Development of Novel Threonine Derived Chiral Phosphines and Their Applications in Morita-Baylis-Hillman Reaction and Enantioselective [3+2] Cycloadditions

Abstract

The phosphine-triggered organic transformations have become a practical and powerful tool in organic chemistry. The unique reactivity of organophosphines, compared to their amine counterparts, has led to the discovery of a variety of novel reactions. This thesis describes the development of novel threonine-derived phosphine organocatalysts and their applications in Morita-Baylis-Hillman reaction and enantioselective [3+2] cycloadditions. Chapter 1 presented a brief introduction of nucleophilic phosphine catalysis and a series of phosphine-promoted enantioselective organic reactions. Selected examples illustrating recent advances in this research field were also presented. In Chapter 2, a highly enantioselective Morita-Baylis-Hillman (MBH) reaction of acrylates with aromatic aldehydes using L-threonine-derived bifunctional phosphine thiourea catalysts was described. The mechanistic aspects of the reaction were also discussed. In Chapter 3, the development of a new family of dipeptide-based chiral phosphines was presented. Such catalysts were applied to the asymmetric [3+2] cycloaddition of allenoates to a-substituted acrylates, yielding functionalized cyclopentenes with quaternary stereogenic centers in high yields and with excellent enantioselectivities. In Chapter 4, acrylamides derived from 3,5-dimethyl-1H-pyrazole were utilized in the asymmetric [3+2] cycloaddition with the allenoate catalyzed by dipeptide-derived phosphines. In Chapter 5, a highly enantioselective [3+2] annulation of aliphatic or aromatic imines with allenoates was realized by employing threonine-based dipeptidic phosphines as catalysts. Highly enantioselective 2-alkyl/aryl-substituted 3-pyrrolines could be generated in short reaction times and with low catalyst loadings. Moreover, synthetic value of this method was demonstrated by using imine?allene annulation as a key step in a concise formal synthesis of (+)-trachelanthamidine.