5-Chloro-2-cyclohexyl-1-oxo-6-sulphamoyl Isoindoline : a New Diuretic

Diastereo‐ and Enantioselective Catalytic Tandem Michael Addition/Mannich Reaction: Access to Chiral Isoindolinones and Azetidines with Multiple Stereocenters

“…Under the optimized reaction conditions, 2 t was subjected to the tandem reaction with different chalcones and the corresponding tandem adducts were obtained in good yields with high stereoselectivities (up to 95 % ee; Table 2 , entries 20-22). The configuration of the major isomer of 3 t was determined to be 1S,2R,3S by singlecrystal X-ray analysis, [8] and the other products were tentatively assigned by analogy.…”

“…Crystals of enantiopure 4 a were obtained and single-crystal X-ray analysis also revealed the configuration to be 1S,2R,3S (Figure 1, left). [8] It was anticipated that the tandem adducts 3 could be employed for the efficient preparation of chiral 2,3,4-trisubstituted N-tosylazetidines (Scheme 3). Azetidines are fourmembered nitrogen-containing heterocyclic compounds, and they possess various important biological properties such as activity against influenza virus A as well as anti-HIV, anti-HSV-1, and anti-HSV-2 activity.…”

“…The structure of 5 a was confirmed unambiguously by single-crystal X-ray analysis, and the newly formed chiral center was determined to have R configuration (Figure 1, right). [8] In summary, we have developed an efficient asymmetric tandem conjugate addition/Mannich reaction for the construction of multiple contiguous acyclic stereogenic centers in product with high diastereo-and enantioselectivity. This protocol provides a reliable and rapid approach for the synthesis of chiral N-tosyl isoindolinones and 2,3,4-trisubstituted N-tosylazetidines.…”

“…We used chalcone 1 a, N-tosyl aldimine 2 a, and Et 2 Zn as the reactants, and the reaction was performed at À10 8C in toluene for 12 hours. With L1 as a ligand, we screened a variety of copper sources including copper(I) and copper(II) species, and found the stereoselectivity was significantly affected by the nature of the counterion of the copper salts (Table 1, entries [1][2][3][4][5][6][7][8]. The more coordinating counterions proved to be more suitable, and among those tested, CuBr led to the best results with respect to reactivity and stereoselectivity ( To extend the application of the reaction, a variety of N-sulfonyl aldimines were subjected to the optimal reaction conditions using chalcone 1 a and Et 2 Zn.…”

Efficient Preparation of the Isoindoline Framework via a Six Component, Tandem Double A3‐Coupling and [2+2+2] Cycloaddition Reaction

“…[2] The first anti-tumour activity for an isoindoline was discovered nearly three decades ago. [3] In the decades to follow so many reports of various biological activities of isoindolines emerged that a comprehensive summary is not possible in this communication.…”