Work

Copper‐Catalyzed Regioselective and Enantioselective Hydropyridylation of Dienes for the Synthesis of Chiral Diaryl Compounds via Concerted Nucleophilic Aromatic Substitution

Year: 2024

Type: article

Abstract: The synthesis of chiral 1,1-diaryl compounds, particularly those containing a pyridine moiety, is of significant interest due to their pharmaceutical applications. Here, we report the development of a copper-catalyzed enantioselective 1,4-hydropyridylation of conjugated dienes. Utilizing 2-fluoropyridine as the electrophile, CuOAc, and the chiral ligand Tol-BINAP, we optimized reaction conditions to achieve the desired chiral 1,1-diaryl products containing both a pyridine and a cis-crotyl group. Mechanistic studies and DFT calculations revealed that the 1,2-hydrocupration step is enantio-determining, and the concerted nucleophilic aromatic substitution proceeds via six-membered cyclic transition states.

Source: Angewandte Chemie International Edition

DOI: 10.1002/anie.202420918

Authors: Minjeong Seo, Sanghyup Seo, Joonho Jung, Hyunwoo Kim

Institution: Korea Advanced Institute of Science and Technology

Language: English

Topic: Catalytic Cross-Coupling Reactions

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: bronze

Funders: National Research Foundation, National Research Foundation of Korea

Awards: G1336057942, G3413640540