ChemInform Abstract: A Modular Synthesis of Polysubstituted Indolizines.

Title compounds are synthesized by [3 + 2] cycloaddition of nitroalkenes (IV) with pyridinium salts.

ChemInform Abstract: 3,4-Dihydro-2H-pyrrole-2-carbonitriles: Useful Intermediates in the Synthesis of Fused Pyrroles and 2,2′-Bipyrroles.

Various heterocyclic structures containing the pyrrole moiety have been synthesized from easily accessible 3,4-dihydro-2H-pyrrole-2-carbonitriles in one-pot procedures. 5,6,7,8-Tetrahydroindolizines, 2,3-dihydro-1H-pyrrolizines as well as 6,7,8,9-tetrahydro-5H-pyrrolo[1,2-a]azepines were obtained from these precursors in high yields in an alkylation/annulation sequence. The same conditions were applied in the synthesis of a 5,8-dihydroindolizine, which could easily be transformed to the corresponding indolizine by dehydrogenation. Furthermore, oxidative couplings of 3,4-dihydro-2H-pyrrole-2-carbonitriles with copper(II)-salts furnished 2,2′-bipyrroles as well as 5,5′-bis(5-cyano-1-pyrroline…

One-Pot Synthesis of Pyrrole-2-carboxylates and -carboxamides via an Electrocyclization/Oxidation Sequence

An electrocyclic ring closure is the key step of an efficient one-pot method for the synthesis of pyrrole-2-carboxylates and -carboxamides from chalcones and glycine esters or amides. The 3,4-dihydro-2H-pyrrole intermediates generated in situ are oxidized to the corresponding pyrroles by stoichiometric oxidants or by catalytic copper(II) and air in moderate to high yields. A wide range of functional groups are tolerated, and further combination with an in situ bromination gives access to polyfunctional pyrrole scaffolds.

3,4-Dihydro-2H-pyrrole-2-carbonitriles: Useful Intermediates in the Synthesis of Fused Pyrroles and 2,2′-Bipyrroles

Various heterocyclic structures containing the pyrrole moiety have been synthesized from easily accessible 3,4-dihydro-2H-pyrrole-2-carbonitriles in one-pot procedures. 5,6,7,8-Tetrahydroindolizines, 2,3-dihydro-1H-pyrrolizines as well as 6,7,8,9-tetrahydro-5H-pyrrolo[1,2-a]azepines were obtained from these precursors in high yields in an alkylation/annulation sequence. The same conditions were applied in the synthesis of a 5,8-dihydroindolizine, which could easily be transformed to the corresponding indolizine by dehydrogenation. Furthermore, oxidative couplings of 3,4-dihydro-2H-pyrrole-2-carbonitriles with copper(II)-salts furnished 2,2'-bipyrroles as well as 5,5'-bis(5-cyano-1-pyrroline…

Two-Step Synthesis of 2-Aminoindolizines from 2-Alkylpyridines

An efficient method for the synthesis of 2-aminoindolizines by the 5-exo-dig cyclization of 2-alkyl-1-(1-cyanoalkyl)pyridinium salts has been developed. These substrates were prepared by N-alkylation of 2-alkylpyridines with readily available cyanohydrin triflates. The method allows the introduction of various substituents at the 1-, 3-, 6-, 7-, and 8-positions and leaves no undesired acceptor groups in the products.

ChemInform Abstract: Two-Step Synthesis of 2-Aminoindolizines from 2-Alkylpyridines.

5-Exo-dig cyclization of 2-alkyl-1-(1-cyanoalkyl)pyridinium triflates offers a convenient method for the synthesis of 2-aminoindolizines.

Simple two-step synthesis of 2,4-disubstituted pyrroles and 3,5-disubstituted pyrrole-2-carbonitriles from enones

The cyclocondensation of enones with aminoacetonitrile furnishes 3,4-dihydro-2H-pyrrole-2-carbonitriles which can be readily converted to 2,4-disubstituted pyrroles by microwave-induced dehydrocyanation. Alternatively, oxidation of the intermediates produces 3,5-disubstituted pyrrole-2-carbonitriles.

Visible Light-Induced Sulfonylation/Arylation of Styrenes in a Double Radical Three-Component Photoredox Reaction

Simultaneous sulfonylation/arylation of styrene derivatives is achieved in a photoredox-catalyzed three-component reaction using visible light. A broad variety of difunctionalized products is accessible in mostly excellent yields and high diastereoselectivity. The developed reaction is scalable and suitable for the modification of styrene-functionalized biomolecules. Mechanistic investigations suggest the transformation to be operating through a designed sequence of radical formation and radical combination.

