Marckwald asymmetric synthesis

What is Marckwald asymmetric synthesis?

The Marckwald asymmetric synthesis, named after its discovery by Marckwald in 1904, is a method for synthesizing chiral L-valeric acid (α-methyl propanoic acid) from the pyrolysis of the brucine salt of racemic α-methyl-α-ethylmalonic acid. Sometimes referred to as the Marckwald method, this reaction involves the separation of a pair of diastereomers of the brucine salts through fractional crystallization, with the less soluble diastereomer being isolated.

Merckwald asymmetric synthesis - general reaction scheme -brucine - Marckwald method
Marckwald asymmetric synthesis

Upon pyrolysis of the crystalline salt at 170 ºC, the corresponding brucine salt of L-valeric acid is formed upon decarboxylation, resulting in a 10% enantiomeric excess.

Marckwald defined asymmetric synthesis as a reaction that produces optically active molecules from symmetrically constituted compounds with the use of optically active materials and exclusion of any analytical processes, such as resolution.

This method serves as a basis for many other preparations of chiral molecules, including tartaric acid. Under its influence, kinetic resolution and true asymmetric synthesis have been developed in modern organic synthesis.