Organic Synthesis Methodology. Preparation and Diastereoselective Birch Reduction−Alkylation of 3-Substituted 2-Methyl-2,3-dihydroisoindol-1-ones

Crucial Role of Selenium in the Virucidal Activity of Benzisoselenazol-3(2H)-ones and Related Diselenides

“…Since several ortho -disubstituted benzenes with both substituents being of electrophilic character, among them the abovementioned 2-(chloroseleno)benzoyl chloride ( 11 ) and 2-(chlorosulfanyl)benzoyl chloride ( 12 ), readily reacted with bisnucleophiles such as primary amines or activated methylene compounds to form a five-membered heterocyclic ring annulated onto the benzene moiety in a one-pot reaction, we decided to apply this approach to synthesize isoindolin-1-ones 3 (phthalimidines) as well. Although several synthetic approaches to particular isoindolin-1-ones have already been known, only a few of them such as reduction of one carbonyl group in phthalimides with zinc in acetic acid [ 17 , 18 ] or reaction of phthalide with primary amines, mostly under elevated pressure [ 19 ], are more general. The attempts to obtain N -substituted isoindolin-1-ones 3 by direct reaction of chloride 13 with primary amines were unsuccessful, because only N -acylation took place while the chloromethyl group remained unreactive [ 20 , 21 ].…”

Thalidomide Metabolites and Analogues. 3. Synthesis and Antiangiogenic Activity of the Teratogenic and TNFα-Modulatory Thalidomide Analogue 2-(2,6-Dioxopiperidine-3-yl)phthalimidine

“…The conversion of the PMB-protected phthalimide 7 to the phthalimidine (isoindolinone) moiety of 10 was based on the chemoselective aluminum-amalgam-mediated reduction of the phthalimide group to the corresponding hydroxylactam, followed by phenylthiation and desulfurization, as briefly described in a preliminary communication (Scheme ) . While the direct phthalimide to phthalimidine conversion may sometimes be facilitated with zinc/acetic acid, the overall procedure described herein is milder and also avoids the employment of the less-selective hydridic reducing agents. Exposure of the N -PMB glutarimide 7 to freshly prepared aluminum amalgam (Al/Hg) in tetrahydrofuran/water followed by removal of the solid byproducts and reaction solvent system provided the crude hydroxylactam-substituted N -PMB-imide 8 without any concomitant reduction of the glutarimide ring.…”

“…The conversion of the PMB-protected phthalimide 7 to the phthalimidine (isoindolinone) moiety of 10 was based on the chemoselective aluminum-amalgam-mediated reduction of the phthalimide group to the corresponding hydroxylactam, followed by phenylthiation and desulfurization, as briefly described in a preliminary communication (Scheme 2). 7 While the direct phthalimide to phthalimidine conversion may sometimes be facilitated with zinc/acetic acid, 18 Treatment of the N-PMB-protected phthalimidinoglutarimide (10) with ceric ammonium nitrate (CAN) in wet acetonitrile resulted in removal of the 4-methoxybenzyl group and furnished (()-1 as a white solid in 61% yield after purification by silica gel column chromatography. The employment of the benzyl group for protection of the glutarimide nitrogen was evaluated as a comparison to the PMB group.…”

Metal‐Free K2S2O8 Mediated Synthesis of 3‐(Substituted)‐2‐Arylisoindolin‐1‐One Derivatives With Cascade C−N/C−C Bond Formations Via Radical Cyclization

“…[19] Another traditional strategy of producing various 3-substituted isoindolinones is the deprotonation reaction of unsubstituted isoindolinone by strong bases. [20] More recent developments in the synthesis of substituted isoindolinones include Pd-/ Rh-/ or Ru-catalyzed CÀ H activation reactions. [21][22][23] Despite the existence of these well-proven pathways for the synthesis of C-3 functionalized isoindolinones, development of new and effective methods for the synthesis of isoindolin-1-ones with various substituent groups from straight-forward, easily accessible starting materials remains an active research area in organic chemistry regarding its broad structural diversity.…”