Construction Of Quaternary Stereocenters Research Articles

Construction of quaternary stereocenters at carbon 2′ of nucleosides

The non-natural nucleosides with a quaternary stereogenic center at C2′ are crucial to drug discovery. They have become a cornerstone for the treatment of cancer and various viral infections as exemplified by gemcitabine and sofosbuvir. Major research effort has been expended to gain synthetic access to these nucleoside analogues with a significant steric bulk at C2′ in the furanoside ring. The 2′-ketonucleosides and 2′-deoxy-2′-methylenenucleosides emerged as key intermediates in these synthetic strategies. For example, α-face addition of methyl lithium to the 2′-ketonucleosides followed by fluorination of resulting tertiary arabino alcohol with DAST provided 2′-fluoro-2′-C-methyluridine - a core nucleoside component of sofosbuvir. The α-face addition of HCN or HN3 to the 2′-deoxy-2′-methylene nucleosides gave access to the synthetically versatile 2′-cyano-2′-C-methyl and 2′-azido-2′-C-methyl nucleosides. Likewise, the addition of diazomethane to the 2′-exomethylene group gave access to the 2′-spirocyclopropyl analogue. This review primarily discusses synthetic strategies which employs natural nucleosides as substrates but selected approaches involving coupling of the preelaborated sugar precursors with nucleobases are also examined.

Asymmetric Construction of Quaternary Stereocenters by Addition of α-Alkynyl Ketones to Allenamides

Asymmetric Construction of Quaternary Stereocenters by Addition of α-Alkynyl Ketones to Allenamides

Time‐Dependent Diastereodivergent Michael Addition Enabled by Phosphazenes Acting as Catalysts and Reactants

AbstractA switching of the step order within cascade process enabled design of a diastereodivergent approach to phosphazenopyrrolines with a 1,3‐relationship of stereocenters. The approach is based on a cascade transformation of readily accessible γ‐azidobutyronitriles that includes Staudinger, aza‐Wittig and Michael steps. Stereodivergence is achieved at the Michael step that is self‐catalyzed by phosphazene intermediates and provides construction of quaternary stereocenter. Depending on the type of phosphazene intermediates, generating either via Staudinger reaction or via subsequent intramolecular aza‐Wittig reaction with nitrile and then reacting with a Michael acceptor, either trans‐ or cis‐isomers of the target product can be produced. Thus, diastereoselectivity can be achieved by varying the time of addition for the Michael acceptor. Therefore, three distinct roles were revealed for phosphazenes in this process: catalysts, reactants and stereoselectivity controllers. This stereodivergent strategy was applied for the synthesis of all stereoisomers of the biorelevant tetrahydro‐7‐aza‐indoles.magnified image

Organo‐Catalyzed Asymmetric Amination of 4‐Arylisoquinoline‐1,3(2H,4H)‐dione Derivatives in the Construction of Quaternary Stereocenters

AbstractAn efficient method has been developed for the enantioselective amination of 4‐arylisoquinoline‐1,3(2H,4H)‐dione derivatives. In the presence of squaramide‐based catalyst, the α‐amination cyclic imides were delivered in excellent yields (up to 99%) and ee (up to 99%) under mild conditions. Moreover, a gram scale synthetic application was also demonstrated.magnified image

Palladium-Catalyzed Construction of Quaternary Stereocenters by Enantioselective Arylation of γ-Lactams with Aryl Chlorides and Bromides.

Herein, we report the first Pd-catalyzed enantioselective arylation of α-substituted γ-lactams. Two sets of conditions were developed for this transformation, allowing for the use of either aryl chlorides or bromides as electrophiles. Utilizing a highly electron-rich dialkylphosphine ligand we have been able to construct α-quaternary centers in good yields (up to 91 % yield) and high enantioselectivities (up to 97 % ee).

Palladium‐Catalyzed Construction of Quaternary Stereocenters by Enantioselective Arylation of γ‐Lactams with Aryl Chlorides and Bromides

AbstractHerein, we report the first Pd‐catalyzed enantioselective arylation of α‐substituted γ‐lactams. Two sets of conditions were developed for this transformation, allowing for the use of either aryl chlorides or bromides as electrophiles. Utilizing a highly electron‐rich dialkylphosphine ligand we have been able to construct α‐quaternary centers in good yields (up to 91 % yield) and high enantioselectivities (up to 97 % ee).

Construction of Quaternary Stereocenters by Palladium-Catalyzed Carbopalladation-Initiated Cascade Reactions.

The enantioselective synthesis of molecules containing quaternary stereocenters is a field of intense research interest and development. Among the known organic transformations, carbopalladation-initiated domino transformations constitutes a general method for the construction of compounds containing cyclic or spiro quaternary stereocenters. In this Minireview, recent achievements in palladium-catalyzed domino Heck/C-H functionalizations and developments in enantioselective carbopalladation-initiated domino processes are summarized.

Construction of Quaternary Stereocenters by Palladium‐Catalyzed Carbopalladation‐Initiated Cascade Reactions

AbstractThe enantioselective synthesis of molecules containing quaternary stereocenters is a field of intense research interest and development. Among the known organic transformations, carbopalladation‐initiated domino transformations constitutes a general method for the construction of compounds containing cyclic or spiro quaternary stereocenters. In this Minireview, recent achievements in palladium‐catalyzed domino Heck/C−H functionalizations and developments in enantioselective carbopalladation‐initiated domino processes are summarized.

