Frans-Epoxides

While generation of a Mn(V)oxo salen intermediate 8 as the active chiral oxidant is widely accepted, how the subsequent C-C bond forming events occur is the subject of some debate. The observation of frans-epoxide products from cw-olefins, as well as the observation that conjugated olefins work best support a stepwise intermediate in which a conjugated radical or cation intermediate is generated. The radical intermediate 9 is most favored based on better Hammett correlations obtained with o vs. o . " In addition, it was recently demonstrated that ring opening of vinyl cyclopropane substrates produced products that can only be derived from radical intermediates and not cationic intermediates. ... 

The transfer of oxygen to alkene may occur by several different mechanisms (Scheme 1.15). Oxygen radicals may be formed as intermediates when radical stabilizing groups are attached. This mechanism is supported by the fact that czs-alkene gives both cis- and frans-epoxide. The formation of the metallaoxetane as an intermediate is also proposed by Norrby et alP However, concerted oxygen delivery has also been proposed. 

Compelling evidence for stepwise C-O bond formation in [Mn(salen)] -catalyzed epoxidation is found in the formation of both cis- and trans-epoxides as primary products from acyclic ds-olefins [68]. The extent of frans-epoxide formation depends strongly on the nature of the substrate. Whereas simple alkyl-substituted ds-olefins are epoxidized stereospecifically, aryl-substituted cis-olefins afford mixtures of cis- and trans-epoxides with the ds-isomers being formed selectively. Epoxidations of conjugated dienes and enynes also afford cis/trans mixtures, with the frans-epoxide product predominating. These observations may be interpreted according to a stepwise mechanism in which a discrete radical intermediate undergoes competitive collapse to ds-epoxide and rotation/collapse to frans-epoxide (Scheme 4). 

In fact, the chemists working on these compounds wanted only one enantiomer of the tmns epoxide— the top left stereoisomer. They were able to separate the frans epoxide from the as epoxide by chromatography, because they are diastereoisomers. However, because they had made both diastereoisomers in the laboratory from achiral starting materials, both diastereoisomers were racemic mixtures of the two enantiomers. Separating the top enantiomer of the trans epoxide from the bottom one was much harder because enantiomers have identical physical and chemical properties. To get just the enantiomer they wanted the chemists had to develop some completely different chemistry, using enantioinerically pure compounds derived from nature. 

Reaction of a,fi-epoxysilanes with organocuprates. Hudrlik et al have shown that the reaction of di-n-propylcopperlithium with a, 3-epoxysilanes is both regio- and stereospecific. Thus the cii-epoxide (1) is converted into the erythro-alc6ho (2), whereas the frans-epoxide (3) is converted into the threo-alcohol (4). ... 

Epoxide Ring Opening. One-pot alkylation-O-silylation reactions of epoxides take place in excellent yields when the epoxides are treated with trialkylaluminum-TMSOTf and EtsN (1.5 equiv of each one) in methylene chloride at —50 °C (eq 92). Other trialkylsilyl triflates also undergo this reaction, which is stereospecific awft -compounds are obtained from fran -epoxides while cis-epoxides yield 5yn-adducts. ... 

Example 5.13 Preparation of enantiomerically pure fran -epoxides 4a-4e is completed by non-catalytic asymmetric epoxidation and the addition of chiral sulfonium yUde 2 to the C=0 bond of aromatic aldehydes (Scheme 5.30) [7]. 

Z, Ph-CH2-0-C(0)C0- Aleii, aza-Leii EP, epoxide Et. etliyl. The frans epoxide is a mixture of S.Sand R.R. wliilethe c s epoxide is a mixture of R.S and S.R. n/a, not applicable. ACso(l) represents tlie concentration of InsPe required to activate half-maxima I c leavage of tlie C PD in the presence of 10 pM of inhibitor. Since the extent of inhibition depends on the concentration of InsPfi in the assay, the higlierthe ACgod) value, the better the inhibitor. ACgod) values were detennined from triplicate experiments ( s.d.). 

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