Cinchona‐Catalyzed Cycloaddition Reactions

Abstract

Asymmetric pericyclic reaction represents one of the most straightforward protocols to access enantioenriched cyclic compounds and triggers continuing interest in organic synthesis. Fruitful results have been achieved by the catalysis of chiral metal complexes over the past decades [1]. On the other hand, recently small organic molecules have also contributed a lot to this area owing to the rapid development of asymmetric organocatalysis [2].Cinchona alkaloids are readily available natural chiral compounds and have a long history to be utilized as organocatalysts in asymmetric catalysis [3,4]. They are multifunctional, tunable, and more importantly, they could promote a diversity of reactions through different catalytic mechanisms, which make them privileged catalysts in organocatalysis. In this chapter, the applications of cinchona alkaloids and their derivatives for asymmetric cycloaddition reactions after 2000, especially for the construction of a variety of five-and six-membered cyclic compounds, are discussed. Asymmetric Cycloadditions Catalyzed by Quinuclidine Tertiary AmineCinchona alkaloids possess a nucleophilic quinuclidine structure and can perform as versatile Lewis bases to react with ketenes generated in situ from acyl halides in the presence of an acid scavenger. The resulting ketene enolates can react with electrophilic C¼O or C¼N bonds to deliver chiral b-lactones [5] or b-lactams [6], respectively, in a [2 þ 2] cycloaddition manner, which is discussed in Chapter 5 in detail. Gaunt et al. also developed practical one pot cyclopropanation processes mediated by the modified cinchona alkaloids via ammonium ylide intermediates [7]. Although the catalytic strategy has been well established, the utilization of ammonium enolate based [4 þ 2] cycloaddition is rare probably because of the relative unreactivity of the Cinchona Alkaloids in Synthesis and Catalysis, Ligands, Immobilization and Organocatalysis Edited by Choong Eui Song