Construction of poly-N-heterocyclic scaffolds via the controlled reactivity of Cu-allenylidene intermediates.

Controlling the sequence of the three consecutive reactive carbon centres of Cu-allenylidene remains a challenge. One of the impressive achievements in this area is the Cu-catalyzed annulation of 4-ethynyl benzoxazinanones, which are transformed into zwitterionic Cu-stabilized allenylidenes that are trapped by interceptors to provide the annulation products. In principle, the reaction proceeds via a preferential γ-attack, while annulation reactions via an α- or β-attack are infrequent.

Two Catalytic Annulation Modes via Cu-Allenylidenes with Sulfur Ylides that Are Dominated by the Presence or Absence of Trifluoromethyl Substituents.

We disclose the Cu-catalyzed enantioselective synthesis of 3-methyl-3-propargyl-indolines, which contain a quaternary stereogenic carbon center, via the decarboxylative [4 + 1] annulation of 4-methyl-4-propargyl-benzoxazinanones with variety of sulfur ylides. The reaction proceeds predominantly through a γ-attack at the Cu-allenylidene intermediates by sulfur ylides to provide the corresponding indolines in good yield and high enantioselectivity (up to 91% ee). In contrast, the reaction of 4-trifluoromethyl-4-propargyl-benzoxazinanones with sulfur ylides delivers 3-trifluoromethyl-2-functionalized indoles in good to high yield via an unexpected α-attack at the Cu-allenylidene intermediates.

Synthesis of novel 1,2-benzothiazine 1,1-dioxide-3-ethanone oxime N-aryl acetamide ether derivatives as potent anti-inflammatory agents and inhibitors of monocyte-to-macrophage transformation.

A series of novel 1,2-benzothiazine 1,1-dioxide-3-ethanone oxime N-aryl acetamide ether derivatives 7a-h and 9a-h were synthesized starting from sodium salt of saccharin 1 in series of steps. Final compounds 7a-h and 9a-h were evaluated for the anti-inflammatory activity and their ability to inhibit monocyte-to-macrophage transformation. Compounds 7e, 9b, 9e and 9h showed impressive anti-inflammatory activities (TNF-α, IL-8 and MCP-1) at micro molar concentration which was found to be better than positive control i.