The Mislow-Evans rearrangement: from mechanistic understanding to modern applications in natural product and functional molecule synthesis (2020-2026).
Abstract
The Mislow-Evans (MBE) [2,3]-sigmatropic rearrangement has emerged as one of the most versatile stereospecific transformations in modern organic synthesis, enabling the efficient construction of allylic alcohols and structurally complex molecules through highly controlled chirality transfer. Owing to significant methodological advances, a critical assessment of recent developments has become timely. This review comprehensively examines progress reported between 2020 and 2026, covering classical sulfoxide-sulfenate rearrangements together with aza-, seleno-, dearomative, organocatalytic, and catalytic variants. Particular emphasis is placed on mechanistic principles, stereochemical control, catalyst design, substrate scope, reaction efficiency, scalability, and sustainability. The synthetic utility of the MBE-rearrangement is critically evaluated through its application in the total synthesis of architecturally complex natural products, including FR901464, zetekitoxin AB, withanolides, tetrodotoxin, pyrenolide D, and trichodermamides, as well as in the preparation of functional molecules such as diols, amino alcohols, aryl thioethers, trifluoromethylthiophosphonium salts, and fluorogenic probes. Rather than providing a descriptive survey, this review comparatively analyzes reported methodologies by correlating reaction design with stereochemical fidelity, synthetic practicality, catalyst loading, substrate generality, and environmental considerations. Current limitations, including challenges in catalytic efficiency, substrate diversity, mechanistic understanding, and sustainable process development, are critically discussed alongside future opportunities. Unlike previous reviews, this work integrates developments reported between 2020 and 2026, mechanistic insights, and comparative analyses of synthetic performance, stereochemical outcomes, catalytic innovation, scalability, and green chemistry, providing a comprehensive framework for evaluating contemporary MBE methodologies and guiding future advances in stereoselective organic synthesis.
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