ASYMMETRIC CATALYSIS BY VITAMIN-B12 - THE MECHANISM OF THE COB(I)ALAMIN-CATALYZED ISOMERIZATION OF 1,2-EPOXYCYCLOPENTANE TO (R)-CYCLOPENT-2-ENOL

The isomerization of 1,2-epoxycyclopentane (1) to enantiomerically enriched (R)-cyclopent-2-enol (2) in protic solvents is catalyzed by cob(I)alamin. The enantiomeric excess (e.e.) of (R)-2 is usually ca. 60%; it is only slightly dependent on the temperature, but increases with decreasing dielectric constant epsilon of the solvent. Standard kinetic methods show the reaction to be first order in vitamin B12 and zero order in 1. The rate constant increases exponentially with increasing epsilon of the solvent. An Arrhenius plot at epsilon = 40 gives activation parameters DELTA-H not-equal = 78 +/- 4 kJ.mol-1 and DELTA-S not-equal = -49 +/- 1 J.mol-1.K-1. The isomerization 1 --> 2 proceeds in two steps (Schemes 2 and 7): i) The epoxide ring is first opened by the proton-assisted fast and irreversible nucleophilic attack of the chiral Co(I) catalyst to form diastereoisomeric (1R,2R)- and (1S,2S)-(2-hydroxycyclopentyl)cob(III)alamins 6 in a ratio of ca. 4:1 which are the dominant species in the steady state; ii) The intermediates 6 then decompose in the rate-limiting step to form 2 and recycled catalyst. Experiments with specifically H-2-labeled 1 showed the hydro-cobalt elimination 6 --> 2 to be non-stereoselective. It proceeds via reversible Co-C bond homolysis to a free 2-hydroxycyclopentyl radical from which stereoelectronically controlled H-abstraction by Co(II) takes place.