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-(1<i>H</i>-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

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 (4<i>S</i>,5<i>S</i>)-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

3,4-Dihydro‑2<i>H</i>‑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-2<i>H</i>-pyrrole-2-carbonitriles in one-pot procedures. 5,6,7,8-Tetrahydroindolizines, 2,3-dihydro-1<i>H</i>-pyrrolizines as well as 6,7,8,9-tetrahydro-5<i>H</i>-pyrrolo­[1,2-<i>a</i>]­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-2<i>H</i>-pyrrole-2-carbonitriles with copper­(II)-salts furnished 2,2′-bipyrroles as well as 5,5′-bis­(5-cyano-1-pyrrolines), depending on the reaction conditions. Overall, these methods give high yielding access to a variety of pyrrole-containing heterocyles in two steps from commercially available starting materials

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-2<i>H</i>-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