Categories: Synthesis of N-Heterocycles > benzo-fused N-Heterocycles >
Synthesis of indolines
Recent Literature
An efficient synthesis of indoline compounds from picolinamide (PA)-protected
β-arylethylamine substrates via palladium-catalyzed intramolecular amination of
ortho-C(sp2)-H bonds features high efficiency, low catalyst
loadings, mild operating conditions, and the use of inexpensive reagents.
G. He, C. Lu, Y. Zhao, W. A. Nack, G. Chen, Org. Lett., 2012,
14, 2936-2939.
A Pd(II)-catalyzed intramolecular C-H amination of 2-pyridinesulfonyl-protected
phenethylamine derivatives using PhI(OAc)2 as a bystanding oxidant
provides access to various substituted indoline derivatives in good yields. The
use of the 2-pyridinesulfonyl protecting group enables a facile deprotection
following C-H functionalization.
T.-S. Mei, D. Leow, H. Xiao, B. N. Laforteza, J.-Q. Yu, Org. Lett., 2013,
15, 3058-3061.
Pd(II)-catalyzed intramolecular amination of arenes using either Ce(SO4)2
as
a one- or
N-fluoro-2,4,6-trimethylpyridinium triflate as a two-electron oxidant tolerates a wide range of
functional groups including acetyl, cyano, and nitro. This catalytic
reaction allows expedient syntheses of broadly useful substituted indolines or
indoles.
T.-S. Mei, X. Wang, J.-Q. Yu, J. Am. Chem. Soc., 2009,
131, 10806-10807.
A lanthanide/B(C6F5)3-promoted hydroboration
reduction of indoles and quinolines with pinacolborane (HBpin) provides a range
of nitrogen-containing compounds in good yields. Large-scale synthesis and
further transformations to bioactive compounds indicate that the method has
potential practical applications.
J. Zhang, Z. Chen, M. Chen, Q. Zhou, R. Zhou, W. Wang, Y. Shao, F. Zhang, J. Org. Chem., 2024, 89,
887-897.
Metal-free reductive N-trifluoroethylation and N-trifluoroacetylation
of indoles provide trifluoroethylated or trifluoroacetylated indolines depending
on the loading of trimethylamine borane as reducing agent and TFA as
trifluoroethyl or trifluoroacetyl source, respectively.
Y.-F. Zeng, M.-X. Zhou, Y.-N. Li, X. Wu, Y. Guo, Z. Wang, Org. Lett.,
2022, 24, 7440-7445.
An efficient, palladium-catalyzed reduction of N-(tert-butoxycarbonyl)indoles
gives N-(tert-butoxycarbonyl)indolines in good yields in the presence of
polymethylhydrosiloxane (PMHS) as reducing agent at room temperature.
S. Chandrasekhar, D. Basu, C. R. Reddy, Synthesis, 2007,
1509-1512.
Iridium-catalyzed tandem dehydrogenation of N-heterocycles and
alcohols enables regio-selective C-H and N-H bond functionalizations of
indolines to provide a diverse range of N- and C3-alkylated indolines/indoles.
The practical applicability of this methodology was demonstrated by the
preparative-scale synthesis and synthesis of a psychoactive drug, N,N-dimethyltryptamine.
M. Maji, I. Borthakur, S. Srivastava, S. Kundu, J. Org. Chem., 2022, 87,
5603-5616.
The use of N,N′-bis(2,6-diisopropylphenyl)dihydroimidazol-2-ylidene (SIPr)
as a ligand and tBuONa as the base for sequential palladium-catalyzed
intra- followed by intermolecular aryl amination enables the synthesis of
N-arylated five-, six- and seven-membered nitrogen heterocycles.
R. Omar-Amrani, R. Schneider, Y. Fort, Synthesis,
2004, 2257-2534.
With the proper choice of palladium catalyst, ligand, and base, five-, six-, and
seven-membered rings are formed efficiently from secondary amide or secondary
carbamate precursors.
B. H. Yang, S. L. Buchwald,
Org. Lett., 1999, 1, 35-37.
