Applications of biocatalytic arene ipso,ortho cis-dihydroxylation in synthesis

Abstract

The dearomatising dihydroxylation of aromatic molecules mediated by arene dioxygenase enzymes can provide cyclohexadiene-diols that are versatile starting materials for organic synthesis. Whereas oxidation of a substituted arene to give its ortho,meta-dihydrodiol has been demonstrated for numerous substrates and dioxygenases, formation of ipso,ortho-dihydrodiols has historically been underutilised in comparison. This feature article presents a chronological account of reported uses of such diols.

Rate-Determining Attack on Substrate Precedes Rieske Cluster Oxidation during Cis-Dihydroxylation by Benzoate Dioxygenase

“…2, 3 Another type of application stems from the ability of RDDs to produce large quantities of regio and stereospecific cis -diols as important synthetic building blocks for streamlining synthesis of drugs and antibiotics. 4 A complete understanding of the catalytic mechanism of RDDs will aid further development and utilization of these applications and provide guiding insights for mechanistic studies of the broad class of Rieske oxygenases.…”

Production of enantiopure β-amino-γ-hydroxyesters from benzoic acid by a selective formal aminohydroxylation

“…(Scheme 1A) [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] Examples are found in the literature for the total synthesis of polyoxygenated materials from benzoic acid, such as (-)-idesolide, [10] (+)-grandifloracin, [9] piperenol B, [13] pleiogenone A [14] and, more recently, a formal approach to xylosmin and flacourtosides E and F. [20] Although the dienic system in 1 does not present any substituent to allow for the differentiation of both olefins, selective oxygenation of either center of the ring can be accomplished by selecting the appropriate sequence of reactions (osmylation, epoxidation, diol protection) as described by Myers et al in 2001. [25] Regarding the preparation of N-containing products, several examples are shown in the literature, such as the synthesis of inosaminoacids, [26] inosamines, [7] pyrrolidines, [12] and tetracyclines [8] from benzoic acid ( Figure 1A). In the majority of these cases, the nitrogen function is incorporated in the diene using a nitroso Diels-Alder methodology via in situ oxidation of hydroxamic acids ( Figure 1B), followed by a reduction of the oxazine to afford the 1,4-hydroxyamino function.…”

“…Mariana cis-Cyclohexadienediols obtained by biotransformation of arenes using bacterial dioxygenases, have been widely used as starting materials for enantioselective synthesis of natural products. [1][2][3][4][5][6][7] Although the clear majority of synthetic examples are derived from diols obtained by the Toluene Dioxygenase enzymatic complex, dienediol 1 obtained by the ipso, ortho cisdihydroxylation of benzoic acid by Benzoate Dioxygenase (expressed in the mutant Ralstonia eutropha B9) has been recently used by several research groups to produce biologically active natural products and/or advanced intermediates. (Scheme 1A) [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] Examples are found in the literature for the total synthesis of polyoxygenated materials from benzoic acid, such as (-)-idesolide, [10] (+)-grandifloracin, [9] piperenol B, [13] pleiogenone A [14] and, more recently, a formal approach to xylosmin and flacourtosides E and F. [20] Although the dienic system in 1 does not present any substituent to allow for the differentiation of both olefins, selective oxygenation of either center of the ring can be accomplished by selecting the appropriate sequence of reactions (osmylation, epoxidation, diol protection) as described by Myers et al in 2001.…”

Palladium-Catalyzed Dearomative syn-1,4-Carboamination

“…Particularly, functional elaboration of arenes has received significant attention, 1 given their ample availability and application within all areas of molecular sciences. While most of the recent focus has been in the area of C–H activation, 2 functionalization with concurrent loss of aromatization 3 (i.e., dearomative functionalization) is significantly less developed, despite the unique synthetic and functional versatility of the products. 4 …”