Mn(III)-Mediated Radical Cyclization of o-Alkenyl Aromatic Isocyanides with Boronic Acids: Access to N-Unprotected 2-Aryl-3-cyanoindoles

Article abstract of DOI:10.1021/acs.orglett.1c01979

The synthesis of N-unprotected 2-aryl-3-cyanoindoles was realized via the Mn(III)-mediated radical cascade cyclization of o-alkenyl aromatic isocyanides with boronic acids. A possible mechanism involving a sequential intermolecular radical addition, intramolecular cyclization, and cleavage of the C-C bond under mild reaction conditions is proposed. Mechanism studies show that H2O or O2 might provide the oxygen source for the elimination of benzaldehyde.

Full text of DOI:10.1021/acs.orglett.1c01979

pubs.acs.org/OrgLett
Letter
Mn(III)-Mediated Radical Cyclization of o‑Alkenyl Aromatic
Isocyanides with Boronic Acids: Access to N‑Unprotected 2‑Aryl-3-
cyanoindoles
Lu Liu, Lei Li,* Xin Wang, Ran Sun, Ming-Dong Zhou, and He Wang*
Cite This: Org. Lett. 2021, 23, 5826−5830
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ABSTRACT: The synthesis of N-unprotected 2-aryl-3-cyanoindoles was realized via the Mn(III)-mediated radical cascade
cyclization of o-alkenyl aromatic isocyanides with boronic acids. A possible mechanism involving a sequential intermolecular radical
addition, intramolecular cyclization, and cleavage of the C−C bond under mild reaction conditions is proposed. Mechanism studies
show that H2O or O2 might provide the oxygen source for the elimination of benzaldehyde.
he indole skeleton is a fundamental structure unit of
numerous biologically active molecules and natural
Notably, the radical cyclization of o-alkenyl aromatic
isocyanides is an effective method to synthesize indole
derivatives. In these transformations, o-alkenyl aromatic
isocyanides are usually the radical acceptors reacting with
heteroatom or carbon-centered radicals to generate the
corresponding imidoyl radicals, which subsequently undergo
intramolecular cyclization to eventually afford indole skeletons
(Scheme 1a). Recently, a new strategy of indirect 6-endo-trig
radical cyclization pioneered by Alabugin was developed for
six-membered aromatic compounds following a sequential 5-
exo-trig addition/3-exo-trig cyclization/ring expansion and C−
C fragmentation process (Scheme 1b).14a,b Subsequently, Yu
and co-workers and our research group achieved progress in
the direct 6-endo-trig radical cyclization strategy of o-alkenyl
aromatic isocyanides for the regiospecific synthesis of quino-
lines (Scheme 1b).14c,d Inspired by these results, we envisioned
that 2-aryl-3-cyanoindoles can be constructed from the
reaction of o-alkenyl aromatic isocyanides with arylboronic
acids as aryl radical precursors through a sequential
intermolecular radical addition, intramolecular cyclization,
and cleavage of the C−C bond under suitable conditions. As
a part of our research results on the synthesis of heterocyclic
compounds,14d,15 we reported the Mn(III)-mediated radical
cyclization reaction of o-alkenyl aromatic isocyanides with
T
products.1 Among them, 3-cyanoindole is a “privileged
structure” that has excellent pharmacological properties,
including IMPDH inhibition,2 acetyl-CoA carboxylase inhib-
ition,3 HCV NS4B inhibition,4 xanthine oxidase inhibition,5
and estrogen receptor ligands6 (Figure 1). Further, 3-
Figure 1. Representative biologically active compounds containing
the 3-cyanoindole core.
cyanoindoles have applications as precursors for various drug
syntheses.7 Owing to their fascinating and important biological
activities, various synthetic methodologies were developed over
the years to construct these scaffolds.8−10 The need to explore
various efficient methodologies toward 3-cyanoindoles under
mild conditions still remains.
Received: June 14, 2021
Published: July 29, 2021
The use of o-alkenyl aromatic isocyanides for the
construction of N-heterocycles via base-mediated domino
reactions,11 transition-metal-catalyzed annulations,12 and rad-
ical cyclization reactions13,14 has been well-established.
https://doi.org/10.1021/acs.orglett.1c01979
© 2021 American Chemical Society
Org. Lett. 2021, 23, 5826−5830
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a b
,
Scheme 1. Radical Cycloaddition of o-Alkenyl Aromatic
Scheme 2. Substrate Scope of Boronic Acid
Isocyanides
a
Reactions were carried out using 1a (0.2 mmol), 2 (0.6 mmol), and
Mn(acac)3 (0.2 mmol) in DCM (2 mL) at room temperature for 24 h
b
c
in air. Isolated yield. Reaction was performed with 4.4 mmol of 1a.
d
Reaction was performed with 4.4 mmol of 1a.
arylboronic acids to access 2-aryl-3-cyanoindoles under mild
conditions.
