Cyclic N-acyliminium Research Articles

The Intramolecular Heck Reaction and the Synthesis of Indolizidinone, Quinolizidinone and Benzoazepinone Derivatives

The intramolecular Heck cyclization of N-allyl-, -aryl- or -benzyl-5-allyl-2-pyrrolidinones and N-allyl-, -aryl- or -benzyl-6- allyl-2-piperidinones ( 1a f), prepared through allyltrimethylsilane addition to the corresponding cyclic N-acyliminium ions, afforded indolizidinones (3a, 5a, 5b), quinolizidinones (3b, 4b) and ben- zoazepinones (7a, 8a, 7b, 8b) in moderate to good yields (56 90%). Exclusive exo-trig over endo-trig mode of cyclization was observed in all examples investigated, and it was accompanied by double bond migration, which precluded our attempts of a one-pot tandem Diels-Alder cycloaddition with dienophiles such as maleic anhydride, methyl vinyl ketone and diethyl azodicarboxylate. Cata- lytic hydrogenation of a 2:1 mixture of regioisomeric indolizidino- nes 5a-5b afforded the stereoisomerically enriched cis indolizidinone 6a (20:1 mixture) in quantitative yield. A similar be- havior was observed in the catalytic hydrogenation of regioisomeric benzoazepinones 7b-8b.

Diastereoselective synthesis of 10b-substituted hexahydropyrroloisoquinolines from l-tartaric acid. Creation of a quaternary carbon stereocentre via N-acyliminium ion cyclization

A simple, three-step synthesis of 10b -substituted-hexahydropyrroloisoquinolines 12– 17 starting from an L-tartaric acid derived imide is described. The methodology presented employs the addition of a Grignard reagent to the imide carbonyl group, followed by a one-pot acetylation–cyclization sequence. The crucial step, an acid-catalyzed carbon–carbon bond forming reaction via an N-acyliminium ion offers moderate to high stereoselectivity, which has been shown to be strongly dependent on the size of the R-substituent. The mixtures of pyrroloisoquinolines obtained can be separated as enantiomerically pure 2-silyloxy-derivatives.

Solid-phase intramolecular N-acyliminium Pictet-Spengler reactions as crossroads to scaffold diversity.

A novel solid-phase intramolecular Pictet-Spengler reaction is presented. The approach utilizes masked aldehyde building blocks protected as their N-Boc-1,3-oxazinanes for the clean generation of solid-supported aldehydes. When exposed to simple acidic treatment, the aldehyde functionality is rapidly released and becomes susceptible to nucleophilic attack from an amide nitrogen of the peptide backbone, which results in the formation of a highly reactive cyclic N-acyliminium ion. Subsequently, a quantitative and highly stereoselective Pictet-Spengler reaction takes place by attack of the indole from a neighboring tryptophan, thus appending two new N-fused rings to the indole moiety. Extension of this intramolecular reaction to substituted indoles, and other reactive heterocycles, such as furane and thiophenes, provides a convenient and rapid access to a range of pharmacologically interesting tri- and tetracyclic scaffolds. Finally, the reaction products may conveniently be released from the solid support (PEGA) by cleavage of the base-labile linker (HMBA).

Addition of carbon nucleophiles to cyclic N-acyliminium ions in SDS/water

The acid-catalyzed addition of 1,3-dicarbonyl compounds and activated olefins (silyl enol ethers and ethyl vinyl ether) to N-Boc-2-methoxypyrrolidine ( 1a ) and N-Boc-2-methoxypiperidine ( 1b ) in SDS/water medium is described. Good yields of the corresponding 2-substituted N-Boc pyrrolidines were generally observed from 1a while moderate yields prevailed from 1b .

Synthesis of Xantheno[1,9-cd]azepines: Electrophilic Cyclization of Carbamates andN-Acyliminium Ions

Tetracyclic xantheno[1,9-cd]azepines and pentacyclic pyrrolo[1,2-a] xantheno[1,9-cd]azepines can be synthesized by assembling the azepine ring via cyclization of tertiary carbamates and N-acyliminium ions, respectively.

