Stilbenes oxidative cyclizations

Reactions.—Nucleophilic Attack at Carbon. (/) Carbonyls. Methyl arylglyoxylates react with trisdimethylaminophosphine (TDAP) to form m-a/S-dimethoxycarbonyl-stilbene oxides.63 The initially formed zwitterion (61) reacts with a second molecule of the ester to form a fra/ -diphenyl-1,4,2-dioxaphospholan intermediate, which undergoes a concerted symmetry-allowed retrograde n2s + 4 cycloaddition to give a carbonyl ylide, conrotatory cyclization of which leads to the cw-oxirans (62) (Scheme 3). 

The valence tautomerism 251 257 has been proposed to account for the formation of iV-methylthiobenzamide by irradiation (2537 A) in methyl cyanide solution. The valence tautomer 257, R = Me, = Ph, has been detected spectroscopically (p , 2060 cm —N=C=S) either during photolysis at 25° or by heating at 160°. Photochemical oxidative cyclization of 4,5-diaryl derivatives (251, R = R = Ar) analogous to the formation of phenanthrene from stilbene has been reported. Thus, irradiation of the 4,5-diphenyl derivative 251, R = R = Ph, yields the tetracyclic meso-ionic compound (258). ... 

Photochemical cyclization of heterocyclic stilbenes. The photochemical oxidative cyclization of stilbenes to phenanthrenes6 proceeds in low yield when applied to heterocyclic analogs. Cava et al have examined a number of oxidants other than 02 for in situ oxidation of the dihydroheterocycle formed initially and find that 5% Pd on carbon is the reagent of choice. In addition, a hydrogen acceptor, p-nitrobenzoic acid, can improve yields. 

Irradiation of 2-acetyl-l-benzylidine-l,2,3,4-tetrahydroisoquino-line (353 R = H) in methanol in the presence of iodine results in the formation in good yield of 8-methylprotoberberinium iodide (354 R = H)384 and not of the dehydroaporphane system which might be expected by analogy with oxidative cyclization of cis-stilbene... 

The epoxy alcohol 47 is a squalene oxide analog that has been used to examine substrate specificity in enzymatic cyclizations by baker s yeast [85], The epoxy alcohol 48 provided an optically active intermediate used in the synthesis of 3,6-epoxyauraptene and marmine [86], and epoxy alcohol 49 served as an intermediate in the synthesis of the antibiotic virantmycin [87], In the synthesis of the three stilbene oxides 50, 51, and 52, the presence of an o-chloro group in the 2-phenyl ring resulted in a lower enantiomeric purity (70% ee) when compared with the analogs without this chlorine substituent [88a]. The very efficient (80% yield, 96% ee) formation of 52a by asymmetric epoxidation of the allylic alcohol precursor offers a synthetic entry to optically active 11 -deoxyanthracyclinones [88b], whereas epoxy alcohol 52b is one of several examples of asymmetric epoxidation used in the synthesis of brevitoxin precursors [88c]. Diastereomeric epoxy alcohols 54 and 55 are obtained in combined 90% yield (>95% ee each) from epoxidation of the racemic alcohol 53 [89], Diastereomeric epoxy alcohols, 57 and 58, also are obtained with high enantiomeric purity in the epoxidation of 56 [44]. The epoxy alcohol obtained from substrate 59 undergoes further intramolecular cyclization with stereospecific formation of the cyclic ether 60 [90]. 

Wang and colleagues found that 10 mol% of FeCl3 catalyzed the intramolecular oxidative cyclization of acceptor-substituted ( )- and (Z)-stilbenes 93 to... 

Further extensions of the stilbene photocyclization are seen in analogous reactions of compounds containing the imine chro-mophore (e.g. 3,71) or an amide group (3.72). The amide reaction can be considered formally as giving a zwitterion intermediate, which undergoes proton shifts and oxidation to form the observed product. Non-oxidative cyclizations that start with either N-vinyl aromatic carboxamides (C=C— N— CO—Ar) or N-aryl a,p-unsaturated carboxamides (Ar— N—CO—C=C) have been extensively used to make quinoline or isoquinoline alkaloids and their derivatives a fairly simple example is given in (3.73). 

The shortest synthesis of papaverine was achieved in the laboratory of R. Hirsenkom starting from racemic stilbene oxide and using a modified Pomeranz-Fritsch reaction The aminolysis of the stilbene oxide led to the formation of the cyclization precursor, which upon treatment with excess benzoyl chloride, underwent cyclization to give the N-benzoyl 1,2-dihydroisoquinoline derivative. Reduction under Wolff-Kishner conditions afforded papaverine. 

Intramolecular Cyclization Reactions This Section is concerned with photo-induced cyclization reactions of aromatic compounds in which the final product is also an arene. Examples of intramolecular cyclization in which the product is a stable aliphatic system (e.g. intramolecular meta photocycloaddition of ethylenes to benzenes) are considered in Section 3 of this Chapter. The present type of process occurs for a wide variety of systems and may involve arene-arene and arene-ethylene photo-oxidative cyclization or reactions proceeding by loss of halogen acid. For several years now one of the major interests in these processes has been in their use as synthetic procedures and again within the review period there have appeared a number of accounts which illustrate this feature. Stilbene-... 

