THE ORBITAL INTERACTION COMPONENT OF CONFORMATIONAL EFFECTS Ronald Y.N. Leung B.Sc., University of Ulster, 1982. THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in the Department of Chemistry @ Ronald Y.N. Leung 1991 SIMON FRASER UNIVERSITY February 1991 All rights reserved. This work may not be reproduced in whole or in part, by photocopy or other means, without permission of the author. APPROVAL Name: Ronald Y. N. Leung Degree: Doctor of Philosophy Title of thesis: The Orbital Interaction Component of Conformational Effects Examining Committee: Chairman : Dr. P. W. Percival Dr. B. M. pinto Senior Supervisor Dr. Y. L. &h&\ Committee Member Dr. A. S. Tracey Committee Member Dr.'s. Wolfe Internal Examiner Dr. A. Rauk External Examiner Department of Chemistry University of Calgary Date of Approval: WQ~15 , 71 PARTIAL COPYRIGHT LICENSE I hereby grant to Simon Fraser University the right to lend my thesis, proJect or extended essay (the title of which is shown below) to users of the Simon Fraser University Library, and to make partial or single copies only for such users or in response to a request from the library of any other university, or other educational Institution, on its own behalf or for one of Its users. I further agree that permission for multiple copying of this work for scholarly purposes may be granted by me or the Dean of Graduate Studies. It is understood that copying or publlcatlon of this work for financial gain shal I not be a1 lowed without my written permission. Title of Thes i s/Project/Extended Essay d IHE OR~IT&L INTERACT~ON COW pofd~NT OF Author: Q.ao, 9) (date) ABSTRACT A combination of experimental and computational approaches has provided details for the analysis of the steric, electrostatic and orbital interaction components of conformational effects operating in substituted heterocycles containing the 0-C-N, S-C-N, 0-C-0, S-C-0, 0-C-C-N, S-C-C-N, 0-C-C-0 and S-C-C-0 fragments. The orbital interactions in these heterocycles have been interpreted in terms of the interplay of the endo- and exo-anomeric gauche interactions and the attractive and repulsive ethane-type gauche interactions. Ab initio molecular orbital calculations of acyclic molecules containing N-C-0 fragments have been used for the parameterization of the MM2(85) force field. The geometric and energetic behaviour of a number of acyclic and heterocyclic molecules containing N-C-0 anomeric fragments are reasonably well reproduced with the parameterized force field. An ab initio MO study, with the MINI-l* and 3-21~*basis sets, of HXCH2YH (X,Y=S,Se,Te) molecules has been used to probe the existence of anomeric interactions involving second, third and fourth row heteroatoms. Bond length and bond angle trends in different conformations, the relative energies of conformers, and the methyl stabilization energies obtained in isodesmic reactions suggest that anomeric effects exist in these systems. Analysis of the results of semi-empirical MO (MNDO) and molecular mechanics calculations of a series of CHZ=CH-CH~X molecules (X=H, CH3, OCH3, OCOCH3, OH, F, C1) and the ab initio MO (3-21G) calculations of the molecules (X=H, OH, F, C1) indicate that the orbital interaction component is significant. Quantitative PMO analysis of the ab initio results for the molecules in which X=F,Cl has shown that the conformational preferences are dominated by the destabilizing orbital interactions and the unfavourable electrostatic interactions in gauche conformations. The geometrical preferences and the rotational barriers in sterically hindered diselenides and ditellurides have been probed by dynamic NMR measurements. Semiempirical MO (MNDO) calculations of model compounds are also described. The results are discussed in terms of steric factors and orbital interaction components. ACKNOWLEDGEMENTS The years I spent at Simon Fraser University have certainly been worthwhile. My senior supervisor, Professor B. M. Pinto has demonstrated his patience and dedication to help me throughout my study. His demand for excellence has set a good example for me to follow, not only in scientific research, but in life as a whole. I would also like to show my appreciation to all the other teachers who have taught me in the various aspects of Chemistry. I am grateful to Dr. B. D. Johnston for his assistance in the synthesis of one of the thiacyclohexanes required for the NMR studies and to Dr. J. Korppi-Tommola for his assistance in the MINI-l* basis set implementation. I am grateful to Professor S. Wolfe for his valuable instruction in the use of ab initio MO methods and for the hospitality shown to me while in his laboratory at Queen's University. I also thank him for the quantitative PMO analysis of ally1 chloride and fluoride. Finally, I thank my wife and my parents for their wholehearted support and patience. TABLE OF CONTENTS Approval ...................................................ii Abstract ..................................................iii Acknowledgements ............................................v Table of Contents ..........................................vi List of Tables .............................................ix List of Figures .......................................... xiv 1 . ~ntroduction .............................................1 1.1 Anomeric effect ......................................2 1.2 Exo-anomeric effect ................................. 