Cu-catalyzed N-3-Arylation of Hydantoins Using Diaryliodonium Salts

Article abstract of DOI:10.1021/acs.orglett.0c00642

A general Cu-catalyzed, regioselective method for the N-3-arylation of hydantoins is described. The protocol utilizes aryl(trimethoxyphenyl)iodonium tosylate as the arylating agent in the presence of triethylamine and a catalytic amount of a simple Cu-salt. The method is compatible with structurally diverse hydantoins and operates well with neutral aryl groups or aryl groups bearing weakly donating/withdrawing elements. It is also applicable for the rapid diversification of pharmaceutically relevant hydantoins.

Full text of DOI:10.1021/acs.orglett.0c00642

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Letter
Cu-catalyzed N‑3-Arylation of Hydantoins Using Diaryliodonium
Salts
Linn Neerbye Berntsen, Ainara Nova, David S. Wragg, and Alexander H. Sandtorv*
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ABSTRACT: A general Cu-catalyzed, regioselective method for the N-3-
arylation of hydantoins is described. The protocol utilizes aryl-
(trimethoxyphenyl)iodonium tosylate as the arylating agent in the presence
of triethylamine and a catalytic amount of a simple Cu-salt. The method is
compatible with structurally diverse hydantoins and operates well with
neutral aryl groups or aryl groups bearing weakly donating/withdrawing
elements. It is also applicable for the rapid diversification of pharmaceuti-
cally relevant hydantoins.
Scheme 1. Prior Work
ydantoin is a heterocyclic scaffold with numerous
1
Happlication areas.
The structure has an impressive
range of biological activities,2 likely due to its high density of
intermolecular interaction points.3 It is encountered in several
drugs, such as nilutamide, sorbinil, and nitrofurantoin, and
constitutes a key molecular component of various agro-
chemicals.4 The nucleus also has synthetic versatility,5 for
example, in the preparation of amino acids.6 Of particular
interest are N-arylated hydantoins due to their important
biological applications (Figure 1).7
The primary access point to N-arylhydantoins (and other
substituted hydantoins) is through de novo cyclization
reactions from linear precursors (Scheme 1).8 A plethora of
such transformations is known,9 and each method has
advantages and limitations. The direct functionalization of
the hydantoin nucleus offers a complementary approach where
Received: February 18, 2020
Figure 1. Some N-3-arylhydantoins with biological properties.
https://dx.doi.org/10.1021/acs.orglett.0c00642
© XXXX American Chemical Society
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A

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the substituent(s) of interest are chemo- and regioselectively
forged onto the ring itself. This scenario allows divergent
modifications of hydantoins as well as potentially quicker and
cheaper access to such structures. Direct functionalization
remains underdeveloped, perhaps due to its challenging
nature.7c,10
For example, the direct N-3-phenylation of unsubstituted
hydantoin has, to the best of our knowledge, not been
described in the literature.
observed as well as small amounts of the corresponding
N,N′-bisarylated product (3−10%). The process was also
efficient and regioselective when the excesses of phenyl-
(trimethoxyphenyl)iodonium tosylate was reduced to 1.5 or
1.1 equiv (entries 2 and 3), although the desired target was
produced in slightly reduced yield. If a small reduction in yield
is tolerable, then the process can therefore be performed with
improved atom efficiency. The scope and limitations of the
process are shown in Scheme 3.
Recently, a breakthrough was achieved by Petit, Evano, and
coworkers (Scheme 1a), who divulged a Cu-mediated N-
arylation protocol.11 The method exhibited a good reaction
scope and mostly good yields. However, it suffered from two
disadvantages: (i) the use of stoichiometric Cu and (ii) clear
structural limitations of the hydantoin starting material.
Whereas 5,5-disubstituted hydantoins were regioselectively
arylated at the N-3 position, removing one or both of the C-5
substituents led to significant competing arylation at N-1,
limiting the substrate scope. The Cu-catalyzed N-arylation of
hydantoins is largely unexplored, and only sparse and highly
specialized examples are reported in the literature (Scheme
1b).7c,12 Herein we describe a general Cu-catalyzed process for
N-3-arylation of hydantoins, a complementary method to the
current Cu-mediated protocol (Scheme 1).