We next explored the scope of o-alkenyl aromatic
Initially, the reaction of (E)-2-(2-isocyanophenyl)-3-phenyl-
acrylonitrile 1a and p-tolylboronic acid 2b in the presence of
1.0 equiv of Mn(acac)3 in CH3CN in air was selected as the
model reaction. The desired product 3ab was isolated in 63%
yield along with quinoline 4ab in 12% yield (see SI, Table S1,
entry 1). Further optimization of the solvents revealed that
DCM was better suited than toluene, THF, 1,4-dioxane,
DMSO, DMF, and DCE, giving a 74% yield of 3ab with a 7%
yield of 4ab (see SI, Table S1, entries 2−8). Examination of
the effect of the reaction temperature revealed that elevating
the temperature was detrimental to the reaction efficiency (see
SI, Table S1, entry 9). Next, lowering the amount of boronic
acid to 2.5 equiv resulted in a diminished yield and selectivity
(see SI, Table S1, entry 10). A similar yield with entry 7 was
obtained increasing the amount of Mn(acac)3 to 2.0 equiv (see
SI, Table S1, entry 11). Finally, poor or no conversion was
observed when Mn(acac)3 was replaced by other catalysts such
as Mn(OAc)3·2H2O, Mn(OAc)2·4H2O, Cu(OAc)2·H2O,
CuCl2, or Co(acac)3 (see SI, Table S1, entries 12−16).
After establishing the optimized reaction conditions, the
scope and generality of boronic acid 2 in the cascade
cyclization reaction were explored (Scheme 2). It was found
isocyanides under the standard conditions (Scheme 3). The
Scheme 3. Substrate Scope of o-Alkenyl Aromatic
a b
,
Isocyanides
t
that electron-donating (Me, OMe, Bu, CHCH2), halogen
(F, Cl, Br), and electron-withdrawing substituents (CF3) at the
para-position of aryl boronic acids were all smoothly converted
into indole products (3ab−3ai) in 52%−82% yields. The use
of ortho- and meta-substituted aryl boronic acids was also
compatible with these reaction conditions, and target products
3aj−3ap were obtained in moderate to good yields. The
disubstituted substrates were fully tolerated, furnishing target
products 3aq−3au in 39%−76% yields. Notably, the thiophene
heterocycle worked well to provide a product 3av in 42% yield.
To further demonstrate the synthesized application of this
cascade cyclization reaction, the gram-scale reaction of 1a with
2b was performed under the standard reaction conditions. The
reaction proceeded smoothly to afford desired product 3ab in
64% yield along with quinoline 4ab in 12% yield. When the
Mn(acac)3 was reduced to 50 mol % in a pure O2 atmosphere,
we obtained 3ab in 52% yield and 4ab in 19% yield.
a
Reactions were carried out using 1a (0.2 mmol), 2 (0.6 mmol), and
Mn(acac)3 (0.2 mmol) in DCM (2 mL) at room temperature for 24 h
b
in air. Isolated yield.
functional groups such as methyl, methoxy, fluoro, chloro, and
trifluoro methyl introduced at different positions of o-alkenyl
aromatic isocyanides reacted smoothly with boronic acids. In
all the cases, target products 3bb−3hb were obtained in
moderate yields. Substrate 1i was also utilized for this
transformation, and desired product 3ib was isolated in 79%
yield. Furthermore, boronic acids 2g and 2h also reacted with
4-Cl-substituted aromatic isocyanide 1o to produce desired
products 3hg and 3hh in 52% and 52% yields, respectively.
