Construction of the Benzomesembrine Skeleton: Palladium(0)-Catalyzed Intermolecular Arylative Dearomatization of α-Naphthols and Subsequent Aza-Michael Reaction.

A novel palladium(0)-catalyzed intermolecular arylative dearomatization of α-naphthols and subsequent aza-Michael reaction is described. Two adjacent stereocenters were constructed efficiently through consecutive arylative dearomatization and Michael addition reactions. By utilizing this method, structurally diverse benzomesembrine derivatives were synthesized with excellent yields and chemoselectivity. The benzomesembrine products were shown to undergo versatile functional-group transformations.

Iridium-Catalyzed Intermolecular Asymmetric Dearomatization of ß-Naphthols with Allyl Alcohols or Allyl Ethers.

An Ir-catalyzed intermolecular asymmetric dearomatization reaction of ß-naphthols with allyl alcohols or allyl ethers was developed. When an iridium catalyst generated from [Ir(COD)Cl]2 (COD=cyclooctadiene) and a chiral P/olefin ligand is employed, highly functionalized ß-naphthalenone compounds bearing an all-carbon-substituted quaternary chiral center were obtained in up to 92 % yield and 98 % ee. The direct utilization of allyl alcohols as electrophiles represents an improvement from the viewpoint of atom economy. Allyl ethers were found to undergo asymmetric allylic substitution reaction under Ir catalysis for the first time. The diverse transformations of the dearomatized product to various motifs render this method attractive.

Construction of Chiral Tetrahydro-ß-Carbolines: Asymmetric Pictet-Spengler Reaction of Indolyl Dihydropyridines.

A highly efficient synthesis of the enantioenriched tetrahydro-ß-carbolines was developed by using a chiral phosphoric acid catalyzed Pictet-Spengler reaction of indolyl dihydropyridines. The reaction proceeds under mild reaction conditions to afford the desired chiral tetrahydro-ß-carbolines in good to excellent yields (up to 96 %) and high enantioselectivities (up to 99 % ee). With this method, a formal synthesis of tangutorine and a total synthesis of deplancheine were achieved in a highly efficient manner.

Copper(I)-Catalyzed Asymmetric Dearomatization of Indole Acetamides with 3-Indolylphenyliodonium Salts.

The rapid and direct asymmetric synthesis of 3-(3a-indolyl)hexahydropyrroloindoline motifs is an extremely important part of the total synthesis of several alkaloid structures. Herein, an intermolecular, asymmetric cascade dearomatization reaction of indole acetamides with 3-indolylphenyliodonium salts has been developed. This protocol provides a straightforward access to 3-(3a-indolyl)hexahydropyrroloindolines bearing an all-carbon quaternary stereocenter at the C3 position of the indoline ring with high enantioselectivities. The utility of the protocol has been demonstrated by the formal asymmetric synthesis of folicanthine.

Palladium(0)-Catalyzed Intermolecular Arylative Dearomatization of ß-Naphthols.

The first Pd0 -catalyzed intermolecular arylative dearomatization of ß-naphthols with aryl halides is described. It was found that Q-Phos could facilitate the palladium-catalyzed cross-coupling-type dearomatization of ß-naphthols, while avoiding O-arylation, to construct 2-naphthalenones in excellent yields and with high chemoselectivity.

Construction of erythrinane skeleton via Pd(0)-catalyzed intramolecular dearomatization of para-aminophenols.

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.

Chiral phosphoric acid catalyzed aminative dearomatization of α-naphthols/Michael addition sequence.

Asymmetric dearomatization reactions have recently emerged as a powerful tool for the rapid build-up of the molecular complexity. Chiral three-dimensional polycyclic molecules bearing contiguous stereogenic centers can be synthesized from readily available planar aromatic feedstocks. Here we report that an intermolecular asymmetric dearomatization reaction of α-naphthols bearing a tethered nucleophile at the C4 position of the naphthol ring is achieved by a chiral phosphoric acid. The reaction proceeds via a highly chemo- and regioselective aminative dearomatization/Michael addition sequence, affording a wide array of functionalized cyclic ketones in good yields (up to 93%) with excellent enantioselectivity (up to >99% ee). The catalyst loading can be reduced to 0.1 mol%. Preliminary mechanistic investigations identify that the enantioselectivity is established in the dearomatization step, while the Michael addition is the rate-limiting step. A working model accounting for the origin of the stereochemistry is proposed based on DFT calculations.

Pd(0)-Catalyzed intramolecular arylative dearomatization of ß-naphthols.

An efficient Pd(0)-catalyzed intramolecular arylative dearomatization of ß-naphthols is described. Using Q-Phos as a ligand, the arylative dearomatization reaction proceeded smoothly affording excellent yields and chemoselectivity even when the catalyst loading was reduced to 0.1 mol%. This method offers an efficient access to a series of structurally diverse spirocarbocycles. Preliminary investigation indicates that an enantioselective reaction is feasible in the presence of a chiral phosphoramidite ligand.

Construction of spirocarbocycles via gold-catalyzed intramolecular dearomatization of naphthols.

A highly efficient, gold-catalyzed intramolecular dearomatization reaction of naphthols via 5-endo-dig cyclization is described. This facile and direct approach furnishes spirocarbocycles in excellent yields under mild conditions.