Disubstituted Pyrrolidines Research Articles

Enantiopure synthesis of all four stereoisomers of carbapenam-3-carboxylic acid methyl ester.

The retro-Dieckmann reaction has been used as a stereodivergent synthetic tool on N-Boc-7-azabicyclo[2.2.1]heptan-2-one-1-carboxylic acid methyl ester to obtain enantiopure trans- and cis-5-(carboxymethyl)pyrrolidine-2-carboxylic acid methyl esters. These disubstituted pyrrolidines have been used as starting materials to develop concise and straightforward syntheses of all four stereoisomers of carbapenam-3-carboxylic acid methyl esters. In this way, we have confirmed unequivocally the stereochemistry of two carbapenams isolated from strains of Serratia and Erwinia species.

Synthesis of geminal bis(hydroxymethyl)pyrrolidine and pyrrolizidine imino sugars

Reductive alkylation of N-Boc-pyrrolecarboxylate methyl ester 1 under Birch conditions with iodomethyl pivalate and subsequent reduction of the ester moieties provided the symmetric diol 3, a flexible building block for the synthesis of geminally disubstituted pyrrolidine imino sugars. This key intermediate was used for the first known synthesis of a 2,2-bis(hydroxymethyl)pyrrolidine imino sugar. In a similar manner a pyrrolizidine imino sugar was synthesised by oxidation of the deprotected pyrrolidine to the nitrone 10, which was subjected to a highly diastereoselective 1,3-dipolar cycloaddition with an allylic alcohol. Reductive cleavage of the N–O bond and recyclisation yielded the polyhydroxylated pyrrolizidine 13.

Organolanthanide-catalyzed intramolecular hydroamination/cyclization of amines tethered to 1,2-disubstituted alkenes.

[reaction: see text] This contribution reports the organolanthanide-catalyzed intramolecular hydroamination/cyclization of amines tethered to 1,2-disubstituted alkenes to afford the corresponding mono- and disubstituted pyrrolidines and piperidines by using coordinatively unsaturated complexes of the type (eta(5)-Me(5)C(5))(2)LnCH(TMS)(2) (Ln = La, Sm), [Me(2)Si(eta(5)-Me(4)C(5))(2)]NdCH(TMS)(2), [Et(2)Si(eta(5)-Me(4)C(5))(eta(5)-C(5)H(4))]NdCH(TMS)(2), and [Me(2)Si(eta(5)-Me(4)C(5))((t)()BuN)]LnE(TMS)(2) (Ln = Sm, Y, Yb, Lu; E = N, CH) as precatalysts. [Me(2)Si(eta(5)-Me(4)C(5))((t)BuN)]LnE(TMS)(2) mediates intramolecular hydroamination/cyclization of sterically demanding amino-olefins to afford disubstituted pyrrolidines in high diastereoselectivity (trans/cis = 16/1) and in good to excellent yield.

Intramolecular Hydroamination/Cyclization of Aminoallenes Catalyzed by Organolanthanide Complexes. Scope and Mechanistic Aspects

Organolanthanide complexes of the general type Cp‘2LnCH(TMS)2 (Cp‘ = η5-Me5C5; Ln = La, Sm, Y, Lu; TMS = SiMe3) serve as effective precatalysts for the rapid, regioselective, and highly diastereoselective intramolecular hydroamination/cyclization (IHC) of aminoallenes having the general formula RCHCCH(CH2)nCHR‘NH2 to yield the corresponding heterocycles (R = CH3, n-C3H7, n-C5H11; R‘ = H, CH3, n-C4H9, CH2CHCH2CH2; n = 2, 3). The mono- and disubstituted pyrrolidines and piperidines produced bear an α-alkenyl functionality available for further synthetic manipulation. Kinetic and mechanistic data parallel organolanthanide-mediated intramolecular aminoalkene and aminoalkyne hydroamination/cyclization, implying turnover-limiting allene insertion into the Ln−N bond followed by rapid protonolysis of the resulting Ln−C bond. The reaction rate is zero-order in [aminoallene] and first-order in [catalyst] over 3 or more half-lives. Hydroamination/cyclization of monosubstituted aminoallenes (R = H; R‘ = H, CH3; n = 1...

Determination of cis and trans configurations in pentahydrobenzopyranopyrroles by FT-IR spectroscopy

A method of distinguishing cis and trans isomers in polyheterocycles containing β,β′-disubstituted pyrrolidines is described. It is based on the relative absorbance of the Bohlmann bands and the normal symmetric CH stretching bands. The method is applied using FT-IR spectroscopy in solution and coupled with gas chromatography. An interpretation is given, with the help of molecular computing.

