute of Organic
Chemistry, 1090 Vienna, Austria; orcid.org/0000-0001-
8895-9969
Adriano Bauer − University of Vienna, Institute of Organic
Chemistry, 1090 Vienna, Austria; orcid.org/0000-0002-
3376-343X
Irmgard Tiefenbrunner − University of Vienna, Institute of
Organic Chemistry, 1090 Vienna, Austria
Scheme 3. Occurrence of a Cyclization Product and
Functionalizations of α-Arylated Enone 7a
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.1c00251
Author Contributions
†B.S.M. and D.K. contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Generous support of this research by the European Research
Council (Horizon 2020, VINCAT CoG 682002 to N.M.), the
Austrian Science Fund (P32607 to N.M.; Fellowship J 4202-
N28 to D.K.), and Boehringer Ingelheim is acknowledged. We
are grateful to the University of Vienna for its continued and
generous support of our research programs.
REFERENCES
■
(1) (a) Bellina, F.; Rossi, R. Transition Metal-catalyzed Direct
Arylation of Substrates with Activated sp3-Hybridized C−H Bonds
and Some of Their Synthetic Equivalents with Aryl Halides and
Pseudohalides. Chem. Rev. 2010, 110, 1082−1146. (b) Johansson, C.
C. C.; Colacot, T. J. Metal-Catalyzed α-Arylation of Carbonyl and
2096
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Organic Letters
pubs.acs.org/OrgLett
Letter
Related Molecules: Novel Trends in C−C Bond Formation by C−H
Bond Functionalization. Angew. Chem., Int. Ed. 2010, 49, 676−707.
(2) (a) Huang, X.; Maulide, N. Sulfoxide-mediated α-Arylation of
Carbonyl Compounds. J. Am. Chem. Soc. 2011, 133, 8510−8513.
(7) (a) Kaiser, D.; de la Torre, A.; Shaaban, S.; Maulide, N. Metal-
free Formal Oxidative C−C Coupling by In Situ Generation of an
Enolonium Species. Angew. Chem., Int. Ed. 2017, 56, 5921−5925.
(b) Maksymenko, S.; Parida, K. N.; Pathe, G. K.; More, A. A.; Lipisa,
Y. B.; Szpilman, A. M. Transition-metal-free Intermolecular α-
Arylation of Ketones via Enolonium Species. Org. Lett. 2017, 19,
6312−6315. (c) More, A. A.; Pathe, G. K.; Parida, K. N.;
Maksymenko, S.; Lipisa, Y. B.; Szpilman, A. M. α-N-Heteroarylation
and α-Azidation of Ketones via Enolonium Species. J. Org. Chem.
2018, 83, 2442−2447. (d) More, A. A.; Santra, S. K.; Szpilman, A. M.
Azido-Enolonium Species in C−C and C−N Bond-Forming Coupling
Reactions. Org. Lett. 2020, 22, 768−771.
(8) (a) Tang, Q.; Chen, X.; Tiwari, B.; Chi, R. Y. Addition of Indoles
to Oxyallyl Cations for Facile Access to α-Indole Carbonyl
Compounds. Org. Lett. 2012, 14, 1922−1925. (b) Vander Wal, M.
N.; Dilger, A. K.; MacMillan, D. W. C. Development of a Generic
Activation Mode: Nucleophilic α-Substitution of Ketones via Oxy-
allyl Cations. Chem. Sci. 2013, 4, 3075−3079. (c) Liu, C.; Oblak, E.
Z.; Vander Wal, M. N.; Dilger, A. K.; Almstead, D. K.; MacMillan, D.
W. C. Oxy-Allyl Cation Catalysis: An Enantioselective Electrophilic
Activation Mode. J. Am. Chem. Soc. 2016, 138, 2134−2137.
(d) Nguyen, T. N.; Setthakarn, K.; May, J. A. Oxyallyl Cation
Capture via Electrophilic Deborylation of Organoboronates: Access to
α,α′-Substituted Cyclic Ketones. Org. Lett. 2019, 21, 7837−7840.
