Larsson AL. E,
Persson BA,
Bäckvall J.-E.
*
Uppsala University, Sweden
Enzymatic Resolution of Alcohols Coupled with Ruthenium-Catalyzed Racemisation of the Substrate Alcohol.
Angew. Chem., Int. Ed. Engl. 1997;
36: 1211-1212
DOI:
10.1002/anie.199712111
Key words
acylation - dynamic kinetic resolution (DKR) - enzyme catalysis - racemization - ruthenium catalysis
Significance
In 1997, Bäckvall and co-workers presented a ruthenium(II)-catalyzed racemization of secondary alcohols coupled with enzymatic kinetic resolution to form the corresponding acetates in high yields and enantiomeric excesses. This protocol’s advantage over common kinetic resolution is a theoretical yield of the enantiomerically enriched acetates of 100%. A monomeric ruthenium complex later introduced is able to racemize alcohols in under 10 min at room temperature with a low catalyst loading of 0.5 mol% (Angew. Chem. Int. Ed.
2004, 43, 6535). This catalyst is still the benchmark for the racemization of secondary alcohols.
Comment
Bäckvall’s dynamic kinetic resolution (DKR) is the first example of a dual catalytic system combining transition-metal and enzyme catalysis. From a mechanistic point of view, a slippage of the Cp ring from η5- to η3-coordination to form a free coordination site was initially assumed in the racemization process, but computations as well as mechanistic experiments strongly suggest a CO dissociation mechanism (Acc. Chem. Res.
2013, 46, 2545).
