Asymmetric Catalysis by Vitamin B₁₂. The Mechanism of the Cob(I)alamin‐Catalyzed Isomerization of 1,2‐Epoxycyclopentane to (<i>R</i>)‐Cyclopent‐2‐enol

Abstract

Abstract 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 B 12 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 Δ H ≠ = 78 ± 4 kJ·mol −1 and Δ S ≠ = −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 (1 R ,2 R )‐ and (1 S ,2 S )‐(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 2 H‐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 11 takes place.