(e) Huang, W.-H.; Huang, G.-B.; Zhu, W.-R.; Weng, J.; Lu, G.
Transition Metal-free Synthesis of α-Aryl Ketones via Oxyallyl Cation
Capture with Arylboronic Acids. Org. Chem. Front. 2020, 7, 2480−
2485. (f) Aota, Y.; Doko, Y.; Kano, T.; Maruoka, K. Bronsted Acid-
Catalyzed Intramolecular α-Arylation of Ketones with Phenolic
Nucleophiles via Oxy-Allyl Cation Intermediates. Eur. J. Org. Chem.
2020, 2020, 1907−1911.
(9) (a) Pichette Drapeau, M.; Fabre, I.; Grimaud, L.; Ciofini, I.;
Ollevier, T.; Taillefer, M. Transition-metal-free α-Arylation of
Enolizable Aryl Ketones and Mechanistic Evidence for a Radical
Process. Angew. Chem., Int. Ed. 2015, 54, 10587−10591. (b) Pandey,
G.; Tiwari, S. K.; Budakoti, A.; Sahani, P. K. Transition-metal-free
Photoredox Intermolecular α-Arylation of Ketones. Org. Chem. Front.
2018, 5, 2610−2614.
(10) (a) Sousa e Silva, F. C.; Van, N. T.; Wengryniuk, S. E. Direct
C−H α-Arylation of Enones with ArI(O2CR)2 Reagents. J. Am. Chem.
Soc. 2020, 142, 64−69. (b) Porte, V.; Kaiser, D.; Maulide, N.
Reductive Iodonium: Teaching an Old Claisen New Tricks. Trends in
Chemistry 2020, 2 (7), 589−592.
(11) Li, J.; Bauer, A.; Di Mauro, G.; Maulide, N. α-Arylation of
Carbonyl Compounds through Oxidative C−C Bond Activation.
Angew. Chem., Int. Ed. 2019, 58, 9816−9819.
(12) Bauer, A.; Di Mauro, G.; Li, J.; Maulide, N. An α-
Cyclopropanation of Carbonyl Derivatives by Oxidative Umpolung.
Angew. Chem., Int. Ed. 2020, 59, 18208−18212.
(13) (a) Zhdankin, V. V. Hypervalent Iodine(III) Reagents in
Organic Synthesis. ARKIVOC 2009, 2009, 1−62. (b) Yoshimura, A.;
Zhdankin, V. V. Advances in Synthetic Applications of Hypervalent
Iodine Compounds. Chem. Rev. 2016, 116, 3328−3435. (c) Bauer, A.;
Maulide, N. Recent Discoveries on the Structure of Iodine(III)
Reagents and their Use in Cross-nucleophile Coupling. Chem. Sci.
2021, 12, 853−864.
(14) For a review on hypervalent iodine-mediated oxidative
rearrangements see: (a) Singh, F. V.; Wirth, T. Oxidative Rearrange-
ments with Hypervalent Iodine Reagents. Synthesis 2013, 45, 2499−
2511. Selected applications using I(III): (b) Boye, A. C.; Meyer, D.;
Ingison, C. K.; French, A. N.; Wirth, T. Novel Lactonization with
Phenonium Ion Participation Induced by Hypervalent Iodine
Reagents. Org. Lett. 2003, 5, 2157−2159. (c) Justik, M. W.; Koser,
G. F. Oxidative Rearrangements of Arylalkenes with [hydroxy-
(tosyloxy)iodo]benzene in 95% Methanol: a General, Regiospecific
Synthesis of α-Aryl ketones. Tetrahedron Lett. 2004, 45, 6159−6163.
