Metal-Catalyzed Enantioselective α-Ketol Rearrangements

Promoted by catalytic amounts of transition-metal complexes, the tertiary α-hydroxy ketones 1, 3, 5/6 undergo α-ketol rearrangements to afford equilibrium mixtures of isomers with a reorganization of the carbon skeleton. The range of metal complexes catalyzing the isomerizations is large; the best results were obtained with the catalyst systems NiCl2/TMEDA, Ni(acac)2, and Ni(acac)2/TMEDA (TMEDA = N,N,N′,N′-tetramethyl-1,2-diaminoethane). The catalytic rearrangements were performed at 130 °C in the absence of solvent, with a NiII/ligand/substrate ratio of 1:2:100. The equilibrium composition of the model system 1/2 is 12.5:87:5. The conversion of the achiral substrates 1 and 3 into the chiral products 2 and 4 can be used for kinetic resolution. However, the reverse reactions 2 → 1 and 4 → 3 in the equilibrations narrow the window for asymmetric induction with enantioselective catalysts of the metal component/optically active ligand type. In system 1, the highest enantiomeric excess was achieved with the catalyst systems NiCl2/pybox [18.9% (S)-2] and Ni(acac)2/pybox [19.3% (R)-2] {pybox = 2,6-bis[(S)-4-isopropyl(oxazolin-2′-yl)]pyridine}. The α-ketol rearrangement of 3 with the Ni(acac)2/pybox catalyst resulted in a maximum enantiomeric excess of 37.1% (S)-4.