18 1.3 Reverse anomeric effect .............................24 1.4 Second and lower row anomeric effect ................31 1.5 Solvent effect ...................................... 38 1.6 Enthalpic anomeric effect ........................... 40 1.7 Attractive and repulsive gauche effect ..............43 1.8 Overview of thesis ..................................61 2 . Experimental ............................................64 2.1 General information .................................64 I . Synthesis and NMR analysis .....................64 I1 . Determination of thermodynamic and kinetic data.66 i . Direct determination of equilibrium constants ....................... 66 ii.Kinetic parameters from line shape analysis .............................. 67 I11 . Molecular mechanics calculations ............... 68 IV . Ab initio calculations ........................69 V . Semi-empirical MO calculations .................70 2.2 synthesis ........................................... 70 I . Synthetic schemes ..............................70 I1 . General description of syntheses ...............82 I11 . Procedures .....................................86 3 . The study of attractive and repulsive gauche effects ..133 3.1 Introduction ......................................133 3.2 Results ...........................................136 I . 5.Substituted.l. 3.diheterocyclohexanes ........136 i . NMR analysis ............................... 136 ii.Conformationa1 analysis .................... 141 I1 . 2.Substituted.1, 4.diheterocyclohexanes ........147 i . NMR analysis ...............................147 ii.Conformationa1 analysis ....................151 3.3 Discussion ........................................ 155 I . Solvent effects on the conformational equilibria of 5.substituted.l. 3~dioxacyclohexanes ........155 I1 . Anomeric effect ...............................163 iv . 2-Methylaminothiacyclohexane ...............168 1II.Ethane.type gauche interactions ............... 171 IV . 2- or 3.Substituted.1, 4.diheterocyclohexanes ..185 V . Additivity of effects ? ....................... 193 vii 4 . Parameterization of the MM2 force field for the 0-C-N system ................................................196 4.1 Introduction ......................................196 4.2 Development of the force field ....................198 I . Ab initio calculations ........................203 I1 . Development of anomeric bond length parameters 207 1II.Development of bond angle parameters ..........208 IV . Development of torsional parameters ...........209 5 . Theoretical investigation of anomeric systems containing second and lower row heteroatoms ...........218 6 . Theoretical investigation of the allylic anomeric effect ................................................252 6.1 Introduction ......................................252 6.2 Results and Discussion ............................259 7 . Rotational barriers in sterically hindered dichalcogenides .......................................275 7.1 Introduction ......................................275 7.2 Compounds .........................................280 7.3 Results ........................................... 281 7.4 isc cuss ion ........................................ 285 I . Interactions in the ground state ..............286 I1 . Interactions in the transition state ..........289 1II.Effects on the rotational barriers ............290 7.5 Theoretical investigation of the rotational barriers in model dichalcogenides .......................... 292 References ................................................ 302 LIST OF TABLES Table Page Low-temperature 13c NMR chemical shift data for 5-substituted-1,3-dioxacyclohexanes ..................138 13c NMR chemical shift data (6, and 6,) of C-5 for compounds 6-11 at 298 K .............................. 138 13c NMR chemical shift data (6, and 6,) of C-4 and C-6 for compounds 6-11 at 298 K ..........................139 Low-temperature 13c NMR chemical shift data of cis-2-methyl-5-methoxy-1,3-dithiacyclohexane and 5-methylamino-1,3-dithiacyclohexanes .................140 13c NMR chemical shift data