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-epcxycyclopentane ( 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 ε 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 ε of the solvent. An Arrhenius plot at ε = 40 gives activation parameters ΔH^≠ = 78 ± 4 kJ·mol^?1 and ΔS^≠ = ?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-hydroxycyclo-pentyl)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 ²H-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 Co¹¹ takes place.