Tandem enzyme‐catalysed reduction/ cis‐dihydroxylation of 2,2,2‐trifluoroace‐ tophenone: chemoenzymatic routes to new enantiopure phenol and benzylic alcohol reagents

Abstract

Factors that control the competition between toluene dioxgenase-catalysed arene cis-dihydroxylation and dehydrogenase-catalysed ketone reduction have been studied, using whole cells of Pseudomonas putida UV and three alkylaryl ketones. The triol metabolite, obtained from 2,2,2-trifluoroacetophenone, has been used in the synthesis of single enantiomer chiral phenols and benzylic alcohols. Potential applications of the methylether derivatives of the chiral phenols and benzylic alcohols, as resolving agents, have been found.

Arene cis‐Diol Dehydrogenase‐Catalysed Regio‐ and Stereoselective Oxidation of Arene‐, Cycloalkane‐ and Cycloalkene‐cis‐diols to Yield Catechols and Chiral α‐Ketols

“…In our earlier studies, with different wild‐type strains of P. putida and enantiomeric mixtures of monocyclic cis ‐dihydrodiol substrates, e.g., 2b S / 2b R , enantiocomplementarity was observed. Thus, P. putida ML2 whole cells had an exclusive preference for the relatively rare 2 R enantiomers,10a and P. putida 8859 for the more common 2 S enantiomers (Scheme ) 8a,d. In this study, using a mixture of cis ‐dihydrodiol enantiomers 2b R / 2b S , enantioselectivity of TCDD, expressed in the P. putida NCIMB 11767 wild‐type strain, was found to be rather poor.…”

“…The study of regio‐ and diastereo‐selectivity of NCDD narB , using E. coli narB for biotransformation of triols 7 , required the resulting catechols 8 to be stable, unlike catechols 8 R′ and 8 S′ (R=Me, Et and Pr) 10d. Triol 7h SR′ had been isolated, as a major metabolite, from biotransformation of 2,2,2‐trifluoroacetophenone using P. putida UV4, after PLC separation from the minor diastereoisomer 7h SS′ 8d. The racemic benzylic alcohol 6g R′ / 6g S′ , as substrate, with P. putida UV4 cells, under similar conditions, gave separable triol diastereoisomers 7g SR′ and 7g SS′ (Scheme ).…”

“…We have reported8d that the dehydration of triol 7h SR′ , under acidic conditions, gave a mixture (1:2) of the corresponding ortho ‐phenol 23h R and meta ‐phenol 24h R . As part of a wider study, to synthesise and evaluate the potential of chiral compounds, obtained by enzymatic hydroxylation of arenes and their derivatives, as ligands and reagents,12a,b monomethyl ethers of phenols 23h R and 24h R were synthesised.…”

“…All meso cycloalkane cis ‐diols, racemic cycloalkane trans ‐diols and cycloalkene cis ‐diols, used as substrates for cis ‐diol dehydrogenase enzymes, were either available commerically ( 9 , 11 , 14 ) or by chemical synthesis through literature methods ( 16 , 18 , 20 ). cis ‐Diols 2b S , 2e S , 3d S , 19 1 S ,2 R , 19 1 R ,2 S , 21 1 S ,2 R , 21 1 R ,2 S and triols 7h SR′ , 7h SS′ were available from earlier biotransformation studies with P. putida UV4 6b,8c,d. The triol diastereoisomers 7g SR′ and 7g SS′ were also obtained under similar conditions.…”

“…This may account for the regio‐ and stereoselectivity aspects of cis ‐diol dehydrogenase‐catalysed formation of catechols having received relatively little attention 7a–h. The recent development of chemoenzymatic routes to 2,3‐ cis ‐dihydrodiol enantiomers 2 R ,8a,b cis ‐dihydrodiol diastereoisomers 2 S 8c,d and 3,4‐ cis ‐dihydrodiol regioisomers 3 S 8e provided the opportunity for further studies of regio‐ and stereoselectivity of benzene cis ‐diol dehydrogenase (BCDD) and naphthalene cis ‐diol dehydrogenase (NCDD) enzymes, during the formation of catechols 4 or 5 (Scheme ).…”