ABSTRACT
An efficient route to highly substituted indoles was developed. It included regioselective functionalization of tetrahydroindol-4(5H)-ones, prepared by ring-opening cyclization of cyclohexane-1,3-dione-2-spirocyclopropanes with primary amines, and subsequent oxidation. The 6-substituted indoles were synthesized from a readily available 5-substituted cyclohexane-1,3-dione-2-spirocyclopropane. The synthesis of 5- and 7-substituted indoles was achieved by regioselective electrophilic alkylation of tetrahydroindol-4(5H)-one, followed by oxidation. The 4-substituted indoles were synthesized by nucleophilic alkylation of the corresponding pyrrole derivative, which was prepared by partial oxidation of tetrahydroindol-4(5H)-one, and sequential oxidation. The synthesis of 4-substituted indoles was also accomplished by palladium-catalyzed coupling of 4-hydroxyindole-derived triflates. Furthermore, the synthesis of 4,5,6,7-tetrasubstituted indoles was achieved by using these regioselective alkylations.
ABSTRACT
An efficient and practical synthesis of 2',3'-nonsubstituted cyclohexane-1,3-dione-2-spirocyclopropanes using a sulfonium salt was achieved. The reaction of 1,3-cyclohexanediones and (2-bromoethyl)diphenylsulfonium trifluoromethanesulfonate with powdered K2CO3 in EtOAc at room temperature (r.t.) provided the corresponding spirocyclopropanes in high yields. The synthetic method was also applied to 1,3-cyclopentanedione, 1,3-cycloheptanedione, 1,3-indanedione, acyclic 1,3-diones, ethyl acetoacetate, and Meldrum's acid.
Subject(s)
Onium Compounds/chemistry , Spiro Compounds/chemical synthesis , Sulfonium Compounds/chemistry , Molecular Structure , Spiro Compounds/chemistryABSTRACT
An efficient ring-opening cyclization of cyclohexane-1,3-dione-2-spirocyclopropanes with primary amines has been developed. The reaction proceeded at room temperature without any additives to provide 2-substituted tetrahydroindol-4-ones in good to excellent yields without the formation of the 3-substituted isomers. The obtained product was readily converted into a 2-substituted 4-hydroxyindole derivative via a synthetically useful indoline intermediate.