Construction of Vicinal All-Carbon Quaternary Stereocenters by Catalytic Asymmetric Alkylation Reaction of 3-Bromooxindoles with 3-Substituted Indoles: Total Synthesis of (+)-Perophoramidine

Abstract

Highly congested vicinal all-carbon quaternary stereocenters were generated via catalytic asymmetric alkylation reaction of 3-bromooxindoles with 3-substituted indoles. These catalytic reactions proceeded in excellent yields with a broad scope on either reaction partner, and with outstanding diastereo- and enantiocontrol. The newly developed method led to the total synthesis of (+)-perophoramidine in a highly efficient manner.

Catalytic enantioselective synthesis of quaternary carbon stereocentres

“…9c. 85 This reaction is suggested to occur by loss of HBr from the 3-bromooxindole to generate an electrophilic indol-2one intermediate, which couples with the indole nucleophile. How the Ni-diamine catalyst organizes this coupling to achieve high enantio- and diastereoselction is unclear at present.…”

“…This reaction sets the two contiguous quaternary stereocenters of (+)-perophoramidine. 85 OAc, acetoxy; MS, molecular sieves; THF, tetrahydrofuran; Me, methyl; Ph, phenyl.…”

Applications of Mitsunobu Reaction in total synthesis of natural products

“…Perophoramidine and Communesin F as two structurally related alkaloids bearing indole moiety was initially isolated from marine types Perophora namei and Enteromorpha intestinalis , respectively . In this line, perophoramidine was screened for possible biological activity which showed high potency towards the HCT116 colon cancer cells.…”

Recent Advances on the Total Syntheses of Communesin Alkaloids and Perophoramidine

“…52 Using this methodology, the authors could forge both quaternary stereocenters in a single enantioselective transformation. Optimization studies on the coupling of indoles with 3-bromoxindole showed that the two substrates could be readily coupled in the presence of a nickel Lewis acid catalyst and chiral diamine ligand.…”