Sulfoxide Reduction/C(sp3)-S Metathesis Cascade in Ionic Liquid

Article abstract of DOI:10.1021/acs.orglett.0c02089

A sulfoxide reduction/C-S bond metathesis cascade between sulfoxides and alkyl bromides has been developed to access high-value sulfides without the use of any catalysts or bases. In this cascade, classical Kornblum oxidation is employed to reduce sulfoxides with alkyl bromides in ionic liquid. This protocol features high functional tolerance, mild conditions, promising scalability, and sustainable solvents.

Full text of DOI:10.1021/acs.orglett.0c02089

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Letter
Sulfoxide Reduction/C(sp3)−S Metathesis Cascade in Ionic Liquid
Chenjing Liu,† Dengfeng Chen,† Yuanyuan Fu, Fei Wang, Jinyue Luo,* and Shenlin Huang*
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ABSTRACT: A sulfoxide reduction/C−S bond metathesis
cascade between sulfoxides and alkyl bromides has been developed
to access high-value sulfides without the use of any catalysts or
bases. In this cascade, classical Kornblum oxidation is employed to
reduce sulfoxides with alkyl bromides in ionic liquid. This protocol
features high functional tolerance, mild conditions, promising
scalability, and sustainable solvents.
ryl sulfoxides and sulfides are important organosulfur
demonstrated by Pan and co-workers, in which hemin was
used as the catalyst (Scheme 1C).19 Very recently, they also
extended this formal metathesis to the reaction of allylic
sulfides with trifluorodiazoethane.20
A
compounds that are widely found in pharmaceuticals,1−3
materials,4,5 ligands,6−8 and natural products.9 Accordingly,
numerous C−S cross-coupling methods have been reported to
build these organosulfur compounds.10−14 In contrast, C−S
bond metathesis has only recently become a focus of increasing
research efforts, as a complementary methodology to tradi-
tional C−S cross-couplings. In 2017, the Morandi group15 first
introduced the concept, C−S bond metathesis,16 and reported
an elegant palladium-catalyzed C(sp2)−S bond metathesis
(Scheme 1A). Later, the same group upgraded the aryl sulfide
Kornblum oxidation, which was reported in 1957, is a well-
known method to convert primary alkyl halides into
aldehydes.21,22 More importantly, it has been extensively
adapted in a variety of cascade reactions described by Wu
and co-workers.23−38 In these reactions, the oxidation product
aldehyde was used for subsequent transformations with
dimethyl sulfide as a byproduct. Inspired by these studies,
we envisioned that aromatic alkyl sulfoxides 1 could be
reduced in the Kornblum oxidation process to provide
aromatic alkyl sulfides 4 (Scheme 1D). Unlike previous
examples, these sulfides would be employed for the subsequent
C(sp3)−S bond metathesis, generating aryl sulfides 3. This
cascade transformation represents the reduction of sulfoxides
with alkyl bromides and catalyst-free, base-free C−S bond
metathesis, which would be especially useful for the late-stage
functionalization.39
Scheme 1. Context of the Work
To explore the viability of this cascade, we focused on the
model reaction of sulfoxide 1a with methyl 2-bromoacetate 2a.
Initial evaluation of organic solvents, such as N,N-dimethyl-
formamide (DMF), N,N-dimethylacetamide (DMA), and
2,2,2-trifluoroethanol (TFE), led to aryl sulfide 3aa in
moderate yields (see Table 1, entries 1−3). Different ionic
liquids were then examined. All acidic ionic liquids used as the
solvent gave lower reaction yields (Table 1, entries 4−6).
