Ring-closing metathesis as a new methodology for the synthesis of monomeric flavonoids and neoflavonoids

Isomerization of Allylbenzenes

“…Related work that involved the use of a thermal Claisen rearrangement to generate the arylallyl functionality on a substrate with the cinnamyl group, viz., 167 → 168 , resulted in the spontaneous isomerization of the terminal allyl group in 168 to the thermodynamically more favored alkene 169 under these conditions (Scheme ). ,− Alkene 169 was then converted into the bis-alkene 170 via a Grignard reaction as described in Scheme . On an interesting aside, Bezuidenhoudt and co-workers were able to obtain the unisomerized 2-(1-phenylallyl)­phenol scaffold 172 , albeit in low yield, when they performed a related Claisen rearrangement on 171 in N , N -dimethylaniline under reflux . In addition, when potassium tert -butoxide was used to isomerize substrate 173 , only moderate amounts of the desired isomer 174 were obtained, in addition to appreciable amounts of the trisubstituted naphthol 175 (this approach has been used before to generate the naphthalene skeleton, , and recently a related palladium-mediated Wacker-type approach to naphthols starting from allylbenzaldehydes also resulted in isomerized substrate under the basic conditions used by the researchers).…”

“…On an interesting aside, Bezuiden-houdt and co-workers were able to obtain the unisomerized 2-(1-phenylallyl)phenol scaffold 172, albeit in low yield, when they performed a related Claisen rearrangement on 171 in N,Ndimethylaniline under reflux. 316 In addition, when potassium tert-butoxide was used to isomerize substrate 173, only moderate amounts of the desired isomer 174 were obtained, in addition to appreciable amounts of the trisubstituted naphthol 175 (this approach has been used before to generate the naphthalene skeleton, 313,317 and recently a related palladium-mediated Wacker-type approach to naphthols starting from allylbenzaldehydes also resulted in isomerized substrate under the basic conditions used by the researchers 318 ). A recent, related synthesis of fluorinated naphthols by Magauer and co-workers makes use of the treatment of substituted 2-allyl-3-(trifluoromethyl)-phenols with potassium tert-butoxide in sulfolane (7 equiv, 120 °C, 7 h, yields 24− 56%).…”

Antigenotoxic and anticytotoxic activity of Duguetia furfuracea in bacteria and mice

“…Literature data have shown that sesquiterpenes are potential anticancer agents (Fraga, 2006). Flavonoids are commonly categorized as anti-inflammatory, anticarcinogenic, diuretic, antimicrobial, antiviral, and antioxidant compounds (Hu et al, 2011;Miller et al, 2012). The presence of certain substances in plants, including flavonoids and terpenoids, may protect cells against DNA damage (Silva et al, 2006).…”

Ring-closing metathesis in flavonoid synthesis, part 2: neoflav-3-enes

“…13 In our endeavours to find benign, catalytic methodologies towards the synthesis of flavonoids, we recently reported a ring-closing metathesis strategy for the preparation of flav-2-enes (6) displaying natural substitution patterns (Scheme 1a). 33 We previously also reported on the preparation of the 7-methoxy derivative of neoflav-2-ene (10) 34 by means of a Claisen rearrangement, vinylation and subsequent ring-closing metathesis with Grubbs second generation catalyst (GII). The yield of the Claisen rearrangement step was unacceptably low, though (21%) (Scheme 1b).…”

“…The yield of the Claisen rearrangement step was unacceptably low, though (21%) (Scheme 1b). 34 In an alternative approach, Wang and co-workers 35,36 prepared a limited series of neoflav-3-enes (16) through the GII-catalyzed ring-closing metathesis of 1-(allyloxy)-2-[1-(phenyl)vinyl]benzenes (15), which in turn could be obtained by Wittig methylenation of the corresponding benzophenones (14). The benzophenone (14) was obtained through either the Grignard reaction of 2-allyloxybenzaldehydes (11) and subsequent MnO2 oxidation, or the Friedel-Crafts acylation of an allylether (17) (Scheme 2).…”