121440-85-5Relevant academic research and scientific papers
Application of chiral mixed phosphorus/sulfur ligands to palladium-catalyzed allylic substitutions
Evans, David A.,Campos, Kevin R.,Tedrow, Jason S.,Michael, Forrest E.,Gagne, Michel R.
, p. 7905 - 7920 (2007/10/03)
A modular approach to the synthesis of a class of mixed phosphorus/sulfur ligands was designed to identify important ligand structural features for enantioselective palladium-catalyzed allylic subsitutions of acyclic and cyclic ayllic esters. After a systematic variation of the ligand substituents at sulfur, phosphorus, and the ligand backbone, ligand 11k was found to be optimal in the palladium-catalyzed allylic substitution of 1,3-diphenylpropenyl acetate with dimethyl malonate or benzylamine in high yield and excellent enantioselectivity (95-98% ee). A similar optimization of the mixed phosphorus/sulfur ligand for the palladium-catalyzed allylic substitution of cycloalkenyl acetates showed that 49g afforded the highest enantioselectivities (91-97% ee). Application of this methodology to heterocyclic substrates was developed as an efficient approach to the enantioselective synthesis of 3-substituted piperidines and dihydrothiopyrans. Models for asymmetric induction are discussed based on the absolute stereochemistry of the products, X-ray crystallographic data, and NMR spectroscopic data for relevant π-allyl complexes.
Asymmetric Synthesis Catalyzed by Chiral Ferrocenylphosphine-Transition-Metal Complexes. 8. Palladium-Catalyzed Asymmetric Allylic Amination
Hayashi, Tamio,Yamamoto, Akihiro,Ito, Yoshihiko,Nishioka, Eriko,Miura, Hitoshi,Yanagi, Kazunori
, p. 6301 - 6311 (2007/10/02)
Chiral ferrocenylphosphine ligands, represented by (R)-N-methyl-N--1-ethylamine ((R)-(S)-1a), which have a pendant side chain bearing a hydroxy group at the terminal position, were designed and used successfully for palladium-catalyzed asymmetric allylic amination of allylic substrates containing a 1,3-disubstituted propenyl structure (RCH=CHCH(X)R: R = Ph, Me, n-Pr, i-Pr; X = OCOOEt, OCOMe, OP(O)Ph2, etc.).Reaction of the allylic substrates with benzylamine in the presence of a palladium catalyst prepared in situ from Pd2(dba)3 and (R)-(S)-1a gave high yields of amination products (RCH=CHC*H(NHCH2Ph)R: >97percent ee (R) for R = Ph, 73percent ee (S) for R = Me, 82percent ee (S) for R = n-Pr, and 97percent ee (S) for R = i-Pr).The allylamines were converted into optically active amino acids and their derivatives.The high stereoselectivity of the ferrocenylphosphine ligand is expected to be caused by an attractive interaction between the terminal hydroxy group on the ligand and the incoming amine, which directs the nucleophilic attack on one of the ?-allyl carbons.The key role of the hydroxy group was supported by an X-ray structure analysis of a ?-allylpalladium complex and (31)P NMR studies.It was demonstrated that the pendant side chain on the ferrocenylphosphine ligand is directed toward the reaction site on palladium and the terminal hydroxy group is located at the position close to one of the ?-allyl carbon atoms and that ?-allyl group on the palladium coordinated with the ferrocenylphosphine 1a adopts one of the two possible conformational isomers with high selectivity (20/1) in an equilibrium state.
