Stereoselective arene formation

Abstract

While aromatic hydrocarbons are ubiquitous in organic chemistry, they are typically not associated with chirality and stereoisomerism. Due to the planarity and symmetry of simple arenes, methods to assemble aromatic rings are not routinely considered for the stereoselective synthesis of chiral compounds. The aim of this tutorial review is to contrast this common perception with the counterintuitive circumstance that stereoselective arene formation offers a means to stereoselectively prepare an exceptional range of chiral aromatic structures. The versatility of these methods across various types of molecular scaffolds allows to control stereocentre configuration, helical chiral compounds, the configuration of rotationally restricted stereogenic axes, planar chiral molecules or curved polyaromatic systems. Furthermore, stereoselective arene formation holds great promise for the selective construction of extended but structurally well-defined chiral structures.

Carbene‐Catalyzed Desymmetrization and Direct Construction of Arenes with All‐Carbon Quaternary Chiral Center

“…[3] However,w hen chiral centers (particularly all-carbon quaternary centers) are present in the neighboring regions of the arenes,t he synthetic tasks become very challenging.There are few effective approaches available for construction of substituted benzenes with simultaneous installation of chiral centers. [4] Among the molecules containing arenes with chiral centers,i ndane derivatives having an all-carbon quaternary chiral center ( Figure 1a)a re particularly difficult to make in optically enriched forms. [5] Forexample,the natural product coprinastatin epimer [6] and preclinical drug [7] MK-3207 are available only in ar acemic form by current synthetic methods (Figure 1a).…”

Synthesis of Axially Chiral Styrenes through Pd‐Catalyzed Asymmetric C−H Olefination Enabled by an Amino Amide Transient Directing Group

“…Recently, asymmetric C−H functionalization has emerged as a powerful synthetic approach for rapid access to axially chiral biaryls . Inspired by the pioneering work by Yu and co‐workers on the construction of central chirality through transient chiral auxiliary (TCA)‐enabled C−H functionalization, we recently reported the highly atroposelective construction of biaryl atropoisomers using tert ‐leucine (Tle) as a TCA .…”

Atroposelective Arene Formation by Carbene‐Catalyzed Formal [4+2] Cycloaddition

“…Most of the methods involve asymmetric modifications of arenes by metal‐catalyzed cross‐couplings, aromatic electrophilic substitutions (Ar‐SE) (Figures 1 a‐i), point‐to‐axial chirality transfer reactions, desymmetrization substitutions, kinetic resolutions [9] (Figure 1 a‐ii) or others . In comparison, the atroposelective methods of de novo construction of arenes are much less studied . Conventionally, transition‐metal‐catalyzed asymmetric [2+2+2] cycloaddition is almost the only method to achieve atroposelective arene formation (Figure 1 a‐iii).…”