Divergent Multigram Access to sp3-Rich Spirocyclic Building Blocks via Iodocyclization of β,γ-Unsaturated Carboxylic Acids
Тип публікації :
Препринт
Дата випуску :
25 серпня 2026 р.
Автор(и) :
Volodymyr V. Semeno
Vadym O. Vasylchenko
Rustam T. Iminov
Dmytro O. Lutsenko
Oleksandra V. Shvek
Yevhen O. Zaika
Bohdan V. Vashchenko
Oleksandr O. Grygorenko
eKNUTSHIR URL :
Журнал :
ChemRxiv
Цитування :
[APA 7] Volodymyr, V. S., Vadym, O. V., Rustam, T. I., Dmytro, O. L., Oleksandra, V. S., Yevhen, O. Z., Bohdan, V. V., & Oleksandr, O. G. (2026). Divergent Multigram Access to sp3-Rich Spirocyclic Building Blocks via Iodocyclization of β,γ-Unsaturated Carboxylic Acids. ChemRxiv,. https://doi.org/10.26434/chemrxiv.15007836/v1
[ДСТУ] Divergent Multigram Access to sp3-Rich Spirocyclic Building Blocks via Iodocyclization of β,γ-Unsaturated Carboxylic Acids / V. S. Volodymyr та ін. ChemRxiv. 2026. DOI: 10.26434/chemrxiv.15007836/v1 (дата звернення: 11.09.2026).
A divergent and scalable approach to three families of spirocyclic sp 3 -rich building blocks was disclosed, based on iodocyclization of common β,γ-unsaturated carboxylic acids bearing a quaternary center. These intermediates were obtained from commercially available ketones through a three-step reaction sequence including Horner-Wadsworth-Emmons olefination, ester reduction with DIBAL, and Johnson-Claisen rearrangement on up to a 100 g scale in a single run without chromatographic purification. The choice of the iodocyclization substrate affected the product type: classical iodolactonization gave γ-lactones, reduction to the alkenol followed by iodoetherification provided tetrahydrofurans, and amidation led to γ-lactams (65–82% yields). O-Cyclizations were promoted by NaHCO3 in THF–H2O, which worked for both substrate types but resulted in different reaction rates, whereas less nucleophilic amides required activation via N,O-bis(silylation). Further modification at the iodomethyl group provided a series of building blocks including primary amines and sulfonyl chlorides; in the lactone series, recyclization to spirocyclic 5-hydroxypiperidin-2-ones was also achieved.
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