Changing the solvent to aprotic ionic liquid [Bmim][OTf]
improved the yield to 62% (Table 1, entry 7). We reasoned
that the ionic liquid, which is capable of ionic or charge−
metathesis with a nickel catalytic system.17 In 2019, Koenigs et
al. disclosed an iron(II) phthalocyanine (FePc)-catalyzed
formal C(sp3)−S bond metathesis of aryl sulfides with in-
situ-generated diazoalkanes in the presence of stoichiometric
sodium nitrite (Scheme 1B).18 Another example of formal
C(sp3)−S bond metathesis of aromatic isopropyl sulfides was
Received: June 24, 2020
https://dx.doi.org/10.1021/acs.orglett.0c02089
© XXXX American Chemical Society
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A

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a b
,
Table 1. Optimization of the Reaction Conditions of
Sulfoxides
Scheme 2. Scope of Sulfoxides
a
b
2a (y
equiv)
temperature, T
(°C)
yield
entry
solvent (x M)
DMF (4)
DMA (4)
(%)
1
2
8
8
8
8
8
8
8
8
8
8
8
8
8
2
4
6
100
100
100
100
100
100
100
90
110
100
100
100
100
100
100
100
47
46
50
23
7
48
62
32
48
19
51
60
77
44
67
76
3
4
5
6
7
8
9
10
11
12
13
14
15
16
TFE (4)
[Hmim][OTf] (4)
[Hmim][HSO4] (4)
[Bsmim][OTf] (4)
[Bmim][OTf] (4)
[Bmim][OTf] (4)
[Bmim][OTf] (4)
[Bmim][OTf] (0.1)
[Bmim][OTf] (0.5)
[Bmim][OTf] (1)
[Bmim][OTf] (2)
[Bmim][OTf] (2)
[Bmim][OTf] (2)
[Bmim][OTf] (2)
a
Reaction conditions: 1a (0.3 mmol), 2a (y equiv) in [Bmim][OTf]
b
a
(x M) at 100 °C for 48 h. HPLC yield with 1,3-dinitrobenzene as the
internal standard.
Reaction conditions: 1 (0.3 mmol), 2a (1.8 mmol) in [Bmim][OTf]
b
(2 M) at 100 °C for 48 h. Isolated yield. cIn the presence of 1.5 equiv
1,1-diphenylethylene. dIn the presence of 3 equiv 1,1-diphenyl-
ethylene.
charge interactions,40 can not only affect the stability of the
ionic intermediates but also increase the nucleophilicity of the
sulfoxide oxygen in this reaction. Lowering or raising the
reaction temperature only resulted in lower reaction efficiency
(Table 1, entries 8 and 9). Further investigation indicated that
the concentration played a pivotal role in the performance of
this reaction (Table 1, entries 10−13). We speculated that a
higher concentration is required to increase the reaction rate
for the first step, SN2 displacement of the bromide with a weak
nucleophilic oxygen in sulfoxide 1a. The optimal concentration
was proved to be 2 M, affording the desired sulfide 3aa in 77%
yield (Table 1, entry 13). Finally, we tried to decrease the
amount of methyl 2-bromoacetate 2a (Table 1, entries 14−
16), suggesting that the reaction efficiency could be maintained
with 6 equiv of 2a (Table 1, entry 16).
With the optimized conditions in hand, we evaluated a range
of aryl sulfoxides under the standard conditions. As shown in
Scheme 2, 3aa was isolated in 74% yield. Alkyl-substituted
phenyl sulfoxides afforded their corresponding sulfide products
(3ba−3fa) in good yields. Besides alkyl substituents, a series of
substituents with either electron-donating or electron-with-
drawing groups, such as −OMe (3ga), −F (3ha), −Cl (3ia
and 3ma), −Br (3ja−3la), −CHO (3na), −CO2Et (3oa),
−COMe (3pa), and −CN (3qa), could be tolerated very well,
demonstrating the broad substrate scope of this trans-
formation. It is noteworthy that ortho-, meta-, and para-
substituents had no effect on the yields (3ca−3ea and 3ja−
3la), except in the case of 2,6-disubstituted aryl derivatives
(3fa and 3ma) with strong steric hindrance. In addition,
naphthyl and benzothiophene groups were amenable to this
cascade, providing 3ra and 3sa in 89% and 66% yield,
respectively. Moreover, a derivative of sulindac, which is a
nonsteroidal anti-inflammatory and anticancer drug,41−43 led
to the desired product 3ta in 66% yield, in which 1,1-
diphenylethylene was used to suppress the undesired
bromination byproduct. Remarkably, the R1 group can be
changed from methyl to other alkyl groups (ethyl, benzyl, and
allyl), as illustrated by sulfoxides 6−8. Unfortunately, alkyl
sulfoxides are proved to be challenging for this cascade under
our conditions and only dimethyl 2,2′-thiodiacetate can be
isolated.
