Pyrrolidine Derivatives Research Articles

ChemInform Abstract: Morita—Baylis—Hillman Adducts as Effective Dipolarophiles in Copper(I)‐Catalyzed 1,3‐Dipolar Cycloaddition with Azomethine Ylides: Asymmetric Construction of Pyrrolidine Derivatives Containing Quaternary Stereogenic Center.

AbstractThe first catalytic asymmetric 1,3‐dipolar cycloaddition of azomethine ylides (II) with Morita—Baylis—Hillman adducts bearing an allylic hydroxyl group is described.

Efficient gold(I)/silver(I)-cocatalyzed cascade intermolecular N-Michael addition/intramolecular hydroalkylation of unactivated alkenes with α-ketones

The gold(I)/silver(I)-cocatalyzed cascade intermolecular N-Michael addition/intramolecular hydroalkylation reaction offers a simple and efficient method for the synthesis of pyrrolidine derivatives in moderate to excellent product yields and with moderate to good diastereoselectivities. The reaction conditions and the substrate scope of this reaction are examined, and a possible mechanism involving AgClO4 catalyzed intermolecular N-Michael addition and the subsequent gold(I)-catalyzed hydroalkylation is proposed.

2-(3,3,4,4-Tetrafluoropyrrolidin-1-yl)aniline

In the title fluorinated pyrrolidine derivative, C10H10F4N2, the dihedral angle between the best planes of the benzene and pyrrolidine rings is 62.6 (1)°. The crystal packing features inter­molecular N—H⋯F hydrogen bonds.

ChemInform Abstract: Syntheses and Biological Activities of 1,4‐Iminoalditol Derivatives as α‐L‐Fucosidase Inhibitors

AbstractReview: 57 refs.

Chiral Silver Amides as Effective Catalysts for Enantioselective [3+2] Cycloaddition Reactions

Asymmetric [3+2] cycloaddition of α-aminoester Schiff bases with substituted olefins is one of the most efficient methods for the preparation of chiral pyrrolidine derivatives in optically pure form. In spite of its potential utility, applicable substrates for this method have been limited to Schiff bases that bear relatively acidic α-hydrogen atoms. Here we report a chiral silver amide complex for asymmetric [3+2] cycloaddition reactions. A silver complex prepared from silver bis(trimethylsilyl)amide (AgHMDS) and (R)-DTBM-SEGPHOS worked well in asymmetric [3+2] cycloaddition reactions of α-aminoester Schiff bases with several olefins to afford the corresponding pyrrolidine derivatives in high yields with remarkable exo- and enantioselectivities. Furthermore, α-aminophosphonate Schiff bases, which have less acidic α-hydrogen atoms, also reacted with olefins with high exo- and enantioselectivities. The stereoselectivities of the [3+2] cycloadditions with maleate and fumarate suggested that the reaction proceeded by means of a concerted mechanism. An NMR spectroscopic study indicated that complexation of AgHMDS with the bisphosphine ligand was not complete, and that free AgHMDS, which did not show any significant catalytic activity, existed in the catalyst solution. This means that significant ligand acceleration occurred in the current reaction system.

Silver-Catalyzed Asymmetric [3+2] Cycloaddition of Amino Esters to Olefins

This report describes a highly enantioselective and exo-selective [3+2] cyclo­addition of α-amino ester Schiff bases with various activated olefins. The corresponding highly substituted pyrrolidine derivatives, which are important building blocks for biologically active molecules, are obtained efficiently.

An Efficient Synthesis of a Cyclopentannulated Pyrrolidine Derivative

A racemic cyclopentannulated pyrrolidine derivative was synthesized utilizing ruthenium oxidation and borane reduction as the key steps. Ruthenium oxidation reaction of the 1,2-dibromoalkene moiety in an N-Boc-protected tetrabromonorbornyl derivative afforded a tricyclic α-hydroxy ketone, which on alkaline hydrogen peroxide cleavage furnished a bicyclic lactam in excellent yield. Borane reduction of the N-Boc-protected bicyclic lactam gave an unexpected product as a single diastereomer resulting from the reduction of not only the lactam and ester moieties but also the ketal to the corresponding methyl ether. A plausible mechanism involving an oxocarbenium ion is discussed.

