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

Article abstract of DOI:10.1002/hlca.19910740706

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. 60percent; 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 vitamine 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(excit.) = 78 +/- 4 kJ*mol^-1 and ΔS(excit.) = -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 nucleophile attack of the chiral Co^I catalyst to form diastereomeric (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 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 Co^II takes place.