Investigation of a Metal Complexing Route to Arene trans - Dihydrodiols

Crystal O'Connor [Thesis], Dublin Institute of Technology

Document Type Theses, Masters

Successfully submitted to the Dublin Institute of Technology for the Degree of Master of Philosophy.


In this work, a route for the conversion of arene cis-dihydrodiols to their trans
isomers was examined. Arene trans-dihydrodiols are potentially important chiral
building blocks in synthetic chemistry and are more stable than their cis analogues.
While the cis-arene dihydrodiols can be produced on a relatively large scale by
fermentation, their trans isomers cannot. The principal aim of this work was to
carry out studies in tandem to inform the development of the synthetic pathway to
convert arene cis-dihydrodiols to their trans isomers by (a) the synthesis of
organometallic intermediates and (b) investigation of their reactivity by means of
kinetic and equilibrium studies. A number of analogues based on sevenmembered ring systems instead of six were also investigated as a comparison. The four-step synthetic route being investigated involved formation of a tricarbonyl iron complex of the arene cis-dihydrodiol substrate, followed by reaction in acid to form a carbocation intermediate. This cation complex is trapped stereoselectively using hydroxide to give a trans isomer and decomplexation to remove the iron tricarbonyl moiety is the final step. Two substrates were examined, 3- bromocyclohexa-3,5-diene-1 ,2-diol and 3-trifluoromethylcyclohexa-3,5-diene-1 ,2- diol. The first three steps in the route were successfully performed on each compound in yields of 52 % and 43 % overall for the 3-bromo and 3-trifluoromethyl starting materials respectively. The final decomplexation step was not successful however and will require optimisation of the conditions. The ionisation of the tricarbonyl iron cis-dihydrodiol intermediates was investigated kinetically in strong acid, and the corresponding rate constant for the bromo substituted complex was
determined to be 8.0 x 1 o-s M-1 s-1 showing a significant lack of reactivity towards cation complex formation. This is expected based on previous work that reports low reactivity towards ionisation for any complexes that have hydroxyl groups endo to the iron centre, as is the case here. The reverse reaction, hydrolysis of the bromo-substituted cation, was too fast to measure but a pKR of 0.5 was estimated. It can be concluded that ionisation of the coordinated endo (i.e. cis-) diol to form the corresponding cation is the difficult step in the route to convert arene cis - dihydrodiols to their trans isomers. Among the seven-membered ring complexes synthesised were salts of the cation
species, tricarbonyl (115-cyclohepta-1 ,3-dienyl) iron and tricarbonyl (117-
cycloheptatrienyl) chromium. Rate constants for the nucleophilic reaction of the
former cation complex with water to give tricarbonyl (115-cyclohepta-2,4-diene-1-ol
iron) and conversion of this complex back to the cation were measured, allowing a
pH profile (log k versus pH) to be constructed. From this, an equilibrium constant,
pKR, = 4.2 was determined for the interconversion between the cycloheptadienyl
complex [R+] and the corresponding hydrolysis product [ROH] in which the
hydroxyl group is exo to the iron centre.
Comparison of this equilibrium constant to that reported for the uncoordinated
cycloheptadienyl cation shows that the iron tricarbonyl moiety is highly stabilising
(~PKR = 15.8). The uncoordinated tropylium (or cycloheptatrienyl) ion however
shows a similar stability to tricarbonyl (115-cyclohepta-1 ,3-dienyl) iron due to
aromatic stabilisation. The effect of having one less methylene group in the ring
was found to be negligible as ~PKR = 0.4 for the coordinated cycloheptadienyl and
cyclohexadienyl cations.
It is proposed that, in weak base, the tricarbonyl cycloheptatrienyl chromium
complex gives a zwitterionic complex in which a carbonyl ligand is converted to a
carboxylate ion. Equilibrium between this zwitterion and a cationic form in which
the carboxylate has been protonated to give the carboxylic acid is postulated to
occur in weakly acid solutions. An acid dissociation constant, pKa of 4.8 was
determined for this equilibrium spectrophotometrically.


Document Type

Master thesis