Niobium Pentachloride‐Mediated Nucleophilic Additions to Cyclic N‐Acyliminium Ions.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis of Tetracyclic Pyrido[2,3‐b]azepine Derivatives as Analogues of Mirtazapine via N‐Acyliminium Ion Cyclization.

AbstractFor Abstract see ChemInform Abstract in Full Text.

First Total Synthesis of a Novel Monoterpenoid Isoquinoline Alkaloid, (.+‐.)‐Alangine.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Niobium Pentachloride-mediatedNucleophilic Additions to CyclicN-AcyliminiumIons

Niobium chloride promoted the nucleophilic addition of allyltrimethylsilane, ethyl acetoacetate, indole and the silyl enol ether derived from acetone to cyclic N-acyliminium ions. The products were obtained in good yields.

Niobium Pentachloride-mediated Nucleophilic Additions to CyclicN-Acyliminium Ions

Niobium Pentachloride-mediated Nucleophilic Additions to Cyclic<i>N</i>-Acyliminium Ions

Synthesis of Cyclopentene‐Fused Pyrroloisoquinolinone Derivative via N‐Acyliminium Ion Cyclization.

AbstractFor Abstract see ChemInform Abstract in Full Text.

A Convenient Solution and Solid‐Phase Synthesis of Δ5‐2‐Oxopiperazines via N‐Acyliminium Ions Cyclization.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis of Tetracyclic Pyrido[2,3-b]azepine Derivatives as Analogues of Mirtazapine via N-Acyliminium Ion Cyclization

Tetracyclic pyrido[2,3-b]azepine derivatives 4a-d and 4f as analogues of mirtazapine were synthesized via N-acyliminium ion cyclization by using aromatic rings such as benzene and thiophene ring as a <TEX>${\pi}-nucleophile$</TEX>, and evaluated for the binding affinity for <TEX>${\alpha}2-adrenoceptor$</TEX>. Among tested compounds, 2,3,9,13b-tetrahydro-1H-benzo[f]pyrrolo[2,1-a]pyrido[2,3-c]azepine (4a) was the most potent (Ki = 0.26 <TEX>${\mu}M)$</TEX> but showed about 3-fold less binding affinity than mirtazapine (Ki = 0.08 <TEX>${\mu}M)$</TEX> for a2-adrenoceptor.

Synthesis via N‐Acyliminium Cyclization of N‐Heterocyclic Ring Systems Related to Alkaloids.

ChemInformVolume 33, Issue 43 p. 269-269 Reviews Synthesis via N-Acyliminium Cyclization of N-Heterocyclic Ring Systems Related to Alkaloids. Charles M. Marson, Charles M. Marson Dep. Chem., Univ. Coll., London WC1H 0AJ, UKSearch for more papers by this author Charles M. Marson, Charles M. Marson Dep. Chem., Univ. Coll., London WC1H 0AJ, UKSearch for more papers by this author First published: 19 May 2010 https://doi.org/10.1002/chin.200243269AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume33, Issue43October 29, 2002Pages 269-269 RelatedInformation

A convenient solution and solid-phase synthesis of Δ 5-2-oxopiperazines via N-acyliminium ions cyclization

An extremely efficient synthesis of Δ 5-2-oxopiperazines in solution phase and on solid support has been established via a Ugi four-component condensation reaction (U-4CC) followed by N-acyliminium ion cyclization between the aldehyde (acetal) functionality and the newly formed amide bond. The desired Δ 5-2-oxopiperazines are obtained in excellent yields and purity.

Mannich-type reactions in the gas-phase: the addition of enol silanes to cyclic N-acyliminium ions.

