Synthesis and Structural Characterization of Ferrocenyl-Substituted Aurones, Flavones, and Flavonols

Abstract

In the context of our studies on the modification of bioactive molecules with ferrocene, we here report the first examples of ferrocenyl flavonoids, where ferrocene replaces the B ring of the flavonoid skeleton. Ferrocenyl aurones possessing an electron-withdrawing or an electron-donating group in the 5′-position were obtained from 5′-R-2′-hydroxy-3-ferrocenyl chalcones via 1,5 oxidative exocyclization using Hg(OAc)2 or AgOTf. Treatment of the ferrocenyl aurones with LDA resulted in a ring opening to form ferrocenyl ynones, which could then be selectively recyclized to the flavone isomer by treatment with NaOEt. Ferrocenyl flavones were also obtained by isomerization of the aurones with KCN and were hydroxylated in the 3-position to form ferrocenyl flavonols with oxone in a biphasic reaction. In many cases the reactivity of the ferrocenyl compounds was significantly different from that of their organic analogues. This reactivity and regioselectivity can be rationalized by ferrocene’s particular ability to destabilize α-anions in reaction intermediates. Representative examples of ferrocenyl aurones, ynones, and flavones were characterized by 2D NMR and X-ray crystallography, and the molecules all show a planar arrangement of the organic skeleton with the cyclopentadienyl ring of the ferrocene group. Putative MLCT bands in the visible region are responsible for the variety of highly saturated colors observed.

Solvent‐Free Synthesis and In Vitro Antitumor Activity of a New Class of (Z)‐3‐Arylidene‐1H‐pyrano[3,4‐b]quinolin‐4(3H)‐ones

“…In addition, it has been well‐established that the introduction of ferrocene ring into heterocycles often lead to new hybrids with enhanced biological activity attributed to the redox behavior of the ferrocene . For example, Tiwari's group and Chen et al . independently reported the synthesis of ferrocenyl‐appended aurone hybrids via oxidative cyclization of 2‐hydroxychalcones as shown in Scheme a.…”

DABCO-catalyzed synthesis of 3-substituted-3-hydroxyindolin-2-ones in aqueous media

“…As a part of our research plan aimed at developing new synthetic methodologies for the creation of biologically important molecules [24][25][26][27][28] , we inspired to investigate greener protocol for generation of substituted oxindoles. In this line, we wish to report the synthesis of 3-substituted-3-hydroxy-indolin-2-ones using water as a solvent catalysed by DABCO with good to excellent yields by aldol reaction (Scheme 1).…”

Ferrocenyl-Appended Aurone and Flavone: Which Possesses Higher Inhibitory Effects on DNA Oxidation and Radicals?

“…13 16 (Z)-6-Hydroxy-2-ferrocenylidene-benzofuran-3-one, 11. R f = 0.55 (ethyl acetate/petroleum ether = 1:1, v/v), 1.90 g of violet solid, yield 55%.…”

“…13 C NMR (100 MHz, CDCl 3 ) δ: 181.2, 163.9, 145.9, 138.5, 127.1, 124.4, 117.9, 115.9, 114.7, 74.7, 72.2, 71.7, 70.0. HRMS (ESI): m/z calcd for C 19 H 13 BrFeO 2 + , 430.93460 and 432.93256; found, 430.93406 and 432.93201 16. 6-Bromo-2-ferrocenyl-chromen-4-one,16.…”

“…HRMS (ESI): m/z calcd for C 19 H 13 BrFeO 2 + , 430.93460 and 432.93256; found, 430.93406 and 432.93201 16. 6-Bromo-2-ferrocenyl-chromen-4-one,16. R f = 0.54 (ethyl acetate/petroleum ether = 1:3, v/v), 40 mg of red solid, yield 40%.…”