1,2-Disubstituted indolines have been prepared in good yields by a Zn-mediated
organometallic Mannich reaction, followed by an intramolecular Buchwald-Hartwig
reaction. The reactions are easy to set up and compatible with a broad range of
simple or commercially available reagents. The method was further extended to
the preparation of a 1,2,3-trisubstituted indolines.
M. Presset, A. Pignon, J. Paul, E. Le Gall, E. Léonel, T. Martens, J. Org. Chem.,
2017, 82, 3302-3310.
In a nickel/photoredox catalyzed synthesis of indolines from iodoacetanilides
and alkenes, very high regioselectivity for 3-substituted indoline products is
obtained for both aliphatic and styrenyl olefins. This process demonstrates the
utility of photoredox catalysts as controlled single electron transfer agents in
multioxidation state nickel catalysis.
S. Z. Tasker, T. F. Jamison, J. Am. Chem. Soc., 2015,
137, 9531-9534.
An intramolecular, Pd-catalyzed C-H alkylation of arenes and heteroarenes is
successful with various unactivated primary and secondary alkyl halides,
including those with β-hydrogens. The mild, catalytic reaction conditions are
highly functional group tolerant and facilitate access to a broad range of
synthetically and medicinally interesting carbocyclic and heterocyclic systems.
A. R. O. Venning, P. T. Bohan, E. J. Alexanian, J. Am. Chem. Soc., 2015,
137, 3731-3734.
A diastereo- and enantioselective CuH-catalyzed method for the preparation of
highly functionalized indolines offers mild reaction conditions and high degree
of functional group compatibility. This method is highly valuable for the
synthesis various cis-2,3-disubstituted indolines in high yield and
enantioselectivity.
E. Ascic, S. L. Buchwald, J. Am. Chem. Soc., 2015,
137, 4666-4669.
A transition-metal-free, iodine-mediated oxidative intramolecular amination of
anilines provides indolines via cleavage of unactivated (sp3)C-H
and N-H bonds. The reaction could be performed on a gram scale for the synthesis
of functionalized indolines.
J. Long, X. Cao, L. Zhu, R. Qiu, C.-T. Au, S.-F. Yin, T. Iwasaki, N. Kambe, Org. Lett.,
2017, 19, 2793-2796.
A palladium-catalyzed tandem [4+1] cycloaddition of 4-vinyl-1,4-dihydro-2H-3,1-benzoxazin-2-ones
with N-tosylhydrazones provides diverse indolines with broad functional
group compatibility in good yields with high levels of diastereoselectivity
under mild conditions.
Y.-H. Ma, F.-X. Meng, R.-N. Wang, Y.-X. Fan, Q.-Q. Su, J.-Y. Du, Synthesis, 2022, 54,
499-505.
A photoinduced metal-free arylboration of unactivated alkenes provides
indoline boronic esters and 1,2,3,4-tetrahydroquinoline boronic ester in good
yields. This mild and environmentally benign approach showed tolerates a broad
range of substrates.
J. Lu, Y. He, L. Ren, D. Li, X. Pan, L. Yang, J. Wang, S. Wei, J. Wei, Synlett, 2024,
35,
1399-1404.
A Pd-catalyzed interceptive decarboxylative benzylic cycloaddition (IDBC) of
nonvinyl, trifluoromethyl benzoxazinanones with sulfur ylides enables a highly
diastereoselective synthesis of trifluoromethyl-substituted indolines via
palladium-π-benzyl zwitterionic intermediates.
N. Punna, P. Das, V. Gouverneur, N. Shibata, Org. Lett.,
2018, 20, 1526-1529.
A one step formal [3+2]-cycloaddition of γ-amino-α,β-unsaturated esters to
arynes provides indolines in a highly regio- and diastereoselective manner in
good yields.
R. D. Aher, G. M. Suryavanshi, A. Sudalai, J. Org. Chem.,
2017, 82, 5940-5946.
An iridium-catalyzed diastereo- and enantioselective [4 + 1] cycloaddition
reaction of hydroxyallyl anilines with sulfoxonium ylides provides 3-vinyl
indolines in good yields with excellent enantioselectivities under mild reaction
conditions.