Boronic acids as radical precursors are widely applied in
radical cascade cyclization in the presence of Mn salt.16
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However, in the reported transformations, usually, the use of
more than 2 equiv of the Mn salt was required for the
corresponding reactions. Until recently, Lei’s group reported a
Mn(III)-catalyzed electrochemical assistance cascade cycliza-
tion reaction of N-substituted 2-arylbenzoimidazoles with
alkylboronic acids.16g Note that 1 equiv of Mn salt was used to
drive the reaction to completion in our reported experimental
results. To gain mechanistic insight into this transformation,
some control experiments were designed and investigated
(Schemes 4, S1, and S2). First, the reaction was performed in
Scheme 5. Plausible Mechanism
Scheme 4. Control Experiments
intermolecular addition to o-alkenyl aromatic isocyanide 1 to
deliver an imidoyl radical B. Subsequently, a 5-exo-trig
cyclization involving an intramolecular radical addition
generates a radical intermediate C, providing two possible
pathways for the formation of 2-aryl-3-cyanoindoles. Radical
intermediate C was oxidized to a carbocation intermediate D
by the Mn(III)/air (O2).16 Next, the nucleophilic attack of
H2O on the carbocation intermediate D and deprotonation
deliver an intermediate E. Finally, the cleavage of the C−C
bond via elimination of benzaldehyde gives the desired 2-aryl-
3-cyanoindoles (path a). Another pathway involves molecular
oxygen addition to furnish a peroxy radical F, which undergoes
a reduction by Mn(II) to afford an alkoxy radical H.19
Subsequent β-scission of the alkoxy radical G is followed by
extrusion of benzaldehyde to produce a radical intermediate I.
Finally, product 3 is obtained by the single-electron oxidation
and protonation from intermediate I (path b). In addition, the
hydroperoxide intermediate G could be reduced by Mn(II) to
generate intermediate E.20 Meanwhile, the radical intermediate
B undergoes an indirect or direct 6-endo-trig cycloaddition to
generate an intermediate J.14d The byproduct 4 is eventually
released by the single-electron oxidation of L by Mn(III)
followed by deprotonation (paths c and d).
an inert Ar atmosphere, resulting in a drastic decrease in the
yield. When the reaction proceeded in pure O2 atmosphere or
in Ar atmosphere in the presence of 2 equiv of Mn(acac)3, the
products 3ab and 4ab were isolated in comparable yields
(Scheme S1). Therefore, we hypothesized that the radical
cyclization reaction might be related with the presence of air
(O2 from air). As far as we know, β-dicarbonyl compounds are
effective radical acceptors,17 but the adduct of the aryl radical
with the acac ligand of Mn(acac)3 was not observed in this
transformation. In addition, we analyzed the 4-bromobenzal-
dehyde coproduct in 29% yield in the coupling of 1j and 2b.
Meanwhile, the acetylacetone and 4,4′-dimethylbiphenyl were
already detected by GC-MS (Scheme 4d). Next, a H2O18-
labeling experiment has been carried out (Scheme 4e). The
observed 18O incorporation into 4-bromobenzaldehyde was
detected by GC-Ms. Next, the reaction was performed in
DCM (dry) and resulted in a diminished yield along with 4-
bromobenzaldehyde in 26% yield (Schemes 4f and S1). These
results imply that the oxygen atom of 4-bromobenzaldehyde
might come from H2O or O2. The reaction was inhibited with
a dramatic decrease of the yield when tert-butylmercaptan
(TBM) was used as the radical inhibitor under the standard
conditions.18 Radical inhibition experiments suggested a
possible radical process for this reaction (Schemes 4g and S2).
On the basis of our preliminary results, a plausible
mechanism was proposed (Scheme 5). The reaction is initiated
by a single-electron transfer from both boronic acids 2 and
Mn(acac)3 to afford an aryl radical A, which undergoes an
In summary, a Mn(III)-mediated radical cascade cyclization
of o-alkenyl aromatic isocyanides with boronic acids to
synthesize N-unprotected 2-aryl-3-cyanoindoles is reported
herein. The reaction involves a sequential intermolecular
radical addition, intramolecular cyclization, and cleavage of the
C−C bond. The radical cascade cyclization reaction has
attractive features such as synthetic simplicity, broad scope of
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(2) Murali Dhar, T.G.; Shen, Z.; Gu, H. H.; Chen, P.; Norris, D.;
Watterson, S. H.; Ballentine, S. K.; Fleener, C. A.; Rouleau, K. A.;
Barrish, J. C.; Townsend, R.; Hollenbaugh, D. L.; Iwanowicz, E. J. 3-
Cyanoindole-based inhibitors of inosine monophosphate dehydrogen-
ase: synthesis and initial structure-Activity relationships. Bioorg. Med.
