Asymmetric Intramolecular Stetter Reaction Research Articles

Remote electronic effect on the N-heterocyclic carbene-catalyzed asymmetric intramolecular Stetter reaction and structural revision of products.

The remote electronic effects of chiral N-heterocyclic carbene catalysts on the asymmetric intramolecular Stetter reaction are investigated. The reaction rate and enantioselectivity were markedly influenced by a substituent at a remote position of the catalyst. The absolute configurations of the products are revised on the basis of X-ray diffraction. Density-functional theory calculations rationalize the improvement of the enantioselectivity using an electron-deficient catalyst.

ChemInform Abstract: Design and Synthesis of a Bis(hydroxyphenyl)diamide Bearing a Pendant Thiazolium Unit; Application to the Catalytic Asymmetric Intramolecular Stetter Reaction.

Abstract The bis(hydroxyphenyl)diamide architecture constitutes as a privileged ligand that promotes a number of catalytic asymmetric transformations in combination with rare-earth metals. A new diamide analog armed with a carbene catalytic function derived from a thiazolium unit was designed, synthesized, and applied to the catalytic asymmetric intramolecular Stetter reaction. Cooperative work between the carbene function and hydrogen bonding interactions was suggested to give the enantioenriched chroman derivatives.

Design and synthesis of a bis(hydroxyphenyl)diamide bearing a pendant thiazolium unit; application to the catalytic asymmetric intramolecular Stetter reaction

The bis(hydroxyphenyl)diamide architecture constitutes as a privileged ligand that promotes a number of catalytic asymmetric transformations in combination with rare-earth metals. A new diamide analog armed with a carbene catalytic function derived from a thiazolium unit was designed, synthesized, and applied to the catalytic asymmetric intramolecular Stetter reaction. Cooperative work between the carbene function and hydrogen bonding interactions was suggested to give the enantioenriched chroman derivatives.

ChemInform Abstract: An Asymmetric Intramolecular Stetter Reaction Catalyzed by a Chiral Triazolium Precatalyst Bearing a Pyridine Moiety.

AbstractThe asymmetric intramolecular Stetter reaction of aromatic aldehydes of type (I) is optimized to proceed in the presence of a chiral triazolium salt as the catalyst.

Design and synthesis of novel chiral dihydroimidazolium cyclophanes as N-heterocyclic carbene precatalysts

A series of novel diphenyl ethylenediamine (DPEN) derived C2 symmetric dihydroimidazolium cyclophanes were designed and synthesized as organo NHC precatalysts. The resultant organo NHC-catalyzed reactions with superior enantioselectivity than traditional C2 dihydroimidazolidine NHCs as exemplified by NHC-catalyzed asymmetric intramolecular Stetter reactions.

An asymmetric intramolecular Stetter reaction catalyzed by a chiral triazolium precatalyst bearing a pyridine moiety

A number of chiral triazolium salts incorporating pyridine rings have been investigated as precatalysts for an asymmetric intramolecular Stetter reaction. The salt structure and reaction parameters were optimized, resulting in very good yield and enantioselectivity. This reaction was found to be applicable to a wide range of salicylaldehyde-derived substrates.

Catalytic asymmetric intermolecular Stetter reactions of enolizable aldehydes with nitrostyrenes: computational study provides insight into the success of the catalyst.

Over the past decade, N-heterocyclic carbenes (NHCs) have been used as catalysts in a variety of C-C bond forming reactions.[1] Our group has been interested in the development of chiral NHCs as catalysts for the asymmetric intra-molecular Stetter reaction[2,3] and more recently the inter-molecular variant.[4,5] We recently reported that hetaryl aldehydes and enals react efficiently with nitroalkenes in the Stetter reaction, leading to β-nitro ketones with high enantioselectivity.[4d] Crucial to the success of this method was the development of a fluorinated triazolium salt pre-catalyst that provides significantly enhanced enantioselectivity over des-fluoro analogues.[6] Although this new catalyst system greatly expands the scope of this method, these conditions are not amenable to the use of unactivated aliphatic aldehydes. Due to their lower electrophilicity than aryl aldehydes, aliphatic aldehydes have rarely been used successfully in the asymmetric inter-molecular Stetter reaction.[7,8]

ChemInform Abstract: Synthesis of (1R,2R)‐DPEN‐Derived Triazolium Salts and Their Application in Asymmetric Intramolecular Stetter Reactions.

AbstractAmong 4 ligands prepared, TRI is found to be the most efficient one to produce benzopyrans and thiopyran (VI) in good to excellent yields and enantioselectivities.

Mechanistic investigation of the enantioselective intramolecular stetter reaction: proton transfer is the first irreversible step.

A study on the mechanism of the asymmetric intramolecular Stetter reaction is reported. This investigation includes the determination of the rate law, kinetic isotope effects, and competition experiments. The reaction was found to be first order in aldehyde and azolium catalyst or free carbene. A primary kinetic isotope effect was found for the proton of the aldehyde. Taken together with a series of competition experiments, these results suggest that proton transfer from the tetrahedral intermediate formed upon nucleophilic attack of the carbene onto the aldehyde is the first irreversible step.

