Research On The One Pot Synthesis Of Spiro [3,5’-pyrrolo [2,1-α] Isoquinolin-oxindoles]

Purpose: To establish an efficient method for the synthesis of structurally novel spirocyclic indolizine derivatives and further enrich the structural diversity of spirocyclic oxindoles.Method: The one pot construction of spiro[3,5’-pyrrolo[2,1-α]isoquinolin-oxindoles] was achieved via the sequential nucleophilic substitution and palladium-catalyzed intramolecular C（sp²）-H arylation of 3-pyrrol-oxindoles with 2-bromomethyl aryl bromides.Results:（1）The optimal reaction conditions were established as follows: 10 mol % of Pd（TFA）2 as the catalyst,20 mol % of PPh3 as ligand,2.5 equiv.of Na₂CO₃ as the base,DMF as solvent and 140 °C as the reaction temperature.（2）Under the optimized reaction conditions,24 spiro[3,5’-pyrrolo[2,1-α]isoquinolin-oxindoles] were obtained with 49%-92% of isolated yields.（3）The catalytic cycle of this sequential transformation was proposed based on the stepwise control experiments.And the compound 44 was successfully synthesized from the derivatization of product 33 u.Conclusion: In this sdudy,we have developed an efficient synthetic strategy for the construction of spirocyclic indolizidine derivatives incorporating the 3,3’-disubstituted oxindole framework.With the sequential nucleophilic substitution and palladiumcatalyzed C（sp²）-H arylation of 3-pyrrol-oxindoles with 2-bromomethyl aryl bromides,a wide range of spiro[3,5’-pyrrolo[2,1-α]isoquinolin-oxindoles] were obtained in up to 92% yield.Moreover,the catalytic cycle of this sequential transformation was also proposed based on the stepwise experiments.