A theoretical study of stereoselectivity in the Diels-Alder reaction

Xidos, James Dimitrios (1999) A theoretical study of stereoselectivity in the Diels-Alder reaction. Doctoral (PhD) thesis, Memorial University of Newfoundland.

[English] PDF (Migrated (PDF/A Conversion) from original format: (application/pdf)) - Accepted Version Available under License - The author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission. Download (24MB) [English] PDF - Accepted Version Available under License - The author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission. (Original Version)

Abstract

The control of stereochemistry in chemical reactions is a primary concern for synthetic organic chemists. The Diels-Alder reaction often provides good yields of a single stereoisomer. However, the reasons for this stereoselectivity are not always obvious. -- The Diels-Alder reaction of 5-substituted-1,3-cyclopentadienes has been the focus of considerable debate. 1,3-Cyclopentadienes substituted at the C₅ position with OR, NRR′, and F yielded 100% syn addition products, while substitution with CH₃, SR and CI yielded mixtures of the products of syn and anti addition, and substitution with Si(CH₃)₃, Br, SePh and I yielded primarily anti addition products. Explanations in the literature for the preferential syn addition of some dienes usually involved electronic phenomena. -- The degree of facial selectivity for the Diels-Alder reactions of 5-substituted-l,3- cyclopentadienes with a variety of dienophiles can be predicted correctly at the ab initio HF/6-31 G(d) level. It has been determined that the energy required to deform the diene into its syn transition state geometry is the primary factor controlling facial selectivity in these reactions. This energy is related to the amount of angular change about C₅ of the diene in the syn transition state. Facial selectivity roughly correlates with empirical measures of the size of the C₅ substituent. -- The size of the bond between C₅ and its substituent (C₅-X bond) has been defined to be the second moment, evaluated at the centroid of charge of the C₅-X bond, of the localized molecular orbital which describes the C₅-X bond. This measure of size correlates with facial selectivity. The C₅-O, C₅-N and C₅-F bonds are predicted to be smaller than the C₅-H bond. -- A substituent factor has been defined by dividing the value of size by the distance between C₅ and the centroid of charge. The substituent factor correlates excellently with facial selectivity. Thus, facial selectivity can be fully accounted for based on steric arguments. An additional electrostatic repulsion has been shown to exist for syn addition of 1,3- cyclopentadienes substituted with halogen atoms, C≡N or C≡CH, with 1,2,4-triazoline-3,5- dione. -- Protonation of the C₅-substituent is predicted to stabilize the anti addition transition state, resulting in more anti addition product. Deprotonation of the C₅-substituent is predicted to stabilize the syn addition transition state, and to destabilize the anti addition transition state, thus increasing the proportion of syn addition product. -- The reaction of 3-substituted-1,2-cyclopropenes with 1,3-butadiene is predicted to yield, in most cases, mainly the product of endo-anti addition, with a lesser amount of the product of exo-anti addition. It is suggested that endo-syn and exo-syn additions are disfavoured due to steric hindrance between the diene and the C₃-substituent of the dienophile. The preference for endo-anti addition is primarily due to a favourable interaction between the methylene hydrogen of 3-substituted-1,2-cyclopropene and 1,3-butadiene. This interaction becomes less favourable as the electronegativity of the C₃-substituent increases. -- The substituent factor correlates well with both steric hindrance and electronegativity. It is transferable to other systems, and correlates with geometric trends.

Actions (login required)

View Item