Premium
Metal‐Catalyzed Enantioselective α‐Ketol Rearrangements
Author(s) -
Brunner Henri,
Stöhr Frank
Publication year - 2000
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/1099-0690(200008)2000:15<2777::aid-ejoc2777>3.0.co;2-0
Subject(s) - chemistry , enantioselective synthesis , catalysis , kinetic resolution , enantiomeric excess , ligand (biochemistry) , isopropyl , medicinal chemistry , stereochemistry , asymmetric induction , organometallic chemistry , enantiomer , pyridine , metal , organic chemistry , biochemistry , receptor
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 NiCl 2 /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 Ni II /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 NiCl 2 /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 .