Benzopyrans synthesis

Scheme 6. Cycloloading and elaboration strategy for benzopyran synthesis according to Nicoloaou et al.

Clayfen preparation from K-10-bentonite clay and Fe(N03)3 in acetone, ref. 4 MENZER Benzopyran Synthesis... 

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 alkaloid reserpiae [50-55-5] which is isolated from the roots of Kauwoljia serpentina T., contains a gaUate trimethyl ether moiety. Reserpiae is used as an antihypertensive and a tranquilizer. A vinylogue of reserpiae, rescinnamine [24815-24-5] is also an antihypersensitive (75). Methoxsalen [298-81-7] (8-methoxypsoralen 7JT-9-methoxy-furo [3,2- ] [l]benzopyran-7-one) (21), a furocoumatia that occurs ia plants, eg, l eguminosae and Umbelliferae is used ia the treatment of vitiligo, as a suntanning promoter, and as a sunburn protectant. It is also available by synthesis (76). 

Coum rinic Acid Compounds. These synthetic phyUoquinone derivatives and congeners have been employed as anticoagulants since the isolation of 3,3 -methylenebis(4-hydroxy-2H-l-benzopyran-2-one) [66-76-2] (bis-4-hydroxycoumarin or dicoumarol) (1) from spoiled sweet clover in 1939. The ingestion of the latter was responsible for widespread and extensive death of bovine animals at that time. The parent compound for the synthesis of many congeners is 4-hydrocoumarin, which is synthesized from methyl salicylate by acetylation and internal cyclization. The basic stmctures of these compounds are shown in Figure 2, and their properties Hsted in Table 6 (see Coumarin). 

Benzofurobenzopyrans, 4, 995-1000 6H-Benzofuro[3,2-c][l]benzopyrans, 6a,l la-dihydro-— see Pterocarpans Benzofurofurans mass spectrometry, 4, 585 Benzofuro[2,3-d]pyridazines synthesis, 4, 985... 

H-l-Benzopyran-4-ones — see Chromones 4H-l-Benzopyran-4-ones, 2-phenyl — see Flavones Benzopyranopyrazoles synthesis, S, 317, 341 Benzopyrano[4,3-c]pytazol-4-one synthesis, 3, 712 Benzopyrano[4,3-6]pyridine synthesis, 3, 712 Benzopyrano[4,3-ii]pyrimidine synthesis, 3, 712 Benzopyrans nomenclature, 1, 23 pyrylium salt synthesis from, 3, 873 reactions... 

Pyrano[3,2-c]benzopyran-2,5-diones synthesis, 3, 808 Pyranobenzopyranones crystal structures, 3, 623 Py rano[3,2-c][ 1 ]benzopyran-2-ones synthesis, 3, 797 Pyranobenzothiazoles mass spectra, 3, 615 Pyrano[2,3-y]benzoxazine synthesis, 3, 714... 

Synthesis ol benzopyran-4-ones (llavones) (rom o-hydroxychalcones or from benzoturan-3-ones... 

This reaction can also be used for the synthesis of substituted 1-benzoxepins with one modification instead of the 4/T-benzopyran the 2/7-isomer must be used. 2-[Diazo(phosphoryl)meth-yl]-2//-benzopyrans decompose in the presence of ))3-allylpalladium chloride dimer with elimination of nitrogen to give 1-benzoxepins 2.192 In some cases, the reaction takes a different course and gives 2-methylene-2//-benzopyrans 3.192 In this respect, the bicyclic system behaves differently to the monocyclic diazo(pyranyl)methane. The 2-isomers of the latter structure could not be isolated and gave l//-l,2-diazepines.190 The 4//-benzopyrans do not form benzoxepins but undergo an intramolecular [2+1] cycloaddition to 3,4-dihydro-2,3,4-metheno-2//-ben-... 

A neat stereoselective synthesis of trans-fused tetrahydropyrano[3,2-c][l]benzopyrans involves treating salicylaldehydes with alk-4-en-l-ols and triethyl orthoformate. The selectivity is attributed to steric repulsion in the endo transition state, the precursor of the cw-fused compound <96CL889>. 

Jason Green has successfully applied the Selenski method to the synthesis of (+ )-bromoheliane (79, Fig. 4.38).34 In this example, two equivalents of the chiral enol ether are added to the benzaldehyde 77 in diethyl ether (0.1 M) and cooled to —78 °C. Methyl Grignard is then added. The cycloaddition occurs while the reaction warms to room temperature. The benzopyran adduct 78 forms in 80% yield with 50 1 diaster-eoselectivity. DFT calculations and experiments suggest that the diastereoselectivity depends on the magnitude of the HOMO-LUMO band gap. In this instance, the LUMO of the supposed o-QM intermediate is computed to be —2.6 eV, whereas the HOMO of the enol ether is —5.9 eV. A 50 1 selectivity is recorded for resulting 3.3 eV gap. For reactions of 2,5-bis-OBoc-4-methyl-benzaldehyde, where the HOMO-LUMO gap is larger (3.6 eV), a 20 1 ratio of diastereomers is observed. 

A wide variety of other functional groups can be employed in these annulations. For example, this chemistry has been extended to the synthesis of 1,2-dihydroisoquinolines, benzofurans and benzopyrans (Scheme 3).3 One can also employ vinylic halides and triflates in this process.4... 