Chem. Lett. 2003, 13, 3557−3560.
substrates, and excellent functional group compatibilities under
mild reaction conditions. Furthermore, the synthetic utility was
showcased by gram-scale synthesis.
ASSOCIATED CONTENT
* Supporting Information
■
sı
(3) Barnes, D. W.; Bebernitz, G. R.; Clairmont, K.; Cohen, S. L.;
Dodd, S. K. Bicyclic acetyl-coa carboxylase inhibitors. PCT Int. Appl.
WO 2012013716 A1 20120202, 2012.
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.1c01979.
(4) Zhang, N.-J.; Zhang, X.-Y.; Zhu, J.; Turpoff, A.; Chen, G.-M.;
et al. Structure-Activity Relationship (SAR) Optimization of 6-(Indol-
2-yl)pyridine-3-sulfonamides: Identification of Potent, Selective, and
Orally Bioavailable Small Molecules Targeting Hepatitis C (HCV)
NS4B. J. Med. Chem. 2014, 57, 2121−2135.
(5) Choi, S. P.; Kim, G. T.; Song, J. U.; Kim, T. H.; Lim, D. C.
Novel compounds effective as xanthine oxidase inhibitors, method for
preparing the same, and pharmaceutical composition containing the
same. PCT Int. Appl. WO 2010093191 A2 20100819, 2010.
(6) Rhoennstad, P.; Kallin, E.; Apelqvist, T.; Wennerstaal, M.;
Cheng, A. Novel Estrogen Receptor Ligands. PCT Int. Appl. WO
2009127686 A1 20091022, 2009.
(7) (a) Swain, C. J.; Baker, R.; Kneen, C.; Moseley, J.; Saunders, J.;
Seward, E. M.; et al. Novel 5-HT3 Antagonists. Indole Oxadiazoles. J.
Med. Chem. 1991, 34, 140−151. (b) Gu, X.-H.; Wan, X.-Z.; Jiang, B.
Syntheses and Biological Activities of Bis(3-indolyl)thiazoles,
Analogues of Marine Bis(indole)alkaloid Nortopsentins. Bioorg.
Med. Chem. Lett. 1999, 9, 569−572.
(8) (a) Peng, J.; Zhao, J.; Hu, Z.; Liang, D.; Huang, J.; Zhu, Q.
Palladium-Catalyzed C(sp2)-H Cyanation Using Tertiary Amine
Derived Isocyanide as a Cyano Source. Org. Lett. 2012, 14, 4966−
4969. (b) Nagase, Y.; Sugiyama, T.; Nomiyama, S.; Yonekura, K.;
Tsuchimoto, T. Zinc-Catalyzed Direct Cyanation of Indoles and
Pyrroles: Nitromethane as a Source of a Cyano Group. Adv. Synth.
Catal. 2014, 356, 347−352. (c) Zhang, L.-P.; Lu, P.; Wang, Y.-G.
Copper-mediated cyanation of indoles and electron-rich arenes using
DMF as a single surrogate. Org. Biomol. Chem. 2015, 13, 8322−8329.
(d) Wang, X.; Makha, M.; Chen, S.-W.; Zheng, H.-J.; Li, Y.-H. GaCl3-
Catalyzed C-H Cyanation of Indoles with N-Cyanosuccinimide. J.
Org. Chem. 2019, 84, 6199−6206.
Experimental procedures, mechanistic experiments, and
characterization data for all compounds (PDF)
FAIR data, including the primary NMR FID files, for
compounds 3aa−3av, 3bb−3ib, 3hg, 3hh, and 4ab
(ZIP)
AUTHOR INFORMATION
Corresponding Authors
■
Lei Li − School of Petrochemical Engineering, Liaoning
Petrochemical University, Fushun 113001, P. R. China;
orcid.org/0000-0003-3174-0186;
Email: lilei0814.com@163.com
He Wang − School of Petrochemical Engineering, Liaoning
Petrochemical University, Fushun 113001, P. R. China;
orcid.org/0000-0001-7196-4913; Email: heliwang123@
126.com
Authors
Lu Liu − School of Petrochemical Engineering, Liaoning
Petrochemical University, Fushun 113001, P. R. China
Xin Wang − School of Petrochemical Engineering, Liaoning
Petrochemical University, Fushun 113001, P. R. China
Ran Sun − School of Petrochemical Engineering, Liaoning
Petrochemical University, Fushun 113001, P. R. China
Ming-Dong Zhou − School of Petrochemical Engineering,
Liaoning Petrochemical University, Fushun 113001, P. R.
