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Tetrahydrofuran Formation through Intramolecular Iodoetherification: Mechanistic Insights into the Neighbouring‐Group Participation of an Ester
Author(s) -
Veiga Nicolás,
Ramos Juan C.,
Seoane Gustavo,
Brovetto Margarita
Publication year - 2017
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201700494
Subject(s) - chemistry , intramolecular force , diastereomer , nucleophile , tetrahydrofuran , alcohol , ether , ring (chemistry) , stereochemistry , group (periodic table) , medicinal chemistry , carbonyl group , organic chemistry , catalysis , solvent
During the iodoetherification of chiral and conformationally restricted 3‐butenyl carbinols to give 2,5‐disubstituted THFs, the presence of an ester in the side chain exerts a profound effect on the chemo‐ and diastereoselectivity of the reaction. When submitted to standard iodoetherification conditions, ester‐containing substrates gave diastereomeric mixtures of THFs, together with variable amounts of iodohydrins. Conversely, when the ester group was reduced to an alcohol or ether, the corresponding trans ‐THFs were obtained more quickly, with complete diastereoselectivity and without contamination by the iodohydrin. In this paper, the mechanistic details of the iodoetherification of protected 3‐butenyl carbinols are revealed. The results show that the carbonyl group decreases the nucleophilicity of the acetonide oxygen atoms, and stabilizes the reactants by a carbonyl–iodonium through‐space interaction. Additionally, it promotes the formation of a stable seven‐membered‐ring carboxonium intermediate, causing an increase in the activation barriers and a decrease in the reaction diastereoselectivity compared to the non‐ester analogues.