Reductive openings of benzylidene acetals revisited: a mechanistic scheme for regio- and stereoselectivity.

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Abstract

Despite the importance of regioselective reductive openings of cyclic acetals, mechanistic details are scarce. In this study 4,6-O-benzylidene acetals were used as model compounds for deciphering the mechanism of regioselective openings using a variety of reducing agents. Competitive isotopic studies aiming at primary and secondary isotope effects, as well as an electron-deficient substrate, were used to evaluate stereo- and regioselectivity. We show that there are three distinctly different mechanistic pathways. In nonpolar solvents, such as toluene, the acetal is activated by the very reactive naked Lewis acid to give a fully developed oxocarbenium ion that is then reduced by the borane, with low stereoselectivity. In THF the reactivity of the Lewis acid is moderated by complex formation with the solvent. These reactions are thus much slower and proceed through an intimate ion pair and thereby show high stereoselectivities. The regioselectivity in these reactions is directed by the interaction between the Lewis acid and the most nucleophilic oxygen of the acetal, thus yielding a free 6-hydroxyl group. Finally, boranes such as BH(3)·NMe(3) are activated by Lewis acid, which results in the borane being the most electrophilic species, and consequently the reaction shows inversed regioselectivity to give a free 4-hydroxyl group. These reactions proceed through an oxocarbenium ion and thus show low stereoselectivity.

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  • Organic Chemistry
Original languageEnglish
Pages (from-to)8003-8011
JournalJournal of Organic Chemistry
Volume75
Issue number23
Publication statusPublished - 2010
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Organic chemistry (S/LTH) (011001240)