Ruthenium-Catalyzed Asymmetric Electrophilic Fluorination of 1,3-Dicarbonyl Compounds

Abstract

Upon activation with (Et3O)PF6 (2 equiv), the ruthenium(II) complex [RuCl2(PNNP)] (1; PNNP is (1S,2S)-N,N‘-bis(o-(diphenylphosphino)benzylidene)cyclohexane-1,2-diamine) catalyzes the electrophilic fluorination of 1,3-dicarbonyl compounds by N-fluorobenzenesulfonimide (NFSI). Oxygen donors, in particular Et2O as cosolvent, increase the activity of the catalyst and, in some cases, the enantioselectivity. The absolute configuration of 2-tert-butoxycarbonyl-2-fluorocyclopentanone (5a), which is obtained with up to 93% ee in catalysis, was determined to be R by derivatization to (1S)-(−)-camphanic acid (1R,2R)-2-tert-butoxycarbonyl-2-fluoro-cyclopentyl ester (7) and X-ray analysis. A model for enantioselection is proposed on the basis of the known structures of the dicationic complex [Ru(4a)(PNNP)]2+ (2a; 4a is 2-tert-butoxycarbonylcyclopentanone), which is formed under catalysis conditions, and of its monocationic enolato analogue (3a). The stoichiometric reactions of 2a and 3a with NFSI in pure CH2Cl2 and in the presence of substrate, product, or Et2O show that proton-transfer processes promoted by oxygen donors are pivotal in catalysis.