Synthesis of (1R,2R)-DPEN-derived triazolium salts and their application in asymmetric intramolecular Stetter reactions

A series of novel chiral triazolium salts has been synthesized from readily available (1R,2R)-DPEN and found to be efficient for the enantioselective intramolecular Stetter reaction. With 10 mol% of the catalyst, the intramolecular Stetter reaction was realized in excellent yields with up to 97% ee.

Scope of the Asymmetric Intramolecular Stetter Reaction Catalyzed by Chiral Nucleophilic Triazolinylidene Carbenes

A highly enantioselective intramolecular Stetter reaction of aromatic and aliphatic aldehydes tethered to different Michael acceptors has been developed. Two triazolium scaffolds have been identified that catalyze the intramolecular Stetter reaction with good reactivity and enantioselectivity. The substrate scope has been examined and found to be broad; both electron-rich and -poor aromatic aldehydes undergo cyclization in high yield and enantioselectivity. The tether can include oxygen, sulfur, nitrogen, and carbon linkers with no detrimental effects. In addition, the incorporation of various tethered Michael acceptors includes amides, esters, thioesters, ketones, aldehydes, and nitriles. The catalyst loading may be reduced to 3 mol % without significantly affecting the reactivity or selectivity of the reaction.

Enantioselective Synthesis of Hydrobenzofuranones Using an Asymmetric Desymmetrizing Intramolecular Stetter Reaction of Cyclohexadienones.

A series of cyclohexadienones were synthesized by dearomatization of phenols followed by Dess-Martin oxidation. Asymmetric intramolecular Stetter reactions of these substrates provide hydrobenzofuranones in good to excellent yields and excellent stereoselectivities. Up to three stereocenters as well as quaternary stereocenter are formed from polysubstituted substrates. A scale up experiment demonstrates the utility of this transformation.

C2 Symmetric Chiral N‐Heterocyclic Carbene Catalyst for Asymmetric Intramolecular Stetter Reaction.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

C2 Symmetric chiral N-heterocyclic carbene catalyst for asymmetric intramolecular Stetter reaction

The asymmetric intramolecular Stetter reaction of ω-formyl α,β-unsaturated carbonyl compounds was catalyzed by a C2 symmetric chiral carbene, generated from (4 S,5 S)-diphenyl-1,3-bis(mesitylmethyl)-4,5-dihydro-1 H-imidazolium tetrafluoroborate, to afford 2-substituted cyclopentanones in good enantioselectivity of up to 80%.

Asymmetric Synthesis of Hydrobenzofuranones via Desymmetrization of Cyclohexadienones Using the Intramolecular Stetter Reaction.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Asymmetric Synthesis of Hydrobenzofuranones via Desymmetrization of Cyclohexadienones Using the Intramolecular Stetter Reaction

Dearomatization of phenols followed by oxidation affords cyclohexadienyloxyacetaldehydes, which produce hydrobenzofuranones via asymmetric intramolecular Stetter reaction in good to excellent yield. Quaternary as well as up to three contiguous stereocenters may be formed in good to excellent enantioselectivities and high diastereoselectivities.

A Highly Enantio- and Diastereoselective Catalytic Intramolecular Stetter Reaction.

A highly enantio- and diastereoselective intramolecular Stetter reaction has been developed. Subjection of α,α-disubstituted Michael acceptors to an asymmetric intramolecular Stetter reaction results in a highly enantioselective conjugate addition and a diastereoselective proton transfer. Available evidence suggests the diastereoselective protonation occurs via intramolecular delivery to the sterically more hindered face of the enolate. The scope of the trisubstituted Michael acceptors has been examined and found to be broad with respect to the size of the α-substituent and nature of the Michael acceptor. Aliphatic and aromatic aldehydes were examined and found to afford the desired product in good overall yield with high enantio- and diastereoselectivity.

A Highly Enantio- and Diastereoselective Catalytic Intramolecular Stetter Reaction

A highly enantio- and diastereoselective intramolecular Stetter reaction has been developed. Subjection of alpha,alpha-disubstituted Michael acceptors to an asymmetric intramolecular Stetter reaction results in a highly enantioselective conjugate addition and a diastereoselective proton transfer. Available evidence suggests the diastereoselective protonation occurs via intramolecular delivery to the sterically more hindered face of the enolate. The scope of the trisubstituted Michael acceptors has been examined and found to be broad with respect to the size of the alpha-substituent and nature of the Michael acceptor. Aliphatic and aromatic aldehydes were examined and found to afford the desired product in good overall yield with high enantio- and diastereoselectivity.

Enantioselective Synthesis of Quaternary Stereocenters via a Catalytic Asymmetric Stetter Reaction.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Enantioselective synthesis of quaternary stereocenters via a catalytic asymmetric Stetter reaction.

A new electron-deficient chiral triazolium salt has been shown to catalyze the formation of quaternary stereocenters by an asymmetric intramolecular Stetter reaction. Pentafluorophenyl substitution on an aminoindanol-derived catalyst affords tertiary ether, thioether, and quaternary stereocenters in typically greater than 90% ee and very good chemical yield. Aromatic and aliphatic aldehydes are equally competent substrates for this reaction. The reaction proceeds at room temperature under mild conditions to provide quaternary stereocenters with functional group relationships that are particularly difficult to access by other methods.