N-acyliminium Ion Research Articles

ChemInform Abstract: Highly Stereoselective trans Addition of π-Type Nucleophiles to a Bicyclic N-Acyliminium Ion - Application to the Synthesis of Indolizidine and Pyrrolizidine Alkaloids.

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.

ChemInform Abstract: Synthesis of Angular-Substituted Tetracyclic Azepino-Indole Derivatives via N-Acyliminium Ion Cyclization.

Abstract A concise and efficient synthesis of tetracyclic azepino-indole derivatives 2 having a substituent at the angular position has been accomplished through an N-acyliminium ion cyclization. The coupling reaction of indol-3-yl-ethylamine 3 with 4-or 5-keto-acid 4 followed by cyclization reaction of the resulting tautomeric mixtures of keto-amide 5 and hydroxylactam 6 in refluxing formic acid provided 2.

ChemInform Abstract: A Kulinkovich Entry into Tertiary N-Acyliminium Ion Chemistry.

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.

ChemInform Abstract: Electrochemical Oxidation of (R)-4-Hydroxy-2-pyrrolidone: A Key Building Block for Stereoselective N-Acyliminium Ion Coupling 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.

ChemInform Abstract: Synthesis of Substituted Pyrrolidines by Sequential Radical Cyclization and N-Acyliminium Ion 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.

ChemInform Abstract: Enantioselective Synthesis of Hydroxy-Substituted DBN-Type Amidines as Potential Chiral Catalysts.

The synthesis and X-ray crystal structures of three enantiopure hydroxy-substituted amidines of the DBN-type are described. The key starting material, a 5-(phenylsulfonyl)pyrrolidin-2-one, was obtained by an oxazaborolidine-catalysed reductive desymmetrization of a meso-imide and was functionalized through N-acyliminium ion chemistry. The hydroxy groups were introduced by ozonolysis or reduction. Preliminary results on the use of the hydroxyamidines as chiral, bifunctional catalysts in selected Michael reactions are described.

ChemInform Abstract: Studies Dealing with Thionium Ion Promoted Mannich Cyclization Reactions.

Treatment of several amido-substituted thioacetals with dimethyl(methylthio)sulfonium tetrafluoroborate (DMTSF) produces synthetically useful thionium ions that are intercepted by the adjacent nitrogen atom to afford both five- and six-membered alkylthio-substituted lactams as transient intermediates. Further reaction of the alkylthio-substituted lactam with DMTSF generates an N-acyliminium ion, which undergoes cyclization with the tethered aromatic ring to produce an azapolycyclic ring system. Related cyclization sequences occur when amido thioacetals possessing simple olefinic tethers were used. The overall procedure represents an efficient one-pot approach toward various nitrogen-containing ring systems. The cyclization reaction was employed for a synthesis of the core skeleton of the erythrina alkaloid family.

ChemInform Abstract: Creation of Quaternary Stereocenters by the Addition of Allyltributyltin to Chiral Cyclic N-Acyliminium Ions.

Abstract 5,5-Disubstituted pyrrolidinones and 5-substituted pyrrolidinones were obtained with moderate to good diastereoisomeric excess through the cis addition of allyltributyltin and triethylsilane, respectively, to the 4-OTBS group in the N-acyliminium ion prepared from the corresponding 5-hydroxy lactams. Cyclization of an N-allyl-5-propargyl pyrrolidinone and N-allyl-5-allyl-5-substituted pyrrolidinones using Grubbs’ catalyst led to the preparation of a dehydropyrrolizinone and dehydroindolizinones containing a quaternary stereocenter.

ChemInform Abstract: Synthesis of Alkaloids from Amino Acids via N-Acyliminium Ions Generated by One-Pot Radical Decarboxylation-Oxidation.

Abstract A one-pot methodology for the synthesis of α-substituted nitrogen heterocycles from commercial amino acids has been developed. Good stereoselectivity can be achieved with chiral substituted rings. This procedure has been applied to the synthesis of piperidine, pyrrolidine and indolizidinone alkaloids.

Synthesis of 5-Substituted 7,8-Benzomorphans by Intramolecular Cyclization of N-Protected 4,4-Disubstituted 1,4-Dihydropyridines

An efficient and high yielding method for the synthesis of 7,8-benzomorphans with varying substituents at C5 has been developed. It is based on an acid-catalyzed intramolecular cyclization reaction of N-protected 4,4-disubstituted 1,4-dihydropyridines, which are easily accessible by the addition of diorganomagnesium compounds to N-silylpyridinium ions. The cyclization reaction proceeds via N-acyliminium ions generated from the 1,4-dihydropyridine moiety that undergo electrophilic aromatic substitution reaction at the benzyl substituent present at C4 of the 1,4-dihydropyridine ring system.

Use of the cascade α-oxo-amidoalkylation/transposition/ p-cationic cyclization of N-acyliminium ions in the synthesis of novel fused heterocyclic N,O-acetals

Use of the cascade α-oxo-amidoalkylation/transposition/ p-cationic cyclization of N-acyliminium ions in the synthesis of novel fused heterocyclic N,O-acetals

Synthetic application of in situ generation of N-acyliminium ions from α-amido p-tolylsulfones for the synthesis of α-amino nitriles

In the presence of catalytic amount of bismuth bromide (5 mol %) the α-amido p-tolylsulfones are converted into N-acyliminium ions, which undergo the nucleophilic addition of trimethylsilyl cyanide (TMSCN) to provide the N-protected α-amino nitriles in very good yield. A variety of α-amido p-tolylsulfones were prepared from aromatic as well as aliphatic aldehydes for the synthesis of α-amino nitriles.

