Phenols cyclization

In a second route phenolic cyclization (in the absence of acid) takes place at the o-position to the hydroxyl of precursor 159 to afford homoberbine 160 (Scheme 40) while the Pictet-Spengler reaction mentioned before yields isomer 161 (69JC874). 

In contrast to many furan syntheses, this method uses 2-(2-hydroxyalkyl)phenoIs containing a leaving group at the benzylic carbon atom. Thus, 2-(I-isopropyl-thio-2-hydroxy)phenol cyclizes on heating with concentrated hydrochloric acid, but when 2-(2-hydroxyethyl)phenol was similarly treated, cyclization did not occur. When R = H, 2-unsubstituted benzofurans are obtained in good yield minor modifications were made in the synthesis of the 2-phenyl derivatives, and... 

Excellent reviews are available concerning the synthesis of various types of isoquinoline alkaloids by phenolic cyclization, by biogenetic type reactions, by the thermolysis of benzocyclobutanes, and by the coupling of phenols or of related non-phenolic compounds. ... 

The condensation of L-dopa and L-tryptamine with acetaldehyde in mammalian systems has been surveyed and a number of the possible compounds formed have been synthesized.The similar reaction of catecholamines has also been reviewed.It has been demonstrated that the optically active tetrahydroiso-quinolines salsolinol, salsoline, and isosalsoline and their antipodes can be prepared by enzyme-catalysed condensation of dopa or appropriate derivatives with acetaldehyde. The cis (IS, 3S) acid (35 R = H), formed as the major component from L-dopa and acetaldehyde under acid catalysis (cf. Vol. 4) and previously isolated from velvet beans cf. Vol. 3), has now been isolated from blackened sake cake. " 3-Carboxytetrahydroisoquinolines of this type have also been synthesized from dopa derivatives by phenolic cyclization.Esters of the acid (35 R = H) and its ethers undergo base-catalysed equilibration to give predominantly the trans (IS, 3R) isomer. The antipodes behave analogously. The reaction of dopamine hydrochloride with acetaldehyde at pH 4.5 has been reported to give not only... 

The synthesis of benzoquinolizine derivatives by phenolic cyclization has been reported. ... 

Phenols. Cyclization of 3,5-alkadienoic acids is readily effected, particularly in the context of a synthesis of C-aryl glycosides. 

In the same report <01BMCL211>, similar acetylide adducts 106 were formed in ihe same manner. After demethylation, the resultant phenol cyclized onto the alkynes using either NaOMe or DBU as the base promoter. All of the cyclizalion processes afforded exclusively the 6-endo-dig products 107. 

Phenolic Cyclization and Coupling Reactions. The oxidation of phenolic compounds which either do not possess benzylic hydrogen atoms, or which have an alternative reaction pathway, can result in a variety of interesting products. Cyclodehydrogenation reactions leading to oxygen heterocycles represent... 

The oxidative cyclization of substituted benzophenones using DDQ can give sensitive spirocoumaranones (eq 35). This phenolic cyclization is unusual in that it involves a highly constrained tetra-orf/zo-substituted benzophenone arrangement which, under other oxidative conditions, traditionally results in decomposition or further reaction to give diphenyl ether products through cleavage of the benzylic ketone. ... 

The synthesis of a variety of tetrahydroisoquinoline alkaloids by phenolic cyclization has been reviewed. A recent example of such an approach resulted in a synthesis of isococlaurine. ... 

Diene/dienophile combinations incorporating one or more hetero atoms have been studied in some detail. The most extensively investigated example has been the further cyclization of one of the condensation products of citral with olivetol [107]. Other o-vinyl phenols cyclize in similar fashion [108,109]. Unsaturated esters [110], aldehydes [111, 112] and ketones [113] can also serve as dienes. 

One other application of this phenolic cyclization is the first asymmetric synthesis of a natural indole alkaloid, (+)-decursivine [104]. The key step in this case is the PIFA-mediated oxidative [3+2] cycloaddition of 5-hydroxy tryptophan with a... 

Acylation of phenols Cyclization of polyenes Hydrolysis of amides COOH = Terminal thiohydantoin hydrolysis... 

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]. 