Scheme 3. Scope and Limitations of the Catalytic N-3-
Arylation Process
c
Diaryliodonioum salts13 have received increasing attention
over the past decade,14 partially due to their ability to transfer
aryl groups to nucleophiles.15 Our reaction discovery process
led to the revelation that unsymmetrical iodonium salts
regioselectively arylated the N-3-position of hydantoin in the
presence of a simple copper salt and tertiary amine under mild
conditions. In contrast, phenyl iodide was an inefficient
arylating agent under Cu-catalyzed conditions and did not
successfully couple to the hydantoin nucleus.
An overview of the optimization studies is provided in
Scheme 2. The best conditions (entry 1) involved the use of
excess aryl(trimethoxyphenyl)iodonium tosylate in the pres-
ence of copper(II)nitrate sesquihydrate and triethylamine in
toluene at 70 °C for 24 h. Under these conditions, trace
amounts (<5%) of the N-1-regioisomer were typically
Scheme 2. Key Controls and Optimization Data for the
Reaction
a
b
5 mol % of catalyst employed. Reaction performed using 1 mmol of
c
diaryl iodonium salt and extended reaction time (31 h). Conditions:
Hydantoin 1a−g (0.2 mmol, 1.0 equiv), [ArI(TMP)]Tos 2a−s (0.6
mmol, 3.0 equiv), Cu(NO3)2·3/2 H2O (0.02 mmol, 0.1 equiv),
triethylamine (TEA) (0.3 mmol, 1.5 equiv), and toluene (2 mL).
Pleasingly, the N-3 arylation proceeded smoothly with
structurally diverse hydantoins, including structures lacking
substituents on C-5 or N-1.11 Aryl rings bearing neutral or
weakly electron-donating/withdrawing groups were efficiently
transferred to the N-3-position on the hydantoin ring. This
trend was also observed for disubstituted aryl rings. The
method was sensitive to iodonium salts bearing aryl groups
congested at the o-position, likely due to steric crowding
around the Cu-center in the catalytic process. The relatively
small fluoride atom was tolerated, providing the corresponding
hydantoins 3j and 3k in moderate yields. The more demanding
o-methyl group was not tolerated under our conditions, and
the coupled product 3q was not observed in the post reaction
a
1
Yield measured using mesitylene as an internal standard in the H
NMR analysis of the crude reaction mixture.
B
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mixture. The mild conditions did not cause epimerization at
the C-5-position of the hydantoin ring. The coupled chiral
hydantoin products (R)-3m and (S)-3o were obtained in good
yield with stereoretention, as indicated by polarimetric analysis.
Strongly electron-poor and electron-rich aryl groups were less
efficient substrates (3c,d, e), and N-3-arylated hydantoins 3y,
3z, and 3aa were isolated in modest yield.
These examples illustrate the potential methods for the rapid
diversification of pharmaceutically relevant agents and high-
light the advantage of direct functionalization.
Two different mechanisms involving the Cu(I)/Cu(III)
species could be envisaged for this process (Scheme 6).
Scheme 6. Two Mechanistic Proposals for the Cu-Catalyzed
N-Arylation Process
To our delight, the method was also applicable to a small
selection of cyclic imide-type structures16 (Scheme 4) such as
a
Scheme 4. N-Arylation of Other N−H Bonds
Pathway 1 corresponds to the mechanism proposed for
Ullman-type C−N bond coupling reactions using aryl
iodides.19 In this process, a Cu(I) species would deprotonate
the hydantoin prior to the oxidative addition of the iodonium
tosylate. In Pathway 2, the first step would consist of an
oxidative addition of the iodonium salt followed by the
deprotonation of hydantoin. The latter pathway has been
proposed in Cu-catalyzed arylation reactions involving diary-
liodonium salts.20 In both pathways, the final product is
formed by reductive elimination of the Cu(III) aryl amido
intermediate. The use of Cu(II) precatalyst for Cu(I)-
mediated reactions is precedented.21 Both one-electron
reduction and disproportionation mechanisms have been
proposed for the reduction of Cu.22 We believe that in the
two mechanisms TEA acts as both a Cu ligand and base,
driving the deprotonation of hydantoin. This double function
was corroborated by using a catalytic amount of TEA and NaH
as a base (see entry 4, Scheme 2). The tosylate anion may also
play an important role when coordinated to the Cu center,
assisting the intramolecular deprotonation of hydantoin at the
N-3 position, which is the most acidic.22 This could account
for the lower yield observed when using bromide or the less
basic OTf anion (see entries 5 and 14, Scheme 2).
