A Dynamic Kinetic Resolution Approach to Axially Chiral Diaryl Ethers by Catalytic Atroposelective Transfer Hydrogenation

Dai, Linlong; Liu, Yuheng; Xu, Qing; Wang, Meifang; Zhu, Qiaohong; Yu, Peiyuan; Zeng, Xiaofei; Zhong, Guofu

doi:10.1002/ange.202216534

“…CPA5 bearing 3,3′-(2,4,6-(Cy) 3 -C 6 H 2 ) produced the planar-chiral cyclophane ( S p )- 3aa in good yield and with good enantioselectivity, while ( R p )- 1a was recovered in 49% yield and with 50% ee value ( s = 96, entry 5). Changing the CPA backbone to H8-BINOL led to increased enantioselectivity ( s = 146, entry 6) . In addition, examination of the solvent indicated that Et 2 O yielded higher selectivity ( 3aa , 98% ee; 1a , 84% ee; s = 381, entry 8), while 1,2-dichloroethane led to poor resolution efficiency ( s = 9, entry 9).…”

Section: Resultsmentioning

confidence: 99%

Highly Enantioselective Synthesis of Planar-Chiral Cyclophanes through a Brønsted Acid-Catalyzed Asymmetric Transfer Hydrogenation

Li,

Zhao

2023

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Planar-chiral cyclophanes have received increasing attention for drug discovery due to their unique properties arising from the conformational strain. However, the catalytic asymmetric synthesis of planar-chiral cyclophanes is one of the long-standing challenges in chemistry. We herein report a Brønsted acid-catalyzed asymmetric transfer hydrogenation (ATH) reaction of cyclophane-derived imines, providing the planar-chiral cyclophanes in good yields (up to 98%) and with high enantioselectivities (up to >99% ee). The mutable ansa bridge allows the ATH reaction to occur through a kinetic resolution or a dynamic kinetic resolution process. The [11]–[14]cyclophanes bearing an appropriate benzene ring substituent undergo a KR process, while [15]–[17]cyclophanes undergo the ATH reaction in a DKR manner. Controlled experiments were performed to understand the reaction mechanism and origin of enantioselectivity.

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Catalytic Asymmetric Synthesis of Axially Chiral Diaryl Ethers through Enantioselective Desymmetrization

Bao

¹

,

Chen

²

,

Yang

³

2023

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Axially chiral diaryl ethers are a type of unique atropisomers bearing two potential axes, which have potential applications in a variety of research fields. However, the catalytic enantioselective synthesis of these diaryl ether atropisomers is largely underexplored when compared to the catalytic asymmetric synthesis of biaryl or other types of atropisomers. Herein, we report a highly efficient catalytic asymmetric synthesis of diaryl ether atropisomers through an organocatalyzed enantioselective desymmetrization protocol. The chiral phosphoric acid‐catalyzed asymmetric electrophilic aromatic aminations of the symmetrical 1,3‐benzenediamine type substrates afforded a series of diaryl ether atropisomers in excellent yields and enantioselectivities. The facile construction of heterocycles by the utilizations of the 1,2‐benzenediamine moiety in the products provided access to a variety of structurally diverse and novel azaarene‐containing diaryl ether atropisomers.

show abstract

Catalytic Asymmetric Synthesis of Axially Chiral Diaryl Ethers through Enantioselective Desymmetrization

Bao

¹

,

Chen

²

,

Yang

³

2023

View full text Add to dashboard Cite

Axially chiral diaryl ethers are a type of unique atropisomers bearing two potential axes, which have potential applications in a variety of research fields. However, the catalytic enantioselective synthesis of these diaryl ether atropisomers is largely underexplored when compared to the catalytic asymmetric synthesis of biaryl or other types of atropisomers. Herein, we report a highly efficient catalytic asymmetric synthesis of diaryl ether atropisomers through an organocatalyzed enantioselective desymmetrization protocol. The chiral phosphoric acid‐catalyzed asymmetric electrophilic aromatic aminations of the symmetrical 1,3‐benzenediamine type substrates afforded a series of diaryl ether atropisomers in excellent yields and enantioselectivities. The facile construction of heterocycles by the utilizations of the 1,2‐benzenediamine moiety in the products provided access to a variety of structurally diverse and novel azaarene‐containing diaryl ether atropisomers.

show abstract

A Dynamic Kinetic Resolution Approach to Axially Chiral Diaryl Ethers by Catalytic Atroposelective Transfer Hydrogenation

Cited by 4 publications

References 106 publications

Highly Enantioselective Synthesis of Planar-Chiral Cyclophanes through a Brønsted Acid-Catalyzed Asymmetric Transfer Hydrogenation

Highly Enantioselective Synthesis of Planar-Chiral Cyclophanes through a Brønsted Acid-Catalyzed Asymmetric Transfer Hydrogenation

Catalytic Asymmetric Synthesis of Axially Chiral Diaryl Ethers through Enantioselective Desymmetrization

Catalytic Asymmetric Synthesis of Axially Chiral Diaryl Ethers through Enantioselective Desymmetrization

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