Synthesis of Chiral-Substituted 2-Aryl-ferrocenes by the Catellani Reaction

Abstract

A palladium-catalyzed and norbornene-mediated methodology has been developed for the synthesis of chiral 2-aryl-ferroceneamides from chiral 2-iodo-N,N-diisopropylferrocencarboxamide, iodoarenes, and alkenes using a JohnPhos ligand and potassium carbonate as a base in dimethylformamide at 105 °C. The developed three-component coupling protocol allows the compatibility of electron-withdrawing fluoro, chloro, ester, and nitro and electron-donating methyl, methoxy, dimethoxy, benzyl ether-substituted iodo-benzenes, other iodoarenes, such as iodo-naphthalene, heteroarenes, such as iodothiophene, and terminating substrates, such as methyl, ethyl, tert-butyl acrylates, and substituted styrenes with 2-iodo-N,N-diisopropylferrocencarboxamide. Furthermore, the developed three-component Catellani method proceeded with the retention of the configuration of the planar chiral ferrocene, which depends on the role of the participating carbon–iodine bond in ferrocene. Consequently, the developed protocol enabled the formation of densely substituted chiral 2-aryl ferroceneamides, exhibiting good to excellent enantioselectivity. The conversion of an ester of the synthesized chiral 2-aryl ferroceneamides has also been carried out to further accommodate the easily expendable acid and alcohol functionalities.

A Planar‐Chiral Palladium Complex Derived from a Weak Oxygen Donor N,N‐Diisopropyl Ferrocenecarboxamide Ligand

“…enables chiral 2‐iodoferrocene carboxamide 14 in gram quantity (Scheme 1). [29] In our earlier attempt to achieve three component Catellani reaction in 2‐iodoferrocene carboxamide 14 , a palladacycle 15 was isolated in poor yield by serendipity [29] . Later, palladacycle 15 obtained in good yield (79 %) by the reaction of 2‐iodoferrocene carboxamide 14 , palladium(II) acetate and triphenylphosphine ligand in acetonitrile under heating conditions at 80 °C for 6 h. The progress of the reaction was monitored by TLC following the disappearance of substrate 14 .…”

Unravelling functions of halogen substituents in the enantioseparation of halogenated planar chiral ferrocenes on polysaccharide-based chiral stationary phases: experimental and electrostatic potential analyses

“…Such phenomenon has led to the huge development of ferrocenyl derivatives as chiral ligands in asymmetric synthesis and catalysis [8,16]. However, only a few enantiomerically enriched haloferrocenes are known [17][18][19][20].…”

“…An alternative could be the resolution of planar chiral ferrocenes through enantioselective HPLC on polysaccharide-based chiral stationary phases (CSPs). However, while moderate to high enantioselectivities were obtained under normal-phase (NP) elution conditions for ferrocenes bearing polar substituents [19,20,22], the enantioseparation of derivatives containing halogens or alkyl groups exclusively remains rather challenging [23][24][25].…”

Tetravalent Spiroselenurane Catalysts: Intramolecular Se···N Chalcogen Bond-Driven Catalytic Disproportionation of H2O2 to H2O and O2 and Activation of I2 and NBS

“… It seems that the high oxidation state of iron­(IV) in hydroxy-perhydroxy intermediate VII makes this intermediate highly oxidizing and abstraction of a proton from the perhydroxy group by the proximal nitrogen base of the histidine unit facilitates the oxidation of H 2 O 2 into O 2 . Our group is engaged in developing new approaches for the construction of C–C, C–N, C–S, and C–Se bonds ,, and finding newer applications for the newly synthesized organochalcogens. Our group has also developed a new methodology for constructing carbon–selenium–nitrogen bonds in the substrates having −OH, −NHR, amide, and ester with acidic protons and also studied their catalytic applications in radical quenching, ,, peroxide decomposing, ,, and activating halogenating reagents , from a biological and synthetic perspective.…”