Enantioselective Organocatalyzed Construction Of γ-Lactones

γ-Lactone ring system represents one of the most ubiquitous structural motifs found in many natural products. Accordingly, construction ofγ-lactone is one of the most fruitful research topics in synthetic organic chemistry all the time. The biological activities of many natural products depend on the absolute configuration and substituent group ofγ-lactone. Therefore, the development of methodologies for construction of diverse chiralγ-lactones is of great importance.Organocatalysis is one of the most rapidly growing and fruitful research areas in synthetic organic chemistry during the last decade. Complementing biocatalysis and metal catalysis, asymmetric organocatalysis covers a wide range of organic processes and methodologies, providing efficient and environmentally friendly access to enantiomerically pure compounds. Only very few reports on the construction of chiralγ-lactone through direct or indirect methods could, however, be found in the literature. In terms of organocatalyzed construction ofγ-lactone, the examples are even rarer.We have been trying to construct the chiralγ-lactones via organocatalysis. In ChapterⅢ, we report an asymmetric organocatalyzed vinylogous Mukaiyama aldol (VMA) reaction of 2-(trimethylsilyloxy)furan (TMSOF) and aldehydes, which gives the desired products with high enantioselectivities and anti-selectivities. This is the first example of asymmetric VMA reactions of TMSOF and aldehydes catalyzed by bifunctional alkaloid thiourea organocatalysts. A wide range of chiralγ-butenolides could be obtained in good yields (up to 90%) and high enantioselectivities (up to 91% ee) under mild conditions.In ChapterⅣ, we tried to apply organocatalyzed Mannich and Michael reactions to construct the chiralγ-lactones and to settle the limitation of substrates. Although the results obtained were not satisfactory, the attempts may still be quotable experiences.In ChapterⅤ, we start out to utilize more simple and inexpensive reactants rather than TMSOF. We report the organocatalyzed Aldol-Lactonization-Michael reaction of ethyl pyruvate and nitroalkenes. Highly enantioselective (up to 99% ee)γ-butenolides with two chiral centers were obtained in one pot reaction, which is more economic and efficient.