Next, various alkyl bromides were tested for this trans-
formation (Scheme 3). Primary α-bromoesters (2a−2c)
a b
,
Scheme 3. Scope of Bromides
a
Reaction conditions: 1j (0.3 mmol), 2 (1.8 mmol) in [Bmim][OTf]
b
(2 M) at 100 °C for 48 h. Isolated yield.
B
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performed well using the standard protocol (3ja−3jc, 45%−
63% yield). In addition, secondary α-bromoester 2d was also
found to be a suitable reaction partner, providing 3jd, albeit in
20% yield. Ethyl 4-bromobutanoate 2e was also a competent
substrate, affording 3je in 38% yield. Notably, alkyl bromides
with different functional groups, including 2-bromoacetic acid
and 2-bromoacetonitrile, as well as benzyl bromide (2f−2h),
all allowed the sulfoxide reduction/C−S bond metathesis
cascade to proceed smoothly to deliver 3jf−3jh in yields of
57%−79%.
of 1j gave product 3jg in 72% yield, and 8.0 mmol of 4a led to
sulfide 3ag in 96% yield (Scheme 5). In addition, ionic liquid
could be recycled without a notable decrease in the yield (see
the Supporting Information).
Scheme 5. Gram-Scale Reaction
Encouraged by the above results and postulating that the
cascade initiates by a sulfoxide reduction to a sulfide
intermediate, we wondered if the sulfide could allow C−S
bond metathesis to proceed under our conditions. Indeed,
methyl phenyl sulfide (4a) underwent the metathesis
efficiently with 2a in [Bmim][OTf], providing 3aa in 85%
yield (Scheme 4). Gratifyingly, a slightly higher yield of 3aa
According to the above results, a plausible mechanism is
depicted in Scheme 6. First, the alkyl bromide 2a undergoes a
a b
,
Scheme 4. Scope of Sulfide Metathesis
Scheme 6. Proposed Mechanism
SN2 reaction with nucleophilic O atom of the sulfoxide 7 to
generate alkoxysulfonium salt A, and subsequent deprotona-
tion provides the corresponding alkoxysulfonium ylide B. This
alkoxysulfonium ylide B can undergo a [2,3]-sigmatropic shift
to afford sulfide 10, along with methyl glyoxylate 5, which was
detected by GC-MS. Sulfide 10 can react with alkyl bromide
2a to form sulfonium salt C. Finally, a nucleophilic substitution
of C with the Br− ion leads to the metathesis product 3aa and
benzyl bromide, which was confirmed by GC-MS.
In summary, we have developed a sulfoxide reduction/C−S
bond metathesis cascade between sulfoxides and alkyl
bromides without the use of any catalysts or bases. This
cascade is proven to start with the classical Kornblum
oxidation, which is employed to reduce sulfoxides in ionic
liquid. Moreover, this methodology demonstrates high func-
tional tolerance, mild conditions, and sustainable solvents.
Thus, it would be especially useful for the late-stage
functionalization of sulfoxide and sulfide derivatives.
a
Reaction conditions: 4 (0.3 mmol), 2a or 2g (1.8 mmol) in TFE (1
b
M) at 100 °C for 24 h. Isolated yield. c[Bmim][OTf] as the solvent.
was isolated, when the reaction was conducted in TFE.
Therefore, we explored the scope of sulfides amenable to this
C−S bond metathesis (Scheme 4). The metathesis tolerates a
range of functionalities, including ethers (3ga), chlorides (3ia),
bromides (3ja−3la), ketones (3pa), carboxylic acids (3ua),
nitroarenes (3va), naphthalenes (3ra), benzothiophenes (3sa),
and nitriles (3ag). Furthermore, complex thioethers, such as
photoinitiator derivative 3wa,44 alkyl sulfide 3xg derived from
trans-androsterone, and sulindac sulfide lactone45 3ya, could
be also prepared under the metathesis conditions. Remarkably,
R1 substituent in sulfide 4 could be varied from methyl to ethyl
(9), benzyl (10), and allyl (11), leading to the desired 3aa in
high yield.
ASSOCIATED CONTENT
* Supporting Information
■
sı
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c02089.
