title: DFT study of a 5-endo-trig-type cyclization of 3-alkenoic acids by using Pd-spiro-bis(isoxazoline) as catalyst: importance of the rigid spiro framework for both selectivity and reactivity.
abstract: The reaction pathway of an enantioselective 5-endo-trig-type cyclization of 3-alkenoic acids catalyzed by a chiral palladium-spiro-bis(isoxazoline) complex, Pd-SPRIX, has been studied by density functional theory calculations. The most plausible pathway involves intramolecular nucleophilic attack of the carboxylate moiety on the C=C double bond activated by Pd-SPRIX and β-H elimination from the resulting organopalladium intermediate. The enantioselectivity was determined in the cyclization step through the formation of a π-olefin complex, in which one of the two enantiofaces of the olefin moiety was selected. The β-H elimination occurs via a seven-membered cyclic structure in which the acetate ligand plays a key role in lowering the activation barrier of the transition state. In the elimination step, the SPRIX ligand was found to behave as a monodentate ligand due to the hemilability of one of the isoxazoline units thereby facilitating the elimination. Natural population analysis of this pathway showed that the more weakly electron-donating SPRIX ligand, compared with the bis(oxazoline) ligand, BOX, facilitated the formation of the π-olefin complex intermediate, leading to a smaller overall activation energy and a higher reactivity of the Pd-SPRIX catalyst.
authors.affiliation: The Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka 567-0047, Japan.
authors.forename: Randa K
authors.initials: RK
authors.lastname: Gabr
authors.forename: Takuji
authors.initials: T
authors.lastname: Hatakeyama
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takenaka
authors.forename: Shinobu
authors.initials: S
authors.lastname: Takizawa
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Okada
authors.forename: Masaharu
authors.initials: M
authors.lastname: Nakamura
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Sasai
keywords: asymmetric catalysis; cyclization; density functional calculations; palladium; reaction mechanisms; spiro compounds