Synthesis stilbene derivatives

Pheuanthrene synthesis. Stilbene derivatives are oxidatively cyclized to phenanthrenes by vanadyl trifluoride in TFA-CH2CI2 at 0°. An example is the conversion of 1 into 2. This reaction had been conducted by photocyclization. 

Synthesis of the phenyl derivative (138) was also described by Simoni et al. [60] and employs the same synthetic strategy as for the pyridine derivative (137) described in Scheme 34. No biological activity was reported for this compound, but it was included in order to provide a broader coverage of stilbene derivatives. 

Stilbene derivatives can be reduced with alkali metals in liquid ammonia. The reaction is usually performed in a homogeneous medium to give substituted diphenylethane compounds as a mixture of enantiomeric forms. However, there are compounds (particularly, biologically active ones) for which the stereospecificity of synthesis has decisive importance. A simple modification of the reduction method with an alkali metal in liquid ammonia was found (Collins and Hobbs 1983), which makes it possible to perform the process stereoselectively. The metal is not predissolved, as is usual, but is added in small portions without trying to make the reaction medium homogeneous. Stereoselectivity is ensured by carrying out the reduction on the surface of the metal and not in the solution bulk. 

Photoamination of a variety of aromatic compounds with ammonia and alkyl-amines under photosensitized electron transfer mediated reaction conditions has been extensively investigated by Yasuda and coworkers (Scheme 70) [320-324]. The photoamination reactions of stilbene derivatives with ammonia have been utilized for the synthesis of a variety of isoquinoline derivatives [324]. The photoamination is initiated by photochemical electron transfer from the arenes to the electron acceptor followed by nucleophilic attack of ammonia or primary amines on the aromatic radical cations (Scheme 70). 

G.R. Pettit and co-workers converted a highly substituted frans-stilbene derivative to the strong cancer cell growth inhibitor and antimitotic agent hydroxyphenstatin. The key step of the synthesis was a BFs-OEta-catalyzed pinacol rearrangement of an optically active vicinal diol to afford a substituted diphenylacetaldehyde in racemic form. From this key intermediate, several derivatives were prepared in addition to the target molecule. 

The use of microwave technology in synthesis continues to gain popularity. A microwave-enhanced synthesis of 3-aryl-4-hydroxyquinolin-2(l//)-oncs by cyclization of a malonodianilide under solvent free conditions was reported <01TL1367>. Microwave irradiation was also used to prepare quinolones from anthranilic acid and ketones <01SC3647>. A microwave promoted, intramolecular cyclization of an isocyanate in the ortho position of a stilbene derivative to afford a quinolone derivative was also reported <01T6197>. 

A large group, consisting of flavonoids, pigments and stilbene derivatives through to the synthesis of naringenin. 

Reproduced with permission from Zhu X, Uu J. Chen T, Su W. Mechanically activated synthesis of (Ej-stilbene derivatives by high-speed ball milling. AppI Organomet Chem 2012 26 145-7. Copyright (2012), Wiley. 

The intramolecular coupling reaction between an aryldiazonium salt (III) with an arene subunit to form five- or six-membered ring by the influence of copper or an acid, is called the Pschorr cyclization reaction [85]. In historical examples the Pschorr cyclization was used in the synthesis of phenanthrene and its derivatives. For example, c -stilbene derivative 49 is diazotized to give 50, and subsequently treated with the activated copper to obtain phenanthrene (51) in 34% yield [86], Scheme 21. 

Because of the chemical stability of phenyl moiety of 1,2-diphenylethylene, stilbene is not a suitable starting compound for synthesis of stilbene derivatives. In order to form more complex molecules, it is necessary to introduce more reactive functional groups. 

Many synthetic routes to stilbene derivatives have been reported, and only most important methods, which were used in the total synthesis, will be considered in this section. Figure 1.1 summarizes the five most important methods for forming the C=C bond of the 1,2-ethenediyl unit in stilbenes. 

The Horner-Wadsworth-Emmons reaction (or HWE reaction) is the reaction of stabilized phosphonate carbanions with aldehydes (or ketones) to produce predominantly -alkenes. In 1958, Horner published a modified Wittig reaction using phosphonate-stabilized carbanions [32]. Wadsworth and Emmons further defined the reaction [33]. Compared to phosphonium ylides used in the Wittig reaction, phosphonate-stabilized carbanions are more nucleophilic and more basic. Likewise, phosphonate-stabilized carbanions can be alkylated, unlike phosphonium ylides. The dialkylphosphate salt by-product is easily removed by aqueous extradion. A reliable and versatile synthesis of a stilbene derivative, 2,2-aryl-substituted cinnamic acid esters, using the Wittig reaction was reported [34—36] (Figure 1.3). 

