Enzymatic and chemoenzymatic synthesis and stereochemical assignment of cis-dihydrodiol derivatives of monosubstituted benzenes

Abstract

Toluene dioxygenase-catalysed oxidation of mono-substituted benzene substrates (R = F, Cl, Br, I, Me, Et, CH₂OAc, CHCH₂, CCH, CF₃, CN, OMe, OEt, SMe) in growing cultures of Pseudomonas putida UV4 yielded the corresponding cis-dihydrodiol metabolites. Palladium-catalysed cross-coupling of cis-(1S,2S)-1,2-dihydroxy-3-iodocyclohexa-3,5-diene with a range of tributyltin compounds provided a chemoenzymatic route to a further series of cis-dihydrodiol derivatives of monosubstituted benzenes (R = D, CH₂CHCH₂, Buⁿ, SEt, SPrⁱ, SBu^t, SPh, SC₆H₄Me-4). The enantiopurities and absolute configurations of the cis-dihydrodiols, obtained by both enzymatic and chemoenzymatic routes, were determined by several new methods including ¹H NMR spectroscopic analysis of the bis-MTPA esters of the 4-phenyl-1,2,4-triazoline-3,5-dione cycloadducts, X-ray crystallography, circular dichroism spectroscopy and stereochemical correlation.