A Selective Synthesis of Fluorinated Cispentacin Derivatives

A facile selective method has been developed for the synthesis of new fluorine-containing cispentacin stereoisomers. Mono- and difluorinated cispentacin derivatives were synthetized from a bicyclic β-lactam in five or six steps involving a regio- and stereoselective hydroxylation through iodooxazoline formation, followed by deoxygenation by fluorination. Starting from an enantiomerically pure bicyclic β-lactam obtained by enzymatic resolution of the racemic compound, an enantiodivergent procedure allowed the preparation of both dextro- and levorotatory difluorinated cispentacins.

Synthesis and Conformational Analysis of Tetrahydroisoquinoline-Fused 1,3,2-Oxazaphospholidines and 1,2,3-Oxathiazol­idines

The cyclizations of tetrahydroisoquinoline 1,2-amino alcohols with phenylphosphonic dichloride, bis(2-chloroethyl)phosphoramidic dichloride, thionyl chloride and sulfuryl chloride were utilized to synthesize 1,5,6,10b-tetrahydro-1,3,2-oxazaphospholo[4,3-a]isoquinolines (2, 3), 1,5,10,10a-tetrahydro-1,3,2-oxazaphospholo[3,4-b]isoquinolines (8, 9), 1,5,6,10b-tetrahydro-1,2,3-oxathiazolo[4,3-a]isoquinolines (4–6) anda 1,5,10,10a-tetrahydro-1,2,3-oxathiazolo[3,4-b]isoquinoline (11), which are the first representatives of these ring systems. NMR spectroscopic analysis revealed the existence of conformational equilibria that are fast on the NMR timescale. Theoretical DFT calculations pointed to t…

Stereocontrolled synthesis of fluorine-containing piperidine γ-amino acid derivatives

An efficient synthetic approach for the construction of fluorine‐containing piperidine γ‐amino acid derivatives has been developed. The synthetic concept was based on oxidative ring opening of an unsaturated bicyclic γ‐lactam (Vince‐lactam) through its ring C=C bond, followed by double reductive amination of the diformyl intermediate performed with various fluoroalkylamines. The method has been extended towards the access of alkylated and perfluoroalkylated substances and for γ‐lactam derivatives. The transformations proceeded with stereocontrol: the configuration of the stereocenters in the products were predetermined by the configuration of the chiral centers of the starting γ‐lactam. The…

Racemization of Secondary-Amine-Containing Natural Products Using Heterogeneous Metal Catalysts

Novel functionalized cispentacin derivatives. Synthesis of 1,2,3-triazole-substituted 2-aminocyclopentanecarboxylate stereoisomers

Four 1,2,3-triazole-substituted ethyl 2-amino-3-hydroxycyclopentanecarboxylate diastereomers (3,4-disubstituted cispentacins) with a cyclopentane skeleton were prepared in enantiomerically pure form from racemic β-lactam 7 via enzymatic ring opening, epoxidation and selective ring opening of the oxirane ring with sodium azide. The formation of the 1,2,3-triazole ring system involved click chemistry: 1,3-dipolar cycloaddition of the corresponding 4-substituted azidocarboxylates with diethyl acetylenedicarboxylate.

Regio- and diastereoselective fluorination of alicyclic β-amino acids.

A regio- and stereoselective approach to fluorinated β-aminocyclohexene or cyclohexane esters has been developed, starting from a bicyclic β-lactam (1). The procedure involves six or seven steps, based on regio- and stereoselective iodolactonization, lactone opening and hydroxy–fluorine exchange. The method has been extended to the synthesis of fluorinated amino ester enantiomers.

Selective Synthesis of New Fluorinated Alicyclic β-Amino Ester Stereoisomers (Eur. J. Org. Chem. 26/2011)

The cover picture shows a waterfall located in the Eastern Carpathians in Transylvania, near Bicaz Canyon. Although fluorinated organic compounds are nonexistent in nature, an increasing number of drugs (25 %) on the market contain at least one fluorine atom. Cyclic fluorinated β-amino acid derivatives have been synthesized by selective hydroxylation and hydroxy?fluorine exchange. Details are discussed in the article by F. Fulop et al. on p. 4993 ff.

Selective Synthesis of New Fluorinated Alicyclic β-Amino Ester Stereoisomers

New fluorinated alicyclic β-amino ester stereoisomers with a cyclohexene or cyclohexane skeleton were prepared from cis- or trans-2-aminocyclohex-3-enecarboxylic acids in five or six steps through a regio- and stereoselective hydroxylation and hydroxy–fluorine exchange. Fluorinated aminoester enantiomers were synthesized from enantiopure cis- or trans-2-aminocyclohexenecarboxylic acid (prepared byenzymatic resolution of the racemic substances).

Retro-Diels-Alder Protocol for the Synthesis of Pyrrolo[1,2-a]pyrimidine and Pyrimido[2,1-a]isoindole Enantiomers

A simple protocol was introduced to prepare several enantiomerically pure heterocycles by using (–)-(1R,2R,3S,4S)-3-aminonorbornene-2-carboxylic acid as a chiral auxiliary. The protocol is based on a domino ring-closure reaction, in which the relative configuration of the new asymmetric center is controlled by the stereochemistry of the amino acid, followed by a microwave-induced retro-Diels–Alder reaction.

