The poor leaving group of alcohols can be overcome by converting the hydroxyl group to a tosylate ester, an excellent leaving group. The tosylate ester undergoes subsequent reactions (typically SN1 or SN2) as part of a multiple step synthesis.
The synthesis of carboxylate esters (the other ester) is commonly the final step of a synthetic pathway.
Tosylate Ester Formation
We can transform an alcohol group into a sulfonic ester using para-toluene sulfonyl chloride (Ts-Cl) or methanesulfonyl chloride (Ms-Cl), creating what is termed an organic tosylate or mesylate:
Notice that unlike the halogenation reactions of alcohols with thionyl chloride or phosphorous tribromide, conversion of an alcohol to a tosylate or mesylate proceeds with retention of configuration at the electrophilic carbon.
Tosylate/mesylate groups are excellent leaving groups in nucleophilic substitution reactions, due to resonance delocalization of the developing negative charge on the leaving oxygen.
The laboratory synthesis of isopentenyl diphosphate - the 'building block' molecule used by nature for the construction of isoprenoid molecules such as cholesterol and b-carotene - was accomplished by first converting the alcohol into an organic tosylate (step 1), then displacing the tosylate group with an inorganic pyrophosphate nucleophile (step 2) (J. Org. Chem 1986, 51, 4768).
The major reactive species of tosylate chemistry are summarized below.
4. Predict the structures of A and B in the following reaction.
Conversion of Alcohols into Esters
Acid chlorides react with alcohols to form esters
5. Predict the products or specify the reagents for the following reactions.
Contributors and Attributions
Prof. Steven Farmer (Sonoma State University)