Syntheses of Spirocyclic Oxindole‐Butenolides by Using Three‐Component Cycloadditions of Isocyanides, Allenoates, and Isatins

Abstract

Spiro workflow! Efficient syntheses of spirocyclic oxindole‐butenolides from readily available isocyanides, allenoates, and isatins are disclosed (see scheme; R1=alkyl, aryl; R2=halide, nitro, methoxy; PG=protecting group). This protocol also allows the insertion of carbon monoxide into organic molecules without the aid of a transition‐metal catalyst after the hydrolysis process.

Benzofuran–Chalcone Hybrids as Potential Multifunctional Agents against Alzheimer’s Disease: Synthesis and in vivo Studies with Transgenic Caenorhabditis elegans

“…A number of useful strategies,6–8 such as the oxonium‐Prins cyclization6a,6b and multistep reactions,6c–6g have been devised for the preparation of tetrahydrofurochromenes. Many elegant approaches have also been developed for the synthesis of tetrahydrofuryl spirooxindoles in previous studies,7,8 including transition‐metal‐catalysed reactions,8a–8f organocatalytic processes,8g,8h and other methods 8i–8k. In contrast, only a few methods have been established for the highly efficient construction of oxindole‐fused spirotetrahydrofurochromans, more complex molecules containing both tetrahydrofurochromene and tetrahydrofuryl spirooxindole moieties.…”

Isocyanide‐Based Multicomponent Reactions: Concise Synthesis of Spirocyclic Oxindoles with Molecular Complexity by Using a [1,5]‐Hydrogen Shift as the Key Step

“…In 2011, we reported the first example of a multicomponent reaction involving an isocyanide and allenoate 8a. Since then, we have spent much time in exploring the potential synthetic utility of the isocyanide‐based [2+2+1] three‐component reactions with allenoate, thus providing a quick access to the syntheses of functionalized carbocycles and natural‐product‐like N‐containing heterocycles 8b.…”

“…The mechanism of this cycloaddition reaction has not been unequivocally established, but one reasonable possibility is proposed in Scheme . The beginning of the reaction involves the formation of reactive zwitterionic species, which exist as a resonance‐stabilized form A ↔ B 8a–c. The allylic carbanion B then adds to the carbon–carbon double bond of substrate 3 to produce intermediate C .…”

Baylis–Hillman Bromides as a Source of 1,3‐Dipoles: Sterically Directed Synthesis of Oxindole‐Fused Spirooxirane and Spirodihydrofuran Frameworks

“…Therefore, the development of simple synthetic strategies for obtaining spirooxindole derivatives has been and continues to be an attractive area in synthetic and medicinal chemistry 1f–i. 2a–f As part of our ongoing research into the Baylis–Hillman (BH) reaction, herein, we report the interesting sterically directed cycloaddition reactions of the dipoles that are generated from Baylis–Hillman bromides with isatins as dipolarophiles, thus providing a facile strategy for the synthesis of spiroepoxy oxindoles and spirodihydrofuran oxindoles in a one‐pot operation.…”