Experimental procedures and characterization data
(PDF)
AUTHOR INFORMATION
Corresponding Authors
■
To further highlight the practicality of these reactions, we
performed two gram-scale reactions. To our delight, 5.0 mmol
Jinyue Luo − Jiangsu Provincial Key Lab for the Chemistry and
Utilization of Agro-Forest Biomass, Jiangsu Co-Innovation
C
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Center of Efficient Processing and Utilization of Forest
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motifs for drug discovery: A critical review. Eur. J. Med. Chem. 2019,
162, 679−734.
Resources, Jiangsu Key Lab of Biomass-Based Green Fuels and
Chemicals, College of Chemical Engineering, Nanjing Forestry
University, Nanjing 210037, People’s Republic of China;
Email: luojinyue@njfu.com.cn
Shenlin Huang − Jiangsu Provincial Key Lab for the Chemistry
and Utilization of Agro-Forest Biomass, Jiangsu Co-Innovation
Center of Efficient Processing and Utilization of Forest
Resources, Jiangsu Key Lab of Biomass-Based Green Fuels and
Chemicals, College of Chemical Engineering, Nanjing Forestry
University, Nanjing 210037, People’s Republic of China;
orcid.org/0000-0001-7322-6981; Email: shuang@
njfu.edu.cn
(2) Ilardi, E. A.; Vitaku, E.; Njardarson, J. T. Data-mining for sulfur
and fluorine: an evaluation of pharmaceuticals to reveal opportunities
for drug design and discovery. J. Med. Chem. 2014, 57, 2832−2842.
(3) Liu, L.; Stelmach, J. E.; Natarajan, S. R.; Chen, M.-H.; Singh, S.
B.; Schwartz, C. D.; Fitzgerald, C. E.; O’Keefe, S. J.; Zaller, D. M.;
Schmatz, D. M.; Doherty, J. B. SAR of 3,4-dihydropyrido[3,2-
d]pyrimidone p38 inhibitors. Bioorg. Med. Chem. Lett. 2003, 13,
3979−3982.
(4) Boyd, D. A. Sulfur and Its Role In Modern Materials Science.
Angew. Chem., Int. Ed. 2016, 55, 15486−15502.
(5) Rosenman, A.; Markevich, E.; Salitra, G.; Aurbach, D.; Garsuch,
A.; Chesneau, F. F. Review on Li-Sulfur Battery Systems: an Integral
Perspective. Adv. Energy Mater. 2015, 5, 1500212.
(6) Otocka, S.; Kwiatkowska, M.; Madalinska, L.; Kielbasinski, P.
Chiral Organosulfur Ligands/Catalysts with a Stereogenic Sulfur
Atom: Applications in Asymmetric Synthesis. Chem. Rev. 2017, 117,
4147−4181.
Authors
Chenjing Liu − Jiangsu Provincial Key Lab for the Chemistry
and Utilization of Agro-Forest Biomass, Jiangsu Co-Innovation
Center of Efficient Processing and Utilization of Forest
Resources, Jiangsu Key Lab of Biomass-Based Green Fuels and
Chemicals, College of Chemical Engineering, Nanjing Forestry
University, Nanjing 210037, People’s Republic of China
Dengfeng Chen − Jiangsu Provincial Key Lab for the Chemistry
and Utilization of Agro-Forest Biomass, Jiangsu Co-Innovation
Center of Efficient Processing and Utilization of Forest
Resources, Jiangsu Key Lab of Biomass-Based Green Fuels and
Chemicals, College of Chemical Engineering, Nanjing Forestry
University, Nanjing 210037, People’s Republic of China
Yuanyuan Fu − Jiangsu Provincial Key Lab for the Chemistry
and Utilization of Agro-Forest Biomass, Jiangsu Co-Innovation
Center of Efficient Processing and Utilization of Forest
Resources, Jiangsu Key Lab of Biomass-Based Green Fuels and
Chemicals, College of Chemical Engineering, Nanjing Forestry
University, Nanjing 210037, People’s Republic of China
Fei Wang − Jiangsu Provincial Key Lab for the Chemistry and
Utilization of Agro-Forest Biomass, Jiangsu Co-Innovation
Center of Efficient Processing and Utilization of Forest
Resources, Jiangsu Key Lab of Biomass-Based Green Fuels and
Chemicals, College of Chemical Engineering, Nanjing Forestry
University, Nanjing 210037, People’s Republic of China;
orcid.org/0000-0001-6428-5111
́
́
(7) Gomez Arrayas, R.; Carretero, J. C. Chiral thioether-based
catalysts in asymmetric synthesis: recent advances. Chem. Commun.
