Single-Step Synthesis of 5,6,7,8-Tetrahydroindolizines via Annulation of 2-Formylpiperidine and 1,3-Dicarbonyl Compounds

Abstract

An expedient single-step synthesis of 5,6,7,8-tetrahydroindolizines has been achieved via the annulation of commercially available 2-formylpiperidine hydrochloride and 1,3-dicarbonyl compounds in THF in the presence of pyrrolidine and 4 Å molecular sieves. A variety of β-ketoesters, ketones, and amides participated in this annulation chemistry, affording the desired 5,6,7,8-tetrahydroindolizines in moderate to good yields.

Synthesis of α-Formylated N-Heterocycles and Their 1,1-Diacetates from Inactivated Cyclic Amines Involving an Oxidative Ring Contraction

“…To date, α-formylated pyridines and their hydrogenated derivatives have been widely used in the synthesis of metal complexes with relevance in medicinal and coordination chemistry. Moreover, they are also versatile intermediates in the synthesis of imidazo­[1,5- a ]­pyridines, tetrahedral metal organic cages, and indolizines, etc . Notwithstanding their importance, efficient preparations of piperidine-2-carbaldehydes have only been sporadically reported .…”

Brønsted Acid‐Mediated Formal [3+3] Annulation Between Propargylic Alcohols and 1,3‐Diketones

“…1,3‐Dicarbonyl derivatives have been extensively used as important synthetic intermediates because they incorporate nucleophilic and electrophilic functionalities . In particular, the use of 1,3‐dicarbonyl derivatives as nucleophilic or electrophilic reagents for the construction of structurally diverse oxygen‐containing compounds, such as pyrroles, indoles, dihydropyrans, tetrahydroindolizines, dihydrofurans, β ‐hydroxyesters, γ ‐alkylidenebutenolides, and olefinic cyclopentanes, has been widely investigated. Inspired by these intriguing reports and our continued interest in the transformations of propargylic alcohols, we herein report a novel Brønsted acid‐mediated formal [3+3] annulation system involving reactions of propargylic alcohols with 1,3‐diketones, which enables an efficient, single‐step, atom‐economical synthesis of chromenone derivatives under mild conditions.…”

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

“…Frequently occurring structural frameworks are the 5,6,7,8-tetrahydroindolizine or the 2,3-dihydro-1 H -pyrrolizine ring system. The development of new synthetic methods for the preparation of these compounds has seen considerable progress in recent years − and 5,6,7,8-tetrahydroindolizines are now often being utilized as a key intermediate in the total synthesis of fully saturated indolizidine alkaloids. − Commonly applied strategies for the synthesis of 5,6,7,8-tetrahydroindolizines or 2,3-dihydro-1 H -pyrrolizines are condensation reactions, ,, Lewis acid ,, or transition metal catalyzed cyclizations, ,,− hydroacylations or hydroaminations, ,, cycloadditions , as well as the reduction of indolizines. , However, most of these methods are limited to the preparation of only one class of the mentioned compounds.…”