Synthesis of [3.4]‐Spirooxindoles through Cascade Carbopalladation of Skipped Dienes

Abstract

A synthetic route to [3.4]-spirooxindoles based on cascade carbopalladation reactions of 1,4dienes is described. While carbopalladation of alkenes have been used to access mainly [4.4]-or [4.5]-spirocycles, 4-exo-trig carbopalladation has not been yet applied to the synthesis of relevant [3.4]-spirooxindole scaffolds bearing a cyclobutyl ring. In addition, the cascade reaction generates an exocyclic double bond that can serve as a platform to further diversify the substitution pattern of the spirooxindole nuclei.

Synthesis of tetrasubstituted alkenyl nitriles via cyanocarbene addition of [1.1.1]propellane

“…28 Meanwhile, dihydroxylation of alkene 3a produced diol 6 in 44% yield. 28 Last but not least, the reduction of 3a with DIBAL-H provided enal 7 in 60% yield. 29 To shed further light on the underlying reaction mechanism of this transformation, the following control experiments were performed (Scheme 4).…”

“…27 Similarly, epoxidation of compound 3a with m -CPBA provided the [3.2]-spirocycle 5 in 42% yield. 28 Meanwhile, dihydroxylation of alkene 3a produced diol 6 in 44% yield. 28 Last but not least, the reduction of 3a with DIBAL-H provided enal 7 in 60% yield.…”

“…28 Meanwhile, dihydroxylation of alkene 3a produced diol 6 in 44% yield. 28 Last but not least, the reduction of 3a with DIBAL-H provided enal 7 in 60% yield. 29…”

Expeditious entry into carbocyclic and heterocyclic spirooxindoles

“…In 2020, Azizollahi et al developed an efficient method to synthesize [3.4] spirooxindoles 2 via cascade reactions involving an intramolecular carbopalladation of alkenes 1 (Scheme 1). 24 Enamides 1 could be prepared by the coupling of anilines and 2-methylenepent-4-enoic acid.…”

Synthesis of Benzofused O- and N-Heterocycles through Cascade Carbopalladation/Cross-Alkylation of Alkynes Involving the C–C Cleavage of Cyclobutanols

“…With these precedents in mind, and given our interest in the topics of Pd chemistry and the processes related to C–C cleavage, − we aimed to extend the applicability of these types of cascades to the synthesis of heterocycles bearing an alkylated olefine moiety (Scheme ).…”