China; orcid.org/0000-0001-9961-4296
(9) (a) Song, J. U.; Choi, S. P.; Kim, T. H.; Jung, C.-K.; Lee, J.-Y.;
Jung, S.-H.; Kim, G. T. Design and synthesis of novel 2-(indol-5-
yl)thiazole derivatives as xanthine oxidase inhibitors. Bioorg. Med.
Chem. Lett. 2015, 25, 1254−1258. (b) Meine, R.; Becker, W.; Falke,
H.; Preu, L.; Loaec, N.; Meijer, L.; Kunick, C. Conrad Kunick. Indole-
3-Carbonitriles as DYRK1A Inhibitors by Fragment-Based Drug
Design. Molecules 2018, 23, 64.
Complete contact information is available at:
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Notes
The authors declare no competing financial interest.
(10) (a) Li, B.; Guo, S.-H.; Zhang, J.; Zhang, X.-J.; Fan, X.-S.
Selective Access to 3-Cyano-1H-indoles, 9H-Pyrimido[4,5-b]indoles,
or 9H-Pyrido[2,3-b]indoles through Copper-Catalyzed One-Pot
Multicomponent Cascade Reactions. J. Org. Chem. 2015, 80, 5444−
5456. (b) Wu, J.; Liu, J.; Zhou, K.; He, Z.; Wang, Q.; Wu, F.; Miao,
T.; Qian, J.; Shi, Q. Efficient Construction of Diverse 3-cyanoindoles
Under Novel Tandem Catalysis. Chem. Commun. 2020, 56, 12660−
12663.
(11) (a) Fang, Y.; Wang, S.-Y.; Shen, X.-B.; Ji, S.-J. Base-promoted
cascade reaction of isocyanides, selenium and amines: a practical
approach to 2-aminobenzo[d][1,3]selenazines under metal-free
conditions. Org. Chem. Front. 2015, 2, 1338−1341. (b) Hu, Z.;
Yuan, H.; Men, Y.; Liu, Q.; Zhang, J.; Xu, X. Cross-Cycloaddition of
Two Different Isocyanides: Chemoselective Heterodimerization and
[3 + 2]-Cyclization of 1,4-Diazabutatriene. Angew. Chem., Int. Ed.
2016, 55, 7077−7080. (c) Hu, Z.; Dong, J.; Li, Z.; Yuan, B.; Wei, R.;
Xu, X. Metal-Free Triple Annulation of En-Yne-Ketones with
Isocyanides: Domino Access to Furan-Fused Heterocycles via
Furoketenimine. Org. Lett. 2018, 20, 6750−6754. (d) Men, Y.; Hu,
Z.-Y.; Dong, J.-H.; Xu, X.-X.; Tang, B. Formal [1 + 2+3] Annulation:
Domino Access to Carbazoles and Indolocarbazole Alkaloids. Org.
Lett. 2018, 20, 5348−5352.
ACKNOWLEDGMENTS
■
We acknowledge financial support from the National Natural
Science Foundation of China (21702087 and 21801105), the
LiaoNing Revitalization Talents Program (XLYC1907010 and
XLYC1902085), the Research Project Fund of Liaoning
Provincial Department of Education (L2020033), and talent
Scientific Research Fund of Liaoning Shihua University
(2016XJJ-078 and 2016XJJ-079).
REFERENCES
■
(1) (a) Kochanowska-Karamyan, A. J.; Hamann, M. T. Marine
Indole Alkaloids: Potential New Drug Leads for the Control of
Depression and Anxiety. Chem. Rev. 2010, 110, 4489−4497.
(b) Ishikura, M.; Abe, T.; Choshi, T.; Hibino, S. Simple indole
alkaloids and those with a non-rearranged monoterpenoid unit. Nat.
Prod. Rep. 2013, 30, 694−752. (c) Stempel, E.; Gaich, T.
Cyclohepta[b]indoles: A Privileged Structure Motif in Natural
Products and Drug Design. Acc. Chem. Res. 2016, 49, 2390−2402.
(d) Li, L.; Chen, Z.; Zhang, X.-W.; Jia, Y.-X. Divergent Strategy in
Natural Product Total Synthesis. Chem. Rev. 2018, 118, 3752−3832.
