aza-Claisen Rearrangement Research Articles

Copper-catalyzed [3+2] annulation of propargylic acetates with anilines in the presence of trimethylsilyl chloride leading to 2,3-disubstituted indoles via an aza-Claisen rearrangement

Described herein is the use of copper triflate to efficiently catalyze a [3+2] annulation of propargylic acetates with N-alkylanilines in the presence of trimethylsilyl chloride (Me3SiCl) to produce 2,3-disubstituted indole derivatives. Also, the copper(II) catalyst efficiently promoted an aza-Claisen rearrangement of N-arylated propargylic amines involving a 3-aza-1,5-enyne skeleton.

One-Pot Conversion of N-Allyl-α-cyano Esters to α-Allyl-α-cyano Lactams through a Hydrolysis/Ketene Formation/Cyclization/Claisen Rearrangement Sequence.

An intramolecular ketene aza-Claisen rearrangement is developed for the first time to enable the stereoselective synthesis of α-ally-α-cyano-lactams from N-allyl amino esters. This reaction also exhibits outstanding chemoselectivity when an unsymmetrical bis-N-allyl group is present in the starting molecule. The usefulness of this method is demonstrated by a short synthesis of optically active bicyclolactam from l-proline.

Studies on the aza-Claisen Rearrangement of 7 to 9-Membered Vinylazacycles

The amide enolate-induced aza-Claisen rearrangement of the vinylazacycles furnishes 11- to 13-membered macrolactams with an internal (E)-olefinic bond, not accessible by conventional methods.

Lewis acid-catalyzed reactions of N-allylanilines with diazo compounds involving aza-Claisen rearrangement

N-Allyl-N-methylanilines react with methyl diazoacetate or diazoacetone in the presence of Y, Sc or Sm triflates to give the corresponding methyl N-(2-allylaryl)-N-methylglycinates or 2-allyl-N-methyl-N-(2-oxopropyl)aniline. The formation of these compounds involves the aza-Claisen rearrangement.

ChemInform Abstract: Recent Advances in Chiral Phosphoric Acid Catalyzed Asymmetric Reactions for the Synthesis of Enantiopure Indole Derivatives

AbstractReview: [84 refs.

Recent Advances in Chiral Phosphoric Acid Catalyzed Asymmetric Reactions for the Synthesis of Enantiopure Indole Derivatives

Chiral indole derivatives are an intriguing class of heterocyclic compounds; their structural motifs are frequently found in natural products and synthetic compounds with significant bioactivity. Among many synthetic transformations leading to the production of enantiopure indole derivatives, chiral phosphoric acid catalyzed reactions are the most attractive methodologies, since these reactions can directly afford enantiomerically pure indole derivatives from readily accessible starting materials under mild conditions. In this review, the most recent achievements in this research area have been gathered and classified according to different reaction types for the synthesis of enantioenriched indole derivatives under the catalysis of chiral phosphoric acids. 1 Introduction 2 Chiral Phosphoric Acid Catalyzed Asymmetric Addition Reactions 2.1 1,2-Addition Reactions 2.2 1,4-Addition Reactions 3 Chiral Phosphoric Acid Catalyzed Asymmetric Cycloaddition Reactions 3.1 [3+2] Reactions 3.2 [4+2] Reactions 3.3 [3+3] Reactions 4 Chiral Phosphoric Acid Catalyzed Asymmetric Cascade Reactions 4.1 Cascade Reactions 4.2 Transition-Metal-Cocatalyzed Cascade Reactions 4.3 Other Organocatalyst-Cocatalyzed Cascade Reactions 5 Other Reactions Catalyzed by Chiral Phosphoric Acids 5.1 Aza-Claisen Rearrangement 5.2 Kinetic Resolution 5.3 Fischer Indolization 6 Conclusions and Perspective

Investigation of cationic Claisen-type electrophilic rearrangements of amides

Herein we report an extension of the electrophilic rearrangement of amides to the preparation of α-prenyl-hydrocoumarins, indoles, isoquinolines and dihydro-isoquinolinones. An unusual competitive sulfonyl migration, uncovered upon attempted aza-Claisen rearrangement, is also described.

First enantioselective synthesis of (2S,3S)-3-hydroxy-l-arginine via proline catalyzed α-aminooxylation of aldehyde and Pd-catalyzed ether-directed aza-Claisen rearrangement

A concise enantioselective synthesis of (2S,3S)-3-hydroxy-l-arginine with an overall yield of 10.9% and 98% ee, starting from commercially available 1,4-butanediol in ten linear steps has been achieved. The key chiral inducing steps are d-proline catalyzed sequential α-aminooxylation/Horner–Wadsworth–Emmons olefination of an aldehyde and the subsequent diastereoselective MOM-ether-directed Pd-catalyzed aza-Claisen rearrangement of allylic trichloroacetimidate.

A concise enantioselective synthesis of (2S,3S)-3-hydroxypipecolic acid via proline catalyzed α-aminooxylation of aldehydes and Pd-catalyzed ether directed aza-Claisen rearrangements

An efficient approach to (2S,3S)-3-hydroxypipecolic acid with an overall yield of 10.2% and 98% ee starting from 1,5-pentanediol has been developed. The key steps employed in the synthesis are the d-proline catalyzed sequential α-aminooxylation/Horner–Wadsworth–Emmons olefination of an aldehyde and the Pd-catalyzed MOM-ether directed aza-Claisen rearrangement of an allylic trichloroacetimidate.

