A Green and Versatile Route to Highly Functionalized Benzofuran Derivatives Using Biomimetic Oxygenation

Abstract

One‐pot green reactions useful for the synthesis of novel and potentially biologically active compounds have been developed using metaloporphyrin catalyzed oxidations of benzofurans. Minor variations of the reaction parameters allow direction of the reactivity (furan versus benzene ring) and the production of multifunctional 2,3‐dihydrobenzofurans, salicyl derivatives or an unusual dimerization product. These studies suggest pathways for the metabolic oxidation and activation of pharmaceuticals and other molecules containing the benzofuran core.

Biomimetic Oxidation of Benzofurans with Hydrogen Peroxide Catalyzed by Mn(III) Porphyrins

“…From a comparison of the present results on the oxidation of benzofurans in the presence of Mn(III) porphyrins with those previously reported for biomimetic oxidation by an Fe(III) porphyrin in ethanol [28], it can be observed that the hydroxylation of the benzene ring is minimized (it is not observed in the isolated products) and a number of new coupling reactions and transformation pathways are detected.…”

“…Previous work on the biomimetic oxidation of BF using iron porphyrins has shown that the products formed depend on the solvent evaporation temperature and on the Ox/S ratio [28]. Lower Ox/S ratios resulted in less degradation of the BF ring system.…”

“…Compound 16 was also analyzed by NMR in CDCl 3 (see Experimental and Supplementary Material, Figure S21) as the oxo form (ring-opened). In DMSO-d 6 , a hydrogen-bond acceptor solvent, the hemiacetal form (ring-closed) of 16 was detected [28].…”

“…The oxidation of benzofuran (BF), 2-methylbenzofuran (2MBF), and 3-methylbenzofuran (3MBF) in the presence of an Fe(III) porphyrin and hydrogen peroxide was recently reported by us, and afforded a one-pot, green, and versatile method for the synthesis of novel and biologically active compounds [28]. The significantly different reactivity observed for iron and manganese porphyrins has been ascribed to the formation of different catalytic intermediates [10,29].…”

C2-Selective, Functional-Group-Divergent Amination of Pyrimidines by Enthalpy-Controlled Nucleophilic Functionalization

“…2-Aminopyrimidines with haloarene motifs (26,27) were synthesized efficiently, providing an orthogonal synthetic handle for conventional cross-coupling reactions. Moreover, the substrates bearing oxidatively labile functional groups, such as alkenyl, 101 benzofuranyl, 102 and amido, 103 were aminated in moderate to high yields (27−29).…”