A cobalt complex of a microbial arene oxidation product

Abstract

We report the first synthesis of a cobalt Cp diene complex wherein the diene is derived by microbial dearomatising dihydroxylation of an aromatic ring. The complex has been characterised crystallographically and its structure is compared to that of an uncomplexed diene precursor.

Exceedingly Efficient Synthesis of (±)-Grandifloracin and Acylated Analogues

“…As such, any derivative must be obtained either by a deprotection–acylation sequence, adding extra steps to such a library synthesis, or by carrying each individual acyl group through the Diels–Alder step. This is potentially troublesome, as electronically differentiated substrates can perform with substantially varying yields . As such, when planning our synthesis, we sought to carry a free hydroxymethyl group through the cyclodimerization in order to facilitate subsequent derivatization for biological study of analogues of the natural product.…”

“…Salicylic acid ( 5 ) was reduced by LiAlH 4 to give the corresponding salicylic alcohol ( 4 , 93% yield). The alcohol was then subjected to known oxidative dearomatization with sodium periodate (NaIO 4 ) in water to afford spiro­epoxy­cyclo­hexadienone ( 6 ) . Diene 6 spontaneously undergoes a Diels–Alder dimerization to yield the dispiro-oxirane 3 in a remarkably stereoselective and efficient overall process (89% yield of a >10:1 mixture of diastereomers).…”

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

“…[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. [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).…”

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

“…Interestingly, formation of an isolobal cobalt cyclopentadienyl complex from 17 did not result in any such acetonide migration and instead gave 85. 22 The metabolism of substituted benzoates by Ralstonia eutropha B9 had been reported (vide infra) and we examined the feasibility of producing arene ipso,ortho cis diols from metabromobenzoate in synthetically useful quantities. Metabolism of a meta-substituted benzoate could potentially give rise to two isomeric products (Scheme 11).…”