The intrinsic gas-phase reactivity of cyclic N-acyliminium ions in Mannich-type reactions with the parent enol silane, vinyloxytrimethylsilane, has been investigated by double- and triple-stage pentaquadrupole mass spectrometric experiments. Remarkably distinct reactivities are observed for cyclic N-acyliminium ions bearing either endocyclic or exocyclic carbonyl groups. NH-Acyliminium ions with endocyclic carbonyl groups locked in s-trans forms participate in a novel tandem N-acyliminium ion reaction: the nascent adduct formed by simple addition is unstable and rearranges by intramolecular trimethylsilyl cation shift to the ring nitrogen, and an acetaldehyde enol molecule is eliminated. An NSi(CH(3))(3)-acyliminium ion is formed, and this intermediate ion reacts with a second molecule of vinyloxytrimethylsilane by simple addition to form a stable acyclic adduct. N-Acyl and N,N-diacyliminium ions with endocyclic carbonyl groups, for which the s-cis conformation is favored, react distinctively by mono polar [4(+) + 2] cycloaddition yielding stable, ressonance-stabilized cycloadducts. Product ions were isolated via mass-selection and structurally characterized by triple-stage mass spectrometric experiments. B3LYP/6-311G(d,p) calculations corroborate the proposed reaction mechanisms.

Highly Diastereoselective Intramolecular α-Amidoalkylation Reactions of Hydroxylactams Derived from N-Phenethylimides. Enantioselective Synthesis of Dihydropyrrolo[2,1-a] isoquinolones

α-Hydroxylactams, derived from organolithium addition to an enantiomerically pure N-phenethylnorborn-5-en-endo-2,3-dicarboxyimide with a 2-exo-hydroxy-10-bornylsulfinyl group as chiral auxiliary, undergo efficient and highly diastereoselective N-acyliminium ion cyclization. Subsequent removal of the auxiliary and retro-Diels-Alder reaction lead to the enantioselective synthesis of C-10b substituted 5,6-dihydropyrrolo[2,1-a]isoquinolines.

SYNTHESIS OF CYCLOPENTENE-FUSED PYRROLOISOQUINOLINONE DERIVATIVE VIA N-ACYLIMINIUM ION CYCLIZATION

ABSTRACT In this research, a new class of pyrrolo[2,1-a]isoquinolinone derivative 7 was prepared. C-4 Hydroxylated 5-ethoxylactam 1b gave 4,5-epoxylactam 2 in high yield instead of isoquinoline derivative 3b under the N-acyliminium ion cyclization condition. The 4,5-epoxylactam 2 was converted to another N-acyliminium ion precursor 6 through base-promoted epoxide ring opening, silylation, and thermal Diels–Alder reaction with cyclopentadiene in high yield. Finally, compound 6 was cyclized in the presence of TiCl4 to provide cyclopentene-fused pyrroloisoquinoline derivative 7.

The stereochemistry of the addition of chlorotitanium enolates of N-acyl oxazolidin-2-ones to 5- and 6- membered N-acyliminium ions

The stereoselective addition of chiral and achiral titanium enolates derived from the corresponding N-acyl oxazolidin-2-ones to 5- and 6- membered N-acyliminium ions afforded 2-substituted pyrrolidines in moderate to good diastereoisomeric ratio (5:1 to 14:1) while lower diastereoselection was generally observed in the formation of the corresponding 2-substituted piperidines. The stereochemical outcome was found to be modulated by the nature of the cyclic N-acyliminium ion (5- or 6-membered) and of its carbamate and by the N-acyl group in the enolate precursor. The preferential lk approach seems to be dictated mainly by the minimization of non-bonding interactions between the N-acyl group in the chlorotitanium (IV) enolate and the carbamate and methylene groups in the cyclic N-acyliminium ion.

The addition of allyltrimethylsilane to cyclic N-acyliminium ions derived from(S)-(+)-mandelic acid and cyclohexyl-based chiral auxiliaries

The TiCl4- promoted addition of allyltrimethylsilane to chiral 5- and 6-membered N-acyliminium ions employing (S)-(+)-mandelic acid, (1R,2S)-trans-2-phenyl-1-cyclohexanol and (1R,2S,5R)-8-phenylmenthol derivatives as chiral auxiliaries occurred with low to moderate diastereoisomeric ratios (1:1-6:1) to afford 2-substituted amides and carbamates in good yields. The best diastereoselection was observed with (1R,2S,5R)-8-phenylmenthol as the chiral auxiliary. The 2-substituted amides and carbamates were converted to the corresponding alkaloids (S)- and (R)-propyl pyrrolidine and coniine with efficient recovery of the chiral auxiliaries.