Stereoselective and Regioselective Assembly of Spirooxindole [2,1‐b]furan Motifs through a Tandem Friedel–Crafts Alkylation/5‐exo‐dig‐Cyclization

Abstract

3‐Alkynyl‐3‐OBoc (Boc = tert‐butoxycarbonyl) oxindole derivatives underwent a CuII‐mediated stereo‐ and regioselective Friedel–Crafts alkylation/5‐exo‐dig‐cyclization with 2‐naphthols or cyclic 1,3‐diketones. This gave spirooxindole [2,1‐b]furan motifs in good to excellent yields under ambient conditions, and the process has a wide substrate scope.

Formal [4+1] annulations of salicylaldehydes with 3‐chlorooxindoles for diastereoselective construction of dihydrobenzofuranspirooxindoles by solvent‐free grinding

“…However, only limited approaches have been developed for highly efficient construction of dihydrobenzofuran‐fused spirooxindoles such as Friedel–Crafts alkylations of phenols with spiroepoxyoxindoles followed cyclization by the Appel reaction [6], Friedel–Crafts alkylation/cyclization of isatin‐derived propargylic alcohols with 2‐naphthols [7], cyclization of propargylic alcohols with aryne [8], Michael addition/iodization/cyclization process of 2‐hydroxynitroolefins and oxindoles [9], [4+1] cycloaddition of 3‐chlorooxindoles with ortho‐quinone methides [10], Michael addition/ring‐opening/closure cascade reaction of 3‐hydroxyoxindoles with coumarin‐3‐carboxylates [11], [4+1]cycloaddition of isatin‐derived oxyphosphonium enolates with with ortho‐quinone methides [12], cyclization reaction of 3‐cinnamyl‐3‐hydroxy‐2‐oxindoles and ortho‐quinone methides [13]. Despite the availability of methodologies to construct these spiro‐oxindoles, most of these synthetic strategies often suffer from prefunctionalized oxindole cores at C3 position, multi‐step synthesis, harsh reaction conditions, inefficiency and stoichiometric waste.…”

Synthesis, Characterization, and Cytotoxicity of New Spirooxindoles Engrafted Furan Structural Motif as a Potential Anticancer Agent

“…Several structural pharmacophores have been coadministrated with the spirooxindole privileged structures inspired by research for structural complexities with their diverse bioactivities. , Due to the urgent need to discover a new cancer agent with more targeting to cancer cells and less harmful for the normal tissue, chemists have synthesized many spirooxindoles for this purpose. In particular, spirooxindoles containing furan scaffold, which are called oxa-spirooxindoles, widely exist in many natural and biologically active molecules. − The designed, synthesized, and reported spirooxindoles show anticancer activity and can serve as an anti-tumor agent, CB2 receptor agonist, antagonists of progesterone receptors, antagonists of progesterone receptors, Nav1.7 blocker (XEN907), and selective cyclooxygenase COX-1 with TNF-α and IL-6 Inhibitors. − …”

“…In particular, spirooxindoles containing furan scaffold, which are called oxa-spirooxindoles, widely exist in many natural and biologically active molecules. 8 − 15 The designed, synthesized, and reported spirooxindoles show anticancer activity and can serve as an anti-tumor agent, CB2 receptor agonist, antagonists of progesterone receptors, antagonists of progesterone receptors, Nav1.7 blocker (XEN907), and selective cyclooxygenase COX-1 with TNF-α and IL-6 Inhibitors. 16 − 19 …”

Enantioselective Formal Arylation of (7‐Aza)isatylidene Malononitriles with α′‐Alkylidene‐2‐cyclohexenones

“…The oxindoles bearing a tetrasubstituted stereogenic center at the benzylic position, especially those with a 3-aryl substituent, are prevalent in a large number of natural products and pharmaceutically important compounds, such as cipargamin (A) (antimalarial drug), [1] 3-spirooxindole benzofuran/benzopyran (B) (anticancer activity), [2] funapide (C) and XEN 907 (D) (sodium channel blockers) ( Figure 1). [3] As a result, the construction of these skeletons with high levels of enantioselectivity has aroused much attention in organic and medicinal chemistry.…”