Asymmetric Dearomatization Reaction Research Articles

Iridium‐Catalyzed Intermolecular Asymmetric Dearomatization of β‐Naphthols with Allyl Alcohols or Allyl Ethers

AbstractAn Ir‐catalyzed intermolecular asymmetric dearomatization reaction of β‐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 β‐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.

Asymmetric fluorinative dearomatization of tryptamine derivatives.

An asymmetric fluorinative dearomatization reaction of tryptamine derivatives was developed by using a chiral anion phase transfer catalyst (PTC) system, and the preliminary results of the reaction mechanistic study were achieved. This method is characterized by a simple operation, facile introduction of a fluorine atom in a highly enantioselective manner and construction of two contiguous quaternary stereogenic centers.

有機分子触媒による脱芳香族化反応を基盤とした全炭素第四級不斉炭素構築法

The asymmetric dearomatization reaction of phenols and their derivatives has emerged as a powerful method for the construction of enantioenriched cyclic enones, which are frequently found in bioactive natural products and pharmaceuticals. This review focuses on recent progress for construction of quaternary stereocenter based on organocatalytic dearomatization reaction.

ChemInform Abstract: Copper(I)‐Catalyzed Asymmetric Dearomatization of Indole Acetamides with 3‐Indolylphenyliodonium Salts.

AbstractAn intermolecular, asymmetric cascade dearomatization reaction of indole acetamides with 3‐indolylphenyliodonium salts is developed.

ChemInform Abstract: MgII‐Mediated Catalytic Asymmetric Dearomatization (CADA) Reaction of β‐Naphthols with Dialkyl Acetylenedicarboxylates.

AbstractThis reaction proceeds under ambient temperature and gives a series of chiral trisubstituted olefins with good chemoselectivities, Z/E ratios, and excellent enantioselectivities.

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.

Asymmetric Dearomatization Reaction of β-Naphthols

Asymmetric Dearomatization Reaction of β-Naphthols

Catalytic Asymmetric Chlorinative Dearomatization Reaction of Benzofurans

AbstractA catalytic asymmetric chlorinative dearomatization reaction of benzofuran derivatives was achieved by using hydroquinidine 1,4‐phthalazinediyl diether [(DHQD)2PHAL] as the catalyst and N‐chlorophthalimide (NCP) as the chlorinating reagent. A series of chlorinated spiro[benzofuran‐2,5′‐oxazole]s bearing two contiguous stereogenic centers was obtained in high yields (up to 99%) with excellent enantioselectivity (up to 99% ee).magnified image

ChemInform Abstract: Catalytic Asymmetric Cascade Dearomatization of Tryptamines with Indol‐3‐ylmethanols: Diastereo‐ and Enantioselective Synthesis of Structurally Complex Indole Derivatives.

A chiral phosphoric acid-catalyzed asymmetric cascade dearomatization reaction of tryptamines with indol-3-ylmethanols has been established. This not only realized the first catalytic asymmetric cascade substitution of indol-3-ylmethanols, but also provided an efficient and stereoselective method (99% yield, >95:5 dr, 95:5 er) for constructing complex pyrroloindoline-based skeletons with three contiguous stereogenic centers, two of which were all-carbon quaternary centers.

Mg(II) -Mediated Catalytic Asymmetric Dearomatization (CADA) Reaction of β-Naphthols with Dialkyl Acetylenedicarboxylates.

A Mg(II) -mediated catalytic asymmetric dearomatization (CADA) reaction of β-naphthols has been developed. The reaction proceeds under ambient temperature and give a series of chiral trisubstituted olefins with good chemoselectivities, Z/E ratios, and excellent enantioselectivities. A fluorinated β-naphthol was designed to generate chiral organofluorine skeletons through the current CADA reaction. Moreover, an interesting tandem cyclization reaction was observed in the following transformation process through an undiscovered intramolecular hydride transfer pathway.

ChemInform Abstract: Catalytic Asymmetric Dearomatization (CADA) Reactions of Phenol and Aniline Derivatives

AbstractReview: 37 refs.

Catalytic asymmetric dearomatization (CADA) reactions of phenol and aniline derivatives.

Phenols are widely used as starting materials in both industrial and academic society. Dearomatization reactions of phenols provide an efficient way to construct highly functionalized cyclohexadienones. The main challenge to make them asymmetric by catalytic methods is to control the selectivity while overcoming the loss of aromaticity. In this tutorial review, an up to date summary of recent progress in CADA reactions of phenol and aniline derivatives is presented.