a
Conditions: Imide 4a−d (0.2 mmol, 1.0 equiv), [ArI(TMP)]Tos 2a
(0.6 mmol, 3.0 equiv), Cu(NO3)2·3/2 H2O (0.02 mmol, 0.1 equiv),
triethylamine (TEA) (0.3 mmol, 1.5 equiv), and toluene (2 mL).
succinimide 4a and phtalamide 4b, exemplifying the usefulness
of the method in an expanded structural space. The linear
imide 4d did not produce the desired product 5d, indicating
that the method is not applicable to linear imides, likely due to
their less constrained confirmation compared with cyclic
imides. Thiohydantoin 4e did not react under our conditions.
To illustrate the practicality of the method, the well-known
antibiotic drug nitrofurantoin 617 was N-3-arylated in good
yield, providing a small library of nitrofurantoin derivatives
7a−c (Scheme 5). The racemate of the aldose reductase
inhibitor sorbinil 818 was also N-3-arylated in good yield.
Scheme 5. Regioselective N-Arylation of Pharmaceutically
Relevant Agents
a
In summary, we have reported the first general Cu-catalyzed
method for the regioselective N-3-arylation of hydantoins. The
method utilizes unsymmetrical iodonium salts, a simple Cu
salt, and triethylamine under mild conditions. The method is
robust and flexible, operates well, with weakly electron-
donating and -withdrawing groups, proceeds without epime-
rization at C-5 of hydantoin, and smoothly arylates structurally
varied hydantoins, including pharmaceutically relevant struc-
tures such as nitrofurantoin and rac-sorbinil. In-depth
mechanistic investigations are currently underway.
ASSOCIATED CONTENT
■
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c00642.
a
Conditions: hydantoin 6 or 8 (0.2 mmol, 1.0 equiv), [ArI(TMP)]-
Tos (0.6 mmol, 3.0 equiv), Cu(NO3)2·3/2H2O (0.02 mmol, 0.1
equiv), triethylamine (TEA) (0.3 mmol, 1.5 equiv), and toluene (2
mL).
Detailed experimental procedures and full spectroscopic
data for all new compounds (PDF)
C
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Accession Codes
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(4) Mizuno, T.; Kino, T.; Ito, T.; Miyata, T. Synth. Commun. 2000,
30, 1675−1688.
CCDC 1975309, 1975600, 1975603, and 1986195 contain the
supplementary crystallographic data for this paper. These data
can be obtained free of charge via www.ccdc.cam.ac.uk/
data_request/cif, or by emailing data_request@ccdc.cam.ac.
uk, or by contacting The Cambridge Crystallographic Data
Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44
1223 336033.
(5) (a) Khazaei, A.; Zolfigol, M. A.; Rostami, A. Synthesis 2004,
2959−2961. (b) Sandtorv, A. H.; Bjørsvik, H.-R. Adv. Synth. Catal.
2013, 355, 499−507. (c) Leitch, J. A.; Cook, H. P.; Bhonoah, Y.;
Frost, C. G. J. Org. Chem. 2016, 81, 10081−10087. (d) Luo, Z.; Liu,
T.; Guo, W.; Wang, Z.; Huang, J.; Zhu, Y.; Zeng, Z. Org. Process Res.
Dev. 2018, 22, 1188−1199.
(6) (a) Burton, S. G.; Dorrington, R. A. Tetrahedron: Asymmetry
2004, 15, 2737−2741. (b) May, O.; Verseck, S.; Bommarius, A.;
Drauz, K. Org. Process Res. Dev. 2002, 6, 452−457. (c) Fernandez-
Nieto, F.; Mas Rosello, J.; Lenoir, S.; Hardy, S.; Clayden, J. Org. Lett.
AUTHOR INFORMATION
Corresponding Author
■
́
2015, 17, 3838−3841. (d) Abas, H.; Mas-Rosello; Amer, M. M.;
Alexander H. Sandtorv − Department of Chemistry, University
of Oslo, N-0315 Oslo, Norway; orcid.org/0000-0003-
2480-0195; Email: a.h.sandtorv@kjemi.uio.no
Durand, D. J.; Groleau, R. R.; Fey, N.; Clayden, J. Angew. Chem., Int.
