Categories: Synthesis of N-Heterocycles > benzo-fused N-Heterocycles >
Synthesis of indolines
An efficient synthesis of indolines 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.
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 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.
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 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.