Fernandes MJG, Gonfalves MST, Costa SPG (2008) Neurotransmitter amino acid - oxo-benzo[/]benzopyran conjugates synthesis and photorelease studies. Tetrahedron 64 11175-11179... 

Ayyangar NR, Srinivasan KV, Daniel T (1991) Polycyclic compounds Part VII. Synthesis, laser characteristics and dyeing behaviour of 7-diethylamino-2H-l-benzopyran-2-ones. Dyes Pigm 16 197-204... 

Dauzonne has reported a simple synthesis of flavanones by radical denitration and dehalo-genation of 3-chloro-2,3-dihydro-3-nitro-2-aryl-4T/- I-benzopyran-4-ones,92 which are readily prepared by the reaction of salicylaldehydes with l-chloro-l-nitro-2-arylethenes (Eq. 7.73).93... 

Reviews of saturated oxygen heterocycles <00JCS(P1)1291>, routes to 2,2-dimethyl-2H-[l]benzopyrans <00H(53)1193> and pyranonaphthoquinone antibiotics <00T1937>, HIV-1 active Calophyllum coumarins <00H(53)453> and of the application of (3-halovinylaldehydes in heterocyclic synthesis <00H(53)941> have appeared. 

The pyrano[3,2-c][l]benzopyran system is available from the reaction between salicylaldehyde and 5-phenylthio-4-penten-l-ols which proceeds by an intramolecular cycloaddition of an o-quinone methide desulfurisation is facile (Scheme 29) <00TL2643>. Mild conditions have been established for the synthesis of (-)-hexahydrocannabinol 50 from the olivetol derivative 49 which also involves a quinone methide (Scheme 30) <00SC1431>. 

In other somewhat related work, the synthesis of pyrano[2,3-c]azepines (and pyrido[2,3-c]azepines has been described. Reaction of hydrazoic with iV-(5,6,7.8-tetrahydro-2,5-dioxo-2W-l-benzopyran-3-yl)benzamide (or 8-hydrazono) derivatives afforded pyrano[2,3-c]azepines, which in turn can be transformed to pyrido[2,3-c]azepines <00H(53)1111>. 

While the DCJTB series replaced the active methyl group with tert-butyl or iso-propyl substituents to avoid bis-Knovenagel condensation reactions during the synthesis of DCM or DCJ series, Zhang et al. came up with the idea of using substituted cyclohexane rings to block the reactive site of the pyran ring. They then synthesized a series of 4H-benzopyran-based red emitters (158-160) as shown in Scheme 3.49 [210]. 

Another example in which literature results were reanalyzed in view of the PSSC concept concerns the development of ligands for the farnesoid X receptor. The farnesoid X receptor is a transcriptional sensor for bile acids, the primary products of cholesterol metabolism, and plays an important role in lipid homeostasis. The farnesoid X receptor was, until recently, an orphan receptor, which means that no specific ligands existed for this receptor. Selective ligands for this receptor have been found in natural product libraries described by Nicolaou et al. The group of Nicolaou developed solid phase synthesis methods to make combinatorial libraries based on a benzopyran core structure. " A 10,000-membered combinatorial library based on the benzopyran core structure was synthesized and screened for activity on the farnesoid X receptor. The first specific ligands for the... 

The dihydro-2//-1-benzopyran skeleton is found in many biologically active compounds. Such moieties have also been used in the synthesis of other biologically active molecules [16-18]. Hence their synthesis has received attention. Some catalysts used for formation of dihydro-2//-1-benzopyran include (Ph3P)2PdCl2, [19] I2 [20], and Sc(OTf)3 [21]. Few of these methods are highly catalytic in nature or have been reported to use environmentally friendly reagents. For example,... 

Scheme 3 Bismuth(III) triflate-catalyzed synthesis of substituted 3,4-dihydro-2//-l-benzopyrans...

I2 vapor is extremely corrosive while scandium compounds are moisture-sensitive and very expensive. In addition, these reactions are carried out in an environmentally unfriendly solvent, CH2CI2. We have reported the bismuth triflate-catalyzed synthesis of substituted dihydro-2//-1-benzopyrans by the condensation of substituted salicylaldehydes with 2,2-dimethoxypropane (Scheme 3) [22]. 

Ahluwalia VK, Nayal L, Kalia N, Bala S, Tehim AK (1987) Synthesis and antimicrobial activity of substituted 3,4-dihydro-2H-l-benzopyrans. Ind J Chem 26B 384—386... 

Approaches used to the development of LC materials with valuable luminescent properties include the synthesis of rod-like mesogens from fluorescent moieties, e.g. benzopyrans, " and discotic LCs with a fluorescent polyaromatic core. ... 

There are a number of examples of the synthesis of chromans using o-quinone methides as the heterodiene in a hDA reaction. Both pyrano[3 -c]-benzopyrans and cyclopenta[c][l]benzopyrans result from an intramolecular cycloaddition of a substituted o-quinonemethide generated under mild conditions. In the former case, salicylaldehyde and an unsaturated alcohol yield the rra/is-fused tetrahydropyranobenzopyran (Scheme 10) <99JOC9507>. However, the latter synthesis (Scheme 11) is less selective <99BCJ73>. 

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