Sudhakar and Katz have devised an improved route to [7] helicene. The bromine atom is found to direct the stilbene cyclization away from occupied positions and those ortho to the substituent so that with (153) the bromo [7] helicene (154) is formed in 75% yield on irradiation of benzene solutions containing iodine, and less than 10% of the planar arene (155) is observed. Such results compare very favourably with those from irradiation of the hydrocarbon (156) when equal quantities of the [7] helicene and (157) are formed.Irradiation of (158), the meta isomer of (156), cyclizes selectively without bromine direction and (159) is formed in 75% from xylene solution in the presence of oxygen and iodine The origins of this selectivity may not be readily evident and it is difficult to appreciate why of the four possible conformers of the first intramolecular photo-oxidative cyclization product only (160) undergoes further reaction. The authors suggest that this feature reflects that of the four conformers (160) has the smallest degree of steric interactions between the two aryl moieties. The photo-cyclizations of halostilbenes have been examined by other workers who report that various o-chloro and bromo-compounds (161) undergo... 

Arguments derived from conformational analysis were used73 to account for the fact that the ion 44 is generated in substantially higher abundance when threo- 1,2-diphenyl-l,2-bis(trimethylsiloxy)ethane (101) serves as precursor in comparison with the erythro-isomer (102). In the former both the cyclization step 103 - 104 and the elimination of trans-stilbene oxide (105) are favoured on stereochemical grounds (reaction 47). In the erythro-precursor 102, however, the destabilizing interaction of the two phenyl groups retards the formation of 44 (reaction 48). 

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. 

Authors found that the vinylalumination reaction is fully diastereoconvergent as the reaction of both cis- and trans-stilbene oxides 90 led to the exclusive formation of the same anti-configured homoallyUc alcohol 39a, which was subsequently cyclized to fS,y-diphenyl-a-methylene-y-lactone trans-29aa under acidic conditions (Scheme 4.23). This experimental result was rationalized by the intermediacy of the corresponding benzyhc carbocation in the reaction. 

The cyclization product is thermally unstable relative to Z-stilbene and reverts to starting material unless trapped by an oxidizing agent. The extent of eyclization is solvent-dependent, with nonpolar solvents favoring cyclization more than polar ones. ° Whereas the quantum yield for Z-E isomerization is nearly constant at about 35%, the cyclization... 

Cis-stilbene (Zl) also undergoes a conrotatory cyclization reaction into trans-4a,4b-dihydrophenanthrene (DHP, 2), a short living, not isolated product with an absorption in the visible spectrum at 450 nm. In the absence of an oxidizing agent DHP will return to the starting material, by both a thermal and a photochemical ring opening reaction. 

In the presence of an oxidizing species (oxygen, iodine, tetracyanoethylene and others) DHP is dehydrogenated into phenanthrene. This oxidation can also be thermal or photochemical. In general, meta substituted stilbenes give rise to two isomeric substituted phenanthrenes ortho-substituted stilbenes can lose the substituent on cyclization. 

A number of l-aryl-2-thienylethylenes have been photocyclized in the presence of an oxidizing agent (usually iodine) to polycyclic aromatic compounds. Representative examples are given in Table 1. The mechanism, as with the conversion of stilbene to phenanthrene, probably involves conversion of the trans-alkene to the c/s-form, cyclization to the dihydro isomer, and oxidation of the latter to the fully aromatic compound. The yield of the cyclized product seems to decrease when the ethylene is attached to the /3-position of the thiophene. 

Anodic oxidation of tetraphenylethylene at a platinum electrode leads to the product of cyclization, namely, to 9,10-diphenylphenanthrene (Stuart Ohnesorge 1971). The intramolecular coupling reaction does not occur when diphenylethylenes, i.e., stilbene and its methyl derivatives, are electrolyzed under the same conditions (Stuart Ohnesorge 1971). This difference in the anodic behavior of these substances was attributed to the low stability of the cation radicals of stilbene and its methyl derivatives in comparison to the cation radicals of tetraphenylethylene. The participation of the cation radicals in cyclization of tetraphenylethylene has been unequivocally proved (Svanholm et al. 1974 Steckhan 1977). 

Tetraphenylethylene cyclizes anodically to 9,10-diphenylphenanthrene analogously to its photooxidative cyclization. The attempted anodic cyclization of cis- or frans-stilbene to phenanthrene however failed due to electrophilic reaction of the intermediate radical cation with the solvent 37S Primary aromatic amines are oxidized to radical cations which, depending on the pH of the electrolyte couple to aminodiphenylamines (C-N coupling (84) in Eq. (172) ), yield benzidines (85) at low pH (C-C coupling) or dimerize to hydrazobenzene (86) (N-N coupling) which is subsequently oxidized to azobenzene (Eq. (172) ) 2 5,376,377)... 

Fig. 7-30. Examples of proposed leucochromophoric and chromophoric structures. Aryl-coumarones (1) and stilbene quinones (2) are thought to be formed from stilbenes after oxidation. Butadiene quinones (3) could arise from oxidation of hydroxyarylbutadienes being formed from phenolic pinoresinol structures during kraft or neutral sulfite pulping. Cyclization may yield intermediates which are further oxidized to cyclic diones (4). A resonance-stabilized structure (5) results from the corresponding condensation product formed during pulping. o-Quinoid structures (7) are oxidation products of catechols (6) formed during alkaline or neutral pulping processes.

There are a large number of photochemical cyclizations of aromatic compounds that lead initially to polycyclic, non-aromatic products, allhough subsequent rearrangement, elimination or oxidation occurs in many instances to form aromatic secondary products. The archety pe for one major class of photocyclization is the conversion of stilbene to phenanthrene by way of a dihydrophenanthrene (3.60). 

A -Acetyltryptophan ethyl ester on reaction with Lawesson s reagent afforded the thioamide 9, which with methyl iodide in acetone yielded the methylthioiminium salt 10 which cyclized spontaneously to the quaternary salt 11 (24). BC 12 on condensation with benzaldehyde gave stilbene 13, which oh oxidation with potassium permanganate afforded... 

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