Fráter–Seebach alkylation
In organic chemistry, the Fráter–Seebach alkylation is a diastereoselective alkylation of chiral beta-hydroxy esters using strong bases. The reaction was first published by Georg Fráter in 1979; in 1980, Dieter Seebach reported about a similar reaction with malic acid ester.Chiral beta-hydroxy esters can be treated with two equivalents of a strong base or lithium bisamide to both remove the proton on the alcohol and enolize the ester.
An alkylating agent is then added. This attacks from the opposite face of the chiral hydroxyl group to avoid steric hindrance as shown below in the 6-membered transition state with chelating metal ions.
This reaction has since been used in the synthesis of many natural products due to its high yield and diastereoselectivity.
