A Comparative Study of the Synthesis of 3‐Substituted Catechols using an Enzymatic and a Chemoenzymatic Method

Abstract

A series of cis-dihydrodiol metabolites, available from the bacterial dioxygenase-catalysed oxidation of monosubstituted benzene substrates using Pseudomonas putida UV4 , have been converted to the corresponding catechols using both a heterogeneous catalyst (Pd/C) and a naphthalene cis-diol dehydrogenase enzyme present in whole cells of the recombinant strain Escherichia coli DH5a(pUC129: nar B). A comparative study of the merits of both routes to 3-substituted catechols has been carried out and the two methods have been found to be complementary. A similarity in mechanism for catechol formation under both enzymatic and chemoenzymatic conditions, involving regioselective oxidation of the hydroxyl group at C-1, has been found using deuterium labelled toluene cis-dihydrodiols. The potential, of combining a biocatalytic step (dioxygenase-catalysed cis-dihydroxylation) with a chemocatalytic step (Pd/C-catalysed dehydrogenation), into a one-pot route to catechols, from the parent substituted benzene substrates, has been realised.

Cycloalkenyl Halide Substitution Reactions of Enantiopure Arene cis‐Tetrahydrodiols with Boron, Nitrogen and Phosphorus Nucleophiles

“…Even in the absence of hydrogen, 10% Pd-C catalyses a concomitant oxidation and reduction of cis-dihydrodiols 1 (R = F, Me, t-Bu, CN, CF 3 ) to catechols and tetrahydrodiols 2 in 30-45% yields. [10] Recently we published [11] our results on the partial and exhaustive hydrogenation of a range of dienes 1, employing a variety of heterogeneous catalysts. Rh/graphite, in methanol as solvent, was found to be the catalyst of choice.…”

Enantiopurity and absolute configuration determination of arene cis‐dihydrodiol metabolites and derivatives using chiral boronic acids

“…The TDO‐catalyzed cis ‐dihydroxylation of substituted benzyl alcohol enantiomers yielded triol diastereomers ( 80a–e and 81a–e , Diagram 5). These triols, in turn, proved to be good substrates for a naphthalene diol dehydrogenase enzyme, which catalyzed their biotransformations, to yield individual (+)‐ and (−)‐catechol enantiomers ( 82a–e ) . As separations (Δ δ OMe ) of diagnostic 1 H–NMR signals of the boronates, formed using MEPBA 4a S with (+) and (−)‐catechols ( 82a–e ), were relatively small ( δ OMe 3.15–3.28), it was considered appropriate to test the new boronic acid (+)‐MPPBA 4c R (Table ) .…”

Multi‐Enzymatic Cascade Reactions: Overview and Perspectives

“…[135] Nevertheless, successful examples of chemo-enzymatic integration have been reported in both aqueous [140,141] and organic media [142,143] and with mixed homogeneous/heterogeneous catalysis. [144,145] Further improvements in multi-step biocatalysis can derive from reactor engineering. Reactor configuration, for example, can not only determine different conversions, but it should be chosen according to the specific needs of a reaction.…”