The Nucleophile-Intercepted Meyer–Schuster Rearrangement of the (Z-enoate and Z-enal) Propargylic Alcohols

Abstract

The classical Meyer–Schuster rearrangement (MSR) of propargylic alcohols to α,β-enones is a century-old transformation. However, its electrophile-intercepted version is a recent modification for the synthesis of α-functionalized enones. During the last decade (2015–2025), our research group at IIT Madras had developed a nucleophile-intercepted version of the classical MSR by employing the Z-enoate– as well as Z-enal–assisted propargylic alcohols. In this account, we have detailed the design, discovery, and development of this novel and robust synthetic process. This modification of the classical MSR has emerged as a powerful tool for the synthesis of highly functionalized α,β-enones, and structurally unique polycyclic frameworks such as butenolide-fused allenes and butenolide-based atropisomeric compounds, naphthofurans, benzofurans, 2-vinylfurans, 2-acylfurans, and carbazoles. This reaction strategy was further utilized for the partial as well as the total synthesis of several natural products, such as amycofuran, frondosin B, carbazoquinocins, lipocarbazoles, carazostatin, and rubrolides, respectively. Several fruitful control experiments and isolation of the relevant intermediates helped us understand the possible mechanistic pathway for this process. We hope that this modified version of the MSR will be further expanded in future.

Keywords

Meyer–Schuster rearrangement - Propargylic alcohols - α,β-Enones - Carbazoles - Butenolides

Publication History

Received: 01 September 2025

Accepted after revision: 08 October 2025

Accepted Manuscript online:
08 October 2025

Article published online:
10 November 2025

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