Ed. 2019, 58, 2418−2422. (e) Amer, M. M.; Abas, H.; Leonard, D. J.;
Ward, J. W.; Clayden, J. J. Org. Chem. 2019, 84, 7199−7206.
(7) For some examples, see: (a) Hamann, L. G.; Manfredi, M. C.;
Sun, C.; Krystek, S. R., Jr.; Huang, Y.; Bi, Y.; Augeri, D. J.; Wang, T.;
Zou, Y.; Betebenner, D. A.; Fura, A.; Seethala, R.; Golla, R.; Kuhns, J.
E.; Lupisella, J. A.; Darienzo, C. J.; Custer, L. L.; Price, J. L.; Johnson,
J. M.; Biller, S. A.; Zahler, R.; Ostrowski, J. Bioorg. Med. Chem. Lett.
2007, 17, 1860−1864. (b) Payen, O.; Top, S.; Vessieres, A.; Brule, E.;
Plamont, M.-A.; McGlinchey, M. J.; Muller-Bunz, H.; Jaouen, G. J.
Med. Chem. 2008, 51, 1791−1799. (c) Wang, C.; Zhao, Q.; Vargas,
M.; Jones, J. O.; White, K. L.; Shackleford, D. M.; Chen, G.; Saunders,
J.; Ng, A. C. F.; Chiu, F. C. K.; Dong, Y.; Charman, S. A.; Keiser, J.;
Vennerstrom, J. L. J. Med. Chem. 2016, 59, 10705−10718.
(d) Tamura, T.; Noda, H.; Joyashiki, E.; Hoshino, M.; Watanabe,
T.; Kinosaki, M.; Nishimura, Y.; Esaki, T.; Ogawa, K.; Miyake, T.;
Arai, S.; Shimizu, M.; Kitamura, H.; Sato, H.; Kawabe, Y. Nat.
Commun. 2016, 7, 13384−13398. (e) Bauman, A.; Piel, M.;
Authors
Linn Neerbye Berntsen − Department of Chemistry, University
of Oslo, N-0315 Oslo, Norway
Ainara Nova − Hylleraas Centre for Quantum Molecular
Sciences, Department of Chemistry, University of Oslo, N-0315
Oslo, Norway; orcid.org/0000-0003-3368-7702
David S. Wragg − Department of Chemistry, University of Oslo,
N-0315 Oslo, Norway
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.0c00642
Notes
The authors declare no competing financial interest.
̈
Hohnemann, S.; Krauss, A.; Jansen, M.; Solbach, C.; Dannhardt,
̈
G.; Rosch, F. J. Labelled Compd. Radiopharm. 2011, 54, 645−656.
ACKNOWLEDGMENTS
(8) (a) Meusel, M.; Gutschow, M. Org. Prep. Proced. Int. 2004, 36,
̈
■
391−443. (b) Konnert, L.; Lamaty, F.; Martinez, J.; Colacino, E.
Chem. Rev. 2017, 117 (23), 13757−13809.
L.N.B. gratefully acknowledges the Department of Chemistry
at the University of Oslo for funding her Ph.D. fellowship.
Arild X. Hagen (Department of Chemistry, University of Oslo)
is acknowledged for technical assistance with the optimization
study, and Brian C. Gilmour (Oslo University Hospital,
University of Oslo) is acknowledged for technical assistance in
the preparation of diaryliodonium salts. The project has
received support from UiO: Life Science and was partially
supported by the Research Council of Norway through the
Norwegian NMR Platform, NNP (226244/F50). A.N.
acknowledges the support from the Research Council of
Norway (FRINATEK grant no. 250044 and Center of
Excellence grant no. 262695). We acknowledge the use of
the Norwegian national infrastructure for X-ray diffraction and
scattering (RECX, Research Council of Norway project
number 208896).
(9) For some recent examples, see: (a) Rajic, Z.; Zorc, B.; Raic-
Malic, S.; Ester, K.; Kralj, M.; Pavelic, K.; Balzarini, J.; De Clercq, E.;
Mintas, M. Molecules 2006, 11, 837−848. (b) Zhao, B.; Du, H.; Shi, Y.
