10.1 Chiral Proline Based Reactions

Enantioselective organocatalysis has emerged as a powerful synthetic method complementary to the metal- and enzyme-catalyzed reactions. The low toxicity associated with organocatalysis and operational simplicity makes it an attractive method to synthesize complex structures. Among the organocatalysts, small molecules like chiral proline, chiral thiourea, chiral TADDOL and chiral alkaloids have special reactivity in the asymmetric synthesis.

Chiral proline is termed as the simplest bifunctional organocatalysts (Scheme 1). This amino acid is called as “simplest enzyme” due to its ability to catalyze reactions with high stereoselectivity.

Scheme 1. Forms of Proline Available

L-Proline is a small molecule, non-toxic, inexpensive, readily available in both enantiomeric forms having bifunctional acid-base sites (Scheme 2). The reaction may proceed through either iminium catalysis, or enamine catalysis or bifunctional acid–base catalysis.

Scheme 2. Reactivity Modes of L-Proline