Cross-Coupling Of N-Tosylhydrazones Research Articles

Sadphos as Adaptive Ligands in Asymmetric Palladium Catalysis.

ConspectusPalladium catalysis, as one of the most important strategies in asymmetric synthesis, has continuously attracted the attention of organic chemists. With the development of chiral ligands, increasingly challenging reactions and substantial progress in asymmetric catalysis are being realized.Since 2014, we have focused on exploiting a series of sulfinamide phosphine ligands called "Sadphos," including Ming-Phos, Xu-Phos, Xiao-Phos, Xiang-Phos, TY-Phos, PC-Phos, GF-Phos, and WJ-Phos. These ligands can be easily prepared in two to four steps using commercial materials. These new types of ligands have shown remarkable performance in transition-metal-catalyzed reactions, especially in Pd-catalyzed transformations. X-ray diffraction analysis, mechanistic studies, and density functional theory calculations have revealed that Sadphos ligands can coordinate with the Pd0 and PdII species in the Pd0/P, Pd0/P,S, or PdII/P,O modes.This Account summarizes our recent efforts toward palladium-catalyzed enantioselective reactions using Sadphos ligands. These ligands were found to be privileged and very crucial to promote the reactions by increasing the reactivity and enantioselectivity. Ming-Phos is an effective ligand in Pd-catalyzed asymmetric coupling and intramolecular Heck reactions, providing highly enantioselective trisubstituted allenes, axially chiral anilides, gem-diarylmethine silanes, and disubstituted dihydroisoquinolinones. Incorporation of an electron-rich cyclohexyl group in the phosphine moiety afforded Xu-Phos, which showed a unique effect in a series of asymmetric transformations, including reductive Heck, dearomative Mizoroki-Heck, tandem Heck/Suzuki coupling, carboiodination, carboamination, and cross-coupling reactions. Using a similar strategy, our group synthesized more electron-rich TY-Phos and Xiang-Phos ligands bearing t-butyl and 1-adamantyl group at P atoms, respectively. Regarding stereoelectronic features, these two characteristic ligands were the best choice to satisfy the requirements of the palladium-catalyzed fluoroarylation of gem-difluoroalkenes, intermolecular α-arylation of aldehydes, carboetherification of alkenyl oximes, and carboheterofunctionalization of 2,3-dihydrofurans. Compared with the aforementioned Sadphos ligands, the attractive features of Xiao-Phos, including high nucleophilicity originating from the CH2PPh2 group and the ortho-substituent effect at the side of the aryl ring, are presumably responsible for its efficiency. The Pd/Xiao-Phos catalyst system shows good performance in a series of cross-coupling reactions of secondary phosphine oxides, affording P-stereogenic products bearing multiple types of molecular skeletons. The modification of the basic Sadphos backbone by introducing a xanthene skeleton motivated us to design and synthesize monophosphines, named PC-Phos and GF-Phos. PC-Phos is effective in various reactions, including arylation of sulfenate anions, denitrogenative cyclization of benzotriazoles, and dearomatization of indoles. The practicability of GF-Phos was validated in the Pd-catalyzed asymmetric three-component coupling of N-tosylhydrazones, aryl halides, and terminal alkynes, as well as in the cross-coupling of N-tosylhydrazones and vinyl iodides with pendent amines. In addition, ferrocene-derived WJ-Phos was employed in the palladium-catalyzed Suzuki-Miyaura cross-coupling reaction, affording axially chiral biaryl monophosphine oxides in excellent enantiomeric excesses.

ChemInform Abstract: Catalyst‐Free Cross‐Coupling of N‐Tosylhydrazones with Chromium(0) Fischer Carbene Complexes: A New Approach to Diarylethanone.

Cross-coupling of N-tosylhydrazones with chromium Fischer carbene complexes under catalyst-free conditions has been developed. This protocol employs stable carbene complexes and reactive diazo compounds, which are in situ generated from N-tosylhydrazones. Through hydrolysis of the initially formed methyl enolate products, the diarylethanone derivatives could be obtained in moderate to good yields.