2011, 47, 2207−2211.
(8) Mellah, M.; Voituriez, A.; Schulz, E. Chiral sulfur ligands for
asymmetric catalysis. Chem. Rev. 2007, 107, 5133−5209.
(9) Dunbar, K. L.; Scharf, D. H.; Litomska, A.; Hertweck, C.
Enzymatic Carbon-Sulfur Bond Formation in Natural Product
Biosynthesis. Chem. Rev. 2017, 117, 5521−5577.
(10) Uyeda, C.; Tan, Y.; Fu, G. C.; Peters, J. C. A new family of
nucleophiles for photoinduced, copper-catalyzed cross-couplings via
single-electron transfer: reactions of thiols with aryl halides under
mild conditions (0 °C). J. Am. Chem. Soc. 2013, 135, 9548−9552.
(11) Beletskaya, I. P.; Ananikov, V. P. Transition-metal-catalyzed
C−S, C−Se, and C−Te bond formation via cross-coupling and atom-
economic addition reactions. Chem. Rev. 2011, 111, 1596−1636.
(12) Alvaro, E.; Hartwig, J. F. Resting state and elementary steps of
the coupling of aryl halides with thiols catalyzed by alkylbisphosphine
complexes of palladium. J. Am. Chem. Soc. 2009, 131, 7858−7868.
́
(13) Fernandez-Rodríguez, M. A.; Shen, Q.; Hartwig, J. F. A general
and long-lived catalyst for the palladium-catalyzed coupling of aryl
halides with thiols. J. Am. Chem. Soc. 2006, 128, 2180−2181.
(14) Kwong, F. Y.; Buchwald, S. L. A general, efficient, and
inexpensive catalyst system for the coupling of aryl iodides and thiols.
Org. Lett. 2002, 4, 3517−3520.
(15) Lian, Z.; Bhawal, B. N.; Yu, P.; Morandi, B. Palladium-catalyzed
carbon-sulfur or carbon-phosphorus bond metathesis by reversible
arylation. Science 2017, 356, 1059−1063.
(16) Bhawal, B. N.; Morandi, B. Catalytic Isofunctional Reactions-
Expanding the Repertoire of Shuttle and Metathesis Reactions. Angew.
Chem., Int. Ed. 2019, 58, 10074−10103.
(17) Delcaillau, T.; Bismuto, A.; Lian, Z.; Morandi, B. Nickel-
Catalyzed Inter- and Intramolecular Aryl Thioether Metathesis by
Reversible Arylation. Angew. Chem., Int. Ed. 2020, 59, 2110−2114.
(18) Empel, C.; Hock, K. J.; Koenigs, R. M. Dealkylative intercepted
rearrangement reactions of sulfur ylides. Chem. Commun. 2019, 55,
338−341.
(19) Yan, X.; Li, C.; Xu, X.; He, Q.; Zhao, X.; Pan, Y. Sulfonium
ylide formation and subsequent C−S bond cleavage of aromatic
isopropyl sulfide catalyzed by hemin in aqueous solvent. Tetrahedron
2019, 75, 3081−3087.
(20) Yan, X.; Li, C.; Xu, X.; Zhao, X.; Pan, Y. Hemin Catalyzed
Dealkylative Intercepted [2,3]-Sigmatropic Rearrangement Reactions
of Sulfonium Ylide with 2, 2, 2-Trifluorodiazoethane. Adv. Synth.
Catal. 2020, 362, 2005−2011.
(21) Kornblum, N.; Powers, J. W.; Anderson, G. J.; Jones, W. J.;
Larson, H. O.; Levand, O.; Weaver, W. M. A New and Selective
Method of Oxidation. J. Am. Chem. Soc. 1957, 79, 6562−6562.
(22) Kornblum, N.; Jones, W. J.; Anderson, G. J. A New and
Selective Method of Oxidation. The Conversion of Alkyl Halides and
Alkyl Tosylates to Aldehydes. J. Am. Chem. Soc. 1959, 81, 4113−4114.
Complete contact information is available at:
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Author Contributions
†These authors contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support provided by the Natural Science Foundation
of China (No. 21502094), and the Natural Science Foundation
of the Jiangsu Higher Education Institutions of China (No.
