Aromatic aza-Claisen Rearrangement Research Articles

Stereoselective synthesis of vinylphosphonates through aromatic aza-Claisen rearrangement of α-aminophosphonates.

A novel and convenient approach for the synthesis of vinyl phosphonates has been developed, utilizing an aromatic aza-Claisen rearrangement of β,γ-unsaturated α-aminophosphonates. The synthetic utility of this method was further examined in a gram-scale synthesis. The DFT calculations have provided insights into the basis of the reaction mechanism.

Aromatic Aza-Claisen Rearrangement of Arylpropargylammonium Salts Generated in situ from Arynes and Tertiary Propargylamines.

The charge-accelerated aza-Claisen rearrangement of ammonium salts serves as a key step in the construction of complex nitrogen-containing molecules. However, much less attention has been paid to the aromatic aza-Claisen rearrangement than to the aliphatic one. Herein, we report an unprecedented aromatic aza-Claisen rearrangement of arylpropargylammonium salts, generated in situ from arynes and tertiary propargylamines, delivering structurally diverse 2-propargylanilines in moderate to good yields with high regioselectivity. This rearrangement proceeds in the absence of strong bases or transition metals, is compatible with moisture and air, tolerates a wide variety of functional groups, and is amenable to forming 11- to 13-membered heterocycles with a triple bond. The 2-propargylaniline products were treated with aluminum chloride in ethanol to afford multisubstituted indoles in moderate to excellent yields. Finally, a series of deuterium-labeling experiments was performed to elucidate the reaction mechanism.

The first synthesis of 7-prenylisatin

The first synthesis of 7-prenylisatin, an isatin-type antibiotic with prominent activity against Bacillus subtilis, has been accomplished in 16% overall yield from 2-methylbut-3-en-2-ol and aniline via a five-step procedure. The protocol includes the aromatic aza-Claisen rearrangement and the Sandmeyer isonitrosoacetanilide isatin synthesis as key steps.

Brønsted Acid Catalyzed Enantioselective Indole Aza-Claisen Rearrangement Mediated by an Arene CH–O Interaction

Although the aromatic aza-Claisen rearrangement is a general strategy for accessing substituted aromatic amines, there are no highly enantioselective examples of this process. We report the first Brønsted acid catalyzed enantioselective indole aza-Claisen rearrangement for the synthesis of chiral 3-amino-2-substituted indoles. We present evidence for an arene CH-O interaction as a source of activation and stereoinduction, which is an unprecedented phenomenon in enantioselective Brønsted acid catalysis. The products of this reaction can be transformed into 3-aminooxindoles, which are prevalent in many biologically active small molecules.

Revitalizing the aromatic aza-Claisen rearrangement: implications for the mechanism of ‘on-water’ catalysis

For too long the aromatic aza-Claisen rearrangement has been the poor relation of its oxygen counterpart. We demonstrate that on-water catalysis facilitates the rearrangement of reverse N-prenylated naphthylamines and anilines, and transforms the aromatic aza-Claisen rearrangement into a synthetically viable reaction. We use this reaction to probe the mechanism of on-water catalysis, and provide compelling support for the acid-catalysis hypothesis.

Synthesis of Coumarin- and Quinolone-Annulated Benzazocinone Frameworks by a Palladium-Catalyzed Intramolecular Heck Reaction

A synthetic strategy based on the sequential application of an aromatic aza-Claisen rearrangement and an intramolecular Heck reaction as the key steps has been developed for the synthesis of various new coumarin- and quinolone-annulated benzazocinone derivatives in 60–70% yields.

Facile Synthesis of Coumarin- and Quinolone-Annulated Benzazoninone Derivatives by an Intramolecular Heck Reaction Strategy via 9-exo-trig Cyclization

A synthetic strategy based on the application of the aromatic aza-Claisen rearrangement followed by an intramolecular Heck reaction sequence as the key step has been developed for the regiocontrolled synthesis of hitherto unreported coumarin- and quinolone-annulated benzazoninone derivatives in 48―69% yield.

Novel Synthesis of Heterocycle-Annulated Azocine Derivatives of Biological Relevance by Aromatic Aza-Claisen Rearrangement and Intramolecular Heck Reaction

A synthetic strategy based on the sequential application of an aromatic aza-Claisen rearrangement and an intramolecular Heck reaction sequence as the key steps has been developed for the synthesis of various hitherto unreported coumarin- and quinolone-annulated benzazocine derivatives in excellent yields.

Synthesis of Azepine- and Azocine-Annulated Heterocycles by Aromatic Aza-Claisen Rearrangement and Ring-Closing Metathesis

Syntheses of hitherto unreported azepine- and azocine-annulated heterocycles have been developed in excellent yields via a catalyzed aromatic aza-Claisen rearrangement followed by ring-closing metathesis using Grubbs first-generation catalyst.

Synthesis of highly substituted dibenzoazocine derivatives by the aza-Claisen rearrangement and intramolecular Heck reaction via 8- exo-trig mode of cyclization

The synthesis of highly substituted dibenzo-azocine systems is still lacking. An efficient synthetic protocol utilizing the sequential aromatic aza-Claisen rearrangement followed by the implementation of the intramolecular Heck reaction as a key step has been developed for the synthesis of various dibenzo-azocine derivatives of biological relevance.