Catalytic Asymmetric Cascade Dearomatization of Tryptamines with Indol-3-ylmethanols: Diastereo- and Enantioselective Synthesis of Structurally Complex Indole Derivatives

A chiral phosphoric acid-catalyzed asymmetric cascade dearomatization reaction of tryptamines with indol-3-ylmethanols has been established. This not only realized the first catalytic asymmetric cascade substitution of indol-3-ylmethanols, but also provided an efficient and stereoselective method (99% yield, >95:5 dr, 95:5 er) for constructing complex pyrroloindoline-based skeletons with three contiguous stereogenic centers, two of which were all-carbon quaternary centers.

Asymmetric Dearomatization of β-Naphthols through a Bifunctional-Thiourea-Catalyzed Michael Reaction.

An intermolecular asymmetric dearomatization reaction of β-naphthols with nitroethylene through a chiral-thiourea-catalyzed Michael reaction is described. Enantioenriched functionalized β-naphthalenones with an all-carbon quaternary stereogenic center could thus be easily constructed from simple naphthol derivatives in good yields and excellent enantioselectivity (up to 79% yield, 98% ee).

Asymmetric Dearomatization of β‐Naphthols through a Bifunctional‐Thiourea‐Catalyzed Michael Reaction

AbstractAn intermolecular asymmetric dearomatization reaction of β‐naphthols with nitroethylene through a chiral‐thiourea‐catalyzed Michael reaction is described. Enantioenriched functionalized β‐naphthalenones with an all‐carbon quaternary stereogenic center could thus be easily constructed from simple naphthol derivatives in good yields and excellent enantioselectivity (up to 79 % yield, 98 % ee).

Asymmetric Dearomatization of 1‐Amino­naphthalene Derivatives through C–C Bond Formation with Electron‐Rich Heterocycles as Nucleophiles

AbstractA cationic gold(I)/axially chiral biaryl bis(phosphine) complex has been employed to catalyze the asymmetric dearomatization reactions of 1‐aminonaphthalene derivatives through a C–C bond‐forming reaction with electron‐rich heterocycles as the nucleophiles. These reactions afford pentacyclic heterocycles in good yields with moderate enantiomeric excess (ee) values.

ChemInform Abstract: Highly Regio and Enantioselective Synthesis of Chiral Polysubstituted 2H‐Pyrroles

AbstractReview: 3 refs.

ChemInform Abstract: Asymmetric Oxidative Dearomatizations Promoted by Hypervalent Iodine(III) Reagents: An Opportunity for Rational Catalyst Design?

AbstractReview: [57 refs.

ChemInform Abstract: Transition‐Metal‐Catalyzed Asymmetric Allylic Dearomatization Reactions

AbstractReview: 72 refs.

Highly regio- and enantioselective synthesis of chiral polysubstituted 2H-pyrroles

As one of the most important five-member heterocyclic aromatic rings, pyrrole is widely distributed in numerous natural products and pharmaceutical agents. Asymmetric dearomatization of pyrroles is very attractive in organic synthesis given the fact that highly functionalized chiral pyrrolines and pyrrolidines could be easily accessed from the readily available pyrroles. However, the reported asymmetric dearomatization reactions of pyrroles are limited to transition-metal-catalyzed [4+3] cycloaddition and hydrogenation reactions. The enantioselective intermolecular alkylative dearomatization of pyrroles is rare and challenging due to multiple selectivity issues including the chemoselectivity (C2&N1), regioselectivity (C2&C4, C2&C5) and enantioselectivity (Scheme 1) [1]. During the past few years, the You group from Shanghai Institute of Organic Chemistry has focused on the transition-metal-catalyzed asymmetric allylic dearomatization reactions [2]. Recently, the researchers in this group found that highly enantioenriched poly-substituted 2H-pyrroles could be easily accessed via Pd-catalyzed intermolecular asymmetric allylic dearomatization reaction of polysubstituted pyrroles (Scheme 1). With the commercially available palladium precursor and chiral ligand, various poly-substituted 2H-pyrrole products containing a chiral quaternary carbon center were obtained with up to 97% ee under mild reaction conditions. Interestingly, they found the reaction occurred smoothly to give good to excellent regioselectivities when tri-substituted and tetra-substituted pyrrole derivatives were used. In addition, chiral pyrrolines and cyclic imines could be conveniently prepared by selective reductions of the enantioenriched 2H-pyrrole products, further demonstrating the synthetic utility of this newly developed method. Moreover, this reaction represents the first example involving the multi-substituted pyrroles as prochiral nucleophiles in Pd-catalyzed asymmetric allylic alkylation reactions.