(d) Silva, L. F., Jr Hypervalent Iodine-mediated Ring Contraction
Reactions. Molecules 2006, 11, 421−434. (e) Singh, F. V.; Rehbein, J.;
Wirth, T. Facile Oxidative Rearrangements Using Hypervalent Iodine
̀
(b) Huang, X.; Patil, M.; Fares, C.; Thiel, W.; Maulide, N. Sulfur(IV)-
Mediated Transformations: From Ylide Transfer to Metal-free
Arylation of Carbonyl Compounds. J. Am. Chem. Soc. 2013, 135,
7312−7323. (c) Zawodny, W.; Teskey, C. J.; Mishevska, M.; Völkl,
M.; Maryasin, B.; González, L.; Maulide, N. α-Functionalisation of
Ketones Through Metal-free Electrophilic Activation. Angew. Chem.,
Int. Ed. 2020, 59, 20935−20939.
(3) Koech, P. K.; Krische, M. J. Phosphine Catalyzed α-Arylation of
Enones and Enals Using Hypervalent Bismuth Reagents: Regiospe-
cific Enolate Arylation via Nucleophilic Catalysis. J. Am. Chem. Soc.
2004, 126, 5350−5351.
(4) For a review on α-functionalization of carbonyl compounds
using hypervalent iodine see: (a) Olofsson, B.; Merritt, E. A. α-
Functionalization of Carbonyl Compounds Using Hypervalent Iodine
Reagents. Synthesis 2011, 2011 (4), 517−538. Selected applications
using iodine(III) for α-arylation of carbonyl compounds: (b) Chen,
K.; Koser, G. F. Direct and Regiocontrolled Synthesis of α-Phenyl
Ketones from Silyl Enol Ethers and Diphenyliodonium Fluoride. J.
Org. Chem. 1991, 56, 5764−5767. (c) Aggarwal, V. K.; Olofsson, B.
Enantioselective α-Arylation of Cyclohexanones with Diaryl Iodo-
nium salts: Application to the Synthesis of (−)-Epibatidine. Angew.
Chem., Int. Ed. 2005, 44, 5516−5519. (d) Norrby, P.-O.; Petersen, T.
B.; Bielawski, M.; Olofsson, B. α-Arylation by Rearrangement: On the
Reaction of Enolates with Diaryliodonium Salts. Chem. - Eur. J. 2010,
16, 8251−8254. (e) Jia, Z.; Gálvez, E.; Sebastián, R. M.; Pleixats, R.;
́
́
Alvarez-Larena, A.; Martin, E.; Vallribera, A.; Shafir, A. An Alternative
to the Classical α-Arylation: The Transfer of an Intact 2-Iodoaryl
from ArI(O2CCF3)2. Angew. Chem., Int. Ed. 2014, 53, 11298−11301.
(f) Wu, Y.; Arenas, I.; Broomfield, L. M.; Martin, E.; Shafir, A.
Hypervalent Activation as a Key Step for Dehydrogenative ortho C−
C Coupling of Iodoarenes. Chem. - Eur. J. 2015, 21, 18779−18784.
(g) Huang, X.; Zhang, Y.; Zhang, C.; Zhang, L.; Xu, Y.; Kong, L.;
Wang, Z.-X.; Peng, Bo The ortho Difluoroalkylation of Aryliodanes
with Enol Silyl Ethers: Rearrangement Enabled by a Fluorine Effect.
Angew. Chem., Int. Ed. 2019, 58, 5956−5961. (h) Hyatt, I. F. D.;
Dave, L.; David, N.; Kaur, K.; Medard, M.; Mowdawalla, C.
Hypervalent Iodine Reactions Utilized in Carbon-carbon Bond
Formations. Org. Biomol. Chem. 2019, 17, 7822−7848.
