Synthesis of Axially Chiral Biaryls via Enantioselective Ullmann Coupling of<i>ortho</i>‐Chlorinated Aryl Aldehydes Enabled by a Chiral 2,2′‐Bipyridine Ligand

Perveen, Saima; Zhang, Shuai; Wang, Linghua; Song, Peidong; Ouyang, Yizhao; Jiao, Jiao; Duan, Xin‐Hua; Li, Pengfei

doi:10.1002/anie.202212108

Cited by 26 publications

(6 citation statements)

References 115 publications

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“…We commenced the investigation by synthesis of an array of chiral half‐sandwich iridium complexes according to a route as shown in Scheme 2. Recently, the enantiopure chiral 2‐ c hlorinated a nnulated p yridine‐derived 1,3‐ diol ( CAP‐diol ) had served as the key intermediate for preparation of chiral N,N and N,B ligands in a modular fashion [15a–d] . In this work, treatment of CAP‐diol with different symmetrical ketones readily afforded CAP‐acetal in high yields [15a] .…”

Section: Resultsmentioning

confidence: 99%

Additive‐Free Transfer Hydrogenative Direct Asymmetric Reductive Amination Using a Chiral Pyridine‐Derived Half‐Sandwich Catalyst

Gao,

Wang,

Zhang

et al. 2023

Angew Chem Int Ed

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Chiral amines are broadly used compounds in pharmaceutical industry and organic synthesis, and reductive amination reactions have been the most appreciated methods for their syntheses. However, one-step transfer hydrogenative direct asymmetric reductive amination (THDARA) that could expand the scope, simplify the operation and eliminate the use of additives has been challenging. In this work, based on the Xiao's racemic transfer hydrogenative reductive amination in 2010 and our recent work in novel chiral pyridine ligands, chiral half-sandwich iridium catalysts were rationally designed and synthesized. Using the optimized catalyst and azeotropic mixture of formic acid and triethylamine as the hydrogen source, a broad range of α-chiral (hetero)aryl amines, including various polar functional groups and heterocycles, were prepared in generally high yield and enantioselectivity under mild and operationally simple conditions. Density functional theory (DFT) calculation of the catalytically active IrÀ H species and the key hydride transfer step supported the chiral pyridine-induced stereospecific generation of the iridium center, and the enantioselection by taming the highly flexible key transition structure with multiple attractive non-covalent interactions. This work introduced a type of effective chiral catalysts for simplified approach to medicinally important chiral amines, as well as a rare example of robust enantioselective transition-metal catalysis.

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Section: Resultsmentioning

confidence: 99%

Additive‐Free Transfer Hydrogenative Direct Asymmetric Reductive Amination Using a Chiral Pyridine‐Derived Half‐Sandwich Catalyst

Gao,

Wang,

Zhang

et al. 2023

Angew Chem Int Ed

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“…After extensive experimentation, highly efficient and enantioselective nickel-catalyzed reductive homocoupling enabled by (+)-DTB-SBpy (20) was achieved to furnish an enantioenriched biphenyl dial (38, 92% yield, 90% ee) (Scheme 5). 2 Variations in acetal substituents on SBpy significantly affected reaction outcomes, with ligands having less (18 and 19) and more (39) steric hindrance, resulting in inferior yields and enantioselectivity. Classical chiral nitrogenous ligands such as (S)-t-Bu-Pyox ( 22), (S,S)-t-Bu-Pybox (40), and (S,S)-t-Bu-Box (41) were not effective in the reaction.…”

Section: Enantioselective Reductive Coupling Of Ortho-chlorinated Ary...mentioning

confidence: 99%

Design and Application of New Pyridine-Derived Chiral Ligands in Asymmetric Catalysis

Zhang,

Ouyang,

Gao

et al. 2024

Acc. Chem. Res.

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Conspectus The innovation of chiral ligands has been crucial for the asymmetric synthesis of functional molecules, as demonstrated by several types of widely applied “privileged” ligands. In this context, chiral pyridine-derived ligands, by far some of the oldest and most widely utilized ligands in catalysis, have attracted considerable research interest in the past half-century. However, the development of broadly applicable chiral pyridine units (CPUs) has been plagued by several intertwining challenges, thus delaying advancements in many asymmetric reactions. This Account aims to summarize the recent progress in new CPU-containing ligands, focusing on a rationally designed, modular, and tunable CPU developed in our laboratory. A significant problem thwarting conventional designs is the paradox between broad reactivity and stereoselectivity; that is, while enhanced stereoselectivity may be achieved by introducing chiral elements close to the N atom, the concomitant increase in local steric hindrance often limits catalytic activity and scope. Our newly developed CPU features a rigid [6-5-3] fused-ring framework and a tunable spirocyclic ketal side wall. The well-defined three-dimensional structure minimizes local (inner layer) steric hindrance and tunes the peripheral environment (outer layer) by remote substituents, thus securing reactivity and stereoselectivity. Different chelating ligands were readily assembled using this chiral structural module, with applications in mechanistically diverse transition-metal-catalyzed reactions. Thus, a series of chiral 2,2′-bipyridine ligands were successfully employed in the development of a general, efficient, and highly enantioselective nickel-catalyzed intermolecular reductive addition, Ullmann coupling of ortho-chlorinated aryl aldehydes, and carboxylation of benzylic (pseudo)halides with CO2. Notably, these chiral 2,2′-bipyridine ligands exhibited superior catalytic activity in the reactions compared to common N-based ligands. In addition, highly enantioselective iridium-catalyzed C–H borylation was developed using a CPU-containing N,B-bidentate ligand. Furthermore, mechanistically challenging, additive-free, and broad-scope transfer hydrogenative direct asymmetric reductive amination was achieved using a half-sandwich iridium catalyst supported by a chiral N,C-bidentate ligand. The new ligands demonstrated excellent performance in securing high catalytic activity and stereoselectivity, which, when combined with experimental and computational mechanistic investigations, supported the “double-layer control” design concept. Considering the broad applications of pyridine-derived ligands, the research progress described herein should inspire the creation of novel chiral catalysts and drive the development of many catalytic asymmetric reactions.

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“…38 Whereas, enantioselective biphenyls 2 were obtained via the reaction of ortho -chlorinated benzaldehyde derivatives 1 in the presence of Ni catalyst (Scheme 2). 39…”

Section: Synthesis Of Biphenyl Systemsmentioning

confidence: 99%

A fruitful century for the scalable synthesis and reactions of biphenyl derivatives: applications and biological aspects

et al. 2023

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Synthesis of Axially Chiral Biaryls via Enantioselective Ullmann Coupling ofortho‐Chlorinated Aryl Aldehydes Enabled by a Chiral 2,2′‐Bipyridine Ligand

Cited by 26 publications

References 115 publications

Additive‐Free Transfer Hydrogenative Direct Asymmetric Reductive Amination Using a Chiral Pyridine‐Derived Half‐Sandwich Catalyst

Additive‐Free Transfer Hydrogenative Direct Asymmetric Reductive Amination Using a Chiral Pyridine‐Derived Half‐Sandwich Catalyst

Design and Application of New Pyridine-Derived Chiral Ligands in Asymmetric Catalysis

A fruitful century for the scalable synthesis and reactions of biphenyl derivatives: applications and biological aspects

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