Enantioselective Synthesis of α-Quaternary Amino Acids by Alkylation of Deprotonated α-Aminonitriles.

A series of α-quaternary arylglycines were prepared in high optical purity (up to 98% ee) by α-alkylation of deprotonated α-aminonitriles derived by the Strecker reaction from (4S,5S)-5-amino-2,2-dimethyl-4-phenyl-1,3-dioxane. The procedure includes only chromatographic purification of the final products and is devoid of chromatography or crystallization operations on intermediates to raise the optical purity.

A Modular Synthesis of Polysubstituted Indolizines

The N-alkylation of pyridines with cyanohydrin triflates or α-halonitriles furnishes 1-(1-cyanoalkyl)pyridinium salts that can react with nitroolefins under basic conditions to furnish polysubstituted indolizines. Overall, the indolizine core can be constructed from a pyridine, two aldehydes, and a nitroalkane, and no undesired functional groups remain in the products. When bromoacetonitrile was used for the N-alkylation, indolizine-3-carbonitriles were obtained instead. The pyridine component may be replaced by other azines, giving rise to related heterocyclic systems.

ChemInform Abstract: Enantioselective Synthesis of α-Quaternary Amino Acids by Alkylation of Deprotonated α-Aminonitriles.

An α-alkylation of deprotonated α-amino nitriles, prepared from chiral phenyldioxanamine (I) by Strecker reaction, leads to α-quaternary arylglycines with high optical purity after hydrolysis and oxidative cleavage of the chiral auxiliary.

Cover Feature: Visible Light‐Induced Sulfonylation/Arylation of Styrenes in a Double Radical Three‐Component Photoredox Reaction (Chem. Eur. J. 38/2019)

One-pot synthesis of polysubstituted indolizines by an addition/cycloaromatization sequence.

Indolizines carrying various substituents in positions 5-8 were obtained from readily available 2-(1H-pyrrol-1-yl)nitriles and α,β-unsaturated ketones or aldehydes in a one-pot procedure. Michael addition of the deprotonated aminonitriles to the acceptors followed by acid-catalyzed electrophilic cyclization produces 5,6-dihydroindolizine-5-carbonitriles. From these stable intermediates, substituted indolizines were obtained via base-induced dehydrocyanation.

ChemInform Abstract: One-Pot Synthesis of Pyrrole-2-carboxylates and -carboxamides via an Electrocyclization/Oxidation Sequence.

An electrocyclic ring closure is the key step of an efficient one-pot method for the synthesis of pyrrole-2-carboxylates and -carboxamides from chalcones and glycine esters or amides. The 3,4-dihydro-2H-pyrrole intermediates generated in situ are oxidized to the corresponding pyrroles by stoichiometric oxidants or by catalytic copper(II) and air in moderate to high yields. A wide range of functional groups are tolerated, and further combination with an in situ bromination gives access to polyfunctional pyrrole scaffolds.

ChemInform Abstract: One-Pot Synthesis of Polysubstituted Indolizines by an Addition/Cycloaromatization Sequence.

Indolizines carrying various substituents in positions 5-8 were obtained from readily available 2-(1H-pyrrol-1-yl)nitriles and α,β-unsaturated ketones or aldehydes in a one-pot procedure. Michael addition of the deprotonated aminonitriles to the acceptors followed by acid-catalyzed electrophilic cyclization produces 5,6-dihydroindolizine-5-carbonitriles. From these stable intermediates, substituted indolizines were obtained via base-induced dehydrocyanation.

CCDC 1055316: Experimental Crystal Structure Determination

Related Article: Dennis Imbri , Natalie Netz , Murat Kucukdisli , Lisa Marie Kammer , Philipp Jung , Annika Kretzschmann , and Till Opatz|2014|J.Org.Chem.|79|11750|doi:10.1021/jo5021823

CCDC 1055315: Experimental Crystal Structure Determination

Related Article: Dennis Imbri , Natalie Netz , Murat Kucukdisli , Lisa Marie Kammer , Philipp Jung , Annika Kretzschmann , and Till Opatz|2014|J.Org.Chem.|79|11750|doi:10.1021/jo5021823

CCDC 1483912: Experimental Crystal Structure Determination

Related Article: Marco M. Nebe, Murat Kucukdisli, and Till Opatz|2016|J.Org.Chem.|81|4112|doi:10.1021/acs.joc.6b00393

CCDC 1004248: Experimental Crystal Structure Determination

Related Article: Murat Kucukdisli, Till Opatz|2014|Eur.J.Org.Chem.|2014|5836|doi:10.1002/ejoc.201402618