New perspectives of vinylogy. Eco-friendly and organocatalytic methods for the selective synthesis of highly diversified molecular scaffolds

Abstract

Since its first conceptualization by R. C. Fuson in 1935, the vinylogy principle has been increasingly attracted the curiosity of organic chemists while challenging their abilities. The design and development of new synthetic methodologies based on the application of this principle experienced an exponential growth in the last few years, especially when this topic was connected to other emerging fields such as stereocontrolled synthetic methods and enantioselective catalysis. Thus, about 80 years later, I am presenting a summary of the work I did during my PhD studies, which covered the period 2010-2013, whose central theme is based on the application of the vinylogy principle toward new synthetic methods. Different strategies were explored, in order to promote novel vinylogous transformations. In the first part of the work, the use of water, as an eco-friendly reaction medium as well as reaction promoter, was successfully investigated, with the development of the first vinylogous Mukaiyama Michael and Mannich reactions. The synthetic potential of the disclosed methods were highlighted by the total synthesis of highly functionalized pyrroles and a stereoisomer of oseltamivir. Further evolution of these concepts culminated with the development of unprecedented organocatalyzed reactivity patterns, involving the use of newly designed vinylogous azlacatones or butyrolactones in enantioselective Michael addition reactions to alfa, beta-unsaturated (or alfa, beta, gamma, delta-unsaturated) aldehydes, including a very first example of doubly vinylogous transformation (vinylogous 1,6-addition). Phenylogous reactions were also investigated through enantioselective organocatalytic methods. Finally, in the last part of this thesis, a still on-going project is presented, focusing on the development of unprecedented regio-divergent vinylogous carbon-carbon bond-forming reactions towards multifunctional carbocycles. Part of the work herein presented was developed during my fruitful visiting period at the Aarhus University (DK), under the supervision of Prof. K. A. Jørgensen (Chapters VI and VII). The remaining part of the work was developed at the Parma University (I), (Chapters II, III, IV and VIII) under the supervision of Prof. F. Zanardi. During my research activity, I have been working with many talented and enthusiastic chemists. I want to highlight that, without their help, their teachings, the discussions, the laughter and deep friendship, the development of my work would have been impossible.