5829
https://doi.org/10.1021/acs.orglett.1c01979
Org. Lett. 2021, 23, 5826−5830

Organic Letters
pubs.acs.org/OrgLett
Letter
(12) (a) Yuan, Y.-C.; Liu, H.-L.; Hu, X.-B.; Wei, Y.; Shi, M. Visible-
Light-Induced Trifluoromethylation of Isonitrile-Substituted Methyl-
enecyclopropanes: Facile Access to 6-(Trifluoromethyl)-7,8-
Dihydrobenzo[k]phenanthridine Derivatives. Chem. - Eur. J. 2016,
22, 13059−13063. (b) Heckman, L. M.; He, Z.; Jamison, T. F.
Synthesis of Highly Substituted 2-Arylindoles via Copper-Catalyzed
Coupling of Isocyanides and Arylboronic Acids. Org. Lett. 2018, 20,
3263−3267. (c) Dong, J.; Zhang, D.; Men, Y.; Zhang, X.; Hu, Z.; Xu,
X. [1 + 2+3] Annulation as a General Access to Indolo[3,2-
b]carbazoles: Synthesis of Malasseziazole C. Org. Lett. 2019, 21, 166−
169. (d) Zhang, L.; Liu, T.; Wang, Y.-M.; Chen, J.; Zhao, Y.-L.
Rhodium-Catalyzed Coupling-Cyclization of Alkenyldiazoacetates
with o-Alkenyl Arylisocyanides: A General Route to Carbazoles.
Org. Lett. 2019, 21, 2973−2977.
(13) Radical 5-exo-trig cyclization, see: (a) Mitamura, T.; Iwata, K.;
Ogawa, A. Photoinduced Intramolecular Cyclization of o-Ethenylaryl
Isocyanides with Organic Disulfides Mediated by Diphenyl
Ditelluride. J. Org. Chem. 2011, 76, 3880−3887. (b) Zhang, B.;
Studer, A. 2-Trifluoromethylated Indoles via Radical Trifluoromethy-
lation of Isonitriles. Org. Lett. 2014, 16, 1216−1219. (c) Wang, C.-H.;
Li, Y.-H.; Yang, S.-D. Autoxidation Photoredox Catalysis for the
Synthesis of 2-Phosphinoylindoles. Org. Lett. 2018, 20, 2382−2385.
(d) Vidyasagar, A.; Shi, J.-W.; Kreitmeier, P.; Reiser, O. Bromo- or
Methoxy-Group-Promoted Umpolung Electron Transfer Enabled,
Visible-Light-Mediated Synthesis of 2-Substituted Indole-3-glyoxy-
lates. Org. Lett. 2018, 20, 6984−6989. (e) Heckman, L. M.; He, Z.;
Jamison, T. F. Synthesis of Highly Substituted 2-Arylindoles via
Copper-Catalyzed Coupling of Isocyanides and Arylboronic Acids.
Org. Lett. 2018, 20, 3263−3267. (f) Santos, M. S.; Betim, H. L. I.;
Kisukuri, C. M.; Campos Delgado, J. A.; Correa, A. G.; Paixao, M. W.
Photoredox Catalysis toward 2-Sulfenylindole Synthesis through a
Radical Cascade Process. Org. Lett. 2020, 22, 4266−4271.
F. J.; Vicente, R.; Rodríguez, F. Manganese-Mediated C-H Alkylation
of Unbiased Arenes Using Alkylboronic Acids. Chem. - Eur. J. 2016,
22, 9068−9071. (c) Yang, W.-C.; Wei, K.; Sun, X.; Zhu, J.; Wu, L.
Cascade C(sp3)-S Bond Cleavage and Imidoyl C-S Formation:
Radical Cyclization of 2-Isocyanoaryl Thioethers toward 2-Sub-
stituted Benzothiazoles. Org. Lett. 2018, 20, 3144−3147. (d) Xu, P.;
Zhu, Y.-M.; Wang, F.; Wang, S.-Y.; Ji, S.-J. Mn(III)-Mediated Cascade
Cyclization of 3-Isocyano-[1,1’-biphenyl]-2-carbonitrile with Arylbor-
onic Acid: Construction of Pyrrolopyridine Derivatives. Org. Lett.
2019, 21, 683−686. (e) Wang, F.; Wei, T.-Q.; Xu, P.; Wang, S.-Y.; Ji,
S.-J. Mn(III)-mediated radical cascade reaction of boronic acids with
isocyanides: synthesis of diimide derivatives. Chin. Chem. Lett. 2019,
30, 379−382. (f) Teng, F.; Hu, W.-M.; Hu, H.; Luo, S.; Zhu, Q.
