Ellagitannins are a family of polyphenols containing more than 1,000 natural products. Nearly 40% of these compounds contain a highly oxygenated diaryl ether that is one of the most critical elements to their structural diversity. Here, we report a unified strategy for the synthesis of highly oxygenated diaryl ethers featured in ellagitannins. The strategy involves oxa-Michael addition of phenols to an orthoquinone building block, with subsequent elimination and reductive aromatization. The design of the building block-a halogenated orthoquinone monoketal of gallal-reduces the usual instability of orthoquinone and controls addition/elimination. Reductive aromatization is achieved with perfect chemoselectivity in the presence of other reducible functional groups. This strategy enables the synthesis of different diaryl ethers. The first total synthesis of a natural ellagitannin bearing a diaryl ethers is performed to demonstrate that the strategy increases the number of synthetically available ellagitannins.

A dihydridoruthenium(II) complex, [RuH2(CO)(PPh3)3], reacts with styrene to give two species: a bis(styrene)ruthenium(0) complex, [Ru(CO)(CH2=CHPh)2(PPh3)2], and a cyclometallated hydridoruthenium(II) one, [Ru(C6H4PPh2)H(CO)(PPh3)2]. The complex [RuH2(CO)(PPh3)3] reacts with isoprene to give a piano-stool type ruthenium(0) complex [Ru(η4-CH2=CMeCH=CH2)(CO)(PPh3)2]. In reactions among [RuH2(CO)(PPh3)3], styrene, and 3′-(trifluoromethyl)acetophenone, three cyclometallated hydridoruthenium(II) complexes: P,P′-cis-C,H-cis-, P,P′-trans-C,H-trans-, and P,P′-trans-C,H-cis-[Ru{C6H3(CF3)C(=O)Me}H(CO)(PPh3)2] are detected by NMR spectroscopy. The 1H NMR spectra of the reaction mixture exhibit the catalytic formation of 2′-(2-phenylethyl)- and 2′-(1-phenylethyl)-5′-(trifluoromethyl)acetophenones. On the basis of these findings, a mechanism for the C-H/olefin coupling reaction is discussed. The first of the three complexes is assigned to an active intermediate in the catalytic coupling reaction, whereas the other two are assigned as quasi-stable ruthenium(II) complexes which are in equilibrium with active species.

No abstract

Herein, a practical synthesis of the macaranoyl group contained in ellagitannins, i.e., a C-O digallate structure with a tetra-ortho-substituted diaryl ether bond, is described. The methodology involved an oxa-Michael addition/elimination reaction between a brominated ortho-quinone monoketal and a phenol with a hexahydroxydiphenoyl moiety in the presence of 18-crown-6 under dark conditions, followed by reductive aromatization. The existence of rotamers originating from the constructed ether moiety is discussed as well.