Organic Free Radical-Promoted Isomerization of α- and β-Alkylcobinamides¹

Abstract

Anaerobic reaction of alpha- or beta-alkylcobinamides (alpha- or beta-RCbi(+)'s) with the corresponding alkyl free radical, R(*) (where R = CH(3), CH(3)CH(2), or CH(3)CH(2)OCH(2)CH(2)), generated by the Fenton reaction using Fe(2+) and an alkyl hydroperoxide, RC(CH(3))(2)OOH, causes isomerization and leads to mixtures of alpha- and beta-RCbi(+)'s. The reaction does not occur, however, under aerobic conditions or under anaerobic conditions in the presence of an excess of the free radical scavenger H-Tempo. In addition, alpha-CH(3)CH(2)Cbi(+) reacts with 50 molar equiv of tert-butyl hydroperoxide and Fe(2+) to give a mixture of alkylcobinamides that contains 6% alpha-CH(3)Cbi(+) and 94% beta-CH(3)Cbi(+), showing that multiple transalkylations occur. A Co(II)-induced isomerization and the S(H)2 mechanism are ruled out on the basis of the known reactivity of RCbi(+) and product analysis. A mechanism is proposed which involves a direct oxidative free radical displacement by an R(*) to the metal of RCbi(+) via a dialkylcobalt(IV) corrinoid species. Since the reaction leads to equilibration of the two diastereomers under mild conditions, it can be used to study the equilibria between diastereomeric RCbi(+)'s. Thus, the equilibrium for the diastereomeric ethyl-13-epicobinamides, in which the e propionamide side chain of the corrin ring has been epimerized from the alpha to the beta face of the corrinoid, lies significantly more toward the alpha diastereomer than that for the normal ethylcobinamides. This represents the most direct experimental evidence obtained to date that the corrin ring side chains control the relative steric accessibility of the two faces of the cobalt corrinoids.

Diastereomeric Control in the Formation of Carbon−Cobalt Bonds in Organocobalt Corrinoids: Reactions of Cobalt(II) Corrinoids with Organic Hydroperoxides1

“…Our original attempt 15 to use reactions of organic hydroperoxides with cob(II)inamide (eqs 1−3) to study the kinetically controlled distribution of RCbi + products resulting from the combination of R • radicals with cob(II)inamide produced the observation that the ratio of diastereomers obtained depended on the ratio of cob(II)inamide to hydroperoxide employed. This unexpected result led to the suspicion and subsequent confirmation that organic radicals could cause the interconversion of the diastereomeric RCbi + 's (eq 5) . We have now studied the effect of reagent ratio on RCbi + product distribution for the reaction of cob(II)inamide with CH 3 CH 2 C(CH 3 ) 2 OOH.…”

“…(H 2 O) 2 Cbi 2+ , (H 2 O) 2 -13-epiCbi 2+ , and (H 2 O) 2 Me 3 BzmCba 2+ were prepared by a previously reported method from the corresponding cyano aquo complexes , …”

“…Multiple samples of the reaction mixture were taken and analyzed by HPLC. The ratio of diastereomers was determined by multiple HPLC chromatogram peak integrations after correcting for differing molar absorptivities of each isomer at the HPLC monitoring wavelengths of 254 and 350 nm as described previously …”

“…Recently, we attempted to directly study the kinetic control of product diastereomerism in the combination of organic radicals with cob(II)inamide by use of the Fenton-like chemistry demonstrated by Espenson and Martin (eqs 1−3) In this reaction, rate-determining abstraction of a hydroxyl radical from an organic hydroperoxide of the type RC(CH 3 ) 2 OOH produces a hydroxocobalt(III) complex and the highly reactive RC(CH 3 ) 2 O • radical.…”