Modeling the selectivity in pericyclic reactions

Abstract

Pericyclic reactions are very powerful and widely utilized transformations to obtain complex molecules. The selective versions have received remarkable interest and have found extensive use in synthetic organic chemistry to access complex biologically active targets. In this work, the mechanistic details of some highly useful pericyclic reactions have been explored and the origins of the selectivity have been investigated. The first reaction of interest was the Diels−Alder reactions of -keto- , -unsaturated phosphonates with cyclopentadiene and 1,3-cyclohexadiene. The reaction constitutes an easy and straightforward method for the synthesis of dihydropyran derivatives, which are efficient substrates in the preparation of chiral building blocks. Second, diastereoselective cycloadditions of different chiral anthracene templates with maleic anhydride were explored. This reaction serves as the key element in determining the final stereochemistry of the product in the preparation of complex biologically active molecules such as butenolides, , -unsaturared lactams and related compounds in their enantiomerically pure forms. Finally, [3,3]- and [1,3]-sigmatropic rearrangements of allylic acetimidates have been studied. These reactions yield -amino acid and allyl amine derivatives that are important building blocks found in many bioactive molecules. In this work, bis-pericyclic, pseudopericyclic and stepwise pathways were shown to play a substantial role in determining the experimental observables such as the product distributions and the selectivity of the reaction, beside the widely accepted concerted pericyclic mechanism. The effect of catalysts on the mechanism and the selectivity have been studied and discussed in detail. The fundamental interactions in the key transition states have been analyzed and the factors affecting the stereoselectivity of the reaction have been elucidated. Comparative studies on highly selective and non selective variants have allowed us to identify the elements responsible for controlling the selectivity of the reactions of interest. This work brings a new perspective to the mechanism of pericyclic reactions and provides a deeper insight into the factors that determine the selectivity. However, the scope of the pericyclic reactions is very large and highly useful examples are not limited to the ones discussed in this dissertation. Future work will undoubtedly uncover many other important aspects of selective pericyclic reactions. Several suggestions for prospective studies have been outlined in the final chapter.