Coumarin ring closure

The biosynthesis of coumarins begins with traw5 -4-cinnamic acid, which is oxidized to ort/io-coumaric acid (2-hydroxy cinnamic acid) followed by formation of the glucoside. This glucoside isomerizes to the corresponding cA-compound, which finally through ring closure forms... 

An important extension of this method has made it possible to synthesize polycyclic benzofurans under the influence of various demethylating and dehydrating media.335 For such ring closures, pyridine hydrochloride is especially suitable thus coumestan has been synthesized from 4-hydroxy-3-(2-methoxyphenyl)coumarin.8 4,7-Di hydroxy-3-(2,4-dimethoxyphenyl)coumarin gives coumestol with aniline hydrochloride 336 other polymethoxycoumestans have been obtained with pyridine hydrochloride or with HBr (or HI) and acetic acid.337-339... 

Two mechanisms have been proposed for the Knoevenagel reaction. In one, the role of the amine is to form an imine or iminium salt (378) which subsequently reacts with the enolate of the active methylene compound. Under normal circumstances elimination of the amine would give the cinnamic acid derivative (379). However, when an o-hydroxy group is present in the aromatic aldehyde intramolecular ring closure to the coumarin can occur. The timing of the various steps may be different from that shown (Scheme 118). 

In addition to the examples of coumarin syntheses given in the reviews mentioned above and in the treatise on heterocyclic compounds (B-51MI22400), more recent studies have made use of the Perkin synthesis. These include the use of substituted phenoxyacetic acids to prepare 3-phenoxycoumarins (78CI(L)628> and the synthesis of chlorocoumarins from chlorosalicylaldehydes (81T2613). The use of DBU in place of sodium acetate was necessary to effect the ring closure of a number of o-hydroxyketones (78BCJ1907). 

Heliannuols are not an exception. Only one year later following the publication of heliannuol A, the first total synthesis of the racemic (+)-heliannuol A using the coumarin 18 as starting material was published.7 A key step in this synthesis was the ring closure achieved by two different methods intramolecular Julia coupling of the sulfone 19 and sulfone ester cyclization of the alternative sulfone 20 (Fig. 5.4.A). Desulfonation and demethylation yielded the desired (+)-heliannuol A. 

The direct irradiation of the parent coumarin in the presence of alkenes results only in an inefficient photodimerization and [2 + 2]-photocycloaddition. Lewis acid coordination appears to increase the singlet state lifetime, and leads to improved yields in the stereospecific [2 + 2]-photocycloaddition [95]. Alternatively, triplet sensitization can be employed to facilitate a [2 + 2]-photocycloaddition. Yields of intramolecular [2 + 2]-photocycloadditions remain, however, even with electron-rich alkenes in the medium range at best. The preference for HT addition and for formation of the exo-product is in line with mechanistic considerations discussed earlier for other triplet [2 + 2]-photocycloadditions [96, 97]. Substituted coumarins were found to react more efficiently than the parent compound, even under conditions of direct irradiation. 3-Substituted coumarins, for example, 3-methoxy-carbonylcoumarin [98], are most useful and have been exploited extensively. The reaction of 3-ethoxycarbonylcoumarin (100) with 3-methyl-l-butene yielded cleanly the cyclobutane 101 (Scheme 6.36) with a pronounced preference for the exo-product (d.r. = 91/9). Product 101 underwent a ring-opening/ring-closure sequence upon treatment with dimethylsulfoxonium methylide to generate a tetrahydrodibenzofur-an, which was further converted into the natural product ( )-linderol A (102) [99]. 

From other o-substituted benzenes. Standard reactions of aliphatic chemistry can be applied for example, chroman 102 can be prepared by ring closure of 101. 4-Quinolones result from the Camps reaction (103 104), and flavonone 106 is prepared by cyclization of 105. The nucleophile-induced cyclization of suitably substituted 0-alkynylanilines 107 provides a general synthetic approach to quinolines 108 (Scheme 66) . Similar cyclizations of o-alkynylphenols lead to the formation of coumarins . 

Some 60 dyes have been selected as possible photovoltaic materials their electrochemical redox potentials, surface adsorption, spectroscopic properties, fluorescence yields, and acid-base properties have been measured. The aim of this work is to produce a low-cost panel for harvesting solar energy as electrical power. The physical principles of fluorescent solar collectors have been discussed by Raue and Harnisch and several classes of dyes examined. Coumarin dyes are suitable convertors, particularly if the amino-group is fixed by ring closure to the aromatic system. 

Condensation-cycUzation. Woods developed a simple synthesis of coumarins by condensation of a phenol with a Q-keto ester in the presence of trifluoroacetic acid. However, in the example formulated the position of ring closure is activated by... 

With increasing chain lengths the number of possible cyclization products rises rapidly. A tetraketoacid can undergo three aldol condensations, a Claisen and additional heterocyclic ring closures. Some of the initial cyclization products can undergo further cyclization reactions. For instance, ketoacid 78 under treatment with aqueous NaHCOs produces mainly the unstable resorcinol 79, which cyclizes further to give the coumarin 80 (equation 84). With aqueous KOH, the resorcinol 79 became a minor product whereas the isomer 81 is the major product in the reaction . ... 

By reaction of phenols with bifunclional molecules, which are able to alkylate and to esterify, several coumarin derivatives have been prepared using H-Bela as the catalyst. Thus resorcinol and propynoic acid react at 150 °C in p-chlorotolucnc as the solvent towards the perfumery ingredient umbelliferone (7-hydroxycoumarin) in good yield, 60 %, [84], Amberlyst-15 gave 40 % yield. II-Beta catalyzes the esterification as well as the ring closure alkylation step. 

The oxidative ring closure of allylsilanes with ceric ammonium nitrate <88T3983> should also be mentioned which gave mixtures ( 1 1) of 2,5,6,7-tetrahydrooxepines with 2-alkenyltetra-hydrofurans. Simple dehydration of 4-hydroxy-3-(4-hydroxy-3-alkylbutyl)coumarines with Amber-lyst 15 leads to the respective annelated tetrahydrooxepines in 50-70% yield <88JHC647>. 

A number of heterocyclics such as coumarins, flavones, and quino-lones have been prepared from o-subst. co-(methylsulfinyl)aceto-phenones . A simple isoindole synthesis with hydrazines has been published Phenolic coupling with PdCl2 has been used efficiently to produce carpanone whereby five contiguous asym. centers with the correct stereochemistry have been introduced in a single step . A facile synthesis of the tetracyclic skeleton of rheadan alkaloids, whidi have a characteristic azepine ring, has been reported Benzimidazoles and benzoxazoles have been prepared by a novel ring closure of a-amino-/9,7-ethylenenitriles . ... 

---