Electron Pushing for a Few Nucleophilic Additions

Classic electron pushing for a Grignard addition to a ketone. 

The epoxide functional group is often an intermediate in organic synthesis sequences because it can be readily opened by a variety of nucleophiles, leading to complex functionalization that starts with just an alkene. Asymmetric variants of epoxidation are important reactions, with the Sharpless and Jacobsen epoxidations being the most well known. Both these reactions involve metal catalysts. 

The Sharpless epoxidation involves a dimeric tita-nium(IV) species with bridging tartrate ligands (A). The tartrates impart a chiral environment to the catalyst centers, leading to asymmetric induction. The dimeric species shown below, involving several alkoxide ligands, has been shown via an NMR study to be the active form 

The Jacobsen epoxidation reaction uses an Mn-salen complex (B). The mechanism has been examined using many of the tools presented in Chapters 7 and 8. Two pathways have been proposed. Path A is a radical pathway and Path B involves a metallaoxetane. Path A is supported by several pieces of data. First, the reaction is enhanced by the addition of N-oxides, which supports the replacement of the chloride by these ligands and subsequent activation of the metal. A metallooxetane (Path B) would be extremely crowded at the metal center with a coordinated 

N-oxide. Recent computational studies find the metallooxetane structure to be too high in energy to be a reasonable intermediate. In homogeneous solution linear Erying plots are found for styrene, indene, and cyclooctadiene. This supports Path A and argues against a mechanism with an equilibrium formation of a metallooxetane prior to rate-determining epoxide formation (as in Path B). 

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