Applications of Chiral Three-membered Rings for Total Synthesis: A Review

Abstract

This review updates recent applications of asymmetric aziridination, azirination, thiirination, epoxidation, and cyclopropanation in the total synthesis of biologically active compounds, including natural products, using chiral substrates or chiral catalysts, covering the literature since 2000. The interest towards these synthetic methodologies of chiral three-membered rings has increased in the last decade, dictated either by the biological activities that display many naturally occurring products bearing a three-membered unit or by the ring strain of three-membered rings making them useful precursors of many more complex interesting molecules. Classic as well as modern protocols in asymmetric aziridinations, azirinations, epoxidations, thiirinations, and cyclopropanations have been widely applied as key steps of a number of syntheses of important products. Although the use of chiral substrates and auxiliaries is still highly employed particularly in asymmetric aziridination and cyclopropanation, the development of enantioselective catalytic methodologies has witnessed exponential growth during the last decade. The present review is subdivided into three parts, dealing successively with the use of chiral nitrogen-containing three-membered rings, chiral epoxides and thiiranes, and chiral cyclopropanes in total synthesis.

A Chiral Macrocyclic Tetra‐N‐Heterocyclic Carbene Yields an “All Carbene” Iron Alkylidene Complex

“…The ability to set stereochemistry during a catalytic reaction is a critical tool in synthetic chemistry, and three‐membered ring formation is an increasingly active research topic . The reason is that prochiral alkenes are widely abundant and can be combined with a variety of oxidants.…”

Unusual Transformations of Strain-Heightened Oxetanes

“…The highly strained heterocycles, oxiranes and oxetanes, have long played key roles in the synthesis of small molecules and materials. , These moieties can also be found in a variety of natural products . Arguably, because of the facility with which they are synthesized, particularly in an asymmetric fashion, − the prominence of epoxides outstrips that of their homologous counterparts.…”

Recent advances and trends in the biomimetic iron‐catalyzed asymmetric epoxidation

“…Enantioselective epoxides are the central building blocks in the synthesis of chiral organic structures. [1,2] Epoxides are extensively distributed in many biologically relevant natural products. [3] Moreover, establishment of epoxide scaffolds are significant and applicable to gain versatile structures in synthetic organic chemistry.…”