Catalytic One‐Pot Synthesis of 1‐Substituted 5,6,7,8‐Tetrahydroindolizine Derivatives

Abstract

The reaction of α,β‐unsaturated aldehydes, carbon monoxide, and but‐3‐en‐1‐amine in the presence of Ru3(CO)12 as a precatalyst yields 1‐substituted 5,6,7,8‐tetrahydroindolizine derivatives for a wide variety of groups R1 at the C‐3 position of the α,β‐unsaturated aldehyde.

Ruthenium‐Catalyzed Synthesis of Highly Substituted Pyrroles from 1‐Vinylpropargyl Alcohols and Amines

“…Because the pyrrole core is an important heteroaromatic system found in many natural products,3 drugs4 and functional materials,5 several metal‐catalyzed methods have been developed for its synthesis 6,7. These catalytic processes include carbonylation reactions,6d,6o the rearrangement of diazo compounds,6e,6h the activation of C–H bonds,6f,6i–6k redox isomerization6r and cycloisomerization processes [6a–6c,6g,6l–6n,6p,6q,6s–6x] or the “borrowing‐hydrogen” method 7. Metal‐free multi‐component reactions for flexible pyrrole synthesis from easily accessible substrates have also been developed 6c,8.…”

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.…”

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

“…Similarly, this chemistry also suffers from multistep operations and low overall yields. A single step synthesis of 5,6,7,8-tetrahydroindolizines has been previously achieved by a ruthenium-catalyzed multicomponent reaction (Scheme C) . Unfortunately, this strategy employs high loading of an expensive ruthenium catalyst (3 mol % Ru 3 (CO) 12 ), high CO pressure (20 bar), and high temperature (140 °C).…”

“…There are several reported approaches to the synthesis of 5,6,7,8-tetrahydroindolizines in the literature, each of which centered on certain substitution pattern of the tetrahydroindolizine core. − For example, 5,6,7,8-tetrahydroindolizines are synthesized via a 1,3-dipolar cycloaddition of münchnones with acetylenic dipolarophiles followed by elimination of CO 2 (Scheme A) . However, this process not only requires multistep synthesis and high reaction temperature (125–140 °C) but also affords low overall yields and poor regioselectivity when unsymmetrical acetylenes are employed.…”