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γ‐ and δ‐Lactams through Palladium‐Catalyzed Intramolecular Allylic Alkylation: Enantioselective Synthesis, NMR Investigation, and DFT Rationalization
Author(s) -
Bantreil Xavier,
Prestat Guillaume,
Moreno Aitor,
Madec David,
Fristrup Peter,
Norrby PerOla,
Pregosin Paul S.,
Poli Giovanni
Publication year - 2011
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.201001300
Subject(s) - tsuji–trost reaction , chemistry , diastereomer , alkylation , enantioselective synthesis , enantiomer , intramolecular force , palladium , diphenylphosphine , catalysis , medicinal chemistry , allylic rearrangement , enantiomeric excess , ligand (biochemistry) , stereochemistry , organic chemistry , phosphine , biochemistry , receptor
The Pd‐catalyzed intramolecular allylic alkylation of unsaturated amides to give γ‐ and δ‐lactams has been studied in the presence of chiral ligands. Ligand ( R )‐3,5‐ t Bu‐MeOBIPHEP (MeOBIPHEP=6,6’‐dimethoxybiphenyl‐2,2‐diyl)bis(diphenylphosphine)) afforded the best results and allowed the cyclization reactions to take place in up to 94:6 enantiomeric ratio. A model Pd–allyl complex has been prepared and studied through NMR spectroscopic analysis, which provided insight into the processes responsible for the observed enantiomeric ratios. DFT studies were used to characterize the diastereomeric reaction pathways. The calculated energy differences were in good agreement with the experimentally observed enantiomeric ratios.