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

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.