Synthesis of derivatives of isoindole and of pyrazino[2,1-a]isoindole

Abstract

Amines were reacted with lactones 7 or with unsaturated nitro derivatives 8 to give isoindole and pyrazino[2,1-a]isoindole derivatives. The mechanisms of formation, proofs of structure, and stereochemistry are presented.

Synthesis of functionalized isoindolinones: Addition of in situ generated organoalanes to acyliminium ions

“…1). Isoindolinones demonstrate a remarkably wide array of biological activities, including anti-inflammatory [4], antihypertensive [5], antipsychotic [6], vasodilatory [7] and antileukemic [8] effects, which renders the development of new synthetic routes toward these heterocycles particularly attractive. While several methods have been reported for the preparation of isoindolinones [9], some leading to the synthesis of natural products [10] and compound libraries [11], many approaches suffer from a lack of generality or functional group compatibility.…”

Synthesis of Phosphonic Acids Possessing Isoindolin-1-one Moiety: Unexpected Acid-Catalyzed C-P-Bond Cleavage

“…IR spectra were obtained in KBr pellets or in CCl 4 solution (for 18) and with a Vertex 70 IR Fourier spectrophotometer. 1 H, 13 C, and 31 P NMR spectra were measured at 300, 100, and 80 MHz, respectively, in DMSO-d 6 …”

Quaternary Ammonium Salt‐Promoted Multi‐Component Reaction in Water: Access to 3‐Alkyl‐2, 3‐Dihydro‐1H‐Isoindolin‐1‐One Derivatives

“…[1] Among the various N-heterocylic compounds, functional isoindolinone frameworks are a privileged class of building blocks since they show a wide range of biological activities and therapeutic potential, [2] such as antihypertensive, [3] antipsychotic, [4] anesthetic, [5] antiulcer, [6] vasodilatory, [7] antiviral, [8] and antileukemic [9] properties. In particular, 3-alkyl-2,3-dihydro-1H-isoindolin-1-ones are omnipresent as key structural scaffolds in many medicinal molecules, in which pagoclone (1 a), [10] pazinaclone (DN 2327, 1 b), [11] (R)-JM 1232 (1 c), [12] (S)-PD 172938 (1 d), [13] and (1 e) [14] are in the most representative ( Figure 1).…”

“…In addition, in the presence of p-methoxyphenylamine, the aliphatic b-keto acid could also react well in this reaction and form the desired product 5q in 70% yield. Finally, the substituted 2-formyl benzoic acid 2b (5, 6-(OCH 3 ) 2 ) was also tested for this decarboxylative cascade transformation upon the addition of p-methoxyphenylamine, and the target product 5r was successfully obtained with satisfactory yield. To gain insight on the mechanism of this multicomponent reaction, several control experiments traced by 1 H NMR were subsequently carried out (Scheme 3).…”