Nucleophilic catalysis, ring-opening

There is an important difference in the regiochemistry of ring opening reactions of epoxides depending on the reaction conditions Unsymmetncally substituted epoxides tend to react with anionic nucleophiles at the less hindered carbon of the ring Under conditions of acid catalysis however the more highly substituted carbon is attacked... 

As we ve just seen nucleophilic ring opening of ethylene oxide yields 2 substituted derivatives of ethanol Those reactions involved nucleophilic attack on the carbon of the ring under neutral or basic conditions Other nucleophilic ring openings of epoxides like wise give 2 substituted derivatives of ethanol but either involve an acid as a reactant or occur under conditions of acid catalysis... 

Nucleophilic Ring Opening. Opening of the ethyleneimine ring with acid catalysis can generally be accompHshed by the formation of an iatermediate ayiridinium salt, with subsequent nucleophilic substitution on the carbon atom which loses the amino group. In the foUowiag, R represents a Lewis acid, usually A = the nucleophile. 

When 6-diazopenicillanates are irradiated in the presence of sulfur nucleophiles, predominantly 6/3-substitution products are obtained (77JOC2224). When BFs-EtiO is used to catalyze the reaction with nucleophiles, however, the products are primarily the 6a-isomers (78TL995). The use of rhodium or copper catalysis led primarily to ring-opened thiazepine products, presumably by way of the intermediate (56 Scheme 39) (80CC798). 

Entries 6 to 11 are examples of nucleophilic ring opening. Each of these entries displays the expected preference for reaction at the less hindered carbon. Entries 8 and 9 involve metal ion catalysis. Entry 11, which involves carbon-carbon bond formation, was part of a synthesis of epothilone A. 

Acid catalysis assists epoxide ring opening by providing a better leaving group (an alcohol) at the carbon atom undergoing nucleophilic attack. 

The nature of antibody catalysis remains to be elucidated, and antibodies will not reach the efficiency of enzymes until they can emulate the conformational changes, acid/base, redox, and/or nucleophilic/electro-philic reactivities of catalytic residues along the entire reaction coordinate. It is worthy of note that Hollfelder et al recently demonstrated that serum albumins catalyze the eliminative ring-opening of a benzoisoxazole at rates that are similar to those observed with catalytic antibodies. They suggest that formal general base catalysis contributes only modestly to the efficiency of both systems, and they favor the view that the antibody catalysis may be enhanced in some cases by nonspecific medium effects. 

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