Palladium-catalyzed allylation and deacylative allylation of 3-acetyl-2-oxindoles with allylic alcohols

Abstract

The Pd-catalyzed allylation of 3-acetyl-2-oxindoles with allyl alcohol is performed using 3 mol% of Pd(dba)2, rac-BINAP and BINOL phosphoric acid as catalytic mixture. This procedure allows the in situ synthesis of 3-allyl-2-oxindole by adding Triton B to the reaction mixture. The deacylative allylation of 3-acetyl-3-methyl-2-oxindoles with allylic alcohols is carried out with 3 mol% of Pd(OAc)2, dppp and 1.5 equiv. of LiOtBu as base affording the corresponding 3,3-disubstituted 2oxindoles in good yields. Both methodologies can be combined for the preparation of unsymmetrical 3,3-diallylated 2-oxindoles such as compound 7. The DaA must be carried out in the absence of oxygen in order to avoid the competitive formation of 3-alkyl-3-hydroxy-2-indoles. The later compounds can be easily obtained by deacylative oxidation of 3-alkylated 3-acetyl-2-oxindoles with LiOEt at rt under air.

Synthesis of 3-substituted 3-fluoro-2-oxindoles by deacylative alkylation

“…In this case, the reaction conditions were slightly modified with respect to the previous ones described for 3-alkyl-3acetyloxindoles. 14 The amount of Pd(OAc) 2 and 1,3bis(diphenylphosphino)propane (dppp) was increased from 3 to 6 mol% and the best solvent was toluene instead of THF. As base litium tert-butoxide was the best and the reaction was also carried out at rt.…”

“…Our group has described the base-mediated alkylation of 3acetyl-2-oxindoles with alkyl halides and electrophilic olefins, 13 and the Pd-catalyzed allylation with allylic alcohols. 14 We envisaged that 3-acetyl-3-fluoro-2-oxindole can be easily generated by fluorination of 3-acetyl-2-oxindole and applied to the synthesis of 3-substituted 3-fluoro-2-oxindoles by basepromoted and Palladium-catalyzed DaA.…”

Deacylative Reactions: Synthetic Applications

“…The DaA of 1,3‐dimethyl‐3‐acetyl‐2‐oxindoles with allylic alcohols has been studied also by our group . This process took place with 3 mol‐% of Pd(OAc) 2 and 1,3‐bis(diphenylphosphanyl)propane (dppp) using LiO t Bu as base at room temp.…”

“…In order to avoid the retro‐Claisen reaction acid conditions were ensured by the employment of the phosphoric acid derived from racemic BINOL as cocatalyst. The second step was performed with a different allylic alcohol using the same DaA reaction conditions affording the corresponding diallylated oxindole in 72 % overall yield (Scheme ) …”

“…of LiOEt as base in THF under air at room temp. (Scheme ) . This base promoted the deacylative oxidation giving the corresponding 3‐hydroxyindoles in good yields.…”