Activating Oxygen as a Leaving Group

Neutral alcohols, ROH, and ethers, ROR, do not undergo either substitution or elimination reactions, presumably because OH (OR ) is a poor leaving group. Acids can activate OH (OR) by converting it into a better leaving group. 

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The triphenylphosphine combines with DEAD to generate a phosphonium intermediate that binds to the alcohol oxygen, activating it as a leaving group. Substitution by the carboxylate, mercaptyl, or other nucleophile completes the process. 

The serine oxygen acts as a leaving group, generating the free carboxylic acid, which diffuses from the active site. The enzyme is now ready for another catalytic cycle. 

The activation of DMSO toward the addition step can be accomplished by other electrophiles. All of these reagents are believed to form a sulfoxonium species by electrophilic attack at the sulfoxide oxygen. The addition of the alcohol and the departure of the sulfoxide oxygen as part of a leaving group generates an intermediate comparable to C in the carbodiimide mechanism. 

There are many transferases catalysing the transfer of a 5-phosphoribosyl group from 5 -ribosyl pyrophosphate to nitrogen, but detailed mechanistic studies are not available. All such enzymes, however, are activated by divalent cations such as Mg ", which coordinates to the pyrophosphate oxygens and increases leaving group ability. 

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