Cobalt‐Catalyzed Carbon‐Carbon Bond Formation: Synthesis and Applications of Enantiopure Pyrrolidine Derivatives[1]

AbstractIn the presence of cobalt catalysts and tetramethylethylenediamine (TMEDA), the iodine atom in (S)‐2‐(iodomethyl)pyrrolidines was replaced by an aryl or an alkynyl group from the corresponding Grignard reagent, and the coupling products were obtained in good to excellent yields (16 examples; 75–94% yields). The scope and limitations of this protocol were examined. The stereochemistry of the pyrrolidines was unaffected by the reaction conditions. The coupling products are important building blocks of phenanthroindolizidine alkaloids. Palladium‐catalyzed formal [4+2] cycloaddition of 2,2′‐diiodobiphenyl with the thus‐generated (S)‐2‐(3‐trimethylsilyl‐2‐propynyl)pyrrolidine gave a good yield of the desilylated phenanthrene, which was then converted into unnatural (+)‐(S)‐tylophorine by the Pictet–Spengler cyclization.

ChemInform Abstract: Synthesis of Bis‐spirocoupled Pyrrolidinooxindoles Derived from Isatinylidene Derivatives of Thiazolotriazinones by [3 + 2] Dipolar Cycloaddition.

Isatines react with 3,4-dihydro-2H-[1,3]thiazolo[3,2-a][1,3,5]triazin-6(7H)-ones to give their isatinylidene derivatives, which add azomethinylide, generated in situ from paraformaldehide and sarcosine, to yield bis-spirocoupled derivatives of pyrrolidine. The [3+2] dipolar cycloaddition reactions studied proceed absolutely diastereoselectively.

ChemInform Abstract: Gold(I)‐Catalyzed Cycloisomerization of 1,6‐Diynes: Synthesis of 2,3‐Disubstituted 3‐Pyrroline Derivatives.

AbstractThe pyrrolidine derivatives can be converted into the corresponding pyrrole as is shown for (III).

Preparación simple de nuevas N-(6-metil-2-nitrofenil-1,2,3,4-tetrahidroquinolin-4-il) pirrolidin-2-onas y su análisis espectroscópico. Objetivos.

<p><strong>Objectives. </strong>To prepare new N-(1,2,3,4-tetrahydroquinolin-4-yl) pyrrolidin-2-one molecules and to characterize them by spectroscopic methods. <strong>Materials and methods. </strong>All reagents were purchased from Aldrich, commercial grade. The purity of the products and the composition of the reaction mixtures were monitored by thin layer chromatography over Silufol UV<sub>254</sub> chromatoplates (0.25 mm). Product isolation and purification were performed by column chromatography (SiO<sub>2</sub>), using ethyl acetate. <strong>Results.</strong> Preparation of new N-(2-nitrophenyl-1,2,3,4-tetrahydroquinolin-4-yl) pyrrolidin-2-ones has been achieved via the one-pot synthesis, based on a BiCl<sub>3</sub>-catalyzed imino Diels-Alder cycloaddition reaction of toluidine, N-vinylpyrrolidin-2-one and 4-nitro- or 3-nitrobenzaldehydes. The structure of the pyrrolidine derivatives was confirmed by <sup>1</sup>H nmr and <sup>13</sup>C nmr studies, in addition to inverse-detected 2D NMR experiments and monocrystal X-ray diffraction. <strong>Conclusions. </strong>An efficient, economic, and fast synthetic route (multi-component imino Diels-Alder reaction) was employed in the construction of several new tetrahydroquinoline derivatives, useful and attractive rigid skeleton with well-defined stereochemistry.</p> <p> </p> <p><strong>Key words: </strong>tetrahydroquinoline derivatives, N-substituted pyrrolidin-2-ones, three component imino Diels-Alder reaction, one-pot synthesis.</p>

Metal‐Free Asymmetric 1,3‐Dipolar Cycloaddition of N‐Arylmaleimides to Azomethine Ylides Catalyzed by Chiral Tertiary Amine Thiourea

AbstractThe first metal‐free asymmetric 1,3‐dipolar cycloaddition of N‐arylmaleimides to azomethine ylides catalyzed by chiral tertiary amine thiourea to form multiply substituted pyrrolidines in excellent yields (up to 89 %) and enantioselectivities (up to 96 % ee) is presented. This procedure allows a rapid diversity‐oriented synthesis of chiral pyrrolidine derivatives with high optical purity.

ChemInform Abstract: Gold(I)‐Catalyzed Intramolecular Amination of Allylic Alcohols with Alkylamines.

AbstractThe process can be applied to a broad spectrum of amines for the synthesis of pyrrolidine and piperidine derivatives.

ChemInform Abstract: Design, Synthesis, and Pharmacological Evaluation of Azetedine and Pyrrolidine Derivatives as Dual Norepinephrine Reuptake Inhibitors and 5‐HT1A Partial Agonists.

