Chlorobenzenes, dihydroxylation

Pseudomonas putida mediated cis-dihydroxylation of bromo or chlorobenzene supplied the requisite chiral starting material 44 for a second synthesis of (+)-7-deoxynarciclasine reported by Hudlicky [18,19]. Subsequent to protection of the diol as the acetonide45 (Scheme 8), its cycloaddition reaction with the N-acylnitroso compound derived from benzyl-N-hydroxycarbamate 46 by in situ oxidation, occurred with complete regio and stereospecificity togive the bromo adduct 47. In a similar fashion, the chloro compound 48 was obtained. 

Yildirim, S., Zezula, J., Hudlicky, T., Witholt, B. and Schmid, A. (2004) Asymmetric dihydroxylation of dnnamonitrile to tra s-3-[(5S,6R)-5,6-dihydroxy[Pg.336]

The c/s-dihydroxylation reaction catalyzed by these dioxygenases is typically highly enantioselective (often >98% ee) and, as a result, has proven particularly useful as a source of chiral synthetic intermediates (2,4). Chiral cis-dihydrodiols have been made available commercially and a practical laboratory procedure for the oxidation of chlorobenzene to IS, 2S)-3-chlorocyclohexa-3,5-diene-l,2-c diol by a mutant strain of Pseudomonas putida has been published (6). Transformation with whole cells can be achieved either by mutant strains that lack the second enzyme in the aromatic catabolic pathway, cw-dihydrodiol dehydrogenase (E.C. 1.3.1.19), or by recombinant strains expressing the cloned dioxygenase. This biocatalytic process is scalable, and has been used to synthesize polymer precursors such as 3-hydroxyphenylacetylene, an intermediate in the production of acetylene-terminated resins (7). A synthesis of polyphenylene was developed by ICI whereby ftie product of enzymatic benzene dioxygenation, c/s-cyclohexa-3,5-diene-1,2-diol, was acetylated and polymerized as shown in Scheme 2 (8). 

Vitamin C Banwell 4 out of 5 Step 1 cis-dihydroxylation of chlorobenzene with Pseudomonas putida... 

When the D-ribonolactone derivative 1 was treated with aqueous KOH followed by acid, L-lyxonolactone, isolated as the benzylidene derivative 2, was formed. i3c-N.m.r. studies indicated the presence of the nbo-epoxide 3 as an intermediate in the basic medium, and similar chemistry was used to convert D-lyxonolactone to L-ribonolactone. Microbial dihydroxylation of chlorobenzene, followed by acetonation and furtho dihydroxylation using permanganate, gave 4 on ozonolysis, followed by work-up under conditions of catalytic hydrogenation and subsequent... 

Figure 11.15 c/s-Dihydroxylation of benzonitrile (a) and cinnamonitrile (b) with chlorobenzene dioxygenase followed by the hydrolysis of the nitrile group with a nitrilase. Reprinted from [79] with permission from Elsevier. 

In an interesting iqtproach to aldondactones and lactams, the cycldiexate qwxide 3, obtained fiom chlorobenzene using microbial dihydroxylation, was cmvoted as outlined in Scheme 1 into the lactam 4 related to mannojirimydn, and into the epimer 5 the route to 4 could... 

Asymmetric Dihydroxylation of Cinnamonitrile 108 Using Chlorobenzene Dioxygenase in E. co/i on Muitigram Scaie... 

Asymmetric dihydroxylation of cinnamonitrile 108 using chlorobenzene dioxygenase in E. colion multigram scale [166],... 

S. Yildirim, J. Zezula, T. Hudlicky, B. Witholt A. Schmid, Asymmetric dihydroxylation ofcin-namonitrile to trans-3-[(5S,6R)-5,6-dihydroxycyclohexa-l,3-dienyl]-acrylonitrile using chlorobenzene dioxygenase in Escherichia coli (pTEZ30), Adv. Synth. Catal. 346 (2004) 933-942. 

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