Chromenes coumarins

The phenolics include anthocyanins, anthraquinones, benzofurans, chromones, chromenes, coumarins, flavonoids, isoflavonoids, lignans, phenolic acids, phenylpropanoids, quinones, stilbenes and xanthones. Some phenolics can be very complex in structure through additional substitution or polymerization of simpler entities. Thus xanthones can be prenylated and flavonoids, lignans and other phenolics can be glycosylated. Condensed tannins involve the polymerization of procyaninidin or prodelphinidin monomers and hydrolysable tannins involve gallic acid residues esterified with monosaccharides. As detailed in this review, representatives of some major classes of plant-derived phenolics are potent protein kinase inhibitors. 

The naturally occurring (-i-)-calanolide A 21, R = n-Pr, and (H-)-inophyllum B 21, R = Ph, are of interest in that the molecules possess chromene, coumarin and chromanol systems. Total syntheses of them start from a coumarin and generate the chromanone unit through an intramolecular Michael addition which under (-)-quinine catalysis affords cis and trans benzodipyrans with 97% and 52% ee, respectively. The chromene moiety is constructed using the phenylboronic acid assisted reaction with senecioaldehyde. Reduction of the chromanone to the chromanol completes the sequence <04JOC2760>. 

Tetrahydrobenzopyrans, chromenes, coumarins, xanthenes, and so on are some of the most important oxygen-containing heterocyclic compounds. Several synthetic methods are available for these compounds. This part of the chapter deals with the synthesis of these heterocyclic compounds using nano-ZnO as a reusable heterogeneous catalyst. 

Chizhov DL, Sosnovskikh VY, Pryadeina MV, Burgart YV, Saloutin VI, Charushin VN (2008) The first synthesis of 4-unsubstituted 3-(trifluoroacetyl)coumarins by the Knoevenagel condensation of salicylaldehydes with ethyl trifluoroacetoacetate followed by chromene-coumarin recyclization. Synlett 2008 281-285... 

R.S. Menon, A.D. Findlay, A.C. Bissember, M.G. BanweU, The Au(l)-catalyzed intramolecular hydroarylation of terminal alkynes under mild conditions application to the synthesis of 2H-chromenes, coumarins, benzofurans, and dihydroquinolines, J. Org. Chem. 74 (2009) 8901-8903. 

The Knoevenagel condensation is one of the most useful C-C bond forming reaction in organic synthesis. This reaction is often the key catalytic step in the synthesis of heterocyclic compounds followed by intramolecular hetero-cyclization. Porous catalytic systems have been reported to be in use in the preparation of O-heterocycles through Knoevenagel condensation, particularly in the synthesis of chromenes, coumarins, and xanthenediones. 

R] (a) Hauser, C. R. Swamer, F. W. Adams, J. T. Org. React. 1954, 8, 59. [R] (b) Ellis, G. P., Chromenes, Chromanones, and Chromones from The Chemistry of Hetereocylic Compounds, Weissberger, A. and Taylor, E. C., eds John Wiley Sons, 1977, vol. 31, New York, p.495. Note The author in the former reference refers to the formation of chromones, coumarins, and flavones as the Kostanecki acylation while the latter author calls the formation of chromones and coumarins the Kostanecki-Robinson reaction. 

On the other hand, alkaline treatment of coumarin derivatives 108 did not lead to the expected cyclization products 107, but isomerization to the corresponding chromenes 109 took place instead (Scheme 17) (96JHC351). 

The 2,2-dialkylchromenes can easily be obtained from the reaction of coumarin 27 with a Grignard reagent.48 This method has been known for a long time and has not been modified much. The parent chromene 28 has been prepared by reduction and dehydration of 4-chromanone.63 Elimin-... 

Cyclization process of arene-yne substrates has been reported with platinum(rv) catalyst (PtCL ), resulting in C-H activation and functionalization.142 This hydroarylation gives 6-< r/o-products in high yields with good tolerance to different functional groups like amine, ester, and ether. This method provides a rapid access to interesting molecules such as coumarins, chromenes, or dihydroquinolines. 

In the above cases, the photoreactivity of indole, coumarin, pyridine, and so forth, does not compete effectively with PFR, which becomes the major reaction. However, in the case of the chromene depicted in Scheme 28, the electrocyclic ring opening prevails over PFR. By contrast, the analogous chromane undergoes clearly acyl migration [86]. 

Hydrogenation to chromanes, oxidative degradation, and oxidation to pyrylium salts in acid medium have been known for a long time.3 A series of substituted benzopyrylium salts has been recently prepared by oxidation of chromenes with tritylium perchlorate.97 Oxidation of 4-phenylchromenes to coumarins with Cr03-pyridine complex or with Se02 in dioxan has been reported.186... 

