Arylative Dearomatization Research Articles

Palladium-Catalyzed Arylative Dearomatization and Subsequent Aromatization/Dearomatization/Aza-Michael Addition: Access to Zephycarinatine and Zephygranditine Skeletons.

We have developed a novel palladium-catalyzed arylative dearomatization and subsequent aromatization/dearomatization/aza-Michael addition process of Ugi adducts, enabling the rapid construction of diverse zephycarinatine and zephygranditine scaffolds containing two adjacent quaternary carbon stereocenters with excellent chemoselectivity and stereoselectivity in a rapid, step-economical, and highly efficient manner. This approach shows broad substrate scope and excellent functional-group tolerance with diverse electron-rich and electron-deficient aromatic substrates. The synthetic utility of this method is further demonstrated by versatile transformations of the products.

Monoamine Oxidase (MAO-N) Biocatalyzed Synthesis of Indoles from Indolines Prepared via Photocatalytic Cyclization/Arylative Dearomatization

The biocatalytic aromatization of indolines into indole derivatives exploiting monoamine oxidase (MAO-N) enzymes is presented. Indoline substrates were prepared via photocatalytic cyclization of arylaniline precursors or via arylative dearomatization of unsubstituted indoles and in turn chemoselectively aromatized by the MAO-N D11 whole cell biocatalyst. Computational docking studies of the indoline substrates in the MAO-N D11 catalytic site allowed for the rationalization of the biocatalytic mechanism and experimental results of the biotransformation. This methodology represents an efficient example of biocatalytic synthesis of indole derivatives and offers a facile approach to access these aromatic heterocycles under mild reaction conditions.

Pd‐Catalyzed Asymmetric Intramolecular Arylative Dearomatization of para‐Aminophenols†

Summary of main observation and conclusionAsymmetric arylative dearomatization reactions of para‐aminophenols are realized by a Pd‐catalyst consisting of a TADDOL (α,α,α',α'‐tetraaryl‐2,2‐disubstituted 1,3‐dioxolane‐4,5‐dimethanol)‐derived chiral phosphoramidite ligand. The tetracyclic products bearing the key skeleton of Erythrina alkaloids are afforded in reasonable yields (up to 73%) with good to excellent enantioselectivity (up to 97% ee). Concise total synthesis of (–)‐3‐demethoxyerythratidinone is achieved by employing this method as the key step.

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

AbstractA 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.

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.

Asymmetric Arylative Dearomatization of β‐Naphthols Catalyzed by a Chiral Phosphoric Acid

An enantioselective arylative dearomatization reaction of β-naphthols with quinone monoimides has been developed for the first time using a chiral phosphoric acid as the catalyst, the desired enantioenriched cyclohexadienones were prepared with excellent yields and enantioselectivities by a domino Michael addition and aromatization process (up to 99 % yield, up to 98 % ee). This process is operationally simple and readily scaled up, as well as a broad substrate scope which includes 1-substituted-2-naphthols with/without 3-substituents. Furthermore, this organocatalytic procedure allows the lowering of catalyst loading to 0.5 mol % without considerable loss in reactivity and enantioselectivity.

Catalytic asymmetric chemodivergent arylative dearomatization of tryptophols

The first catalytic asymmetric arylative dearomatization of tryptophols has been established. By using quinone imine ketals as aryl group surrogates and modulating the reaction conditions, the cascade reaction of tryptophols with quinone imine ketals in the presence of chiral phosphoric acid afforded two series of arylative dearomatization products with generally high yields (up to 99%), and excellent diastereo- and enantioselectivities (all > 95 : 5 dr, 90% to 99% ee) in a chemoselective manner.

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

An efficient Pd(0)-catalyzed intramolecular arylative dearomatization of β-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.

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

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

Palladium(0)‐Catalyzed Intermolecular Arylative Dearomatization of β‐Naphthols

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

ChemInform Abstract: Catalytic Enantioselective Arylative Dearomatization of 3‐Methyl‐2‐vinylindoles Enabled by Reactivity Switch.

