February 2023

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.1 Introduction2 Synthesis of 2,2-Disubstituted Indoxyls via Dearomatization of Indoles: Background3 Oxidative Dearomatization of 2-Alkylindoles to 2,2-Disubstituted Indoxyls: Development4 Selected Scope and Preliminary Investigations toward an Asymmetric Coupling5 Application to the Total Synthesis of Complex Alkaloids6 Conclusions

A bioinspired formal synthesis of the montanine-type Amaryllidaceae alkaloid pancracine through selective hydrogenation of a 3-arylindole derivative is disclosed. The key features of this synthesis include a hexahydroindole synthesis by a chemoselective hydrogenation of an aryl-substituted indole and a diastereoselective silyl hydride reduction of an iminium intermediate generated from an enaminone through Tf2O activation. The eight-step assembly of the 5,11-methanomorphanthridine framework represents a novel and efficient strategy that permits one of the shortest syntheses of pancracine reported so far.

The Vilsmeier–Haack reaction has historically been a topic of significant interest to organic chemists, and it continues to attract considerable attention. The reaction itself provides a facile route towards a large number of aromatic and heteroaromatic systems. The Vilsmeier–Haack reagent, generated from amides and halides, is found to be very important in organic synthesis. This account highlights recent developments in the synthetic utility of the Vilsmeier–Haack reagent.1 Introduction2 Formylation3 Formylation and Chlorination4 Formylation and Acetylation5 Chlorination6 ortho-Formylation7 Miscellaneous8 Conclusions

Biomimetic dimerization is a fascinating pathway to natural product synthesis. By using structurally inferior monomers, complex molecular architectures can be readily established with distinct efficiency and elegance. In this Account, our investigation on biomimetic dimerization in natural product synthesis has been summarized, which includes our synthetic exploration of linderaspirone A, bi-linderone, parvistemin A, (±)-diperezone, scabellone B, and spiroxins A/C/D.1 Introduction2 Biomimetic Dimerization in the Synthesis of Linderaspirone A and Bi-linderone3 Biomimetic Dimerization in the Synthesis of Parvistemin A and (±)-Diperezone4 Biomimetic Dimerization in the Synthesis of Scabellone B5 Dimerization Investigation in the Synthesis of Spiroxins A/C/D6 Conclusion