- Palladium-Catalyzed Direct and Specific C-7 Acylation of Indolines with 1,2-Diketones
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The indole scaffold is a ubiquitous and useful substructure, and extensive investigations have been conducted to construct the indole framework and/or realize indole modification. Nevertheless, the direct selective functionalization on the benzenoid core must overcome the high activity of the C-3 position and still remains highly challenging. Herein, a palladium-catalyzed direct and specific C-7 acylation of indolines in the presence of an easily removed directing group was developed. This strategy usually is considered as a practical strategy for the preparation of acylated indoles because indoline can be easily converted to indole under oxidation conditions. In particular, our strategy greatly improved the alkacylation yield of indolines for which only an unsatisfactory yield could be achieved in the previous studies. Furthermore, the reaction can be scaled up to gram level in the standard reaction conditions with a much lower palladium loading (1 mol %).
- Xie, Guilin,Zhao, Yuhan,Cai, Changqun,Deng, Guo-Jun,Gong, Hang
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- Synthesis and KCNQ2 opener activity of N-(1-benzo[1,3]dioxol-5-yl-ethyl, N-[1-(2,3-dihydro-benzofuran-5-yl)-ethyl, and N-[1-(2,3-dihydro-1H-indol-5-yl)- ethyl acrylamides
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Bioisosteric replacement studies led to the identification of N-(1-benzo[1,3]dioxol-5-yl-ethyl)-3-(2-chloro-phenyl)-acrylamide ((S)-3) as a highly potent KCNQ2 opener, and 3-(2,6-difluoro-phenyl)-N-[1-(2,3-dihydro- benzofuran-5-yl)-ethyl]-acrylamide ((S)-4), and N-[1-(2,3-dihydro-1H-indol-5-yl) -ethyl]-3-(2-fluoro-phenyl)-acrylamide ((S)-5) as highly efficacious KCNQ2 openers. In contrast, their respective R enantiomers showed significantly less or no appreciable KCNQ2 opener activity even at the highest concentration tested (10μM). Because of its high potency and moderate efficacy as well as its convenient synthesis, (±)-3 was selected as a reference compound for analyzing efficacies of KCNQ openers in electrophysiology studies. Compounds (S)-4 and (S)-5 demonstrated significant activity in reducing neuronal hyperexcitability in rat hippocampal slices. The synthesis and the KCNQ2 opener activity of these acrylamides are described.
- Wu, Yong-Jin,Sun, Li-Qiang,He, Huan,Chen, Jie,Starrett Jr., John E.,Dextraze, Pierre,Daris, Jean-Paul,Boissard, Christopher G.,Pieschl, Rick L.,Gribkoff, Valentin K.,Natale, Joanne,Knox, Ronald J.,Harden, David G.,Thompson, Mark W.,Fitzpatrick, William,Weaver, David,Wu, Dedong,Gao, Qi,Dworetzky, Steven I.
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p. 4533 - 4537
(2007/10/03)
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- Regioselective Friedel-Crafts Acylation of 1,2,3,4-Tetrahydroquinoline and Related Nitrogen Heterocycles: Effects of NH Protective Groups and Ring Size
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Regioselectivity of the Friedel-Crafts acylation of the following nitrogen heterocyles was studied: 2,3-dihydro-1H-indoles 3, 1,2,3,4-tetrahydroquinolines 4, 2,3,4,5-tetrahydro-1H-1-benzazepines 5 and 1,2,3,4,5,6-hexahydro-1-benzazocines 6.It was found that though the ratio of regioisomers depends on ring size, it can be controlled by changing the NH protective groups.A molecular orbital (MO) calculation of the Lewis acid co-ordinated substrates gave a rational explanation of the regioselectivity.
- Ishihara, Yuji,Tanaka, Toshimasa,Goto, Giichi
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p. 3401 - 3406
(2007/10/02)
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- THE SYNTHESIS OF 5- and 7-ACETYLINDOLE DERIVATIVES. I. THE PHOTOCHEMICAL REARRANGEMENT OF 1-ACETYLINDOLINE
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5- and 7-Acetyl substituted indole derivatives have been prepared via intramolecular photo rearrangement of acyl radical and intramolecular electrophilic acylation of 1-acetylindoline.
- Akagi, Masao,Ozaki, Kazuko
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- Synthese d'(indolyl-3)-4 dihydro-2,5 furanonnes-2 hydrosolubles
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Une cyclisation du type Dieckmann suivie d'une decarboxylation permet d'acceder directement aux (indolyl-3)-4 dihydro-2,5 furanonnes-2 acetylees ou non sur l'homocycle a partir des ethoxycarbonylacetoxyacetyl-3 indoles correspondants sans protection prealable de la position 1 du cycle indolique et du substituant acyle de l'homocycle.
- Baron, Michel,Cointet, Paul de,Bauduin, Gerard,Pietrasanta, Yves,Pucci, Bernard
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p. 249 - 256
(2007/10/02)
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