Nazarov cyclization of fully substituted dienones : catalytic diastereospecific and enantioselective construction of vicinal all-carbon atom quaternary stereocenters

by Anais Jolit

Institution: University of Hawaii – Manoa
Year: 2015
Keywords: organic synthesis; orbital symmetry controlled process
Posted: 02/05/2017
Record ID: 2120403
Full text PDF: http://hdl.handle.net/10125/100339


Ph.D. University of Hawaii at Manoa 2014. Vicinal all-carbon atom quaternary stereocenters are found in many complex natural products. However the direct construction of such motifs remains a difficult challenge in organic synthesis. Only a few methods for catalytic asymmetric synthesis that have been reported recently address this synthetic problem. One new approach is to take advantage of an orbital symmetry controlled process. The Nazarov reaction is a 4π electrocyclization that has the potential to form two vicinal quaternary centers within a five-membered ring with good diastereocontrol in one step. This thesis describes the development of the first catalytic enantio-and diastereospecific Nazarov cyclization of fully substituted dienones to form vicinal all-carbon atom quaternary stereocenters. Chapter 1 will introduce the Nazarov cyclization. Presentation of the reaction mechanism will be followed by a discussion that emphasizes the influence of substituents of the dienones on the outcome of the cyclization. Recent advances in the field will be reviewed and will mainly focus on the development of new catalytic and asymmetric Nazarov cyclizations. Chapter 2 describes the first catalytic diastereospecific Nazarov cyclization of fully substituted dienones that generate vicinal all-carbon atom quaternary centers. The discussion will describe the careful design of the Nazarov substrate and the selection of reaction conditions. The scope and limitations of the methodology will also be presented. The α-hydroxycyclopentenones that can be prepared by means of the method described in Chapter 2 bear two contiguous quaternary carbons within a five-membered ring. Such compressed systems are in general very difficult to modify. We were able to carry out a number of diastereo-and regiospecific transformations of these cyclic products. This work will be presented in Chapter 3. In Chapter 4, we describe the first organocatalytic asymmetric Nazarov cyclization of fully substituted dienones using a BINOL-derived N-triflylphosphoramide catalyst. The substrate and catalyst have been carefully designed leading to the formation of the cyclopentenone products having vicinal all-carbon atom quaternary stereocenters in high optical purity and as single diastereoisomers. A variety of dienones were able to undergo asymmetric cyclization and will be discussed in the scope and limitations of the reaction.