Pd/Ming-Phos-Catalyzed Asymmetric Three-Component Arylsilylation of N-Sulfonylhydrazones: Enantioselective Synthesis of gem-Diarylmethine Silanes

Abstract

A Pd-catalyzed enantioselective three-component reaction of N-sulfonylhydrazones, aryl bromides, and silylboronic esters is developed, enabling the synthesis of chiral gem-diarylmethine silanes in high enantioselectivity with the use of a newly identified Ming-Phos. Compared with N-tosyl, the more easily decomposed N-mesitylsulfonyl is more suitable as the masking group of electron-rich hydrazone to improve the reaction efficiency. The reaction features a broad scope concerning both coupling partners, high enantioselectivity, and mild reaction conditions. The ready access to enantiomers and utility of this catalytic method are also presented.

A four-component reaction to access 3,3-disubstituted indolines via the palladium–norbornene-catalyzed ortho amination/ipso conjunctive coupling

“…22 At this stage, a range of different classes of readily available chiral ligands were evaluated in this conjunctive ipso coupling reaction, including phosphoramidites (L4, L5), monodentate phosphines (L6, L8), bidentate phosphines (segphos, L7), and Zhang's sulnamide-containing phosphine (Sadphos, L9-L12) ligands. 23 It is encouraging to observe that the chiral monodentate phosphoramidite ligand, i.e., L5, can afford the desired product (4z) in 89% e.e. While the yield remains low at this stage, this result indicates the feasibility to control the enantioselectivity in the conjunctive ipso coupling.…”

Sadphos as Adaptive Ligands in Asymmetric Palladium Catalysis

“…In another set of reactions, we performed the Pd-catalyzed asymmetric three-component coupling of N -sulfonylhydrazones, aryl bromides, and silylboronic esters (Scheme ). Compared with traditional ligands and the Sadphos series, a newly identified Ming-Phos ( R , Rs )- M20 ligand with a bulky steric hindrance on the side chain and a strong electron-withdrawing group on the phenyl backbone exhibited the highest reaction efficiency and enantioselectivity. This strategy provided a convenient approach to accessing chiral gem -diarylmethine silanes 55 with two similar aromatic groups.…”

“…This opens opportunities for the synthesis of a pair of aldehyde enantiomers. 4 This study shows a Pdcatalyzed enantioselective three-component coupling of Nsulfonylhydrazones, aryl bromides, and silylboronic esters using a newly identif ied Ming-Phos ligand, which provides a facile access to chiral gem-diarylmethine silanes.…”

Who is Who in the Carbene Chemistry of N‐Sulfonyl Hydrazones

“…The employment of the newly identified chiral Ming‐Phos ligand provided the gem ‐diarylmethine silanes with high yield and enantioselectivity. [ 205 ] More importantly, the use of the N ‐mesityl sulfonyl group as the masking group could significantly improve the efficiency of the reaction with electron‐rich hydrazones compared to N ‐tosyl moiety. The suggested mechanism follows a sequence of Pd‐carbene generation (via the oxidative addition of aryl halide to Pd(0) catalyst and subsequent reaction with diazo species), followed by transmetallation, carbene migratory insertion, and stereoretentive reductive elimination of benzylic Pd complex to afford the final product (Scheme 30b).…”