Polymer-Supported Stereoselective Synthesis of Tetrahydrobenzopyrazino-thiadiazinone Dioxides via N-Sulfonyl Iminiums

Abstract

The stereoselective synthesis of 1,2,11,11a-tetrahydrobenzo[e]pyrazino[1,2-b][1,2,4]thiadiazin-3(4H)-one 6,6-dioxides on a solid support via tandem N-sulfonyl iminium ion cyclization, followed by nucleophilic addition is reported. The synthesis proceeded with full control of stereoselectivity at the newly formed asymmetric carbon, under mild conditions, and using commercially available building blocks. The synthetic route provided high-purity crude products.

Solid‐Phase Synthesis of Trisubstituted Benzo[f][1,2,3]triazolo[1,5‐a][1,4]diazepin‐6(5H)‐ones and Their Sulfonyl Analogues under Mild Reaction Conditions

“…[30] Overall yields were calculated according to loadings determined after the first immobilization step: 1(1) 0.43 and 0.51 mmol/g, 1(2) 0.29 mmol/g, 1(3) 0.75 mmol/g, 1(4) 0.23 mmol/g, 1(5) 0.25 mmol/g, 1(6) 0.3 mmol/g. [30] Overall yields were calculated according to loadings determined after the first immobilization step: 1(1) 0.43 and 0.51 mmol/g, 1(2) 0.29 mmol/g, 1(3) 0.75 mmol/g, 1(4) 0.23 mmol/g, 1(5) 0.25 mmol/g, 1(6) 0.3 mmol/g.…”

“…Preparation of Resin-Bound Amines: The reaction conditions for the individual steps of the solid-phase synthesis of compounds 1 have been reported in a previous communication. [30] Overall yields were calculated according to loadings determined after the first immobilization step: 1(1) 0.43 and 0.51 mmol/g, 1(2) 0.29 mmol/g, 1(3) 0.75 mmol/g, 1(4) 0.23 mmol/g, 1(5) 0.25 mmol/g, 1(6) 0.3 mmol/g.…”

“…[20,21] In this report, we introduce a new approach based on solid-phase synthesis, suitable for the preparation of target triazolobenzodiazepine derivatives with three sites of diversity. [23,[28][29][30] In contrast, the use of polymer-supported Npropargylnitrobenzenesulfonamides has not been reported. Recently, immobilized N-phenacylor N-benzylnitrobenzenesulfonamides have been extensively used for the preparation of various five-, [22,23] six-, [24] and sevenmembered [25][26][27] heterocyclic scaffolds, including fused systems.…”

“…Recently, immobilized N-phenacylor N-benzylnitrobenzenesulfonamides have been extensively used for the preparation of various five-, [22,23] six-, [24] and sevenmembered [25][26][27] heterocyclic scaffolds, including fused systems. [23,[28][29][30] In contrast, the use of polymer-supported Npropargylnitrobenzenesulfonamides has not been reported. Due to the significant advantages of solid-phase synthesis, it is frequently used in the field of combinatorial chemistry for research into drug-like molecules.…”

From Amino Acids to Nature-Inspired Molecular Scaffolds: Incorporation of Medium-Sized Bridged Heterocycles into a Peptide Backbone

“…The reaction conditions for the individual steps of the synthesis have been reported in previous communications. 27,28 Analytical Data of Individual Compounds. (2S,6R)-3-((4-Nitrophenyl)sulfonyl)-2,3,4,5,6,7-hexahydro-1H-6,2-(epiminomethano) azocino [5,4-b]indol-13-one [(S,R)-5f].…”