Synthesis of conformationally restricted 1,2,3-triazole-substituted ethyl β- and γ-aminocyclopentanecarboxylate stereoisomers. Multifunctionalized alicyclic amino esters

Abstract Stereoisomers of 1,2,3-triazole-functionalized, conformationally restricted β- or γ-amino esters with a cyclopentane skeleton were efficiently synthetized from the bicyclic β-lactam 6-azabicyclo[3.2.0]hept-3-en-7-one (1) and Vince γ-lactam (15) in five or six steps involving the azide–alkyne 1,3-dipolar cycloaddition of azido-substituted amino ester stereoisomers with nonsymmetric acetylenes. The azide–alkyne click reactions were investigated under thermal and Cu(I)-catalyzed conditions. Surprisingly, the thermally induced cycloaddition furnished the corresponding 1,4-triazoles regioselectively, which also took place selectively in response to Cu(I) catalysis.

Diversity-Oriented Stereocontrolled Synthesis of Some Piperidine- and Azepane-Based Fluorine-Containing β-Amino Acid Derivatives

AbstractStructural diversity-oriented synthesis of some azaheterocyclic β-amino acid derivatives has been accomplished by selective functionalization of readily available cyclodienes. The stereocontrolled synthetic concept was based on the oxidative ring cleavage of unsaturated cyclic β-amino acids derived from cycloalkadiene, followed by ring closing with double reductive amination, which furnished some conformationally restricted β-amino acid derivatives with a piperidine or azepane core.

Stereocontrolled Synthesis of Fluorine-Containing Piperidine γ-Amino Acid Derivatives

Front Cover: Stereocontrolled Synthesis of Fluorine-Containing Piperidine γ-Amino Acid Derivatives (Eur. J. Org. Chem. 12/2019)

Synthesis of mono- and dihydroxy-substituted 2-aminocyclooctanecarboxylic acid enantiomers

Abstract (1R,2S,6R)-2-Amino-6-hydroxycyclooctanecarboxylic acid (−)-10 was synthesized from (1R,2S)-2-aminocyclooct-5-enecarboxylic acid (+)-2 via an iodolactone intermediate, while (1R,2S,3R,4S)-2-amino-5,6-dihydroxycyclooctanecarboxylic acid (−)-12 was prepared by using the OsO4-catalyzed oxidation of Boc-protected amino ester (−)-5. The stereochemistry and relative configurations of the synthesized compounds were determined by 1D and 2D NMR spectroscopy (based on 2D NOE cross-peaks and 3J(H,H) coupling constants) and X-ray crystallography.

Synthesis of novel isoxazoline-fused cispentacin stereoisomers

Abstract New isoxazoline-fused cispentacins were prepared by the 1,3-dipolar cycloaddition of nitrile oxides to β-amino esters containing a cyclopentene skeleton. This synthetic procedure gave regio- and diastereoisomers of the cispentacins. The synthetic route was extended to the synthesis of these compounds in enantiomerically pure form.

Synthesis of densely functionalized cispentacin derivatives through selective aziridination and aziridine opening reactions: Orthogonally protected di- and triaminocyclopentanecarboxylates

A novel substrate-directed synthetic route to a series of highly functionalized, orthogonally protected di- or triaminocyclopentanecarboxylate derivatives with multiple chiral centres from an unsaturated bicyclic β-lactam has been accomplished by applying stereoselective ring C–C double bond aziridination with chloramine-T and phenyltrimethylammonium tribromide, followed by regioselective aziridine opening with different N,O nucleophiles and hydrides. The functionalization strategy was successfully extended for access to enantiomerically pure orthogonally protected triaminocarboxylates.

CCDC 924270: Experimental Crystal Structure Determination

Related Article: Ferenc Miklós, Zita Tóth, Mikko M. Hänninen, Reijo Sillanpää, Enikő Forró and Ferenc Fülöp|2013|Eur.J.Org.Chem.|2013|4887|doi:10.1002/ejoc.201300452

CCDC 924268: Experimental Crystal Structure Determination

Related Article: Ferenc Miklós, Zita Tóth, Mikko M. Hänninen, Reijo Sillanpää, Enikő Forró and Ferenc Fülöp|2013|Eur.J.Org.Chem.|2013|4887|doi:10.1002/ejoc.201300452

CCDC 924269: Experimental Crystal Structure Determination

Related Article: Ferenc Miklós, Zita Tóth, Mikko M. Hänninen, Reijo Sillanpää, Enikő Forró and Ferenc Fülöp|2013|Eur.J.Org.Chem.|2013|4887|doi:10.1002/ejoc.201300452

CCDC 924267: Experimental Crystal Structure Determination

Related Article: Ferenc Miklós, Zita Tóth, Mikko M. Hänninen, Reijo Sillanpää, Enikő Forró and Ferenc Fülöp|2013|Eur.J.Org.Chem.|2013|4887|doi:10.1002/ejoc.201300452

CCDC 982910: Experimental Crystal Structure Determination

Related Article: Loránd Kiss, Melinda Nonn, Enikő Forró, Reijo Sillanpää, Santos Fustero, Ferenc Fülöp|2014|Eur.J.Org.Chem.|2014|4070|doi:10.1002/ejoc.201402121

CCDC 982909: Experimental Crystal Structure Determination

Related Article: Loránd Kiss, Melinda Nonn, Enikő Forró, Reijo Sillanpää, Santos Fustero, Ferenc Fülöp|2014|Eur.J.Org.Chem.|2014|4070|doi:10.1002/ejoc.201402121

CCDC 1008231: Experimental Crystal Structure Determination

Related Article: Melinda Nonn, Loránd Kiss, Enikő Forró, Reijo Sillanpää, Ferenc Fülöp|2014|Tetrahedron|70|8511|doi:10.1016/j.tet.2014.09.071