Tandem Annulations of Propargylic Alcohols to Indole Derivatives

Abstract

Indole derivatives are important heterocycles in organic synthesis for serving as privileged building blocks for functional material and as key components in a lot of bioactive compounds. Propargylic alcohols, bearing alkynyl and hydroxyl functional groups, have emerged as promising feedstock materials for the construction of carbo-and heterocycles. Especially, in the last decade, the Lewis or Brønsted acid catalysed tandem annulations of propargylic alcohols to build structurally diverse indole derivatives have been well-investigated. In this review, we summarize two main synthetic strategies toward indole derivatives via the cascade reactions of propargylic alcohols: indole-ring formation involved tandem reactions and the direct function-alization of indole skeletons. We hope this review would help to develop new and more efficient protocols for the synthesis of indole-included N-heterocycles. Direct Functionalization of Indole Skeletons 3.1. Reactions Initiated with Prior Activation of the Alkyne Moiety 3.2. Reactions Initiated with Prior Activation of the Hydroxyl Group 4. Conclusions

Chiral phosphoric acid-catalyzed regio- and enantioselective reactions of functionalized propargylic alcohols

“…As universal and versatile synthons in organic synthesis, propargylic alcohols have been successfully exploited in a range of useful reactions, such as propargylic substitutions, 1 rearrangements, 2 indole syntheses, 3 annulations, 4 allene formation, 5 and so on. 6 However, these impressive transformations were largely limited to transition-metal-mediated processes.…”

Relay Cu(I)/Brønsted Base Catalysis for Phospha‐Michael Addition/5‐exo‐dig Cyclization/Isomerization of in situ Formed aza‐Alkynyl o‐quinone methides with P(O)−H compounds to C3‐Phosphorylated Indoles

“…In conjunction with our continuing interest in the chemistry of propargylic alcohols [4b,5a] and the design novel tandem reactions [14] based on the dehydrative couplings between P(O)‐H species and alcohols [14] for the synthesis of phosphorylated heterocycles, [9,15b–c,k–l] herein, we report a new approach for the assembly of C3‐phosphorylated indoles 3 via a relay Cu(I)/Et 3 N‐catalyzed one‐pot reaction of in situ generated aza ‐ o ‐AQMs and P(O)‐H compounds, involving a sequential phospha ‐Michael addition/5‐ exo ‐ dig cyclization/isomerization process (Scheme 2).…”

Synthesis of functionalized indoles via cascade benzannulation strategies: a decade's overview

“…In general, the synthesis of indoles can be broadly classified into two general categories – (a) the construction of the pyrrole ring; 5 and (b) the construction of the benzene ring into a pre-existing pyrrole core. Apart from a few exceptions, the majority of known methods lie in the first category and several well-known named reactions such as Fischer–Jourdan, Möhlau–Bischler, Resseirt, Madelung, Batcho–Leimgruber, and Gassman have paved their way over the years.…”

“…Over the years, landmark signs of progress have been recorded in the field of indole synthesis and, consequently, several reviews have documented the synthesis and functionalization of indoles. 5,7,9 However, to the best of our knowledge, there exists no such analysis based on the benzannulation approach. This review aims to be a comprehensive overview of timely developments in this area and gives critical insights into mechanistic approaches towards the benzannulation approach in the last decade starting from 2010.…”