Steglich rearrangement

What is Steglich rearrangement?

In 1968, Steglich and Höfle reported a nucleophilic organic molecule-catalyzed transformation of 5-carboxyl oxazole derivatives. This transformation results in the formation of a new carbon-carbon bond and a new quaternary stereocenter, along with the corresponding 4- or 2-carboxyl azlactones. This reaction is commonly known as the Steglich rearrangement.

Steglich rearrangement - general reaction scheme
Steglich rearrangement

The resulting carboxyl azlactones have been used to produce α,α-disubstituted α-amino acid derivatives and α-alkylated α-amino acids, but the regioselectivity of this transformation depends on the steric and electronic properties of the substituents at the 2- and 4-positions.

Furthermore, the carboxyl azlactones can be transformed into dipeptides by treatment with an amino ester and α-alkyl substituted serine derivatives when reduced by NaBH4. The carboxyl azlactones can also be converted into corresponding α-amino esters under conditions controlled by dynamic kinetic resolution, in which the azlactones with a smaller alcoholic moiety proceed faster but with lower enantioselectivity.