Asymmetric aza-Claisen Rearrangement Research Articles

Asymmetric Aza-Claisen Rearrangement between Enantioenriched α-Chiral Allylamines and Allenones.

An unprecedented asymmetric aza-Claisen rearrangement between enantioenriched α-chiral allylamines and allenones was found to proceed in the absence of catalysts and additives at room temperature. The rearrangement, followed by hydrolysis, provides convenient access to structurally diverse δ-chiral β-diketones in good to excellent yields with excellent retention of enantiopurity. This protocol proved powerful for the construction of an all-carbon quaternary stereocenter with high enantiopurity.

Asymmetric Synthesis of Heterobimetallic Planar Chiral Ferrocene Pallada-/Platinacycles and Their Application to Enantioselective Aza-Claisen Rearrangements

Ligand exchange reactions are usually slower for Pt(II) in comparison to Pd(II) centers. Mainly for that reason Pt(II) catalysts have often shown a reduced catalytic activity as compared to their Pd(II) counterparts. We are interested in the question if this inherently slower ligand exchange might also provide a chance for heterobimetallic catalysts to accomplish an improved catalytic performance with substrates in which the reactive center has a lower binding constant than an additional Lewis basic moiety. For that purpose we have prepared the first diastereo- and enantiomerically pure mixed pallada-/platinacycles based on ferrocene. These complexes have been prepared by sequential direct diastereoselective cycloplatination and cyclopalladation. The investigation of the asymmetric aza-Claisen rearrangement of Z-configured trifluoroacetimidates showed that a heterodinuclear Pt–Pd bis-metallacycle is an excellent catalyst for this reaction type, in general allowing for very high enantioselectivities. Moreover, at a slightly elevated temperature (55 °C), the heterodinuclear platina-/palladacycle could in certain cases outperform the corresponding bis-Pd complex, previously known to be the by far most active highly enantioselective catalyst for the rearrangement of Z-configured trifluoroacetimidates. This effect, which might be surprising at first sight due to the low efficiency of other Pt catalysts for aza-Claisen rearrangements, might be explained by an enhanced lifetime of a productive monodentate olefin coordination of the substrate at the Pt center due to slower ligand exchange processes.

Construction of an asymmetric quaternary carbon via an asymmetric aza-Claisen rearrangement and its application in the total synthesis of (+)-α-cuparenone

Excess lithium hexamethyldisilazide (LHMDS) with LiCl prompted the asymmetric aza-Claisen rearrangement of carboxamide and retarded the decomposition of its amide enolate. The addition of these two reagents was a key step that led to the total synthesis of (+)-α-cuparenone with a stereogenic quaternary center.

Promotion of Asymmetric Aza-Claisen Rearrangement of N-Allylic Carboxamides Using Excess Base

The aza-Claisen rearrangement of the enolate of N-(Z)-crotyl-N-(S)-phenethylpropanamide did not proceed in the presence of 1.5 equivalents of LHMDS as a base. However, the use of a large excess of base (10 equiv) promoted the reaction to give N-(S)-phenethyl-anti-2,3-dimethylpent-4-enamide with good stereoselectivities (anti/syn = ca. 95:5). An excess of base stabilized the amide enolates and prevented the decomposition to the ketene to prompt the rearrangement of various carboxamides with good stereoselectivity. This reaction provided a new method for the construction of asymmetric quaternary carbon centers.

The Asymmetric Aza‐Claisen Rearrangement: Development of Widely Applicable Pentaphenylferrocenyl Palladacycle Catalysts

Systematic studies have been performed to develop highly efficient catalysts for the asymmetric aza-Claisen rearrangement of trihaloacetimidates. Herein, we describe the stepwise development of these catalyst systems involving four different catalyst generations finally resulting in the development of a planar chiral pentaphenylferrocenyl oxazoline palladacycle. This complex is more reactive and has a broader substrate tolerance than all previously known catalyst systems for asymmetric aza-Claisen rearrangements. Our investigations also reveal that subtle changes can have a big impact on the activity. With the enhanced catalyst activity, the asymmetric aza-Claisen rearrangement has a very broad scope: the methodology not only allows the formation of highly enantioenriched primary allylic amines, but also secondary and tertiary amines; allylic amines with N-substituted quaternary stereocenters are conveniently accessible as well. The reaction conditions tolerate many important functional groups, thus providing stereoselective access to valuable functionalized building blocks, for example, for the synthesis of unnatural amino acids. Our results suggest that face-selective olefin coordination is the enantioselectivity-determining step, which is almost exclusively controlled by the element of planar chirality.

