Synthesis and Reactions of Enantiopure Substituted Benzene cis‐Hexahydro‐1,2‐diols

Abstract

Enantiopure cis-dihydro-1,2-diol metabolites, obtained from toluene dioxygenase-catalysed cis-dihydroxylation of six monosubstituted benzene substrates, have been converted to their corresponding cis-hexahydro-1,2-diol derivatives by catalytic hydrogenation via their cis-tetrahydro-1,2-diol intermediates. Optimal reaction conditions for total catalytic hydrogenation of the cis-dihydro-1,2-diols have been established using six heterogeneous catalysts. The relative and absolute configurations of the resulting benzene cis-hexahydro-1,2-diol products have been unequivocally established by X-ray crystallography and NMR spectroscopy. Methods have been developed to obtain enantiopure cis-hexahydro-1,2-diol diastereoisomers, to desymmetrise a meso-cishexahydro-1,2-diol and to synthesise 2-substituted cyclohexanols. The potential of these enantiopure cyclohexanols as chiral reagents was briefly evaluated through their application in the synthesis of two enantiomerically enriched phosphine oxides from the corresponding racemic phosphine precursors.

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.…”

“…Recently we published11 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.…”

Stereoselective Synthesis of cis,cis‐Configured Perhydroquinoxaline‐5‐Carbonitrile from Cyclohex‐2‐en‐1‐ol

“…The residue was purified by fc ( d = 5 cm, l = 5 cm, V = 20 mL, cyclohexane:ethyl acetate = 1:0 ➔ 7:1 ➔ 7:3 ➔ 0:1, R f = 0.22 (tlc, cyclohexane:ethyl acetate = 1:1, detection: Hanessian 's stain)) to afford the diol 4 (84 mg, 62%) as a colorless solid, mp 82–83°C. See supplementary information and report for spectroscopic data.…”

Benzoate dioxygenase fromRalstonia eutrophaB9 – unusual regiochemistry of dihydroxylation permits rapid access to novel chirons

“…Perhaps surprisingly, this compound has not been reported previously, although the diastereoisomeric trans-diol is known. 18 Saturation of ortho,meta arene cis-diols of type 2 to give 3-substituted cyclohexane-1,2-diols and applications of these in catalysis have been reported; 19 the analogous approach has not previously been applied to ipso,ortho-arene cis-diols of type 4, however. We wished to target derivatives of 5 with the diol protected, but direct acetonide introduction was surprisingly unsuccessful.…”

“…Synthesis of methyl (2R,3aS,7aR)-2-phenyltetrahydrobenzo- [d] [1,3]dioxole-3a(4H)-carboxylate (19) and methyl (2S,3aS,7aR)-2-phenyltetrahydrobenzo [d] [1,3]dioxole-3a(4H)-carboxylate (20). Diol 6 (30 mg, 0.27 mmol) was dissolved in toluene (15 mL).…”