Selective C-H or N-H Imidoylative Annulation of 2-(2-Isocyano-
phenyl)-1H-indoles Leading to Diverse Indole-fused Scaffolds. Adv.
Synth. Catal. 2019, 361, 1414−1418. (g) Yuan, Y.; Zheng, Y.; Xu, B.;
Liao, J.; Bu, F.; Wang, S.; Hu, J.-G.; Lei, A. Mn-Catalyzed
Electrochemical Radical Cascade Cyclization toward the Synthesis
of Benzo[4,5]imidazo[2,1-a]isoquinolin-6(5H)-one Derivatives. ACS
Catal. 2020, 10, 6676−6681. (h) Xu, P.; Zhu, Y.-M.; Liu, X.-Y.; Zhou,
X.-Z.; Wang, S.-Y.; Ji, S.-J. Mn(III)-mediated radical reaction of 2-
isocyano-6-alkenyl(alkynyl)benzonitriles with arylboronic acids: Syn-
thesis of pyrroloisoquinoline derivatives. Chin. Chem. Lett. 2021, 32,
413−416. (i) Ramalingaiah, G.; Kumar, Y.; Begum, N. S. Mn(III)-
mediated cascade cyclization of 1-(azidomethyl)-2-isocyanoarenes
with organoboronic acids: construction of quinazoline derivatives
New. New J. Chem. 2021, 45, 9811−9817.
(17) (a) Terent'ev, A. O.; Borisov, D. A.; Yaremenko, I. A.;
Chernyshev, V. V.; Nikishin, G. I. Synthesis of Asymmetric Peroxides:
Transition Metal (Cu, Fe, Mn, Co) Catalyzed Peroxidation of β-
Dicarbonyl Compounds with tert-Butyl Hydroperoxide. J. Org. Chem.
2010, 75, 5065−5071. (b) Terent'ev, A. O.; Krylov, I. B.; Timofeev,
V. P.; Starikova, Z. A.; Merkulova, V. M.; Ilovaisky, A. I.; Nikishin, G.
I. Oxidative C−O Cross Coupling of 1,3-Dicarbonyl Compounds and
Their Heteroanalogues with N-Substituted Hydroxamic Acids and N-
Hydroxyimides. Adv. Synth. Catal. 2013, 355, 2375−2390. (c) Krylov,
I. B.; Terent'ev, A. O.; Timofeev, V. P.; Shelimov, B. N.; Novikov, R.
A.; Merkulova, V. M.; Nikishin, G. I. Iminoxyl Radical-Based Strategy
for Intermolecular C−O Bond Formation: Cross-Dehydrogenative
Coupling of 1,3-Dicarbonyl Compounds with Oximes. Adv. Synth.
Catal. 2014, 356, 2266−2280. (d) Zhou, Z.-H.; Li, C.-K.; Zhou, S.-F.;
Shoberu, A.; Zou, J.-P. Copper-catalyzed methylation of 1,3-diketones
with tert-butyl peroxybenzoate. Tetrahedron 2017, 73, 2740−2746.
(e) Krylov, I. B.; Paveliev, S. A.; Shumakova, N. S.; Syroeshkin, M. A.;
Shelimov, B. N.; Nikishin, G. I.; Terent'ev, A. O. Iminoxyl radicals vs.
tert-butylperoxyl radical in competitive oxidative C−O coupling with
β-dicarbonyl compounds. Oxime ether formation prevails over
Kharasch peroxidation. RSC Adv. 2018, 8, 5670−5677. (f) Mulina,
O. M.; Pirgach, D. A.; Nikishin, G. I.; Terent'ev, A. O. Switching of
Sulfonylation Selectivity by Nature of Solvent and Temperature: The
Reaction of β-Dicarbonyl Compounds with Sodium Sulfinates under
the Action of Iron-Based Oxidants. Eur. J. Org. Chem. 2019, 2019,
4179−4188.
(14) Radical 6-endo-trig cyclization, see: (a) Evoniuk, C. J.; Ly, M.;
Alabugin, I. V. Coupling cyclizations with fragmentations for the
preparation of heteroaromatics: quinolines from o-alkenyl arylisocya-
nides and boronic acids. Chem. Commun. 2015, 51, 12831−12834.
(b) Evoniuk, C. J.; Gomes, G. D. P.; Ly, M.; White, F. D.; Alabugin, I.