J. Am. Chem. Soc. 2008, 130, 7220−7221. (c) Gao, M.; Yang, Y.; Wu,
Y.-D.; Deng, C.; Shu, W.-M.; Zhang, D.-X.; Cao, L.-P.; She, N.-F.;
Wu, A.-X. Org. Lett. 2010, 12, 4026−4029. (d) Bogolubsky, A. V.;
Moroz, Y. S.; Savych, O.; Pipko, S.; Konovets, A.; Platonov, M. O.;
Vasylchenko, O. V.; Hurmach, V. V.; Grygorenko, O. O. ACS Comb.
Sci. 2018, 20, 35−43. (e) Saunthwal, R. K.; Cornall, M. T.; Abrams,
R.; Ward, J. W.; Clayden, J. Chem. Sci. 2019, 10, 3408−3412.
(f) Declas, N.; Le Vaillant, F.; Waser, J. Org. Lett. 2019, 21, 524−528.
(g) Liu, S. L.; Haung, J.-Y.; Barve, I. J.; Huang, S.-C.; Sun, C.-M. ACS
Comb. Sci. 2019, 21 (4), 336−344.
(10) (a) Hugel, H. M.; Rix, C. J.; Fleck, K. Synlett 2006, 2006,
2290−2292. (b) Bigg, D.; Auvin, S.; Lanco, C.; Prevost, G.
Imidazolidine-2,4-dione Derivatives, Their Preparation and Use for
Treating Hormone-Dependent Cancer. WO 2010119194 A1, 2010.
(c) Cowley, P. M.; McGowan, M. A.; Brown, T. J.; Han, Y.; Liu, K.;
Pu, Q.; Wise, A.; Zhang, H.; Zhou, H. Novel Substituted
Imidazopyridine Compounds as Inhibitors of indoleamine 2,3-
Dioxygenase and/or Tryptophan-2,3-dioxygenase. WO 2017189386
A1, 2017. (d) Qin, X.; Fang, L.; Zhao, J.; Gou, S. Inorg. Chem. 2018,
57, 5019−5029.
REFERENCES
■
(1) Konnert, L.; Lamaty, F.; Martinez, J.; Colacino, E. Chem. Rev.
2017, 117, 13757−13809.
(2) For some examples, see: (a) Sarges, R.; Goldstein, S. W.; Welch,
W. M.; Swindell, A. C.; Siegel, T. W.; Beyer, T. A. J. Med. Chem. 1990,
33, 1859−1865. (b) Tan, L.; Maji, S.; Mattheis, C.; Zheng, M.; Chen,
Y.; Caballero-Díaz, E.; Gil, P. R.; Parak, W. J.; Greiner, A.; Agarwal, S.
Macromol. Biosci. 2012, 12, 1068−1076. (c) Su, M.; Xia, D.; Teng, P.;
Nimmagadda, A.; Zhang, C.; Odom, T.; Cao, A.; Hu, Y.; Cai, J. J.
(11) Thilmany, P.; Gerard, P.; Vanoost, A.; Deldaele, C.; Petit, L.;
Evano, G. J. Org. Chem. 2019, 84, 392−400.
(12) Preliminary communication: (a) Lopez-Alvarado, P.;
Avendano, C.; Carlos Menendez, J. Tetrahedron Lett. 1992, 33,
6875−6878. Full report: (b) Lopez-Alvarado, P.; Avendano, C.;
Menendez, J. C. J. Org. Chem. 1996, 61, 5865−5870. (c) Suresh, M.;
Ravi, S.; Sudhakar, K. Synthesis of Nilutamide and Development of C-
N Bond Formation by Reusable Green Catalyst. IN 201741010702,
2017. (d) Pierce, J. M.; Hale, J. J.; Miao, S.; Vachal, P. Substituted-
1,3,8-triazaspiro[4.5]decane-2,4-diones. WO2010147776 A1, 2010.
̇
Med. Chem. 2017, 60, 8456−8465. (d) Zesławska, E.; Kincses, A.;
Spengler, G.; Nitek, W.; Tejchman, W.; Handzlik, J. Chem. Biol. Drug
Des. 2019, 93, 844−853. (e) Cho, S.; Kim, S.-H.; Shin, D. Eur. J. Med.
Chem. 2019, 164, 517−545. (f) Fetzer, C.; Korotkov, V. S.; Sieber, S.
A. Org. Biomol. Chem. 2019, 17, 7124−7217.
(3) Mendgen, T.; Steuer, C.; Klein, C. D. J. Med. Chem. 2012, 55,
743−753.
