Catalytic Asymmetric Dearomatization Research Articles

Catalytic Asymmetric Dearomatization of Indolyl Dihydropyridines through an Enamine Isomerization/Spirocyclization/Transfer Hydrogenation Sequence

AbstractA highly efficient synthesis of enantioenriched spiroindolines by catalytic asymmetric dearomatization of indolyl dihydropyridines through a chiral phosphoric acid catalyzed enamine isomerization/spirocyclization/transfer hydrogenation sequence has been developed. This reaction proceeds under mild reaction conditions, affording novel spiroindolines in good yields (up to 88 %) with excellent enantioselectivity (up to 97 % ee). DFT calculations provide insights into the reaction mechanism as well as the origin of stereochemistry.

Catalytic Asymmetric Dearomatization of Indolyl Dihydropyridines through an Enamine Isomerization/Spirocyclization/Transfer Hydrogenation Sequence.

A highly efficient synthesis of enantioenriched spiroindolines by catalytic asymmetric dearomatization of indolyl dihydropyridines through a chiral phosphoric acid catalyzed enamine isomerization/spirocyclization/transfer hydrogenation sequence has been developed. This reaction proceeds under mild reaction conditions, affording novel spiroindolines in good yields (up to 88 %) with excellent enantioselectivity (up to 97 % ee). DFT calculations provide insights into the reaction mechanism as well as the origin of stereochemistry.

Catalytic Asymmetric Dearomative [3 + 2] Cycloaddition of Electron-Deficient Indoles with All-Carbon 1,3-Dipoles.

The first catalytic asymmetric dearomative [3 + 2] cycloaddition of 3-nitroindoles with vinylcyclopropanes has been established, which constructed chiral cyclopenta[b]indoline scaffolds in generally high enantioselectivities (up to 97% ee). This reaction also represents the first application of all-carbon 1,3-dipoles in catalytic asymmetric dearomative [3 + 2] cycloadditions of 3-nitroindoles. This approach will not only advance the catalytic asymmetric dearomatization reactions of electron-deficient indoles but also provide an efficient method for constructing chiral cyclopenta[b]indoline scaffolds.

Palladium-Catalyzed Highly Stereoselective Dearomative [3 + 2] Cycloaddition of Nitrobenzofurans

Summary Stereoselective construction of highly functionalized heterocyclic molecules is an ongoing concern for the chemical community. Among the various strategies developed with this goal, catalytic asymmetric dearomatization, an attractive method for constucting cyclic molecules with multiple stereocenters from readily available aromatic compounds, has received extensive attention in recent years. Here, we report a highly stereoselective construction of tetrahydrofurobenzofurans and tetrahydrofurobenzothiophenes via palladium-catalyzed dearomative [3 + 2] cycloaddition of nitrobenzofurans and nitrobenzothiophenes, respectively. Good to excellent yields (63%–92%), diastereoselectivity (13/1 → >20/1 dr), and enantioselectivity (75%–95% ee) were obtained, leading to products with vicinal stereogenic carbon centers. The reaction features wide substrate scope and diverse transformations of the products.

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.

Catalytic asymmetric hydroxylative dearomatization of 2-naphthols: synthesis of lacinilene derivatives.

An enantioselective hydroxylative dearomatization of 2-naphthols with oxaziridines has been accomplished using a N,N'-dioxide-scandium(iii) complex catalyst. Various substituted ortho-quinols could be obtained in high yields (up to 99%) and enantioselectivities (up to 95 : 5 er). This methodology could be applied in the synthesis of bioactive lacinilenes in a gram-scale reaction. Based on the experimental investigations and previous work, a possible catalytic model was proposed.

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.

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.

ChemInform Abstract: Chiral N,N′‐Dioxide—Scandium(III)‐Catalyzed Asymmetric Dearomatization of 2‐Naphthols Through an Amination Reaction.

A catalytic asymmetric dearomatization of 2-naphthols with azodicarboxylates has been accomplished by using a N,N′-dioxide-scandium(III) complex as a chiral catalyst. A number of optically active β-naphthalenone compounds with a nitrogen-containing quaternary carbon stereocenter were obtained in up to 99 % yield and up to 99 % ee under mild reaction conditions. The reaction could be scaled up to a gram-scale with the yield and ee maintained. Based on these experiments and on previous reports, a possible transition state was proposed.

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.

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 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

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.

Chiral N,N'-Dioxide-Scandium(III)-Catalyzed Asymmetric Dearomatization of 2-Naphthols through an Amination Reaction.

A catalytic asymmetric dearomatization of 2-naphthols with azodicarboxylates has been accomplished by using a N,N'-dioxide-scandium(III) complex as a chiral catalyst. A number of optically active β-naphthalenone compounds with a nitrogen-containing quaternary carbon stereocenter were obtained in up to 99 % yield and up to 99 % ee under mild reaction conditions. The reaction could be scaled up to a gram-scale with the yield and ee maintained. Based on these experiments and on previous reports, a possible transition state was proposed.

Direct asymmetric dearomatization of 2-naphthols by scandium-catalyzed electrophilic amination.

Catalytic asymmetric aminative dearomatization of 1-substituted 2-naphthols was successfully implemented with electrophilic azodicarboxylates under the catalysis of chiral Sc(III)/pybox complexes. This intermolecular reaction represents a hitherto unknown enantioselective C-N bond-forming process through direct dearomatization of phenolic compounds to generate chiral nitrogen-containing quaternary carbon stereocenters.

Asymmetric Dearomatization of β‐Naphthols through an Amination Reaction Catalyzed by a Chiral Phosphoric Acid

AbstractA highly efficient catalytic asymmetric dearomatization of naphthols by means of an electrophilic amination reaction catalyzed by chiral phosphoric acid is presented. This protocol provides a facile access to functionalized β‐naphthalenone compounds with a chiral quaternary carbon center in excellent yields and enantioselectivity (up to 99 % yield, up to 96 % ee).

Asymmetric dearomatization of β-naphthols through an amination reaction catalyzed by a chiral phosphoric acid.

A highly efficient catalytic asymmetric dearomatization of naphthols by means of an electrophilic amination reaction catalyzed by chiral phosphoric acid is presented. This protocol provides a facile access to functionalized β-naphthalenone compounds with a chiral quaternary carbon center in excellent yields and enantioselectivity (up to 99% yield, up to 96% ee).