Catalytic Enantioselective Synthesis of Azepine-Fused Planar-Chiral Ferrocenes by Pt-Catalyzed Cycloisomerization

Abstract

Enantioselective synthesis of azepine-fused planar-chiral ferrocenes was achieved by the chiral cationic Pt-catalyzed intramolecular cycloisomerization of N-propargyl-2-ferrocenylanilines. A mechanistic study using an N-allenyl analogue indicated that the reaction proceeded selectively in a 7-exo-dig manner along with isomerization of the exo-olefin moiety. A methanesulfonylamino tether was crucial for selective cycloisomerization. This is the first example of the enantioselective synthesis of heteropin-fused planar-chiral ferrocenes.

Synthesis and Applications of Ferrocene‐Fused Nitrogen Heterocycles

“…In 2019, Ito, Shibata and co-workers reported the synthesis of azepine-fused planar-chiral ferrocenes through a Pt-catalyzed cycloisomerization of N-propargyl-2-ferrocenylanilines (Scheme 23). [57] Enantioselectivities ranging from 37 to 90 % ee were obtained when 1,2-bis((2S,5S)-2,5diphenylphospholano)ethane was used as a chiral ligand. This cycloisomerization reaction is proposed to proceed through initial 7-exo-dig cyclization and subsequent isomerization of the resulting exocyclic olefin.…”

Asymmetric C–H Bond Functionalization of Ferrocenes: New Opportunities and Challenges

“…The major pathway of this reaction is the activation of the alkyne moiety by π-acidity of the chiral cationic Pt catalyst followed by 6-endo-dig cyclization. Recently, Shibata, and Ito also used similar strategy to achieve an enantioselective synthesis of azepine-fused planar-chiral ferrocenes with a chiral cationic Pt catalyst (Figure 5C) [93].…”

Planar Chiral Pseudo‐Isocoumarins by Copper Catalysed Desymmetrisation

“…Unsymmetrically substituted ferrocenes have planar chirality, so when an isocoumarin ring is fused to a cyclopentadienyl ligand of ferrocene, issues about enantioselective synthesis are unavoidable, especially since for development of a new drug candidate, enantiopure compounds are much preferred to racemates when assessing bioactivity. The synthesis of planar chiral ferrocenes, usually by directed lithiation mediated by a chiral directing group, [18–23] is of ongoing interest while metal catalysed enantioselective cyclisations on activated alkynyl ferrocenes and desymmetrisation strategies for the installation of planar chirality are becoming more frequently used [24–29] . We report here a new method of asymmetric synthesis of isocoumarin‐fused ferrocenes, based on our interest in the desymmetrisation of prochiral ferrocene diynes [30] by asymmetric click chemistry [31] …”