Carbene‐Catalyzed Three‐Component Cascade Reaction of Benzofuran‐2‐ones and Enals: Construction of Spirobenzofuranone‐δ‐lactones

Abstract

A convenient method was developed via an NHC mediated three-component cascade reaction for the construction of medicinally important spirobenzofuranone derivatives. The reaction features mild reaction conditions and generates three consecutive stereocenters, one of which is an all-carbon substitution. The protocol can accommodate various substituents and substitution patterns, afford the products in moderate to good yields with excellent diastereoselectivities and moderate enantioselectivity.

Recent Advances in NHC‐Catalyzed Chemoselective Activation of Carbonyl Compounds

“…In 2021, Liu and co‐workers discovered a one‐pot NHC‐catalyzed reaction, with benzofuran‐2‐ones, α ‐bromoenals and substituent aldehydes used as substrates, leading to the formation of highly chemo‐ and diastereoselective spirobenzo‐ furanone δ ‐lactones [50a] . These molecules possess three consecutive stereocenters and an all‐carbon quaternary carbon, making them valuable motifs found in various natural products and bioactive compounds [50b,c] .…”

NHC-Catalyzed Reaction of Aldehydes for C(sp2)–O Bond Formation

“…The NHC-catalyzed cascade reactions were widely investigated under the redox conditions [206][207][208][209][210][211][212][213][214][215][216][217]. The α,β-unsaturated acyl azoliums were Michael acceptors acting as a C2 synthon for the cascade annulation reactions [206][207][208][209][210][211]. Under the optimized conditions using the precursor (5aR,10bS)-A4a (7.5 mol%) and DABCO (1.65 equiv.…”

Diastereoselective synthesis of chroman bearing spirobenzofuranone scaffolds via oxa-Michael/1,6-conjugated addition of para-quinone methides with benzofuranone-type olefins

“…Benzofuran-2-(3 H )-ones as one of the important oxygen-containing heterocycles that exist in a broad array of natural products 9 and potential medicines. 10 The streamlined synthesis of benzofuran-2-ones pose considerable challenge due to their quaternary carbon centers at the C-3 position, 11 especially those featuring relatively congested spirocyclic motifs represent challenging synthetic targets.…”