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Electronegativity Governs Enantioselectivity: Alkyl‐Aryl Cross‐Coupling with Fenchol‐Based Palladium‐Phosphorus Halide Catalysts
Author(s) -
Trillo Roberto Blanco,
Leven Matthias,
Neudörfl Jörg M.,
Goldfuss Bernd
Publication year - 2012
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201100924
Subject(s) - chemistry , aryl , electronegativity , nucleophile , halide , moiety , catalysis , medicinal chemistry , intramolecular force , halogen , alkyl , palladium , iodide , enantioselective synthesis , denticity , organic chemistry , crystal structure
A series of bulky, modular, monodentate, fenchol‐based phosphites has been employed in an intramolecular palladium‐catalyzed alkyl‐aryl cross‐coupling reaction. This enantioselective α‐arylation of N ‐(2‐bromophenyl)‐ N ‐methyl‐2‐phenylpropanamide is accomplished with [Pd(C 3 H 5 )(BIFOP‐X)(Cl)] as precatalysts, which are based on biphenyl‐2,2′‐bisfenchol phosphites (BIFOP‐X, X=F, Cl, Br, etc.). The phosphorus fluoride BIFOP‐F gives the highest enantioselectivity and good yields (64% ee , 88%). Lower selectivities and yields are found for BIFOP halides with heavier halogens (Cl: 74%, 47% ee , Br: 63%, 20% ee ). NMR studies on catalyst complexes reveal two equilibrating diastereomeric complexes in equal proportions. In all cases, the phosphorus‐halogen moiety remains intact, pointing to its remarkable stability, even in the presence of nucleophiles. The increasing enantioselectivity of the catalysts with the phosphorus halide ligands correlates with the rising electronegativity of the halide (bromine