Abstract
Ubiquitous tyrosinase catalyses the aerobic oxidation of phenols to catechols through the binuclear copper centres. Here, inspired by the Fischer indole synthesis, we report an iridium-catalysed tyrosinase-like approach to catechols, employing an oxyacetamide-directed C–H hydroxylation on phenols. This method achieves one-step, redox-neutral synthesis of catechols with diverse substituent groups under mild conditions. Mechanistic studies confirm that the directing group (DG) oxyacetamide acts as the oxygen source. This strategy has been applied to the synthesis of different important catechols with fluorescent property and bioactivity from the corresponding phenols. Finally, our method also provides a convenient route to 18O-labelled catechols using 18O-labelled acetic acid.
Highlights
Ubiquitous tyrosinase catalyses the aerobic oxidation of phenols to catechols through the binuclear copper centres
Tremendous progress has been achieved in directed C–H hydroxylation/oxygenation by metal catalysis with O2, H2O, peroxides[13,14,15,16,17,18] or the in situ hydrolysis of newly installed acyloxy groups as oxygen sources such as OAc, OTFA and so on refs 19–30 (Fig. 1b)
Gevorgyan and colleagues[31] recently reported an ingenious silanol-directed Pd-catalysed C–H oxygenation of phenols followed by desilylation of the silacyle with tetrabutylammonium fluoride (TBAF), furnishing catechols with PhI(OAc)[2] as the oxygen source
Summary
Of di-tert-butyl peroxide (DTBP) as a possible oxygen source and heating in MeOH at 70 °C for 12 h, the target product catechol 2a was obtained in 25% yield (Table 1, entry 12). The reaction proceeded to give 67% yield (Table 1, entry 14). The scope of the one-step neutral ortho-hydroxylation from N-phenoxyacetamides 1 to obtain catechols 2 was investigated (Table 2). Meta- and parasubstituents on N-phenoxyacetamides shared the same products This finding showed a good selectivity of hydroxylation in the ortho position, which was far away from the meta-substituents (2c and 2d, 2j and 2k). Bioactive catechols natural products such as L-dopa and estradiol were tested under the standard reaction conditions, the protected L-dopa 2x, protected dopamine 2y and estradiol 2z were successfully obtained directly with high selectivity and excellent yields, highlighting the method’s mild conditions,excellent functional group tolerance and selectivity
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