Diastereoselective Synthesis of Six‐Membered Carbocyclic Spirooxindoles via 6π‐Electrocyclization of 3‐Dienylidene‐2‐ oxindoles

Abstract

TheW ittig reaction of isatin derivatives with Morita-Baylis-Hillman bromides of cinnamaldehydes afforded 3-dienylidene-2-oxindoles.T hese trienes were converted into the corresponding spirooxindoles in as tereoselective manner in refluxing toluene in good yields.T he diastereomeric spirooxindoles could be obtained stereoselectively by adding ac atalytic amount of palladium(II)a cetate via the palladium-catalyzed isomerization of EEEtrienes to ZEE-trienes followed by am ore facile 6p-electrocyclization process.T he obtained spirooxindoles could be further functionalized by palladium-catalyzed oxidative arylation, thionation with Lawessons reagent, catalytic hydrogenation and Friedel-Crafts-type reaction.

Synthesis of Spiroindanyl‐2‐oxindoles via PPA‐mediated Intramolecular Friedel–Crafts Reaction

“…Spirooxindoles are found in numerous biologically interesting synthetic and natural substances . As a result, various synthetic methods of spirooxindoles have been developed . Recently, many spirooxindoles bearing indane or indene moieties have been reported .…”

“…Recently, we reported the synthesis of spirooxindoles 5a and 3‐aryl‐2‐oxindoles 2d,5b from isatin‐derived propargylic alcohol 1a . As a continuous study, we reasoned out that catalytic hydrogenation of the triple bond of 1a would provide 3‐phenylethyl‐2‐oxindole 2a , which could be converted to spiroindanyl‐2‐oxindole 3a by intramolecular Friedel–Crafts (IMFC) reaction, as shown in Scheme .…”

“…As a next experiment, the thionation of 3a with Lawesson's reagent (LR) was examined, as shown in Scheme 2a,b . The reaction of 3a and LR (2.5 equiv.)…”

Synthesis of Spirooxindoles Bearing Iminothiolactone Moiety from Morita–Baylis–Hillman Carbonates of Isatins and Phenyl Isothiocyanate

“…Thus, tremendous efforts have been devoted to efficient protocols to access these important motifs over the past years . Recently, we also reported diastereoselective synthesis of six‐membered carbocyclic spirooxindoles via 6π‐electrocyclization of 3‐dienylidene‐2‐oxindoles, 2a palla‐dium‐catalyzed synthesis of spirooxindoles by arylative cyclization of 3‐(γ,δ‐disubstituted)allylidene‐2‐oxindoles, 2b and one‐pot synthesis of spirofluorenyl‐ and spiroindeno[1,2‐ b ]indolyloxindoles via sequential inter‐ and intramolecular Friedel–Crafts reactions 2c . The Morita–Baylis–Hillman (MBH) adducts of isatins have been extensively used for the synthesis of various spirooxindoles, especially by Chen et al 3a–j …”