AbstractThe first catalytic asymmetric dearomatization of 3‐methyl‐2‐vinylindoles is established by using quinone monoimides as suitable electrophiles in the presence of a chiral phosphoric acid, which affords chiral indole derivatives bearing a quaternary stereogenic center in a chemospecific and highly enantioselective fashion.

Inside Back Cover: Catalytic Enantioselective Arylative Dearomatization of 3-Methyl-2-vinylindoles Enabled by Reactivity Switch (Adv. Synth. Catal. 18/2015)

Inside Back Cover: Catalytic Enantioselective Arylative Dearomatization of 3-Methyl-2-vinylindoles Enabled by Reactivity Switch (Adv. Synth. Catal. 18/2015)

Catalytic Enantioselective Arylative Dearomatization of 3‐Methyl‐2‐vinylindoles Enabled by Reactivity Switch

AbstractThe first catalytic asymmetric dearomatization of 3‐methyl‐2‐vinylindoles has been established by using quinone monoimides as suitable electrophiles in the presence of chiral phosphoric acid, which afforded chiral indole derivatives bearing a quaternary stereogenic center in a chemospecific and highly enantioselective fashion (up to 81% yield, >99% ee). The success of this reaction was enabled by the reactivity switch of 3‐methyl‐2‐vinylindoles, which has not been reported before. This reaction also represents the first catalytic asymmetric arylative dearomatization of vinylindoles, which will help confront the challenges in catalytic asymmetric arylative dearomatization and dearomatization of vinylindoles.magnified image

Connecting Tyrosine and Tryptophan Units of Diazonamide A and Azonazine by a Diastereodivergent Arylative Dearomatization.

We report the Friedel-Crafts coupling of a tyrosine unit with tryptophan-derived pyrrolindolenium ions which are configurationally stable. The reaction allowed the stereoselective and divergent access to the required quaternary stereocenters found in diazonamide A and azonazine at the junction of the tyrosine and tryptophan units.

ChemInform Abstract: Enantioselective Arylative Dearomatization of Indoles via Pd‐Catalyzed Intramolecular Reductive Heck Reactions.

A highly enantioselective intramolecular arylative dearomatization of indoles via palladium-catalyzed reductive Heck reactions was developed. The new strategy led to a series of optically active indolines bearing C2-quaternary stereocenters in modest to good yields with excellent enantioselectivities (up to 99% ee).

ChemInform Abstract: Construction of Erythrinane Skeleton via Pd(0)‐Catalyzed Intramolecular Dearomatization of para‐Aminophenols.

AbstractA novel Pd(0)‐catalyzed intramolecular arylative dearomatization of substrates having a p‐aminophenol subunit and an alkyl tether bearing an ortho‐haloaryl substituent is shown to yield products representing the erythrinane skeleton and related spirocyclic compounds.

ChemInform Abstract: Organocatalytic Asymmetric Arylative Dearomatization of 2,3‐Disubstituted Indoles Enabled by Tandem Reactions.

AbstractArylative dearomatization of indoles in presence of chiral BINOL‐derived phosphate TBP gives 3‐aryl‐3H‐indoles with quaternary stereocenters in high yields with excellent enantioselectivities.

Enantioselective Arylative Dearomatization of Indoles via Pd-Catalyzed Intramolecular Reductive Heck Reactions.

A highly enantioselective intramolecular arylative dearomatization of indoles via palladium-catalyzed reductive Heck reactions was developed. The new strategy led to a series of optically active indolines bearing C2-quaternary stereocenters in modest to good yields with excellent enantioselectivities (up to 99% ee).

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.

Organocatalytic asymmetric arylative dearomatization of 2,3-disubstituted indoles enabled by tandem reactions.

The organocatalytic asymmetric arylative dearomatization of indoles was achieved through two tandem approaches involving 2,3-disubstituted indoles and quinone imine ketals. One approach utilized the enantioselective cascade 1,4 addition/alcohol elimination reaction, the other employed the one-pot tandem arylative dearomatization/transfer hydrogenation sequence. In both cases, enantiomerically pure indole derivatives that bear an all-carbon quaternary stereogenic center were generated in high yields and excellent stereoselectivities (all d.r.>95:5, up to 99% ee).