6.4 C–C Bond Formation: Aldol Reaction with Proline Derivatives

Abstract

The aldol reaction, which was discovered by Kane in 1838, is one of the most fundamental reactions in synthetic organic chemistry. In addition, it is also an essential biological process involved in glycolysis, gluconeogenesis, and the Calvin cycle. Near the end of the twentieth century, small metal-free organic molecules renewed attention as aldolase-type organocatalysts. Organocatalytic asymmetric direct aldol reactions of carbonyl compounds have become highly advantageous in modern synthetic organic chemistry, especially in generating chiral building blocks that previously have not been easily available by traditional methods. Research in this area has advanced rapidly over the past decade. This chapter addresses significant achievements in asymmetric synthesis focusing on organocatalytic direct aldol reactions over two chapters. Aldol reactions catalyzed by proline and related amino acid derivatives are reviewed in this chapter, and reactions catalyzed by nonproline derivatives are reviewed in Chapter 6.5.