AbstractOptimization of a recently developed dual norepinephrine reuptake inhibitor and serotonin 1A partial agonist leads to the identification of an oxygen‐linked azetidine (I) or pyrrolidine derivative (II) as a suitable piperidine A‐ring replacement in this novel biaryl‐ether series.

ChemInform Abstract: [3 + 2] Cycloaddition on Carbohydrate Templates: Stereoselective Synthesis of Pyrrolidines.

Pyrrolidine derivatives were prepared in high diastereoselectivities and good yields via a [3 + 2] cycloaddition of a tert-butyldimethylsilyl protected carbohydrate-based allene with a diverse range of imines. The subsequent removal of the carbohydrate auxiliary afforded a variety of pyrrolidines with excellent enantioselectivities (up to 99% ee). Selective reduction of the pyrrolidines further demonstrated the potential of this strategy.

Stereoselective Syntheses of Aza, Amino and Imino Sugar Derivatives by Hydroboration of 3,6‐Dihydro‐2H‐1,2‐oxazines as Key Reaction

AbstractStarting from enantiopure 3,6‐dihydro‐2H‐1,2‐oxazinessyn‐1 we introduced an additional hydroxy group in a stereoselective fashion by a standard hydroboration/oxidation protocol. Under “regular“ conditions substrate control was sufficient to achieve a very high degree of stereoselectivity. However, a diastereomeric product was isolated when a partially “degraded” borane reagent was used. We could synthesise this new diastereomer on purpose by addition of alcohols to the “fresh“ hydroboration reagent. The level of stereoinduction increased with the steric bulk of the added alcohol: MeOH < nBuOH < iPrOH < tBuOH. After a two‐step oxidation/reduction sequence, another 5‐hydroxy‐1,2‐oxazine epimer was accessible. The obtained 5‐hydroxy‐1,2‐oxazine diastereomers 2 were used as versatile intermediates in a series of transformations leading to several amino polyol derivatives. Complete deprotection of both diastereomers without cleavage of the N–O bond led to the novel polyhydroxylated tetrahydro‐2H‐1,2‐oxazines 3 and epi‐3. By change of the deprotection conditions the open‐chain amino polyol 4 with D‐iditol configuration became accessible. In an alternative sequence 5‐hydroxy‐1,2‐oxazines were utilised to synthesise imino sugars (polyhydroxylated pyrrolidines). Samarium diiodide induced cleavage of the 1,2‐oxazine N–O bond furnished 1,4‐amino alcohols, which were cyclised to give the corresponding pyrrolidine derivatives after activation by mesyl chloride. This sequence either led to a 3‐methoxy‐substituted trihydroxylated pyrrolidine derivative or to the related fully deprotected compound.

Synthesis of Decahydropyrrolo[2,1,5-cd]indolizine through Consecutive [2 + 3] Cycloadditions and 6-Exo-Trig Cyclization

Azomethine ylide formed from glycine methyl ester and cinnamaldehyde adds to N-phenylmaleimide to form pyrrolidine derivative, further treatment of which with cinnamaldehyde and N-phenylmaleimide affords the second [2 + 3] cycloaddition adduct, a pyrrolizine derivative with two styrenyl groups at the 3,5-positions. Addition of ICl to the pyrrolizine derivative results in the 6-exo-trig cyclization of the styrenyl groups to form a cycl[3.2.2]azine derivative. The reactions are highly stereoselective affording 11 chiral carbons in three steps. The structure of the cycl[3.2.2]azine derivative was determined by single-crystal X-ray analysis.

ChemInform Abstract: Catalytic Activity of Gold Nanoclusters in Intramolecular Hydroamination of Alkenes and Alkynes with Toluenesulfonamide under Aerobic and Basic Conditions.

AbstractUnder conditions A), 5‐ and 6‐aminoalkenes as well as 5‐aminoalkynes smoothly undergo cyclization to afford pyrrolidine and piperidine derivatives.

ChemInform Abstract: CCC—N‐Heterocyclic Carbene Pincer Complexes: Synthesis, Characterization and Hydroamination Activity of a Hafnium Complex.

AbstractThe hafnium compound HFC effectively promotes the intramolecular hydroamination of unactivated alkenes yielding pyrrolidine and piperidine derivatives.

ChemInform Abstract: Gold(I)‐Catalyzed Enantioselective Intramolecular Hydroamination of Allenes with Ureas.

AbstractIt allows access to pyrrolidine and piperidine derivatives with up to 93% e.e.