Mechanistic Understanding of Proline Analogs and Related Protic Lewis Bases (n - π*)

Proline has played a pivotal role in the development of the field of organocatalysis and is regarded by many as the archetypal organocatalyst. Indeed, proline has been known as a catalyst of the intramolecular aldol reaction since the 1970s, in what was originally thought to be a solitary example of novel reactivity. A mechanistic understanding of proline catalysis has the potential to allow the design of improved catalysts and reaction conditions. The chapter discusses the mechanism of the proline-catalyzed aldol reaction, including the Hajos-Parrish-Eder-Sauer-Wiechert (HPESW) reaction, the Houk-List model, the Seebach-Eschenmoser Model. It also discusses the proline-catalyzed α-amination and α-aminoxylation reactions. Proline-mediated conjugate addition reactions, in which the nucleophile is the carbonyl α-carbon, were first reported in 2001. Then, the chapter explains the modified proline derivatives including proline tetrazole, and the Houk-List model and proline analogs.