A study of the effects of orbital topology on the regiochemistry and stereospecificity of cyclopropyl ring opening
Degree GrantorUniversity of Canterbury
Degree NameDoctor of Philosophy
The regiochemistry and stereochemistry of cyclopropane ring opening has been investigated by both theoretical and experimental methods to determine the factors which govern the selectivity of electrophilic addition to a cyclopropane ring. The experimental work entailed the syntheses of compounds I-VII and the investigation of their reactions with electrophiles. The required tricyclic molecules were generally synthesised by literature procedures; however, for compounds VI and VII new synthetic routes were examined in an attempt to overcome the low yields and/or multiple step syntheses of the literature procedures. The cyclopropyl moieties were contained within tricyclo[188.8.131.52²,⁴]octane I-IV or tricyclo[184.108.40.206²,⁴]non-6-ene V-VII carbon skeletons to allow the stereochemical (edge verses corner) and regiochemical (which bond of the cyclopropane ring is broken) preferences of electrophilic addition to be determined. Incorporation of both a cyclopropane ring and an alkene functionality in the tricyclic hydrocarbons allowed the regiochemical preference for electrophilic addition to the cyclopropane ring or double bond to be elucidated. The structures of the products obtained from the electrophilic addition reactions were elucidated by detailed NMR studies using a variety of one and two dimensional NMR techniques and, in some cases, by X-ray crystallography. The experimental results obtained indicate Br⁺ addition for I-III to occur at the most substituted cyclopropyl bond with inversion of configuration at the site of electrophilic attack, and that substantial charge development occurs in the intermediate carbocations. For compounds IV and V Br⁺ addition occurs predominantly at the double bond in preference to the cyclopropane ring. The reaction of V with H⁺/D⁺ gave predominantly electrophilic addition to the most substituted cyclopropyl bond with both edge and comer attack occurring to similar extents. [Diagram here] Semiempirical and ab initio molecular orbital techniques were used to investigate the mechanisms of proton addition to cyclopropane and to endo- and exo-tricyclo[220.127.116.11²,⁴]octane (I and II, respectively) from both edge and comer trajectories. The effects of HOMO-LUMO interactions, orbital distributions, and secondary orbital interactions were found to be important in determining the stereoselectivity of electrophilic addition to a cyclopropane ring. The stabilities of the possible cations resulting from H⁺ and Br⁺ addition to cyclopropane and various saturated and unsaturated tricyclic hydrocarbons containing a cyclopropane ring were studied The results of these investigations were used to evaluate the effect of cation stability in determining the regiochemical selectivity of electrophilic addition to a cyclopropane ring and the preference between addition to a double bond or cyclopropane ring. The results of these calculations were compared with those of experimental studies performed as part of the present work and with literature results. For the addition of H⁺, the semiempirical calculations show cation stability to be important in determining the regiochemical selectivity of addition between a double bond or cyclopropane ring. However, for Br⁺ addition the effects of carbocation stability are predicted not to be the dominant factor in determining the regiochemical selectivity between reaction at a double bond or cyclopropane ring.