Efficient strategy for the stereoselective synthesis of 2,3-disubstituted benzo[α]quinolizidine alkaloids: concise synthesis of (−)-protoemetinol

The stereoselective synthesis of (−)-protoemetinol has been accomplished through nine steps from a known homoallylic amine. The key steps of the synthesis involve the efficient preparation of an aza-Claisen rearrangement (ACR) precursor using cross metathesis and amide enolate-induced ACR followed by acid-catalyzed transannulation for the elaboration of the benzo[α]quinolizine skeleton and three stereogenic centers. This unique synthetic route envisages a unified and versatile strategy for the synthesis of 2,3-disubstituted benzo[α]quinolizidine.

A computational (DFT) study on aza-Claisen rearrangement: Effect of temperature, solvent and substitution on activation barrier

The effect of temperature, solvent and substitution on aza-Claisen rearrangement has been studied using DFT. A contour diagram of potential energy surface (PES) of transition state (TS) is represented to explain the variation of activation barrier of aza-Claisen rearrangements for different substitutions. A comparison of aza-Claisen rearrangement with aza-cope, oxy- and thio-Claisen rearrangement has also been presented. The possible causes have been explored for the drastic conditions required for aza-Claisen rearrangement.

Copper-catalyzed cyclization/aza-Claisen rearrangement cascade initiated by ketenimine formation: an efficient stereocontrolled synthesis of α-allyl cyclic amidines.

An efficient and convenient synthesis of α-allyl cyclic amidines has been achieved by applying a novel cascade reaction. Copper(I)-mediated in situ N-sulfonyl ketenimine formation from the reaction of a terminal alkyne with sulfonyl azide is followed by an intramolecular nucleophilic attack on the central carbon atom by an allylic tertiary amine, and then an aza-Claisen rearrangement takes place through a chair transition state to furnish the titled amidines with complete stereocontrol.

ChemInform Abstract: One‐Pot Synthesis of Pyridines from 3‐Aza‐1,5‐enynes.

AbstractA convenient one‐pot method allows the conversion of 3‐aza‐1,5‐enynes into pyridines via sequential aza‐Claisen rearrangement, 6π‐electrocyclization and elimination of aryl sulfinic acid.

ChemInform Abstract: Synthesis of Polyfluoroalkyl Cyclobutenes from 3‐Aza‐1,5‐enynes via an Aza‐Claisen Rearrangement/Cyclization Cascade.

AbstractHeating 3‐aza‐1,5‐enynes in dioxane leads to the formation of an allene‐imine intermediate via aza‐Claisen rearrangement.

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.

Synthesis of Polyfluoroalkyl Cyclobutenes from 3-Aza-1,5-enynes via an Aza-Claisen Rearrangement/Cyclization Cascade

A facile synthetic route to access polyfluoroalkyl functionalized cyclobutenes bearing an exo cyclic double bond from 3-aza-1,5-enynes is reported. The reaction proceeds via a thermal aza-Claisen rearrangement to give an allene-imine intermediate; subsequent cyclization affords the cyclobutene core. The kinetics of the transformation of starting material and the intermediate was studied by (1)H NMR spectroscopy, where a consecutive reaction was revealed.

Synthesis of Cyclopentenimines from N-Allyl Ynamides via a Tandem Aza-Claisen Rearrangement–Carbocyclization Sequence

We describe here details of our investigations into Pd-catalyzed and thermal aza-Claisen-carbocyclizations of N-allyl ynamides to prepare a variety of α,β-unsaturated cyclopentenimines. The nature of the ynamide electron-withdrawing group and β-substituent plays critical roles in the success of this tandem cascade. With N-sulfonyl ynamides, the use of palladium catalysis is required, as facile 1,3-sulfonyl shifts dominate under thermal conditions. However, since no analogous 1,3-phosphoryl shift is operational, N-phosphoryl ynamides could be used to prepare similar cyclopentenimines under thermal conditions through zwitter ionic intermediates that undergo N-promoted H-shifts. Alternatively, by employing ynamides bearing tethered carbon nucleophiles, the zwitter ionic intermediates could be intercepted, giving rise rapidly to more complex fused bi- and tricyclic scaffolds.

Cyclization and N-Iodosuccinimide-Induced Electrophilic Iodocyclization of 3-Aza-1,5-enynes To Synthesize 1,2-Dihydropyridines and 3-Iodo-1,2-dihydropyridines

Metal-free cyclization and N-iodosuccinimide-induced electrophilic iodocyclization of readily available 3-aza-1,5-enynes have been developed. The reactions selectively give 1,2-dihydropyridines and 3-iodo-1,2-dihydropyridines involving an aza-Claisen rearrangement and a 6π-electrocyclization step. Furthermore, the reaction could be carried out in 10 g scale for the synthesis of 1,2-dihydropyridines.

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.

Total synthesis of N,O,O,O-tetraacetyl-d-ribo-phytosphingosine and its 2-epi-congener

AbstractTotal synthesis of the natural d-ribo-phytosphingosine I and its 2-epimer III in the protected form was achieved through a common strategy. The aza-Claisen rearrangement of allylic thiocyanate (Z)-V incorporated the new stereogenic centre with nitrogen and the subsequent Wittig olefination constructed a non-polar side chain. Hydrogenation, followed by removal of protecting groups, completed the syntheses of I and III.