D
https://dx.doi.org/10.1021/acs.orglett.0c00642
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
(e) Vachal, P.; Miao, S.; Pierce, J. M.; Guiadeen, D.; Colandrea, V. J.;
Wyvratt, M. J.; Salowe, S. P.; Sonatore, L. M.; Milligan, J. A.; Hajdu,
R.; Gollapudi, A.; Keohane, C. A.; Lingham, R. B.; Mandala, S. M.;
DeMartino, J. A.; Tong, X.; Wolff, M.; Steinhuebel, D.; Kieczykowski,
G. R.; Fleitz, F. J.; Chapman, K.; Athanasopoulos, J.; Adam, G.;
Akyuz, C. D.; Jena, D. K.; Lusen, J. W.; Meng, J.; Stein, B. D.; Xia, L.;
Sherer, E. C.; Hale, J. J. J. Med. Chem. 2012, 55, 2945−2959.
(13) For some reviews, see, for example: (a) Deprez, N. R.; Sanford,
M. S. Inorg. Chem. 2007, 46 (6), 1924−1935. (b) Merritt, E. A.;
Olofsson, B. Angew. Chem., Int. Ed. 2009, 48, 9052−9070.
(c) Yusubov, M. S.; Maskaev, A. V.; Zhdankin, V. V. ARKIVOC
́
2011, 2011, 370−409. (d) Aradi, K.; Toth, B. L.; Tolnai, G. L.;
́
Novak, Z. Synlett 2016, 27, 1456−1485. (e) Olofsson, B. Top. Curr.
Chem. 2015, 373, 135−166.
(14) Stuart, D. R. Chem. - Eur. J. 2017, 23, 15852−15863.
(15) For some recent examples, see: (a) Jalalian, N.; Ishikawa, E. E.;
Silva, L. F.; Olofsson, B. Org. Lett. 2011, 13, 1552−1555. (b) Phipps,
R. J.; McMurray, L.; Ritter, S.; Duong, H. A.; Gaunt, M. J. J. Am.
Chem. Soc. 2012, 134, 10773−10776. (c) Sandtorv, A. H.; Stuart, D.
R. Angew. Chem., Int. Ed. 2016, 55, 15812−15815. (d) Bhattarai, B.;
Tay, J.-H.; Nagorny, P. Chem. Commun. 2015, 51, 5398−5401.
(e) Modha, S. G.; Greaney, M. F. J. Am. Chem. Soc. 2015, 137, 1416−
́
́
́
́
́
1419. (f) Aradi, K.; Meszaros, A.; Toth, B. L.; Vincze, Z.; Novak, Z. J.
Org. Chem. 2017, 82, 11752−11764. (g) Purkait, N.; Kervefors, G.;
Linde, E.; Olofsson, B. Angew. Chem., Int. Ed. 2018, 57, 11427−
11431. (h) Wang, L.; Chen, M.; Zhang, J. Org. Chem. Front. 2019, 6,
32−35.
(16) Metal-free coupling of imides with unsymmetric iodonoum
salts is also known: Basu, S.; Sandtorv, A. H.; Stuart, D. R. Beilstein J.
Org. Chem. 2018, 14, 1034−1038.
(17) Wijma, R. A.; Huttner, A.; Koch, B. C. P.; Mouton, J. W.;
Muller, A. E. J. Antimicrob. Chemother. 2018, 73, 2916−2926.
(18) Huang, Q.; Liu, Q.; Ouyang, D. Med. Chem. 2019, 15, 3−7.
(19) Gurjar, K. K.; Sharma, R. K. ChemCatChem 2017, 9, 862−869.
(20) (a) Chen, B.; Hou, X.-L.; Li, Y.-X.; Wu, Y.-D. J. Am. Chem. Soc.
2011, 133, 7668−7671. (b) Ichiishi, N.; Canty, A. J.; Yates, B. F.;
Sanford, M. S. Organometallics 2014, 33, 5525−5534.
(21) Allen, S. E.; Walvoord, R. R.; Padilla-Salinas, R.; Kozlowski, M.
C. Chem. Rev. 2013, 113, 6234−6458.
(22) For similar acetate-assisted deprotonation reactions, see:
Davies, D. L.; Macgregor, S. A.; McMullin, C. L. Chem. Rev. 2017,
117, 8649−8709.
E
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