Total Synthesis of Mesembrine – The Construction of Quaternary Stereocenters by Gold‐Catalyzed Diyne Desymmetrization

AbstractThis review gives an overview on synthetic methodology developed for the synthesis of the naturally occurring alkaloid mesembrine. Its all‐carbon‐substituted quaternary stereocenter has fuelled creativity in the application of ex‐chiral‐pool‐synthesis, chiral auxiliaries, and asymmetric catalysis alike. The gold‐catalyzed desymmetrization of 1,4‐diynes has been demonstrated as a selective method for the enantioselective preparation of methylene pyrrolidines incorporating a quaternary stereocenter. The applicability of this method has therefore been demonstrated in the context of a mesembrine total synthesis.

Silver‐Promoted Cascade Reaction of 4‐Hydroxycoumarins with α‐Keto Acids under Microwave Irradiation: One‐Step Construction of Quaternary Stereocenters

A new Ag2O‐promoted cascade reaction of 4‐hydroxycoumarins with α‐keto acids under mircowave irradiation has been developed. The reaction provides an efficient approach to fused chromenes with quaternary stereocenters in 10 min, and gives good yields. Chromene derivatives can be prepared on a gram scale using this method.

ChemInform Abstract: Palladium‐Catalyzed Asymmetric Decarboxylative Cycloaddition of Vinylethylene Carbonates with Electrophiles: Construction of Quaternary Stereocenters.

AbstractThe scalable title reaction between of aryl, hetaryl, and alkyl substituted vinylethylene carbonates with unsaturated electrophiles such as aldehydes, arylcyanates, substituted benzylidenemalonitriles, and other Michael acceptors is elaborated.

Palladium-Catalyzed Asymmetric Decarboxylative Cycloaddition of Vinylethylene Carbonates with Electrophiles: Construction of Quaternary Stereocenters

Correction to: Palladium-Catalyzed Asymmetric Decarboxylative Cycloaddition of Vinylethylene Carbonates with Electrophiles: Construction of Quaternary StereocentersSynlett 2015; 26(07): 853-860DOI: 10.1055/s-0034-1380170

Construction of Quaternary Stereocenters: Asymmetric α‐Amination of Branched Aldehydes Catalyzed by Monoimide Substituted Cyclohexane‐1,2‐Diamines

A highly efficient enantioselective α-amination of branched aldehydes catalyzed by chiral imide monosubstituted 1,2-diamine derivatives was reported to afford the quaternary stereogenic centers in excellent yields (up to 99%) and enantioselectivities (up to 97% ee). Chirality 25:668-672, 2013. © 2013 Wiley Periodicals, Inc.

ChemInform Abstract: Development of Transition Metal‐Catalyzed Asymmetric Reactions Using Chiral Diaminophosphine Oxide Preligands and Their Applications

AbstractReview: about 50 refs.

ChemInform Abstract: The Construction of Quaternary Stereocenters by the Henry Reaction: Circumventing the Usual Reactivity of Substituted Glyoxals.

The enantioselective Henry reaction between alkyl- and arylglyoxal hydrates and nitromethane catalyzed by Cu(II)-iminopyridine complexes takes place regioselectively on the ketone carbonyl group to give chiral tertiary nitroaldols with high functional group density and enantiomeric excesses of up to 96 %. Both aromatic and aliphatic glyoxals are suitable substrates for this reaction.

The Construction of Quaternary Stereocenters by the Henry Reaction: Circumventing the Usual Reactivity of Substituted Glyoxals

The enantioselective Henry reaction between alkyl- and arylglyoxal hydrates and nitromethane catalyzed by Cu(II)-iminopyridine complexes takes place regioselectively on the ketone carbonyl group to give chiral tertiary nitroaldols with high functional group density and enantiomeric excesses of up to 96 %. Both aromatic and aliphatic glyoxals are suitable substrates for this reaction.

ChemInform Abstract: Copper‐Catalyzed Enantioselective Conjugate Addition

AbstractReview: 87 refs.

ChemInform Abstract: Construction of Quaternary Stereocenters by Nickel-Catalysis of Asymmetric Michael Reactions.

ChemInform 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.

Construction of Quaternary Stereocenters by Efficient and Practical Conjugate Additions to α,β‐Unsaturated Ketones with a Chiral Organic Catalyst.

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.

Construction of Quaternary Stereocenters by Efficient and Practical Conjugate Additions to α,β‐Unsaturated Ketones with a Chiral Organic Catalyst

Die korrekten Fußnoten [e] und [g] von Tabelle 3 lauten: [e] The reaction was performed by treatment of 2 B (0.3 mmol) with 5 a (0.75 mmol, 2.5 equiv) and QD-1 b in CH2Cl2 (0.6 mL). [g] The reaction was performed by treatment of 2 B (0.3 mmol) with 5 b (0.75 mmol, 2.5 equiv) and QD-1 b in CH2Cl2 (0.6 mL).