Hydroxychalcones, cyclization

Phenolic oxygen participates in facile oxypalladation. The intramolecular reaction of 2-hydroxychalcone (105) produces the flavone 106[127]. The ben-zofuran 107 is formed from 2-allyIphenol by exo cyclization with Pd(OAc)2, but benzopyran 108 is obtained by endo cyclization with PdChf S], Normal cyclization takes place to form the furan 109 from 2-(l-phenylethenyl)phe-nol[129]. Benzofuran formation by this method has been utilized in the synthesis of aklavinione (110)[130]. 

The stereospecific cyclization of chalcones to (2S)-flavanones is a prerequisite for the synthesis of the majority of fiavonoid subclasses derived from this branch point metabolite. This reaction is catalyzed by chalcone isomerase (CHI, CFI EC 5.5.1.6). CHI exists in two forms, one that accepts only 6 -hydroxychalcones and another that accepts both 6 -hydroxy-(naringenin chalcone) and 6 -deoxychalcones (isoliquirgentin), the latter generally found in legumes. Although 6 -hydroxychalcones will spontaneously convert to a racemic flavanone mixture, the CHI-catalyzed reaction proceeds at a rate 36 million-fold faster and is highly stereoselective for the formation of (25)-flavanones [60]. Spontaneous isomerization of 6 -deoxychalcones does not substantially occur without enzyme catalysis. 

Phenol esters of a,(3-unsaturated carboxylic acids have an interesting reactivity due to the synthetic utility of the resulting hydroxychalcones (Scheme 19). This aspect will be illustrated in Section IV. However, from the basic point of view, it is worth mentioning that the cis or trans configuration of the olefinic part of the acyl moiety can have a marked influence on the photochemical reactivity of the ester. When para-methoxyphenyl fumarates are irradiated, the normal ortho-rearranged products are obtained. By contrast, irradiation of para-me-thoxyphenyl maleates does not lead to rearrangement. Instead, cyclization products are obtained (Scheme 20). 

The carbamates formed from 2-hydroxychalcones and alkyl or aryl isocyanates readily cyclize to 3,4-dihydro-l,3-benzoxazin-2-one derivatives <1996CHEC-II(6)301>. When hydroxychalcones 318 with a benzofuran moiety were heated under reflux with phenyl isocyanate in benzene in the presence of a catalytic amount of potassium hydroxide, l,3-benzoxazin-2-one derivatives 320 were formed through the intermediate open-chain carbamates 319 (Scheme 61) <2006JHC437>. 

It is of interest to note that the thallium(III) acetate oxidation of a 2 -hydroxychalcone yields a mixture of a flavone, through participation of the 2 -hydroxy group in the cyclization, and a coumaranone, which presumably arises by further oxidation of an intermediate acetal <70JCS(C)119). 

Another example of an equilibrium involving ring-formation is the cyclization of 2-hydroxychalcones (12) to form chromanones (8 b). The... 

A phenolic oxygen participates in facile oxypalladation. 2-Allylphenol (55) undergoes clean cyclization to 2H-l-benzopyran (56) in DMSO under air with a catalytic amount of Pd(OAc)2 without a reoxidant. 2-Methylbenzofuran (57) is obtained when PdCl2 is used [50]. But different chemoselectivity with the Pd(II) salts was also reported [51]. Catalytic asymmetric cyclization of the tetrasubstituted 2-allylic phenol 58 using the binaphthyl-type chiral ligand 60, called (.S, .S )-ip-borax, afforded the furan 59 with 96% ee. Use of Pd(CF3 002)2 as a catalyst is essential in the presence of benzoquinone [52]. Formation of the benzofuran 62 from 61 has been utilized in the synthesis of aklavinione [53]. The intramolecular reaction of 2-hydroxychalcone (63) produces the flavone 64 [54]. 

