2,2-Disubstituted Indoxyls via Oxidative Dearomatization: Generalization to 2-Alkylindoles and Application to Alkaloid Synthesis

Abstract

2,2-Disubstituted indoxyls are commonly found within natural products and bioactive molecules. Among the numerous methods to access such motifs, the dearomative transformation of indoles represents an attractive approach. Despite much development, a potential gap exists in the oxidative union of readily accessible 2-substituted indoles with nucleophilic partners, where a general transformation accommodating 2-alkyl substitution and a broad range of nucleophiles is lacking. Herein, we describe the development of a user-friendly solution to this challenge and highlight its utility in the synthesis of complex alkaloids.

Silver-Enabled Dearomative Trifluoromethoxylation of Indoles

“…Nitrogen heterocycles are commonly found in natural products and drugs . Dearomatization of indoles to generate indolines has thus received considerable attention. Moreover, dearomatization of indoles using fluorine-containing groups has emerged as an important research topic because fluorine atoms can markedly alter the physicochemical properties and metabolic stability of bioactive molecules .…”

Total Synthesis of Alanense A through an Intramolecular Friedel–Crafts Alkylation

“…Not surprisingly, a stoichiometric amount of Lewis acid was required to efficiently induce the formation of cyclization product 4 . In this regard, we were gratified to find that the cyclization was accomplished by treatment of 5 with 10 mol % p -TsOH·H 2 O in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) (entry 5). ,− A survey of solvents revealed that HFIP is critical for this cyclization (entry 5 vs entries 6–9). While the reaction in 2,2,2-trifluoroethanol (TFE) also proceeded smoothly, the yield of 4 (70%) in the reaction in TFE did not exceed that in HFIP (entry 6).…”