Chemical consequences of long-range orbital interactions in Perhydronaphtalene-1,4-diol monosulfonate esters

R.V.A. Orru

Research output: Thesisinternal PhD, WU


<p>In this thesis the base-induced reactions of perhydronaphthalene-1,4-diol monosulfonate esters are described. These compounds undergo smoothly, typical carbocationic processes upon treatment with sodium <em>tert</em> -amylate in refluxing benzene. The product outcome, product ratio, and (relative) rate of these reactions is satisfactorily explained when through-bond orbital interactions (TBI) over four abonds are invoked. In order to gather more detailed information about the basic stereochemical and stereoelectronic principles underlying these processes, synthetical organic, computational, and kinetic investigations were undertaken.<p>Most experimental studies on TBI have focussed on its spectroscopic manifestations and are reviewed repeatedly. On the other hand, there are relatively few reviews on the chemical consequences of TBI over three or more σ-bonds. A number of illustrative examples of chemical reactions in which long-range orbital interactions are believed to play an essential role are discussed in chapter 1. In the same chapter also attention is drawn to the synthetic utility of some of these reactions.<p>In chapter 2 the syntheses of the mesylates <strong>39</strong> , <strong>40</strong> , and <strong>58-67</strong> are described. The compounds <strong>39</strong> , <strong>40</strong> , <strong>58</strong> , and <strong>59</strong> are prepared in order to investigate how the orientation of the sulfonate ester group in combination with the orientation of the tertiary hydroxyl group determines the outcome and rate of their reactions with sodium <em>tert</em> -amylate. The results of these investigations are described in chapter 3. It was found that an equatorial sulfonate ester group favors homofragmentation leading to the cyclopropane derivative <strong>105</strong> . In case of an axial sulfonate ester group β-elimination, which strongly depends on the stereochemistry of the tertiary deprotonated hydroxyl group, is the main reaction path. In the chapter 3 the synthesis of the O-silylated mesylates <strong>106</strong> and <strong>107</strong> is also described. These compounds show no reaction at all upon treatment with strong base. On the other hand, fast reactions are observed when <strong>106</strong> and <strong>107</strong> are treated with TBAF. Generation of an alcoholate is crucial for the observed reactions. Homofragmentation and an internal return reaction with inversion of configuration of the mesylate group in the axial mesylates <strong>39</strong> and <strong>58</strong> is explained by assuming a 1,3-bridged intermediate carbocation.<p>The mesylates <strong>60-65</strong> are prepared (Chapter 2) to determine the influence of the geometry of the relaying σ-bonds on the reactions with sodium <em>tert</em> -amylate. In chapter 4 the results of these studies are described in detail. An alcoholate function intramolecularly induces heterolysis of the sulfonate ester group in an apolar solvent via orbital interactions through three intervening C-C single bonds. It is shown that the reactivity of the compounds 60-65 is only affected by the relative position of the hydroxyl function to the sulfonate ester group and not by the orientation of the hydroxyl group. The two chief pathways by which these compounds react are rearrangement ( <strong>60</strong> , <strong>62</strong> , and <strong>63</strong> ) and homofragmentation ( <strong>64</strong> and <strong>65</strong> ). Stereoelectronic effects play a dominant role here, except in compound <strong>61</strong> where steric factors primarily determine the reactivity and product outcome (ether formation). Homofragmentation is much faster than rearrangement and is only possible when a 1,3-bridged through-space interaction accompanies TBI. The extent of TBI as well as the product composition is strongly determined by the σ-relay of the four σ-bonds between the electron donor (alcoholate) and the electron acceptor (sulfonate ester bond). These results are consistent with the " <em>trans</em> rule", which is in line with predictions from theoretical models regarding TBI.<p>The product outcome, product ratio, and relative rate of the base-induced reactions of perhydronaphthalene-1,4-diol monosulfonate esters described in chapter 4 are satisfactorily explained with the concept of TBI. However, the conclusions are all based on empirical results. In chapter 5 the results of semi-empirical calculations, using the MNDO method, performed on model systems are presented. In this way a more detailed understanding of the stereoelectronic features underlying the homofragmentation and rearrangement reaction is obtained. The trends in the results of the MNDO simulations are the same as those found in the reactions of the compounds <strong>60-65</strong> . Whether rearrangement or homofragmentation takes place depends on the geometry of the σ-relay and the inductivity of the system. Cyclopropanoid bridged structures seem to be involved in the rearrangement process as well as in the homofragmentation process.<p>In order to explore the effects of the order of substitution of the carbon atom that borders the carbon atom to which the mesylate group is attached the compounds <strong>40</strong> , <strong>66</strong> , and <strong>67</strong> were synthesized. This subject is discussed in chapter 6. The product formation is strongly dependent on the steric consequences of alkyl substituents at βcarbon atoms. Homofragmentation is highly favored when the repulsive steric interactions do not prevent a homohyperconjugatively stabilized transition state. This is only possible in an ideal "W" arrangement of theσ-relay ( <strong>40</strong> ). Due to the repulsive 1,3- <em>peri</em> -effect in <strong>66</strong> , and a combination of the 1,3- <em>peri</em> -effect and the 1,3- <em>diaxial</em> -effect in <strong>67</strong> the σ-relay diverges from the ideal "all <em>trans</em> " geometry as a result of which other reaction pathways (elimination, 1,3-H, and 1,2-Me shifts) are favored over homofragmentation. Introduction of inductively electron-donating substituents leads to an increase in reaction rate, despite the (slight) deviation of the "W" arrangement. It is concluded that although bridged ions are important intermediates in the observed reaction paths, they are not decisive for the reactivity of these compounds.<p>The O-silylated mesylates <strong>106</strong> and <strong>107</strong> react fast upon treatment with TBAF in refluxing benzene (Chapter 3). At room temperature only desilylation takes place. To investigate the influence of a remote nucleofugal mesylate group on the rate of desilylation, apart from <strong>106</strong> and <strong>107</strong> , also the O-silylated compounds <strong>127-131</strong> are synthesized and treated with TBAF as is described in chapter 7. The rates of desilylation are determined conveniently by HPLC monitoring of the disappearance of the starting material. The desilylation rate of compounds with a mesylate group is much higher than the desilylation rate of corresponding compounds with a hydroxyl group instead ( <strong>130</strong> and <strong>131</strong> ). Furthermore, compounds having a "W" arrangement ( <strong>107</strong> and <strong>129</strong> ) of the relaying σ-bonds react considerably faster than their "sickle relay" analogs ( <strong>106</strong> , <strong>127</strong> , and <strong>128</strong> ). The results presented in this chapter show nicely that longrange electronic effects of distant substituents can exert a substantial influence on the reactivity of certain functional groups in general.<p>In conclusion, the concept of TBI offers a good explanation for the reactivity of the compounds studied throughout this thesis. The stereochemical and stereoelectronic requirements for the base-induced reactions of perhydronaphthalene-1,4-diol monosulfonate esters are now well established. The general utilitly of the concept of σ-delocalization and TBI in everyday chemistry is demonstrated
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • de Groot, Æ., Promotor, External person
  • Wijnberg, J.B.P.A., Promotor
Award date17 Oct 1994
Place of PublicationS.l.
Print ISBNs9789054852995
Publication statusPublished - 1994


  • diterpenoids
  • sesquiterpenoids
  • terpenoids
  • essential oils
  • sesquiterpenes
  • chemical structure
  • chemical reactions
  • sulfonates (esters)

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