17KJA220003) is warmly acknowledged. We also grateful for
support by the advanced analysis and testing center of Nanjing
Forestry University. C.D. thanks the Doctorate Fellowship
Foundation of Nanjing Forestry University and Postgraduate
Research & Practice Innovation Program of Jiangsu Province.
REFERENCES
■
(1) Zhao, C.; Rakesh, K. P.; Ravidar, L.; Fang, W.-Y.; Qin, H.-L.
Pharmaceutical and medicinal significance of sulfur (SVI)-Containing
D
https://dx.doi.org/10.1021/acs.orglett.0c02089
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
(23) Geng, X.; Wang, C.; Huang, C.; Bao, Y.; Zhao, P.; Zhou, Y.;
Wu, Y.-D.; Feng, L.-L.; Wu, A.-X. Employing TosMIC as a C1N1
″Two-Atom Synthon″ in Imidazole Synthesis by Neighboring Group
Assistance Strategy. Org. Lett. 2020, 22, 140−144.
(41) Brogden, R. N.; Heel, R. C.; Speight, T. M.; Avery, G. S.
Sulindac: A Review of its Pharmacological Properties and Therapeutic
Efficacy in Rheumatic Diseases. Drugs 1978, 16, 97−114.
(42) Giardiello, F. M.; Hamilton, S. R.; Krush, A. J.; Piantadosi, S.;
Hylind, L. M.; Celano, P.; Booker, S. V.; Robinson, C. R.; Offerhaus,
G. J. A. Treatment of Colonic and Rectal Adenomas with Sulindac in
Familial Adenomatous Polyposis. N. Engl. J. Med. 1993, 328, 1313−
1316.
(43) Takayama, T.; Nagashima, H.; Maeda, M.; Nojiri, S.; Hirayama,
M.; Nakano, Y.; Takahashi, Y.; Sato, Y.; Sekikawa, H.; Mori, M.;
Sonoda, T.; Kimura, T.; Kato, J.; Niitsu, Y. Randomized Double-Blind
Trial of Sulindac and Etodolac to Eradicate Aberrant Crypt Foci and
to Prevent Sporadic Colorectal Polyps. Clin. Cancer Res. 2011, 17,
3803−3811.
(44) Buback, M.; Kuelpmann, A. A Suitable Photoinitiator for
Pulsed Laser-Induced Free-Radical Polymerization. Macromol. Chem.
Phys. 2003, 204, 632−637.
(45) Halder, S.; Satyam, A. Accidental discovery of a ‘longer-range’
vinylogous Pummerer-type lactonization: formation of sulindac
sulfide lactone from sulindac. Tetrahedron Lett. 2011, 52, 1179−1182.
(24) Wang, C.; Geng, X.; Zhao, P.; Zhou, Y.; Wu, Y.-D.; Wu, A.-X.
Employing thiocyanate salts as a nitrogen source via C≡N bond
cleavage: divergent synthesis of α-ketoamides and 2-acyloxazoles. Org.
Chem. Front. 2019, 6, 2534−2538.
(25) Geng, X.; Wang, C.; Zhao, P.; Zhou, Y.; Wu, Y.-D.; Wu, A- X.
Iodine-Promoted N−H/α,β-C(sp3)-Trifunctionalization of -Proline:
L
Access to 3,4-Dihydrobenzo[b][1,7]naphthyridines via Consecutive
Decarboxylation/Ring Opening/Dicyclization. Org. Lett. 2019, 21,
4939−4943.
(26) Geng, X.; Wang, C.; Huang, C.; Zhao, P.; Zhou, Y.; Wu, Y.-D.;
Wu, A.-X. I2-Promoted Multicomponent Dicyclization and Ring-
Opening Sequences: Direct Synthesis of Benzo[e][1,4]diazepin-3-
ones via Dual C-O Bond Cleavage. Org. Lett. 2019, 21, 7504−7508.
(27) Geng, X.; Wu, X.; Wang, C.; Zhao, P.; Zhou, Y.; Sun, X.; Wang,
L.-J.; Guan, W.-J.; Wu, Y.-D.; Wu, A.-X. NaHS·nH2O -induced
umpolung: the synthesis of 2-acyl-3-aminoindoles from aryl methyl
ketones and 2-aminobenzonitriles. Chem. Commun. 2018, 54, 12730−
12733.
