HFIP Solvent Effects on Enantioselectivity of Dirhodium Tetracar-boxylate-Catalyzed Cyclopropanation
Year: 2025
Type: preprint
Abstract: In recent years, additives that modulate both reactivity and selectivity in rhodium catalyzed-reactions of aryldiazoacetaes have become increasingly prominent. 1,1,1,3,3,3-Hexafluoroisopropanol (HFIP) has been shown to have a profound effect on rhodium carbene reac-tivity and selectivity, especially on enabling carbene cyclopropanation in the presence of various nucleophilic poisons. HFIP also has a variable influence on the enantioselectivity of the reactions catalyzed by chiral dirhodium tetracarboxylates, and this study examines the fundamental properties of the rhodium carbene/HFIP system through experimentation, density functional theory (DFT), and molecu-lar dynamics (MD) simulations. These studies revealed that the C4-symmetric bowl-shaped catalysts, which have been previously consid-ered to be relatively rigid, experience far greater flexibility in this hydrogen bonding media, resulting in distortion of the bowl-shaped cata-lysts. These studies explain why even though a majority of the catalysts have a drop in enantioselectivity in HFIP, some catalysts such as Rh2(TCPTAD)4, lead to a switch in enantioselectivity, whereas others, such as Rh2(NTTL)4, lead to a considerably enhanced enantiose-lectivity.
Source: ChemRxiv
Authors: Turki Alturaifi, Kristin Shimabukuro, Jack Sharland, Binh Khanh Mai, Evan Weingarten, Mithun Madhusudhanan, Djamaladdin Musaev, Peng Liu, Huw Davies
Institutions: University of Pittsburgh, Emory University
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W4407773263