Diastereoselective C−H Bond Amination for Disubstituted Pyrrolidines

Abstract

We report herein the improved diastereoselective synthesis of 2,5-disubstituted pyrrolidines from aliphatic azides. Experimental and theoretical studies of the C–H amination reaction mediated by the iron dipyrrinato complex (AdL)FeCl(OEt2) provided a model for diastereoinduction and allowed for systematic variation of the catalyst to enhance selectivity. Among the iron alkoxide and aryloxide catalysts evaluated, the iron phenoxide complex exhibited superior performance towards the generation of syn 2,5-disubstituted pyrrolidines with high diastereoselectivity.

Radical‐Type Reactivity and Catalysis by Single‐Electron Transfer to or from Redox‐Active Ligands

“…[47] This system is at least one order of magnitude morea ctive than all other reporteds ystems to date, all of which operate through metalloradicalc atalysis. [48][49][50][51] The Fe III -complex could be quantitatively recycled and re-used after catalysis. It was established that in situ reduction under the same conditions as for the Pd-system led to Fe-centered rather than ligand-centered reduction, with subsequent disproportionation to afford ac rystallographically characterized homoleptic Fe II (L1 ISQ ) 2 complex that was completely inactive for the CÀHa mination reaction.…”

Recent Advances in Iron‐Catalyzed C—H Bond Amination via Iron Imido Intermediate

“…[80] Importantly, as the iron-catalyzed cyclization of (R)-2-phenyl-5-azidopentane shows the feature of stereo-retention, and the radical clock experiment with 2-(4-azidobutyl)cyclopropyl)benzene gave exclusively cyclopropanyl substituted pyrollidine (Scheme 13), the C-H bond amination step in this iron-catalyzed reaction was thought to proceed very fast due to its intramolecu- )]-catalyzed C-H amination reaction allows for the synthesis of 2,5-disubstituted pyrrolidines, but most of these reactions have modest diastereoselectivity (Tables 18 and 19). Aiming to develop effective iron catalysts for the diastereoselective synthesis of 2,5-disubstituted pyrrolidines, Betley and coworkers screened the series of dipyrrinato iron(II) alkoxide and aryloxide complexes [( Ad DP ClAr )Fe II (OR)(solv)] (R = alkyl or aryl) and found the phenolate complex [( Ad DP ClAr )Fe II (OPh)(THF)] can catalyze the cyclization reaction of alkyl azides to produce selectively syn 2,5-disubstituted pyrrolidines [81] (Table 19). Among the reactions examined, all the allylic C-H bond amination reactions have their dr values higher than 20 : 1.…”

Spontaneous Resolution by Crystallization of an Octanuclear Iron(III) Complex Using Only Racemic Reagents

“…[5,6] Enantioselective synthetic techniques employing chiral catalysts have been developed to circumvent the difficult problem of racemate resolution. [9] Most homogeneous racemic catalysts are transition-metal complexes,w hich can undergo facile isomerization, because of the lability of metalligand bonds and flexibility of their coordination sphere (e.g., Berry pseudo-rotation, Bailar twist). [9] Most homogeneous racemic catalysts are transition-metal complexes,w hich can undergo facile isomerization, because of the lability of metalligand bonds and flexibility of their coordination sphere (e.g., Berry pseudo-rotation, Bailar twist).…”