(28) Zhang, J.; Wu, X.; Gao, Q.; Geng, X.; Zhao, P.; Wu, Y.-D.; Wu,
A.-X. Diamination/Oxidative Cross-Coupling/Bicyclization of Ani-
lines and Methyl Ketones: Direct I2-Promoted Synthesis of 1,2-Fused
Oxindoles. Org. Lett. 2017, 19, 408−411.
(29) Zhang, J.; Gao, Q.; Wu, X.; Geng, X.; Wu, Y.-D.; Wu, A. Dual
Roles of Methyl Ketones in Radziszewski-Type Reaction: Formal [2 +
1 + 1 + 1] Synthesis of 1,2,5-Trisubstituted Imidazoles. Org. Lett.
2016, 18, 1686−1689.
(30) Xiang, J.-C.; Cheng, Y.; Wang, M.; Wu, Y.-D.; Wu, A.-X. Direct
Construction of 4-Hydroxybenzils via Para-Selective C−C Bond
Coupling of Phenols and Aryl Methyl Ketones. Org. Lett. 2016, 18,
4360−4363.
(31) Wu, Y.-D.; Geng, X.; Gao, Q.; Zhang, J.; Wu, X.; Wu, A.-X.
Iodine-promoted sequential dual oxidative Csp3−H amination/Csp3
−
H iodination reactions: efficient synthesis of 1-iodoimidazo[1,5-
a]pyridines. Org. Chem. Front. 2016, 3, 1430−1434.
(32) Gao, Q.; Zhang, J.; Wu, X.; Liu, S.; Wu, A. Direct regioselective
oxidative cross-coupling of indoles with methyl ketones: a novel route
to C3-dicarbonylation of indoles. Org. Lett. 2015, 17, 134−137.
(33) Gao, Q.; Liu, S.; Wu, X.; Zhang, J.; Wu, A. Coproduct
Promoted Povarov Reaction: Synthesis of Substituted Quinolines
from Methyl Ketones, Arylamines, and α-Ketoesters. J. Org. Chem.
2015, 80, 5984−5991.
(34) Gao, Q.; Liu, S.; Wu, X.; Zhang, J.; Wu, A. Direct Annulation of
Hydrazides to 1,3,4-Oxadiazoles via Oxidative C(CO)−C(Methyl)
Bond Cleavage of Methyl Ketones. Org. Lett. 2015, 17, 2960−2963.
(35) Wu, X.; Gao, Q.; Liu, S.; Wu, A. I2-catalyzed oxidative cross-
coupling of methyl ketones and benzamidines hydrochloride: a facile
access to α-ketoimides. Org. Lett. 2014, 16, 2888−2891.
(36) Gao, Q.; Wu, X.; Liu, S.; Wu, A. I2-promoted selective oxidative
cross-coupling/annulation of 2-naphthols with methyl ketones: a
strategy to build naphtho[2,1-b]furan-1(2H)-ones with a quaternary
center. Org. Lett. 2014, 16, 1732−1735.
(37) Gao, Q.; Liu, S.; Wu, X.; Wu, A. Povarov-type reaction using
methyl as new input: direct synthesis of substituted quinolines by I2-
mediated formal [3 + 2 + 1] cycloaddition. Org. Lett. 2014, 16, 4582−
4585.
(38) Gao, Q.; Wu, X.; Jia, F.; Liu, M.; Zhu, Y.; Cai, Q.; Wu, A.
Design and synthesis of 2-acylbenzothiazoles via in situ cross-trapping
strategy from benzothiazoles with aryl ketones. J. Org. Chem. 2013, 78,
2792−2797.
(39) Jadhav, P. D.; Shen, J.; Sammynaiken, R.; Reaney, M. J. T. Site
Covalent Modification of Methionyl Peptides for the Production of
FRET Complexes. Chem. - Eur. J. 2015, 21, 17023−17034.
(40) Martins, M. A. P.; Frizzo, C. P.; Moreira, D. N.; Zanatta, N.;
Bonacorso, H. G. Ionic Liquids in Heterocyclic Synthesis. Chem. Rev.
2008, 108, 2015−2050.
E
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