A similar pathway is thought to be involved in the synthesis of chromenes from coumarin (see Section 2.23.6.4.1), whilst the spontaneous dehydration of the alcohol (97) to the ketochromene (98), which occurs during acid hydrolysis, also presumably proceeds through the same type of intermediate. This step is an important feature of the synthesis of siccanochromene A, a fungal metabolite, from orcinol and the aldehyde (96) outlined in Scheme 10. Another point of interest in this route is the use of heteroatom-facilitated metallation to achieve the correct orientation (71T6073). 

The synthesis of chromenes from other six-membered oxygen heterocycles has much to offer because of the accessibility of the precursors. Thus much of the earlier work on chromenes was based especially on their synthesis from coumarins or chromanols. 

The acid-catalyzed cyclization of 3-(2-hydroxyphenyl)propan-l-ones leads to chrom-2-enes. This reaction accounts for the formation of 2,4-diphenylchrom-2-ene from the reaction of phenylmagnesium bromide on coumarin. The organometallic reagent ring-opens the coumarin to the ketone which cyclizes to the chromene on boiling with acetic acid (Scheme 26) (63T839). In a similar manner, various benzocoumarins afford propanones which cyclize readily in acetic acid to the naphthopyran (70JCS(C)1758). 

Coumarins (also called 2H-l-benzopyran-2-ones or 2-oxo-2H-chromenes) are common in nature and find their main applications as fragrances, pharmaceuticals and... 

Coumarin, 7-diethylamino-4-methyl-fluorescence, 3, 879 Coumarin, dihydro-chroman synthesis from, 3, 785 4H-chromene synthesis from, 3, 765 coumarin synthesis from, 3, 810 mass spectra, 2, 23 synthesis, 3, 848 Coumarin, 3,4-dihydro-4,4-disubstituted synthesis, 3, 754... 

The hyperbaric 4 + 2-cycloaddition of 1,2,4-trioxegenated 1,3-dienes with dieno-philes, A-phenylmaleimide, and methyl and phenyl acrylates produced the expected endo-cycloadducts with excellent stereo- and regio-control.113 The high-pressure (g) Diels-Alder reactions of 3-substituted coumarins with methylbuta-1,3-dienes in water formed tetrahydro-6H-benzo[c]chromen-6-ones in high yields (85-95%).114... 

The use of coumarin in Diels-Alder reactions is, by comparison to pyran-2-ones, still largely unexplored. This is likely due to the low reactivity of the double bond at positions 3 and 4. Diels-Alder reactions with 3-substituted coumarins are rare, despite the potential to synthesize tetrahydro-6//-benzo[c]chromen-6-ones, important precursors to functionalized biphenyls and several natural products. Electron-withdrawing substitution at C-3 does not serve to efficiently activate the dienophilic system thus, it has been found that high temperatures and pressures are necessary to effect the reaction (e.g., Equation 25) <2006JOC70>. 

In the presence of a ruthenium catalyst, 3-diazochroman-2,4-dione 716 undergoes insertion into the O-H bond of alcohols to yield 3-alkyloxy-4-hydroxycoumarins 717 (Equation 285) <2002TL3637>. In the presence of a rhodium catalyst, 3-diazochroman-2,4-dione 716 can undergo insertion into the C-H bond of arenes to yield 3-aryl-4-hydroxy-coumarins (Equation 286) <2005SL927>. In the presence of [Rh(OAc)2]2, 3-diazochroman-2,4-dione 716 can react with acyl or benzyl halides to afford to 3-halo-4-substituted coumarins (Equation 287) <2003T9333> and also with terminal alkynes to give a mixture of 477-furo[3,2-f]chromen-4-ones and 4/7-furo[2,3-3]chromen-4-ones (Equation 288) <2001S735>. 

The high diastereoselective synthesis of multifunctionalized 3,4-dihydro-coumarins bearing a quaternary stereocenter was developed through tandem Michael additions of indole and its derivatives (1-methyl, 2-methyl, 4-methoxy, 5-methoxy, 5-bromo, 6-benzyloxy) to 3-nitrocoumarines (3-nitro-chromen-2-one, 6- and 7-methyl-3-nitro-chromen-2-one) followed by methyl vinyl ketone in a one-pot step. For the tandem Michael additions, after the first Michael reaction of indole (2) with 3-nitrocoumarine (51) catalyzed... 

Quaternary ammonium hydroxides anchored on MCM-41 provide stronger base catalysts than amine analogues11731 and were able to catalyse the same reaction as previously reported namely for the intermolecular Michael reaction leading to flavanone.[181] Moreover, this catalyst induced the successive intramolecular olefinic attack of the phenolic group from the Knoevenagel condensation product of salicylaldehyde and diethyl glutaconate (Scheme 9.6). This fast cyclization leads to chromene derivatives (1) from which subsequent conversions induced by proton abstraction from the alpha position of the ester function gives coumarin... 

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