Ruthenium-Catalyzed Diastereoselective Synthesis of Fully Substituted Pyrrolidines from Anilines and Diazo Pyruvates

Abstract

An unprecedented synthesis of polysubstituted pyrrolidines from anilines and diazo pyruvates by ruthenium catalysis under mild reaction conditions is reported. An enol intermediate derived from the N−H insertion of aniline toward the ruthenium carbene species as well as an imine ester intermediate generated by SET-mediated oxidation of enol were proposed as the key intermediates. This strategy provides various pyrrolidines containing four contiguous stereocenters in good efficiency with high diastereoselectivities.

Structure revision and chemical synthesis of ligandrol's main bishydroxylated long-term metabolic marker

“…Thus, contrary to the reported long-term persistence of this metabolite, 9,11 a N-bridged bis-hemiaminal, such as 3, would be anticipated to be extremely labile, especially in aqueous media. Indeed, a literature survey revealed few examples of analogous compounds that, unless embedded in strategically functionalized 16 or fused polycyclic structures, [17][18][19][20] have been observed only as fleeting intermediates. 21,22 Furthermore, it is interesting that the reported 1 H NMR chemical shift for H-11 ‡ of compound 3 (δ = 4.00 ppm) is upfield from the corresponding proton of the closely related compound 2 (δ = 5.41 ppm).…”

Synthesis and biological evaluation of substituted pyrrolidines and pyrroles as potential anticancer agents

“…A series of polysubstituted pyrrolidines 3a – k were obtained by separating the reaction mixture through flash chromatography on silica gel. [ 20 ] The related pyrrole derivatives were synthesized from corresponding pyrrolidines upon treating with p ‐toluenesulfonic acid ( p ‐TsOH) in dichloromethane (Scheme 1b).…”

“…[ 7,19 ] During our methodology studies on metal carbene‐involved transformations, we recently happened to develop a novel method to synthesize fully substituted pyrrolidines via ruthenium‐catalyzed tandem cyclization of diazo pyruvates and anilines. [ 20 ] Biological activities of these series of compounds were also evaluated and compounds with the most potent activities were further subjected to broader anticancer studies as well as the evaluation of their effects on cell cycle and apoptosis.…”

Diastereoselective Synthesis of Polysubstituted Pyrrolidines/Dihydropyrroles: Photochemical Properties of Polysubstituted Pyrroles

“…1). Hu and coworkers [4] have described a pseudo five‐component synthesis of polysubstituted pyrrolidines via ruthenium‐catalyzed cascade cyclization of diazo pyruvates and anilines as well as their corresponding pyrrole analogs via acid‐mediated dehydration (Scheme 1, Eq. 2).…”