Beyond the Corey–Chaykovsky Reaction: Synthesis of Unusual Cyclopropanoids via Desymmetrization and Thereof

Abstract

Desymmetrization-based protocols for the synthesis of highly functionalized indeno-spirocyclopropanes and cyclopropa-fused indanes have been established through unexpectedr eactions triggered by the Corey-Chaykovsky reagent. These structures were further elaborated in one step to privileged scaffolds such as fluorenones, indenones, and naphthaphenones. For instance, an acid-catalyzedt ransformation of indeno-spirocyclopropanes provided fluorenones via ah omo-Nazarov-type cyclization, and naphthaphenones were obtained via an acidcatalyzed cyclopropane ring-opening/retro-Michael sequence.Cyclopropanes are important structural units presenti ns everal bioactive natural productsa nd pharmaceutically relevant compounds including af ew marketed drugs (Figure 1). [1] Medicinal chemists take advantage of the enhanced metabolic stability and conformational rigidity offered by cyclopropanes during drug design and development. [2] In addition, the strained Supporting information and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

Annulations involving 1-indanones to access fused- and spiro frameworks

“…During the course of their study, Ramasastry and co-workers synthesized chiral indanone scaffolds 13 from symmetrical enone compounds 12. 35 This diastereoselective transformation was facilitated by the Corey–Chaykovsky reagent, namely dimethyloxosulfonium methylide (DOSM) through initial Michael addition followed by aldol-type reaction. The indanone containing allylic-benzylic tertiary alcohol moiety 13 could be converted to fluorenone 14 in excellent yields with catalytic amount of p -TSA.…”

Ring-Opening Cyclization of Spirocyclopropanes Using Sulfoxonium Ylides

“…Using density functional theory calculations, Yu and colleagues recently reported that these different reaction outcomes can be attributed to thermodynamics, as sulfonium ylide 1a is less stable, and therefore more highly reactive, than sulfoxonium ylide 2a. 4) To date, sulfur ylides 1a and 2a have been widely used in the synthesis of various epoxides, 5,6) cyclopropanes, 7,8) and heterocyclic compounds. [9][10][11] Doubly-activated cyclopropanes are versatile intermediates for the synthesis of a wide range of carbocycles 12) and heterocycles.…”

“…However, sulfonium ylides used in this reaction were limited to EWG-stabilized ones 1b. Since sulfur ylides with various reactivities have been used in organic synthesis, [5][6][7][8][9][10][11] this study focused on the reaction between different sulfur ylides and spirocyclopropanes. Herein, the ring-opening cyclization of spirocyclopropanes 3 using non-, alkyl-, and phenyl-substituted sulfoxonium ylides 2 as a carbon nucleophile is reported (Chart 2B).…”