1. Synthesis of 3,3-Disubstituted Oxindoles by Palladium-Catalyzed Asymmetric Intramolecular α-Arylation of Amides: Reaction Development and Mechanistic Studies.
- Author
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Katayev, Dmitry, Jia, Yi‐Xia, Sharma, Akhilesh K., Banerjee, Dipshikha, Besnard, Céline, Sunoj, Raghavan B., and Kündig, E. Peter
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OXINDOLES , *ARYLATION , *AMIDE synthesis , *REDUCTIVE elimination (Chemistry) , *ASYMMETRIC synthesis , *OXIDATIVE addition - Abstract
Palladium complexes incorporating chiral N-heterocyclic carbene (NHC) ligands catalyze the asymmetric intramolecular α-arylation of amides producing 3,3-disubstituted oxindoles. Comprehensive DFT studies have been performed to gain insight into the mechanism of this transformation. Oxidative addition is shown to be rate-determining and reductive elimination to be enantioselectivity-determining. The synthesis of seven new NHC ligands is detailed and their performance is compared. One of them, L8, containing a tBu and a 1-naphthyl group at the stereogenic centre, proved superior and was very efficient in the asymmetric synthesis of fifteen new spiro-oxindoles and three azaspiro-oxindoles often in high yields (up to 99 %) and enantioselectivities (up to 97 % ee; ee=enantiomeric excess). Three palladacycle intermediates resulting from the oxidative addition of [Pd(NHC)] into the aryl halide bond were isolated and structurally characterized (X-ray). Using these intermediates as catalysts showed alkene additives to play an important role in increasing turnover number and frequency. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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