Strain‐Driven Dyotropic Rearrangement: A Unified Ring‐Expansion Approach to α‐Methylene‐γ‐butyrolactones

Abstract

An unprecedented strain‐driven dyotropic rearrangement of α‐methylene‐β‐lactones has been realized, which enables the efficient access of a wide range of α‐methylene‐γ‐butyrolactones displaying remarkable structural diversity. Several appealing features of the reaction, including excellent efficiency, high stereospecificity, predictable chemoselectivity and broad substrate scope, render it a powerful tool for the synthesis of MBL‐containing molecules of either natural or synthetic origin. Both experimental and computational evidences suggest that the new variant of dyotropic rearrangements proceed in a dualistic pattern: while an asynchronous concerted mechanism most likely accounts for the reactions featuring hydrogen migration, a stepwise process involving a phenonium ion intermediate is favored in the cases of aryl migration. The great synthetic potential of the title reaction is exemplified by its application to the efficient construction of several natural products and relevant scaffolds.

Synthesis of α-exo-Methylene-γ-butyrolactones: Recent Developments and Applications in Natural Product Synthesis

“…The reaction mechanism was further examined by computational studies, indicating an asynchronous concerted mechanism. 39 This is distinct from the previously reported dyotropic reactions. The 3,4-cis-disubstituted -lactone 72 underwent a different rearrangement pathway with alkyl migration instead of C5-H to give lactone 73.…”

“…38 For -methylene--lactones, an unprecedented strain-driven dyotropic rearrangement has been realized by Tang's group, which enabled efficient access to a wide range of -exo-methylene--butyrolactones (Scheme 16). 39…”

Tailored Synthesis of Skeletally Diverse Stemona Alkaloids through Chemoselective Dyotropic Rearrangements of β‐Lactones

“…Apparently, in the absence of notable steric factor, the reaction pathways were mainly determined by the migration aptitude of C5 substitutes. Although some previous studies [20a, 21c] indicated that hydrogen displays a greater migratory capability than alkyl groups, allyl migration takes place as a competing reaction in the current scenario due to its increased migratory capability. To improve the selectivity of the reaction, we conducted an extensive condition optimization (for details, see Supporting Information).…”

Strain‐Driven Dyotropic Rearrangement: A Unified Ring‐Expansion Approach to α‐Methylene‐γ‐butyrolactones

“…Fortype I substrates that bear two alkyls and one hydrogen on the C-5 position, all reactions underwent CÀHm igration exclusively, delivering 5,5-dialkyl-substituted MBL (9-24)i ns atisfactory yields.S everal 5/6-spiro bicyclic MBL (9-11)w ere prepared by this method with high diastereoselectivity,among which 10 was unambiguously confirmed by the X-ray crystallographic study. [23] For a-methylene-b-lactones bearing two different alkyls (R 1 ¼ 6 R 2 ), ap air of diastereoisomeric precursors (ca. 1:1r atio) were used directly,a st hey eventually resulted in identical products (14-21)a fter migration.…”