V. Coupling Radical Homoallylic Expansions with C-C Fragmenta-
tions for the Synthesis of Heteroaromatics: Quinolines from
Reactions of o-Alkenylarylisonitriles with Aryl, Alkyl, and Perfluor-
oalkyl Radicals. J. Org. Chem. 2017, 82, 4265−4278. (c) Liu, Y.; Li, S.-
J.; Chen, X.-L.; Fan, L.-L.; Li, X.-Y.; Zhu, S.-S.; Qu, L.-B.; Yu, B.
Mn(III)-Mediated Regioselective 6-endo-trig Radical Cyclization of o-
Vinylaryl Isocyanides to Access 2-Functionalized Quinolines. Adv.
Synth. Catal. 2020, 362, 688−694. (d) Mao, S.; Wang, H.; Liu, L.;
Wang, X.; Zhou, M.-D.; Li, L. Trifluoromethylation/Difluoromethy-
lation-Initiated Radical Cyclization of o-Alkenyl Aromatic Isocyanides
for Direct Construction of 4-Cyano-2-Trifluoromethyl/Difluorometh-
yl-Containing Quinolines. Adv. Synth. Catal. 2020, 362, 2274−2279.
(15) (a) Zhou, M.-D.; Peng, Z.; Wang, H.; Wang, Z.-H.; Hao, D.-J.;
Li, L. Ruthenium(II)-Catalyzed Homocoupling of Weakly Coordinat-
ing Sulfoxonium Ylides via C-H Activation/Annulations: Synthesis of
Functionalized Isocoumarins. Adv. Synth. Catal. 2019, 361, 5191−
5197. (b) Sun, R.; Du, Y.; Tian, C.; Li, L.; Wang, H.; Zhao, Y.-L.
Copper(II)-catalyzed Domino Reaction of the Acyclic Ketene-(S,S)-
Acetals with Diazo Compounds: Convenient Synthesis of Polysub-
stituted Thiophenes. Adv. Synth. Catal. 2019, 361, 5684−5689.
(c) Liu, L.; Li, L.; Mao, S.; Wang, X.; Zhou, M.-D.; Zhao, Y.-l.; Wang,
H. Synthesis of pyrazolo[1,5-c]quinazoline derivatives through the
copper-catalyzed domino reaction of o-alkenyl aromatic isocyanides
with diazo compounds. Chem. Commun. 2020, 56, 7665−7668.
(d) Wang, Z.-H.; Wang, H.; Wang, H.; Li, L.; Zhou, M.-D.
Ruthenium(II)-Catalyzed C-C/C-N Coupling of 2-Arylquinazoli-
nones with Vinylene Carbonate: Access to Fused Quinazolinones.
Org. Lett. 2021, 23, 995−999.
(18) Li, L.; Zhao, Y. L.; Wang, Q.; Lin, T.; Liu, Q. Base-promoted
oxidative C-H functionalization of alpha-amino carbonyl compounds
under mild metal-free conditions: using molecular oxygen as the
oxidant. Org. Lett. 2015, 17, 370−373.
(19) (a) Sun, X.; Li, X.; Song, S.; Zhu, Y.; Liang, Y.-F.; Jiao, N.
Mncatalyzed highly efficient aerobic oxidative hydroxyazidation of
olefins: A direct approach to β-azido alcohols. J. Am. Chem. Soc. 2015,
137, 6059−6066. (b) Pal, P.; Mainkar, P. S.; Nayani, K.;
Chandrasekhar, S. Mn-catalyzed radical initiated domino trans-
formation of alkynylated cyclohexadienones with TMSN3 and O2 to
bicyclic azido alcohols. Chem. Commun. 2020, 56, 3453−3456.
(20) Shen, T.; Zhang, Y.; Liang, Y. F.; Jiao, N. Direct tryptophols
synthesis from 2-vinylanilines and alkynes via C≡C triple bond
cleavage and dioxygen activation. J. Am. Chem. Soc. 2016, 138,
13147−13150.
(16) (a) Tobisu, M.; Koh, K.; Furukawa, T.; Chatani, N. Modular
Synthesis of Phenanthridine Derivatives by Oxidative Cyclization of
2-Isocyanobiphenyls with Organoboron Reagents. Angew. Chem., Int.
Ed. 2012, 51, 11363−11366. (b) Castro, S.; Fernández, J. J.; Fananás,
̃
5830
https://doi.org/10.1021/acs.orglett.1c01979
Org. Lett. 2021, 23, 5826−5830