A selenium dioxide induced oxidative cyclization of the 2 -hydroxychalcone 745 is a key step in the total synthesis of ( )-5 -methoxyhydnocarin-D (Scheme 189) <2005T4149>. DMSO containing catalytic amounts of iodine also effectively promotes the oxidative cyclization of 2 -hydroxychalcones to afford flavones <1996CHEC-II>. The DMSO-iodine mediated cyclization of the bis(2 -hydroxychalcone) 746 is a key step in the synthesis of the natural atropisomer4 4 ",7,7 -tetra-O-methylcupressuflavone (Equation 298) <1997TL1087>. Likewise, silica gel supported indium(in) halides catalyze the oxidative cyclization of 2 -hydroxychalcones to afford flavones in excellent yield (Equation 299) <2005TL253>. 

The treatment of various chalcones 210 with HTIB or DAIB-TSOH in a methanolic medium leads to the / -keto dimethylacetals 211 (Scheme 59) (02S2490). This rearrangement can also be effected with poly[4-(diacetoxy)-iodo]styrene and has been developed into a one-pot synthesis of isoflavones (e.g., 213) from benzoyl-protected 2/-hydroxychalcones (e.g., 212), via base-catalyzed cyclization of the acetal intermediates. 

FUlvones. 2 -Hydroxychalcones are oxidized in good yield to flavones in boiling amyl alcohol or xylene. This was the first example of use of the reagent for oxidative cyclization and is still one of the two best methods for the synthesis of flavones. ... 

Anodic addition of an oxygen function to a C = N or C = C double bond may be exemplified by the oxidative cyclization of aryl semicarbazones to 1,3,4-oxadiazoles in acetonitrile-acetic acid containing H2SO4 or, under strictly anhydrous conditions (in the presence of acetic anhydride), to triazolinones [40]. Other examples are the anodic oxidation of benzaldehyde-2-hydroxyanil to 2-phenyl-1,3-benzoxazole derivatives [41] and the indirect oxidation of 2-hydroxychalcones to flavonoids using tris(4-bromophenyl)amine in MeOH-CH2Cl2 as mediator [42] ... 

Hydroxychalcone is readily cyclized with hot aqueous alkali this is the basis of a widely applicable synthesis of flavanones [B-4]. In addition to the examples of dehydrogenative cyclization of chalcones described in Part 1 (pp. 191, 192), that produced by DDQ should be mentioned. In boiling dioxan, the reaction takes 20-72 h and produces flavones together with smaller amounts of flavanones and aurones. 

Hydroxychalcones (202) react with either alkyl or aryl isocyanates to give 3,4-dihydro-4-phenacyl-l,3-benzoxazin-2-ones (203). Carbamates form initially and these require heating in the presence of potassium hydroxide in order to effect cyclization to the benzoxazinones (Scheme 56). By heating a mixture of all of the reactants at once the preparation can be run as a one-pot reaction <88S246>. 

Selenophenes. Ring contraction of dihydroselenopyrans is effected by NalO. 2 -Hydroxychalcones - flavones. The oxidative cyclization proceeds in DMSO at 100-120°C. 

Oxidative cyclization. Treatment of 2 -hydroxychalcones (1) with mercuric acetate in DMSO gives cyclized adducts (2) and aurones (3) the adducts are converted into (3) by further treatment with CaO in DMSO. ... 

A similar study of ortho-hydroxychalcones in dry media using silica gel has been reported [171]. Conventional thermal cyclization, under the same conditions as for microwave irradiation, required a much longer reaction time (Eq. (89), Table 4.30, Scheme 4.23). 

Conversion of 2 -hydroxychalcones to 2-aryl-3-hydroxy-4/f-l-benzopyran-4-ones (flavonols) by an oxidative cyclization. 

Also, Bids adsorbed on silica gel, catalyzes the intramolecular cyclization of 2 -hydroxychalcones under dry conditions. The reaction proceeds efficiently giving... 

With the structurally similar 2 -hydroxychalcones, Lier et al. reported that either InCl3 or InBr3 supported on silica gel catalyze the intramolecular cyclizations in the absence of solvent at elevated temperatures [62]. However, the expected flavanones were not isolated, but the corresponding flavones were obtained instead. The supported In(III) catalyst had not only catalyzed the 1,4-addition, but had proceeded to catalyze the oxidation. This was proven from the authors oxidation of flavanones to flavones under the same reaction condition (Figure 8.35). 

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