C. He, Y. Tang, S. Tang, J. Sun, Org. Lett., 2023, 25,
4621-4626.
A copper-catalyzed asymmetric decarboxylative [4 + 1] cycloaddition of
propargylic carbamates and sulfur ylides provides chiral indolines with
synthetically flexible alkyne groups in good yields and with high enantio- and
diastereoselectivities.
Q. Wang, T.-R. Li, L.-Q. Lu, M.-M. Li, K. Zhang, W.-J. Xiao, J. Am. Chem. Soc., 2016,
138, 8360-8363.
A Pd-catalyzed intermolecular 1,2-carboamination route to indolines from N-aryl
ureas and 1,3-dienes proceeds under mild conditions in relatively nonacidic
media via a C-H insertion/carbopalladation/nucleophilic displacement process.
The in situ generation, or preformation of a palladium tosylate emerges as a key
parameter in gaining the requisite reactivity.
C. E. Houlden, C. D. Bailey, J. G. Ford, M. R. Gagné, G. C. Lloyd-Jones, K. I.
Booker-Milburn, J. Am. Chem. Soc., 2008,
130, 10066-10067.
An electrochemical protocol using the CO2 radical anion produces
unprecedented trans-oriented 2,3-dicarboxylic acids from N-Ac-,
Boc-, and Ph-protected indoles. Further heteroaromatics with reduction
potentials more positive than -3V undergo dicarboxylation, including benzofuran,
benzothiophene, electron-deficient furans, thiophenes,
1,3-diphenylisobenzofuran, and N-Boc-pyrazoles.
Y. You, W. Kanna, H. Takano, H. Hayashi, S. Maeda, T. Mita, J. Am. Chem. Soc.,
2022, 144, 3685-3695.
A Brønsted acid catalyzed transfer hydrogenation of indole derivatives with
Hantzsch dihydropyridine as the hydrogen source enables an efficient synthesis
of various optically active indolines with high enantioselectivities.
M. Rueping, C. Brinkmann, A. P. Antonchick, I. Atoresei, Org. Lett., 2010,
12, 4604-4607.
A Pd-catalyzed arylative carboxylation of allenes proceeded in an
intramolecular manner to afford the corresponding β,γ-unsaturated carboxylic
acids in high yields in the presence of ZnEt2 under 1 atm of CO2.
The obtained products could be efficiently converted into 3-substituted
indole-2-carboxylate derivatives.
Y. Higuchi, T. Mita, Y. Sato, Org. Lett.,
2017, 19, 2710-2713.
Auto-tandem catalysis with an organosuperbase as the catalyst enables a
reductive cyclization of alkynyl α-iminoesters in the presence of
1-dodecanethiol as the reductant to provide N-H indoline derivatives under mild
conditions via formation of α-aminoesters and an intramolecular addition of
ester enolates to an alkyne.
A. Kondoh, M. Terada, Org. Lett.,
2018, 20, 5309-5313.
A metal-free photocatalytic selective hydroxylation of benzylic methylenes to
secondary alcohols utilizes low-cost eosin Y as photocatalyst, O2 as
green oxidant, and inexpensive triethylamine as inhibitor for overoxidation. The
mild reaction conditions enable the production of secondary benzylic alcohols in
good yields.
Z. Tan, T. Chen, J. Zhu, W. Luo, D. Yu, W. Guo, J. Org. Chem., 2024, 89,
2656-2664.
A metal-free electrochemical intramolecular C(sp2)-H amination
using iodine as a mediator enables a switchable synthesis of indoline and indole
derivatives from easily available 2-vinyl anilines.
K. Hu, Y. Zhang, Z. Zhou, Y. Yang, Z. Zha, Z. Wang,
Org. Lett., 2020, 22, 5773-5777.
The one-pot reaction of N-(2-formylaryl)sulfonamides, secondary
amines, and calcium carbide as convenient alkyne source enables a switchable
synthesis of 2-methylene-3-aminoindolines and 2-methyl-3-aminoindoles in good
yields.
Z. Wang, Z. Zhang, Z. Li, Org. Lett., 2022, 24,
8067-8071.