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

Abstract

The isomerization of 1,2-epoxycyclopentane (1) to enantiomerically enriched (R)-cyclopent-2-enol (2) in protic solvents is catalyzed by coh(1)abdmin. The enantiomeric excess (e.e.) of (R)-2 is usually ca. 60%; it is only slightly dependent on the temperature, hut increases with decreasing dielectric constant E of the solvent. Standard kinetic methods show the reaction to be first order in vitamin B,, and zero order in 1. The rate constant increases exponentially with increasing E of the solvent. An Arrhenius plot at E = 40 gives activation parameters A H f = 78 + 4 kJ.mol-I and A S f = -49 ! C 1 J.mo1-I.K-l. 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' catalyst to form diastereoisomeric (1 R,2R)-and (lS,2S)-(2-hydroxycyclopentyl)cob(III)alamins 6 in a ratio of ca. 4:l 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-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" takes place.

Asymmetric Catalysis by Vitamin B12: The Isomerization of Achiral Aziridines to Optically Active Allylic Amines

“…GC: 97% purity. IR (film): 3250s,3000s, 2930s, 2850s, 1440s, 1245m, 1140m, (27), 58 (30), 57 (IOO), 56 (1 I), 55 (13), 42 (24), 41 (39), 29 (9), 18 (6).…”

“…194O) for 22 h. The brown soh. was then extracted with Et20 (4 x 80 ml), the combined Et20 phase washed with brine (2 x 20 ml), dried (MgS04), and evaporated, and the residue crystallized 2 x from benzene/petroleum ether 1 : 1 : 2.58 g ( 30 % (5),93 (3), 82 (27), 80 (6), 79 (7) To the red soln. of OH-Cbl'HCI (0.130 g, 0.09 mmol), Et3N (0.20 g, 2.00 mmol), and MeOH (15 ml) was added at O0 activated Zn powder (1.5 g) under Ar.…”

“…Ion-exchange chromatography afforded 9 ((R)) in 75% yield; its [a] Mechanism of Isomerization. Even without having detailed information about kinetics, thermodynamics, or the structure of intermediates of the isornerization 1+2, it is believed, that the reaction mechanism is generally the same as that described for the Cbl-catalyzed isomerization of epoxides to allylic alcohols [27]. However, there are two remarkable differences: i ) there is no increase in the ee of 2e in lowering the polarity of the solvent (Cf Table I , Entries 2 and I U ) , ii) the colour of the reacting mixture is not orange-red (colour of alkylcob(II1)alamins) but dark brown-grey ; the UVjVIS spectrum of the mixture during the whole reaction is dominated by the sharp absorption signal at ca.…”

Desymmetrization and Kinetic Resolution of Anhydrides; Desymmetrization of meso ‐Epoxides and other Prochiral Substrates

“…The catalytic isomerization of meso-epoxides to allylic alcohols has been achieved with chiral cobalt complexes, in particular with cobalamin (vitamin B 12 ) [47,48]. Preparatively more relevant is the use of chiral lithium amide bases, which have been successfully used both for enantioselective generation of allylic alcohols from meso-epoxides and for the related kinetic resolution of racemic epoxides [49,50].…”

Vitamin B12

“…The rearrangement of aziridines can proceed catalytically with ee's of up to 95% (eq 9). 38 Analogous rearrangements on achiral epoxides (typically 60% ee) 39 and achiral peroxides (low ee's) 40 …”