Proline organocatalysis is the use of proline as an organocatalyst in organic chemistry.
Contents
Some proline-catalyzed Michael reactions initially provided poor enantioselectivity. Newer modifications, such as MacMillan’s catalyst and Jorgensen's catalysts, improved the stereocontrol.
Background
Proline catalysis was initially reported by two groups at Schering AG and Hoffmann-La Roche. Proline's chiral structure enables enantioselective synthesis, favoring a particular enantiomer or diastereomer.
Reactions
Proline catalysis has been reviewed.
In the Hajos–Parrish–Eder–Sauer–Wiechert reaction, proline catalyses an asymmetric aldol reaction. The zwitterionic character and the H-bonding of proline in the transition state plays an important role in explaining the reaction outcome. An enamine transition state is formed during the reaction and only one proline molecule is involved in forming the transition state.
Asymmetric synthesis of the Wieland-Miescher ketone is also based on proline. Additional reactions include aldol reactions, Mannich reaction, Michael reaction, amination, α-oxyamination, and α-halogenation.
MacMillan’s and Jorgensen’s groups introduced modifications on the basic proline structure, achieving more enantioselective and regioselective catalysts. These proline-derived auxiliaries and catalysts, including the Enders hydrazone reaction and Corey–Itsuno reduction, have been reviewed, as have MacMillan’s iminium catalysts, Miller catalysts, and CBS-oxazaborolidines.