Open AccessLewis Acid-Catalyzed Vinyl Acetal Rearrangement of 4,5-Dihydro-1,3-dioxepines: Stereoselective Synthesis of cis- and trans-2,3-Disubstituted Tetrahydrofurans
Author(s) -
Arun K. Ghosh,
Miranda Belcher
Publication year - 2020
Publication title -
journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.2
H-Index - 228
eISSN - 1520-6904
pISSN - 0022-3263
DOI - 10.1021/acs.joc.0c00390
Subject(s) - tetrahydrofuran , chemistry , stereoselectivity , lewis acids and bases , isomerization , olefin fiber , catalysis , acetal , medicinal chemistry , stereochemistry , organic chemistry , solvent
Lewis acid-catalyzed rearrangements of 4,5-dihydro-1,3-dioxepines have been investigated. Rearrangement of vinyl acetals under a variety of conditions resulted in cis - and trans- 2,3-disubstituted tetrahydrofuran derivatives in a highly stereoselective manner. Rearrangements at lower temperatures typically provided the cis -2,3-disubstituted tetrahydrofuran carbaldehydes. At higher temperatures, the corresponding trans -2,3-disubstituted tetrahydrofuran carbaldehydes are formed. The requisite substrates for the vinyl acetal rearrangement were synthesized via ring-closing olefin metathesis of bis(allyoxy)methyl derivatives using Grubbs second-generation catalyst followed by olefin isomerization using a catalytic amount of RuCl 2 (PPh 3 ) 3 . We examined the substrate scope using substituted aromatic and aliphatic derivatives. Additionally, the rearrangement was utilized in the synthesis of a stereochemically-defined bis-tetrahydrofuran (bis-THF) derivative, which is one of the key structural elements of darunavir, an FDA-approved drug for the treatment of HIV/AIDS.