Aromatizative Inverse‐Electron‐Demand Hetero‐Diels‐Alder Reaction in the Synthesis of Benzothiophene Derivatives

Abstract

The Front Cover shows the inverse‐electron‐demand hetero‐Diels‐Alder cycloaddition between azlactones and α,β‐unsaturated ketones derived from thioisatine. The metal gears shown in the picture directly refer to the aromatization process that constitutes the main driving force of the developed transformation. Artwork by Jan Bojanowski. More information can be found in the Communication by Ł. Albrecht et al.

Access to Spirocyclic Benzothiophenones with Multiple Stereocenters via an Organocatalytic Cascade Reaction

“…Since the pioneering work by Córdova et al based on the sulfa-Michael addition-initiated construction of tetrahydrothioxanthones, various enantioselective sulfa-Michael additions have been developed using electron-deficient alkenes, such as enones, ,, dienones, acrylates, and unsaturated amides . Other valuable protocols for the synthesis of enantiomerically enriched, sulfur-bearing full-substituted carbon stereocenters include Mannich reactions of thiols into ketimines and electrophilic sulfenylation reactions of α-branched aldehydes, β-keto esters, nitroacetates, oxindols, benzofuran-2­(3 H )-ones, and oxazolones. , An alternative organocatalytic strategy for the preparation of such enantiomerically enriched compounds containing a sulfur-bearing full-substituted stereogenic center is based on the stereoselective formation of C–C or C–N bonds using prochiral sulfur-based substrates, such as α-sulfenylated acrylates and enals, rhodanines, 3-thiooxindoles, and thiazolones. , Yet, only a few reports on organocatalytic reactions on benzo­[ b ]­thiophene derivatives have been published to date . Considering the above and our interest in the enantioselective preparation of heterocycles with a full-substituted stereogenic center bearing a sulfur atom, we aimed to use an enantioselective double-Michael-cascade reaction of benzo­[ b ]­thiophenone derivatives with less reactive enones, based on in situ generation of 2-aminobuta-1,3-diene intermediates …”

Organocatalyzed Oxa-Diels–Alder Reactions: Recent Progress

“…Several cinchona-derived bifunctional tertiary amines (including thioureas and squaramides) were screened for the reaction, however, promising stereoselectivities were not obtained. 19c…”

Six-membered ring systems: with O and/or S atoms

“…a,b-Unsaturated ketones derived from thioisatin underwent IEDehDA reactions with azlactones under N-methylmorpholine catalysis in dichloromethane to form benzothiophene-fused 3,4-dihydro-2H-pyran-2-ones. The enantioselective version Scheme 45 was also developed by applying quinine-derived catalysts (19EJO6592). Organocatalyzed sequential vinylogous aldol reaction/transesterification of isatins with methyl-substituted olefinic butyrolactones led to a series of 6-spiroxindolin-2-one 5,6-dihydro-2H-pyran-2-ones, in high yields and enantioselectivities (Scheme 46) (19CC9327).…”