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.

1 Introduction

2 Synthesis of 2,2-Disubstituted Indoxyls via Dearomatization of Indoles: Background

3 Oxidative Dearomatization of 2-Alkylindoles to 2,2-Disubstituted Indoxyls: Development

4 Selected Scope and Preliminary Investigations toward an Asymmetric Coupling

5 Application to the Total Synthesis of Complex Alkaloids

6 Conclusions

Key words

indoxyl - alkaloids - synthetic methods - total synthesis - dearomatization

Publication History

Received: 16 January 2023

Accepted after revision: 26 January 2023

Accepted Manuscript online:
26 January 2023

Article published online:
28 February 2023

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