Stereoselective Construction of α-Tetralone-Fused Spirooxindoles via Pd-Catalyzed Domino Carbene Migratory Insertion/Conjugate Addition Sequence

Abstract

An efficient diastereoselective synthesis of α-tetralone-fused spirooxindoles is reported. The Pd-catalyzed domino reaction proceeds through a carbene migratory insertion followed by a 6-endo-trig mode of conjugate addition sequence from easily accessible isatin-derived N-tosylhydrazones and 2'-iodochalcones. The versatility of the protocol has been showcased by high functional group tolerance, broad substrate scope, and extension to an expedient synthesis of spiroacenaphthylenes. NMR reaction profiling and deuterium-labeling investigations provide insight into the mechanistic pathway.

Stereoselective synthesis and applications of spirocyclic oxindoles

“…344 Another approach is Pd-catalysed migratory insertion of diazo compounds and Michael addition. 345 Chiral hypervalent iodine mediated. In the sole example of the application of asymmetric hypervalent iodine mediated dearomative spirocyclisation, Gong synthesised spirooxcyclohexene oxindoles in moderate yields but high enantioselectivity (Scheme 70).…”

Stereoselective Domino Reactions in the Synthesis of Spiro Compounds

“…The formation of 615 via a 5- exo - trig mode of closure is disfavored presumably due to increased steric hindrance involved in the approach of the Pd to α-position of the double bond. 134…”

“…In addition, a transition-state model has been proposed to understand the observed stereoselectivity (Scheme 129 ). 134…”

Recent Advances in Transition‐Metal‐Catalyzed Reactions of N‐Tosylhydrazones

“…In the same year, the group of Sekar reported a stereoselective construction of α‐tetralone‐fused spirooxindoles via isatin‐derived N ‐tosylhydrazones and 2’‐iodochalcones (Scheme 81). [103] By performing a palladium‐catalyzed domino carbene migratory insertion/conjugate addition sequence, a high functional group tolerance with a broad substrate scope could be reached, bearing quaternary or tertiary carbon centers with high diastereoselectivity. With this protocol, a first approach with isatin‐derived N ‐tosylhydrazones and metal‐carbenoid involving domino process was furnished, to construct novel spirocycles.…”