A general stereocontrolled synthesis of cis-2,3 disubstituted pyrrolidines and piperidines

A general synthetic method is reported for the preparation of cis-2,3-disubstituted pyrrolidines and piperidines from readily available acyclic precursors. The key reaction involves the stereoselective reduction of a cyclic imine controlled by the C-3 substituent.

ChemInform Abstract: Stereoselective Cyclization of δ‐Alkenylamines (I), (III) Catalyzed with Butyllithium. Synthesis of cis‐N‐Methyl 3,5‐ Disubstituted Pyrrolidines (II), (IV).

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Synthesis of enantiomerically pure (2R, 5R) disubstituted pyrrolidines from D-mannitol

Pyrrolidines 1 and 2 are obtained from D-Mannitol, giving good total yields and in an enantiomerically pure form. Some comments and studies regarding pyrrolidine ring closure (key step) are also reported.

Stereoselective route to highly functionalised amino alcohols

Acyclic amino alcohols can be obtained in high stereoisomeric purity by Stevens [2,3] rearrangement of tetrahydropyridine salts followed by reduction of the ketones and ring opening of the disubstituted pyrrolidine.

Synthesis and properties of a novel 1-pyrroline fatty ester derivative from methyl isoricinoleate

Reaction of methyl isoricinoleate [(Z)-methyl 9-hydroxyoctadec-12-enoate] with toluene-p-sulphonyl chloride gave a mixture of (Z)-methyl 9-chlorooctadec-12-enoate 2 and (Z)-methyl 9-tosyloxyoctadec-12-enoate 3, and with methane sulphonyl chloride the corresponding mesyloxy derivative 4. Treatment of compounds 2–4 with NaN3 in N,N-dimethylformamide at 50 °C gave (Z)methyl 9-azidooctadec-9-enoate 5, while at 80 °C methyl 8-(5-hexyl-2-pyrrolin-1-yl)octanoate 6 was obtained. The 1-pyrroline ring was characterized by IR,1H and 13C NMR spectroscopy, while the ring cleavage products (methyl 9-acetamido-12-oxooctadecanoate 7 and methyl 9-benzamido-12-oxooctadecanoate 8) were characterized by GC–MS. Reduction of the CN bond in compound 6 with NaBH4 gave a mixture of E- and Z-isomers of the corresponding disubstituted pyrrolidine fatty esters 9a and 9b.

Stereoselectivity in electrophile-mediated cyclisations. Ag I -Catalysed synthesis of disubstituted pyrrolidines; crystal structure of cis-5-phenyl-N-tosylpyrrolidin-2-ylmethyl 4-bromobenzoate

Download options Please wait... Article information DOI https://doi.org/10.1039/P19910002193 Article type Paper Download Citation J. Chem. Soc., Perkin Trans. 1, 1991, 2193-2198 BibTex EndNote MEDLINE ProCite ReferenceManager RefWorks RIS Permissions Request permissions Stereoselectivity in electrophile-mediated cyclisations. AgI-Catalysed synthesis of disubstituted pyrrolidines; crystal structure of cis-5-phenyl-N-tosylpyrrolidin-2-ylmethyl 4-bromobenzoate T. Gallagher, S. W. Jones, M. F. Mahon and K. C. Molloy, J. Chem. Soc., Perkin Trans. 1, 1991, 2193 DOI: 10.1039/P19910002193 To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page. If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given. If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page. Read more about how to correctly acknowledge RSC content. Search articles by author Timothy Gallagher Stephen W. Jones Mary F. Mahon Kieran C. Molloy

Tandem michael reactions for the construction of pyrrolidine and piperidine ring systems

A convergent one-pot construction of disubstituted pyrrolidine and piperidine frameworks has been accomplished through a simple protocol involving intermolecular conjugate addition of a nitrogen nucleophile to an electrophilic olefin followed by intramolecular trapping of the generated enolate by a built-in α,β,-unsaturated acceptor.

ChemInform Abstract: Stereoselectivity in the Synthesis of 2,5‐Disubstituted Pyrrolidines.

AbstractThe allenic amine derivatives (II), prepared from the protected amino ester (I), undergo Ag(I)‐catalyzed cyclization to form a cis/trans‐mixture of the disubstituted pyrrolidines (III).