In the synthesis of morphine, bis-cyclization of the octahydroisoqtiinolinc precursor 171 by the intramolecular Heck reaction proceeds using palladium trifluoroacetate and 1,2,2,6,6-pentamethylpiperidine (PMP). The insertion of the diene system forms the rr-allylpalladium intermediate 172, which attacks the phenol intramolecularly to form the benzofuran ring (see Section 1.1.1.3). Based on this method, elegant total syntheses of (-)- and (+ )-dihydrocodei-none and (-)- and ( + )-morphine (173) have been achieved[141]. 

Unusual cyclocarbonylation of allylic acetates proceeds in the presence of acetic anhydride and an amine to afford acetates of phenol derivatives. The cinnamyl acetate derivative 408 undergoes carbonylation and Friedel-Crafts-type cyclization to form the a-naphthyl acetate 410 under severe condi-tions[263,264]. The reaction proceeds at 140-170 under 50-70 atm of CO in the presence of acetic anhydride and Et N. Addition of acetic anhydride is essential for the cyclization. The key step seems to be the Friedel-Crafts-type cyclization of an acylpalladium complex as shown by 409. When MeOH is added instead of acetic anhydride, /3,7-unsaturated esters such as 388 are... 

Phenol reacts with some acryUc acid derivatives to produce coumaria. With 3-ethoxyacryHc acid chloride, phenol gives phenyl ethoxyacrylate that cyclizes iato coumaria on treatment with sulfuric acid (41). Coumaria is also formed by reactioa of pheaol with methyl acrylate ia acidic medium and ia the presence of air (42). 

The following compounds have been obtained from thiete 1,1-dioxide Substituted cycloheptatrienes, benzyl o-toluenethiosulfinate, pyrazoles, - naphthothiete 1,1-dioxides, and 3-subst1tuted thietane 1,1-dioxides.It is a dienophile in Diels-Alder reactions and undergoes cycloadditions with enamines, dienamines, and ynamines. Thiete 1,1-dioxide is a source of the novel intermediate, vinylsulfene (CH2=CHCH=SQ2). which undergoes cyclo-additions to strained olefinic double bonds, reacts with phenol to give allyl sulfonate derivatives or cyclizes unimolecularly to give an unsaturated sultene. - Platinum and iron complexes of thiete 1,1-dioxide have been reported. 

A -acetyl groups attached to the aniline have been shown to withstand the Conrad-Limpach reaction. Phenols and alcohols also survived unless in proximity to a reactive center. Jaroszewski reported the formation of 64 by reaction of aniline 63 with ethyl acetoacetate (5). Cyclization under thermal conditions in paraffin gave a mixture of quinolone 65 and quinoline 66. 

Nearly every substitution of the aromatic ring has been tolerated for the cyclization step using thermal conditions, while acid-promoted conditions limited the functionality utilized. Substituents included halogens, esters, nitriles, nitro, thio-ethers, tertiary amines, alkyl, ethers, acetates, ketals, and amides. Primary and secondary amines are not well tolerated and poor yield resulted in the cyclization containing a free phenol. The Gould-Jacobs reaction has been applied to heterocycles attached and fused to the aniline. 

Treatment of that intermediate with aluminum chloride leads to selective demethylation of that ether para to the carbonyl group (23). Cyclization by means of tosic acid gives the dihydronaphthalene nucleus (24). Alkylation of the phenol with N-(2-chloroethyl)pyrrolidine affords nafoxidine (25). ... 

Reaction of the potassium salt of salicylaldehyde with chlo-roacetone affords first the corresponding phenolic ether aldol cyclization of the aldehyde with the ketonic side chain affords the benzofuran (1). Reduction of the carbonyl group by means of the Wolf-Kischner reaction affords 2-ethyl-benzofuran. Friedel-Crafts acylation with anisoyl chloride proceeds on the remaining unsubstituted position on the furan ring (2). The methyl ether is then cleaved by means of pyridine hydrochloride (3). lodina-tion of the phenol is accomplished by means of an alkaline solution of iodine and potassium iodide. There is thus obtained benziodarone (4)... 

Starting material for the first of these agents can in principle be obtained by alkylation of phenol with benzyl chloride 89. Cyclization of the product (90) under Friedel-Crafts conditions leads directly to isoxepac (91). ... 

---