Highly Enantioselective Allylic C–H Alkylation of Terminal Olefins with Pyrazol-5-ones Enabled by Cooperative Catalysis of Palladium Complex and Brønsted Acid

Abstract

A highly enantioselective allylic C-H alkylation reaction of allylarenes with pyrazol-5-ones has been established by the cooperative catalysis of a chiral palladium complex and chiral Brønsted acid to afford a wide spectrum of functionalized chiral N-heterocycles with an all-carbon quaternary stereogenic center in high yields and with high levels of enantioselectivity (up to 96% ee), wherein the chiral ligand and phosphoric acid showed synergistic effect on the control of stereoselectivity. In addition, a palladium-catalyzed asymmetric allylic C-H alkylation of 1,4-pentadienes with pyrazol-5-ones has been realized to furnish highly functionalized pyrazol-5-ones in high enantioselectivities. In this case, the chiral ligand controls the stereoselectivity while the achiral Bronsted acid, 2-fluorobenzoic acid, turns out to be a better cocatalyst than the chiral phosphoric acid. The installation of electron-deficient substituents at 3,3'-positions of binaphthyl backbone of chiral phosphoramidites is actually beneficial to the allylic C-H oxidation due to their survival in the presence of quinone derivative oxidants. These allylic C-H alkylation reactions undergo smoothly under mild conditions and tolerate a wide range of substrates. The resultant highly functionalized chiral pyrazol-5-ones have been applied to the preparation of more structurally diverse heterocycles by classical transformations.

Nucleophile Coordination Enabled Regioselectivity in Palladium‐Catalyzed Asymmetric Allylic C−H Alkylation

“…By means of DFT calculations, we identified that the geometry and coordination pattern of nucleophiles lead to different bond‐forming transition states and thereby determine the Z / E selectivites and regioselectivities (Scheme B) . For instance, the allylic C−H alkylation of 1,4‐dienes with pyrazol‐5‐ones and 5‐aryl‐substituted thiazol‐4(5 H )‐ones greatly favor branched E ‐dienyl products via the inner‐sphere transition‐state TS1 , while branched Z ‐dienyl products were obtained via the inner‐sphere TS2 upon using azlactones as nucleophiles . In contrast, the outer‐sphere TS3 became dominant and linear E ‐dienyl products were given when 5‐alkyl‐substituted thiazol‐4(5 H )‐ones were used .…”

Cu/Pd Synergistic Dual Catalysis: Asymmetric α‐Allylation of an α‐CF3 Amide

“…Transition‐metal‐catalyzed asymmetric allylic alkylation offers broad opportunities to construct carbon frameworks with excellent stereocontrol, which has rich applications for the enantioselective synthesis of various biologically active natural products . Expanding the scope of applicable carbon nucleophiles beyond active methylene compounds is a challenge in asymmetric allylic alkylation, and readily enolizable azlactones,– 3‐aryl oxindoles,, pyrazole‐5‐ones,, and glycine Schiff bases, have been used to generate the corresponding active nucleophiles in a catalytic manner (Scheme b) ,. Further advances have been made through synergistic dual catalyst systems, where specific catalysts responsible for generating active nucleophiles are used in addition to the transition‐metal catalyst to generate π‐allyl electrophiles .…”

Synergistic N‐Heterocyclic Carbene/Palladium‐Catalyzed Umpolung 1,4‐Addition of Aryl Iodides to Enals

“…With these formidable challenges in mind, our optimization was initiated with trans-cinnamaldehyde (1a)a nd iodobenzene (2a). Our hypothesis was that multidentate ligands on palladium would be needed to prevent coordination of the NHC.T hus,w ee xamined 4d ifferent NHC precursors (N1-N4,1 5mol %, 4 under the conditions of entry 1, but these complexes did not promote this transformation (entry 1vs. 5and 6).…”