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Suzuki–Miyaura Cross‐Coupling Reactions of Highly Fluorinated Arylboronic Esters: Catalytic Studies and Stoichiometric Model Reactions on the Transmetallation Step
Author(s) -
Kohlmann Johannes,
Braun Thomas,
Laubenstein Reik,
Herrmann Roy
Publication year - 2017
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201700549
Subject(s) - transmetalation , chemistry , aryl , stoichiometry , reactivity (psychology) , catalysis , medicinal chemistry , coupling reaction , palladium , stereochemistry , organic chemistry , pathology , medicine , alkyl , alternative medicine
Fluorinated 4‐aryl phenylalanine amino acid derivatives (aryl=2‐C 5 NF 4 , 4‐C 6 H 4 SF 5 , 2‐C 6 H 4 SCF 3 , C 6 F 5 ) were obtained in Suzuki–Miyaura cross‐coupling reactions of phenylalanine precursors with highly fluorinated aryl boronic acid and esters in the presence of CsF. Pd II complexes that possessed phenyl alanine derived ligands, such as trans ‐[PdBr{4‐C 6 H 4 CH 2 CH{NHC(O)CH 3 }CO 2 Et}(P i Pr 3 ) 2 ], were used as catalysts. Stoichiometric model reactions indicate the intermediate generation of the boronate Cs[BF(2‐C 5 NF 4 )(pin)] (pin=pinacolato=O 2 C 2 Me 4 ). The transmetallation step with Cs[BF(4‐C 6 H 4 SF 5 )(pin)], [NMe 4 ][BF(2‐C 5 NF 4 )(pin)] and/or the fluorido complex trans ‐[PdF{4‐C 6 H 4 CH 2 C{NHC(O)CH 3 }(CO 2 Et) 2 }(P i Pr 3 ) 2 ] was investigated. A comparison of the reactions of trans ‐[PdX{4‐C 6 H 4 CH 2 C{NHC(O)CH 3 }(CO 2 Et) 2 }(P i Pr 3 ) 2 ] (X=Br, F) with 2‐Bpin‐C 5 NF 4 or [NMe 4 ][BF(2‐C 5 NF 4 )(pin)] revealed the remarkable high reactivity of the fluorido complex towards 2‐BpinC 5 NF 4 . Low‐temperature NMR studies indicated the ionic species trans ‐[Pd{4‐C 6 H 4 CH 2 C{NHC(O)CH 3 }(CO 2 Et) 2 }(P i Pr 3 ) 2 ][BF(2‐C 5 NF 4 )(pin)] to be a highly reactive intermediate.