The synthesis of several aza-stilbene derivatives similar to was carried out (Figure 1.15) [81]. The compounds were tested for their c-RAF enzyme inhibition. 

Figure 1.15 Synthesis of several aza-stilbene derivatives. Reagents and conditions (a) tributylvinyl tin, LiCI, BHT, Pd(PPh3)2Cl2, DMF, 70°C (b) aryl bromide(iodide), Pd2dba3, TEA, P(o-tol)3, DMF, 95°C [81]. (Reproduced with permission from Elsevier.)...

New labeled stilbene derivatives, such as ris-3,5-dimethoxy-4 -[ C]methoxystilbene, as-3,4, 5-trimethoxy-3 -[ C]methoxystilbene, trans-3,5-dimethoxy-4 -[ C]methoxys-tilbene, trans-3,4, 5-trimethoxy-3 -[ CJmethoxystilbene, cis-3,5-dimethoxy-4 -[ F] fluorostilbene, and trans-3,5-dimethoxy-4 -[ F]fluorostilbene, were designed and synthesized [94]. The synthesis of ( )-tris-0-methylresveratrol and ( )-3,5-dimethox-ystilbene via the Miyaura-Suzuki coupling was described [95]. This reaction has been carried out in air without solvent/substrate purification and in the absence of additional free ligand. Figure 1.18 shows a scheme of deoxyschweinfurthin synthesis accomplished in Ref [96]. 

V and 1 GHz, respectively. A ne v nonconjugated polymer electroluminescent material, including stilbene derivatives, vas patented [19]. The preparation process for this electroluminescent material involved monomer synthesis and polymer synthesis. The author suggested that this electroluminescent material can be used in electroluminescent devices, luminescent devices, and so on. 

Synthesis of stilbene derivatives and their use in binding and imaging amyloid plaques were patented [39]. The invention described a method of imaging amyloid... 

CYP53 Benzoic acid (and derivatives) hydroxylation and trimethoxy-trans-stilbene 0-demethylation Benzoate and its derivatives degrada-tion/detoxification and synthesis of stilbene derivatives A. niger,A. nidulans, Cochliobolus luna-tus, P. chrysosporium and Postia placenta [502, 827 830]... 

The substituted diphenylacrylonitrile LI (related to a new group of stilbene derivatives) has been found to be as active as triparanol in the rat [106]. Synthesis of a number of substituted stilbenes has been described by Morgan et al. [162]. Some of these stilbenes were shown to inhibit the bios5mthesis of cholesterol. 

According to the Woodward-Hoffmann rules for electrocychc reactions, a 6k electrocychzation is thermally allowed in a disrotatory manner and photochemically allowed in a conrotatory manner. However, in the present context of synthesis of aromatic compounds as final products, which are devoid of any stereocenters, the stereochemical aspects of the substituents in the intermediate dihydroaromatic compound should not matter. The photochemical 6x electrocychzation of c/s-stilbene derivatives followed by oxidation of the dihydroaromatic intermediate provides access to angularly fused polycyclic aromatic compounds (Scheme 16.2) [4]. 

The formation of compound 15 is favored since HF. = 1.126. Generally, the regioselectivity leading to helicenes is favored. For this reason, the electrocyclization of stilbene derivatives is one of the standard methods for the synthesis of these compounds. 

SCHEME 13.69 Model reaction for the multicomponent synthesis of stilbene derivatives 315 [122]. 

The photoelectrocyclization of stilbene derivatives under oxidative conditions (air or iodine generally used as oxidants) has been largely exploited for the synthesis of various natural product systems. As an example, the benzophenan-thridine ring of kibdelone 15 was best prepared from the stilbene derivative 14 by irradiation in the presence of 1.1 equivalent iodine and excess THF as a trap for the cogenerated HI that would otherwise cause extensive degradation of the products (Scheme 8.4) [4]. 

In fact, we recently reported the first synthesis of and electro-optic characterization of a 4-amino-4 -phosphorylated stilbene derivative (19). This, indeed, exhibited second-order NLO properties. 

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