Construction of Erythrinane Skeleton via Pd(0)-Catalyzed Intramolecular Dearomatization of para-Aminophenols

Abstract

A novel Pd(0)-catalyzed intramolecular arylative dearomatization of para-aminophenol derivatives is described. In the presence of 1.25 mol % [Pd(C3H5)Cl]2 and 3.75 mol % RuPhos, the arylative dearomatization reaction proceeds smoothly for a broad range of substrates, offering an efficient synthetic route to erythrinane derivatives in excellent yields.

Catalytic Asymmetric Dearomatization by Transition-Metal Catalysis: A Method for Transformations of Aromatic Compounds

“…Originally reported by the Buchwald group, 64 the You group, 65 and the Tang group. 66 Recently, the scope of this Pd-catalyzed arylative dearomatization was successfully expanded to various para-aminophenols by our group.…”

“…This method allowed facile access to the unique tetracyclic skeleton of erythrinane alkaloids. 65 Although satisfactory yields could be achieved for the racemic reactions of a large array of substrates with RuPhos as the ligand, the asymmetric version of this reaction was far less effective. A screen of several commercially available chiral phosphine ligands disclosed that TADDOL-derived phosphoramidite L16 was the best choice.…”

Enantioselective Palladium‐Catalyzed Dearomative Cyclization for the Efficient Synthesis of Terpenes and Steroids

“…Herein, we present a powerful asymmetric palladium-catalyzed dearomative cyclization that has led to a series of chiral phenanthrenone derivatives bearing an allcarbon quaternary center in excellent enantioselectivities. The new method has been successfully applied in the highly efficient synthesis of a chiral kaurene intermediate, the facile construction of the skeleton of the anabolic steroid boldenone, and an enantioselective total synthesis of the diterpene natural product (À)-totaradiol.Although dearomative cyclizations have been frequently applied in natural product synthesis, the asymmetric transition-metal-catalyzed dearomative cyclization has remained underdeveloped, and only a few examples of efficient intramolecular dearomative arylations have been reported thanks to the pioneering work from the Buchwald, [9] Bedford, [10] and You [11] groups. Buchwald [9] and co-workers developed efficient dearomative cyclizations to form chiral benzocarbazole derivatives and spirocyclohexadienones bearing all-carbon quaternary centers.…”

“…Although dearomative cyclizations have been frequently applied in natural product synthesis, the asymmetric transition-metal-catalyzed dearomative cyclization has remained underdeveloped, and only a few examples of efficient intramolecular dearomative arylations have been reported thanks to the pioneering work from the Buchwald, [9] Bedford, [10] and You [11] groups. Buchwald [9] and co-workers developed efficient dearomative cyclizations to form chiral benzocarbazole derivatives and spirocyclohexadienones bearing all-carbon quaternary centers.…”

“…Gratifyingly, when a new ligand L6 [13] bearing a 2,5-diphenylpyrrole moiety was employed, the cyclization product was formed in 94 % yield and 92 % ee (entry 8). Further studies on the solvents and catalyst precursors showed that toluene and [{Pd(cinnamyl)Cl} 2 ] were most suitable for this cyclization (entries [9][10][11][12][13][14].…”