N‐acyliminium intermediates in solid‐phase synthesis

N-Acyliminium ions are powerful intermediates in synthetic organic chemistry. Examples of their use are numerous in solution-phase synthesis, but there are unmerited few reports on these highly reactive electrophiles in solid-phase synthesis. The present review covers the literature to date and illustrates the methods used to generate N-acyliminium intermediates on solid support and their further elaboration to a range of pharmacologically interesting peptidomimetics, heterocycles, and other small molecules.

Spirocyclization of an N-Acyliminium Ion with Substituted Pyridine: Stereoselective Synthesis of Tetracyclic Spirolactams Possessing the Pyridone Nucleus

An efficient method for the stereoselective synthesis of tetracyclic spirolactams was developed based on a spirocyclization of an N-acyliminium ion with 2-methoxypyridine as the aromatic π-nucleophile.

Stereoselective Cycloaddition of N‐Acyliminium Ions with α,β‐Unsaturated Ketones and Esters

AbstractThe [4+2] reactions of N‐acyliminium ions, produced from 2‐aryl‐3‐hydroxy‐2,3‐dihydroisoindol‐1‐ones or 5‐hydroxy‐1‐phenyl‐2,5‐dihydro/2,3,4,5‐tetrahydropyrrol‐2‐ones in the presence of BF3OEt2, with α,β‐unsaturated ketones or esters were examined, and the dependence of these reactions on the substituents at double bonds was clarified. For β‐aryl substituted α,β‐unsaturated ketones and esters such as 4‐aryl‐3‐buten‐2‐ones, chalcones and methyl cinnamate, the [4+2] reactions could proceed smoothly at room temperature to afford 6‐acyl‐5,6,6a,11‐tetrahydroisoindolo[2,1‐a]quinolin‐11‐ones and 4‐acyl‐1,3a,4,5‐tetrahydropyrrolo[1,2‐a]quinolin‐ 1‐ones or 4‐acyl‐1,2,3,3a,4,5‐hexahydropyrrolo[1,2‐a]quinolin‐1‐ones in moderate to high yields; while for simple α,β‐unsaturated ketones and esters such as methyl crotonate and ethyl 3‐methylbut‐2‐enoate, except mesityloxide, the [4+2] reactions were difficult to proceed. The cycloaddition reactions were highly stereoselective, and only one stereoisomer was produced in each reaction.

Asymmetric Brønsted Acid Catalyzed Nucleophilic Addition to in situ Generated Chiral N-Acyliminium Ions

A new enantioselective Brønsted acid catalyzed nucleophilic substitution of γ-hydroxylactams with indole is presented. The reaction proceeds via an intermediary N-acyliminium ion and provides disubstituted γ-lactams in good yields and with high enantioselectivities.

A Formal Synthesis of Porantheridine and an Epimer

A formal synthesis of porantheridine and a synthesis of its C6-epimer have been completed, employing silver-catalyzed allene cyclization to form a common cis-isoxazolidine intermediate and related N-acyl iminium ion intermediates for side-chain introduction. The stereochemistry of this step can be controlled by choice of the N-protection method.

A Flexible Approach to Grandisine Alkaloids: Total Synthesis of Grandisines B, D, and F

This article describes in detail the first total synthesis of grandisine alkaloids, grandisines B, D, and F, which show affinity for the human delta-opioid receptor. The key steps in this synthesis are construction of the isoquinuclidinone moiety of 2 by intramolecular imine formation and the tetracyclic ring system of 4 by stereoselective ring closure of the enolate of amine 8 generated by 1,4-addition of ammonia to 9. Synthesis of key intermediate 9 featured a highly stereoselective Brønsted acid mediated Morita-Baylis-Hillman (MBH) reaction via the N-acyl iminium ion.

Four-Component Reactions toward Fused Heterocyclic Rings

A multicomponent reaction between H(2), CO, an unsaturated carboxylic acid derivative, and binucleophiles has been discovered. This process represents a combination of diversity-oriented synthesis and multicomponent reactions including amidation and hydroformylation, followed by nucleophilic addition to an N-acyliminium ion allowing the generation of six new bonds. Using pi-nucleophiles, the sequence turns into a multicomponent Pictet-Spengler reaction.

Palladium asymmetric reduction of β-carboline imines mediated by chiral auxiliaries assisted by microwave irradiation

An alternative synthetic approach for the introduction of chirality in β-carboline moiety through in situ reduction of N-acyliminium ion intermediates generated from imine 2 and chloroformate of 8-phenylmenthyl as chiral auxiliary was achieved. The method applied microwave-assisted irradiation and used PdCl 2/Et 3SiH protocol as a mild reducing agent, which decreased reaction times to minutes when compared to the conventional thermal reactions. The diastereoselectivity (4–12:1) of the reduction produced R-amines, which were assigned after chiral auxiliary removal and spectroscopic data compared to products obtained from Noyori asymmetric hydrogenation catalyst.