Chemoenzymatic synthesis of monocyclic arene oxides and arene hydrates from substituted benzene substrates

Abstract

Enantiopure cis-dihydrodiol bacterial metabolites of substituted benzene substrates were used as precursors, in a chemoenzymatic synthesis of the corresponding benzene oxides and of a substituted oxepine, via dihydrobenzene oxide intermediates. A rapid total racemization of the substituted benzene 2,3-oxides was found to have occurred, via their oxepine valence tautomers, in accord with predictions and theoretical calculations. Reduction of a substituted arene oxide to yield a racemic arene hydrate was observed. Arene hydrates have also been synthesised, in enantiopure form, from the corresponding dihydroarene oxide or trans-bromoacetate precursors. Biotransformation of one arene hydrate enantiomer resulted in a toluene-dioxygenase catalysed cis-dihydroxylation to yield a benzene cis-triol metabolite.

Reactions of nitrogen nucleophiles with enantiopure cyclohexenyl electrophiles: a stereo‐ and regio‐ selective study

“…[14] Chemoselective activation of diols 3a-c was readily accomplished using Maddock's reagent (1-bromocarbonyl-1-methylethyl acetate) [15] and gave trans-bromoacetates 4a-c. [14] Using sodium methoxide as base, treatment of compounds 4a-c, gave the corresponding vinyl epoxides 5a-c. [14] The new phenyl-substituted compounds 3c-5c were synthesized and characterized while compounds 2a-c, 3a, 3b, 4a, 4b, 5a, and 5b had been reported earlier and were available for this study. [14] Cyclic compounds 4 and 5 were considered as ideal substrates for studying subsequent stereoand regio-selective reactions, as all the possible products of these reactions were readily identified and distinguished by NMR spectroscopy. Furthermore, for geometrical reasons, all of the compounds studied adopted s-cis conformations, which greatly simplified subsequent stereochemical analysis.…”

“…This prompted the synthesis of the corresponding substituted cyclohexenes 3a , 3b , 3c , 4a , 4b , 4c , and 5a , 5b , 5c as more stable derivatives. Regioselective catalytic hydrogenation of the unsubstituted alkene double bond gave the corresponding cis ‐tetrahydrodiols 3a , 3b , 3c (Scheme ) . Chemoselective activation of diols 3a , 3b , 3c was readily accomplished using Maddock's reagent (1‐bromocarbonyl‐1‐methylethyl acetate) and gave trans ‐bromoacetates 4a , 4b , 4c .…”

“…Regioselective catalytic hydrogenation of the unsubstituted alkene double bond gave the corresponding cis ‐tetrahydrodiols 3a , 3b , 3c (Scheme ) . Chemoselective activation of diols 3a , 3b , 3c was readily accomplished using Maddock's reagent (1‐bromocarbonyl‐1‐methylethyl acetate) and gave trans ‐bromoacetates 4a , 4b , 4c . Using sodium methoxide as base, treatment of compounds 4a , 4b , 4c , gave the corresponding vinyl epoxides 5a , 5b , 5c .…”

“…Chemoselective activation of diols 3a , 3b , 3c was readily accomplished using Maddock's reagent (1‐bromocarbonyl‐1‐methylethyl acetate) and gave trans ‐bromoacetates 4a , 4b , 4c . Using sodium methoxide as base, treatment of compounds 4a , 4b , 4c , gave the corresponding vinyl epoxides 5a , 5b , 5c . The new phenyl‐substituted compounds 3c , 4c , 5c were synthesized and characterized while compounds 2a , 2b , 2c , 3a , 3b , 4a , 4b , 5a , and 5b had been reported earlier and were available for this study .…”

A Chemoenzymatic Route to the (+)-Form of the Amaryllidaceae Alkaloid Narseronine

“…A single-crystal X-ray analysis of this material established that it was the arene hydrate 24 (Scheme 4). [15] This presumably arises via a two-fold N-methylation of substrate 22 to produce the methiodide salt 23 which itself fragments in the illustrated manner to give, after loss of the elements of hydrogen iodide, the observed product. Eventually, it was established that when a THF solution of compound 22 maintained at 0-188C was treated with ,4 molar equivalents of potassium hydride and 8 equivalents of methyl iodide (Scheme 3), then a relatively clean N,O-bismethylation reaction took place and thus finally providing (þ)-narseronine [(þ)-2] in 83 % yield after chromatographic purification.…”