(5) (a) Ramtohul, Y. K.; Chartrand, A. Direct C-Arylation of β-
Enamino Esters and Ketones with Arynes. Org. Lett. 2007, 9, 1029−
1032. (b) Mohanan, K.; Coquerel, Y.; Rodriguez, J. Transition-Metal-
free α-Arylation of β-Keto Amides via an Interrupted Insertion
Reaction of Arynes. Org. Lett. 2012, 14, 4686−4689. (c) Chen, Q.;
Zhang, C.; Chen, L.; Wen, C.; Du, Z.; Chen, H.; Zhang, H. α-
Monoarylation and Tandem Arylation-insertion of Malonates with
Arynes. Tetrahedron Lett. 2015, 56, 2094−2097. (d) Talero, A. G.;
Martins, B. S.; Burtoloso, A. C. B. Coupling of Sulfoxonium Ylides
with Arynes: A Direct Synthesis of Prochiral Aryl Ketosulfoxonium
Ylides and Its Application in the Preparation of α-Aryl Ketones. Org.
Lett. 2018, 20, 7206−7211. (e) Picazo, E.; Anthony, S. M.; Giroud,
M.; Simon, A.; Miller, M. A.; Houk, K. N.; Garg, N. K. Arynes and
Cyclic Alkynes as Synthetic Building Blocks for Stereodefined
Quaternary Centers. J. Am. Chem. Soc. 2018, 140, 7605−7610.
(6) (a) Miyoshi, T.; Miyakawa, T.; Ueda, M.; Miyata, O.
Nucleophilic α-Arylation and α-Alkylation of Ketones by Polarity
Inversion of N-Alkoxyenamines: Entry to the Umpolung Reaction at
the α-Carbon Position of Carbonyl Compounds. Angew. Chem., Int.
Ed. 2011, 50, 928−931. (b) Miyoshi, T.; Sato, S.; Tanaka, H.;
Hasegawa, C.; Ueda, M.; Miyata, O. One-pot Method for α-
Phenylation of Ketones Using Isoxazolidine and Triphenylaluminum.
Tetrahedron Lett. 2012, 53, 4188−4191. (c) Takeda, N.; Furuishi, M.;
Nishijima, Y.; Futaki, E.; Ueda, M.; Shinada, T.; Miyata, O. Chiral
Isoxazolidine-mediated Stereoselective Umpolung α-Phenylation of
Methyl Ketones. Org. Biomol. Chem. 2018, 16, 8940−8943.
2097
https://dx.doi.org/10.1021/acs.orglett.1c00251
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pubs.acs.org/OrgLett
Letter
Reagents. ChemistryOpen 2012, 1, 245−250. (f) Malmedy, F.; Wirth,
T. Stereoselective Ketone Rearrangements with Hypervalent Iodine
Reagents. Chem. - Eur. J. 2016, 22, 16072−16077. (g) Murai, K.;
Kobayashi, T.; Miyoshi, M.; Fujioka, H. Oxidative Rearrangement of
Secondary Amines Using Hypervalent Iodine(III) Reagent. Org. Lett.
2018, 20, 2333−2337. (h) Sun, Y.; Huang, X.; Li, X.; Luo, F.; Zhang,
L.; Chen, M.; Zheng, S.; Peng, B. Mild Ring Contractions of
Cyclobutanols to Cyclopropyl Ketones via Hypervalent Iodine
Oxidation. Adv. Synth. Catal. 2018, 360, 1082−1087.
(15) Arava, S.; Santra, S. K.; Pathe, G. K.; Kapanaiah, R.; Szpilman,
A. M. Direct Umpolung Morita−Baylis−Hillman like α-Functional-
ization of Enones via Enolonium Species. Angew. Chem., Int. Ed. 2020,
59, 15171−15175.
(16) Yield determined by NMR analysis, using mesitylene as an
internal standard. The products were not isolated due to a tendency
towards polymerization, in particular, for 7o, and comparable
volatility. On the basis of literature precedent, we do not anticipate
this to be a general problem for alkyl-substituted enones: Harada, S.;
Matsuda, D.; Morikawa, T.; Nishida, A. Direct Synthesis of Enones by
Visible-Light-Promoted Oxygenation of Trisubstituted Ole-fins Using
Molecular Oxygen. Synlett 2020, 31, 1372−1377.
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