Efficient Synthesis of Polysubstituted Furans through a Base‐Promoted Oxacyclization of (Z)‐2‐En‐4‐yn‐1‐ols

Abstract

An efficient base catalyzed oxacyclization of Z‐enynols has been developed under transition metal‐free reaction conditions, thus resulting in a variety of new di‐, tri‐, and tetra‐substituted furans. This approach allowed us to obtain 32 new compounds. Furthermore, DFT calculations were realized to depict a relationship between the natural population analysis and experimental results with alkyl or aryl groups for the synthesis of 2‐benzylfuran. A one‐pot Sonogashira/oxacyclization approach offers a flexible, robust and efficient alternative to base catalyzed cyclization is also carried out.

Synthesis of Polysubstituted Furans: An Update Since 2019

“…[96][97][98][99][100] Thibonnet et al in 2021 disclosed substituted furans 167 via transition-free, base-promoted oxacyclization of enynols i. e., (Z)-2-en-4-yn-1-ols 162 in good to excellent yields. [101] Mechanistically, the anion 163 is formed by the deprotonation of the OÀ H function of 162 by t BuOK. Intermediate 164 is formed by intramolecular 5-exo-dig oxacyclization.…”

Dess–Martin Periodinane/Brønsted Acid-Mediated Tandem Oxidation/Cyclization of Homopropargylic Alcohols for Synthesis of Trisubstituted Furans

“…15 Unfortunately, the poor functional-group tolerance of methods used to synthesize β-alkynylated ketones hinder efficient access to functionalized furans. Liu and co-workers demonstrated a 2-iodoxybenzoic acid (IBX)-mediated synthesis of 3,5-substituted 2-acylfurans from ( Z )-alkynylated allylic alcohols by using a tandem oxidation/cyclization process (Scheme 1c ), 16 and base-promoted oxacyclizations of ( Z )-alkynylated-allylic alcohols have also recently been reported to afford polysubstituted furans; 17 however, these methods require the synthesis of geometrically defined ( Z )-alkene substrates. On the other hand, electrophilic cyclizations of homopropargylic ketones or 4-dimethoxyphosphoryl-substituted allenyl alcohols promoted by a stoichiometric amount of NBS, NIS, 18 I 2 , 19 or a Brønsted acid 20 afford the corresponding tri- or tetrasubstituted furans (Scheme 1d ).…”