Atroposelective brominations to access chiral biaryl scaffolds using high-valent Pd-catalysis

Abstract

Compounds featuring atropisomerism are ubiquitous in natural products, therapeutics, advanced materials, and asymmetric synthesis. However, stereoselective preparation of these compounds presents many synthetic challenges. This Article introduces streamlined access to...

C−H Functionalization of Aldehydes and Ketones with Transient Directing Groups: Recent Developments

“…Very recently, Rezayee's team achieved atropselective brominations with NBS as brominating agent (Scheme 15.b). [32] In function of the amount of NBS, mono-or dibromination were observed and the chiral brominated biaryls were used in the synthesis of several enantiopure biaryl scaffolds.…”

“…This method was applied to the synthesis of an axially chiral amino‐phenol organocatalyst which was used in an asymmetric diethylzinc addition onto aldehydes. Very recently, Rezayee's team achieved atropselective brominations with NBS as brominating agent (Scheme 15.b) [32] . In function of the amount of NBS, mono‐ or dibromination were observed and the chiral brominated biaryls were used in the synthesis of several enantiopure biaryl scaffolds.…”

Stereodynamic Strategies to Induce and Enrich Chirality of Atropisomers at a Late Stage

“…In 2023, Rezayee and co-workers employed a Pd-Catalyzed C–H fuctionalization strategy for the enantioselective bromination of aldehyde containing biaryl compounds (see Figure , 37.1 ) using a transient directing group to afford di- and monobrominated products ( 37.2 and 37.3 , respectively) . To achieve this bond formation, the authors employed a high-valent Pd-catalytic cycle.…”

“…In 2023, Rezayee and co-workers employed a Pd-Catalyzed C−H fuctionalization strategy for the enantioselective bromination of aldehyde containing biaryl compounds (see Figure 37, 37.1) using a transient directing group to afford di-and monobrominated products (37.2 and 37.3, respectively). 192 To achieve this bond formation, the authors employed a high-valent Pd-catalytic cycle. Subjection of 37.1 to reaction conditions consisting of Pd(OAc) 2 , chiral transient directing group 37.4, and Ag 2 CO 3 with 10 equiv of TFA furnished 37.2 in 75% yield and >99% ee.…”

Chiral Phosphoric Acid–Palladium(II) Complex Catalyzed Asymmetric Desymmetrization of Biaryl Compounds by C(sp3)–H Activation

“…The C–H activation mediated by the directing group has realized regioselective functionalization. Furthermore, chiral transition metal catalysts have enabled enantioselective C–H functionalization, and its application to the enantioselective synthesis of axially chiral biaryls has been achieved. , Shi and coworkers have reported an enantioselective C­(sp 2 )–H olefination by use of a palladium­(II)/CPA system (Figure a-ii), resulting in the formation of chiral biaryls. In addition to C­(sp 2 )–H activation, C­(sp 3 )–H activation has been developed, and enantioselective C­(sp 3 )–H functionalization has been employed to synthesize chiral carbon centers using chiral ligands .…”