Asymmetric Formation of Allylic Amines with N‐Substituted Quaternary Stereocenters by PdII‐Catalyzed Aza‐Claisen Rearrangements

With the ferrocene imidazoline palladacycle FIP-Cl as precatalyst, quaternary N-substituted stereocenters can be generated in an asymmetric aza-Claisen rearrangement. Excellent enantioselectivities are obtained even if R and R′ have a similar or identical size (see scheme: e.g. 96 % ee for CH3/CD3).

Oxazoline‐Mediated Interannular Cyclopalladation of Ferrocene: Chiral Palladium(II) Catalysts for the Enantioselective Aza‐Claisen Rearrangement

Formation of a carbon–palladium bond to the unsubstituted cyclopentadiene ring occurs during the cyclopalladation of 4-ferrocenyl-1,3-oxazolines and leads to a new type of metalated ferrocene (see scheme). These chiral complexes catalyze the asymmetric aza-Claisen rearrangement of allylic imidates.

不斉アザクライゼン転位を利用した不斉四級炭素の構築と(+)-(α)-Cuparenoneの全合成

不斉アザクライゼン転位を利用した不斉四級炭素の構築と(+)-(α)-Cuparenoneの全合成

Total Synthesis of Halipeptin A: A Potent Antiinflammatory Cyclic Depsipeptide

The antiinflammatory drug halipeptin A (1) is a 17-membered cyclic depsipeptide made up of L-alanine, α-methylcysteine, decanoic acid, and isoleucine residues. Key steps in its total synthesis, which helped to confirm the stereochemistry of the natural product, include a borane-mediated aldol reaction and an asymmetric aza-Claisen rearrangement.

Total synthesis of the (+)-antimycin A3 family: structure elucidation of (+)-antimycin A3a

(+)-Antimycin A3a (AA3a), one component of the natural antibiotic antimycin A3, was synthesized using an asymmetric aza-Claisen rearrangement. The stereochemistry at the 2′ position on the acyloxy side chain of AA3a was established as S-configuration by comparison of the synthetic AA3a and the natural AA3a.

Preparation of Bis[palladacycles] and Application to Asymmetric Aza‐Claisen Rearrangement of Allylic Imidates.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Preparation of bis[palladacycles] and application to asymmetric aza-Claisen rearrangement of allylic imidates

A variety of optically active bis[palladacycles] 1– 3 were prepared from ferrocene. The synthetic application of these chiral catalysts in asymmetric aza-Claisen rearrangement of allylic imidates was carried out with high enantioselectivity.

ChemInform Abstract: A Total Synthesis of (-)-Antimycin A3b.

Abstract (−)-Antimycin A 3b , the antipode of natural antibiotic antimycin A 3b , was synthesized utilizing the asymmetric aza-Claisen rearrangement.

A total synthesis of (−)-antimycin A 3b

(−)-Antimycin A 3b, the antipode of natural antibiotic antimycin A 3b, was synthesized utilizing the asymmetric aza-Claisen rearrangement.

Asymmetric aza-Claisen rearrangement of allyl imidates catalyzed by homochiral cationic palladium(II) complexes

The asymmetric aza-Claisen rearrangement of ( E)-3-alkyl-2-propenyl N-[4-trifluoromethyl)phenyl]benzimidates was catalyzed by a homochiral cationic palladium(II) complex generated from PdCl 2{( S)-2-(2-diphenylphosphino)phenyl-4-benzyloxazoline} and silver tetrafluoroborate (Pd:silver=1:1) to give ( S)- N-(1-alkyl-2-propenyl)- N-[4-(trifluoromethyl)phenyl]benzamide of up to 81% ee.

A Stereoselective Synthesis of (−)-Isoiridomyrmecin. Application of the Asymmetric Aza-Claisen Rearrangement

Abstract (−)-Isoiridomyrmecin was synthesized stereoselectively in 6 steps starting from 1-hydroxymethyl-5-methylcyclopentene and utilizing tlle asymmetric aza-Claisen rearrangement as a key step.

ChemInform Abstract: Asymmetric Aza‐Claisen Rearrangement of Glycolamide and Glycinamide Enolate. Synthesis of Optically Active α‐Hydroxy and α‐ Amino Acids.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Asymmetric aza-Claisen rearrangement of glycolamide and glycinamide enolates. Synthesis of optically active α-hydroxy and α-amino acids

The aza-Claisen rearrangement of the enolates of N-crotyl glycolamide and glycinamide proceeded with excellent syn : anti (98:2) and facial selectivities (89:11). Optically pure (−)-verrucarino-lactone and D-allo-isoleucine were derived from the rearrangement products.

Asymmetric aza-Claisen rearrangement: Synthesis of (+)-dihydropallescensin-2 [(+)-penlanpallescensin

Synthetic confirmation of the C(1′)-(S)-configuration of (+)-dihydropallescensin-2 ( 1) is reported, the key reaction being a chiron-mediated asymmetric aza-Claisen rearrangement (6→7).