Aryl-substituted 2,3-dihydrobenzo

A palladium-catalyzed one-step synthesis of dihydrobenzo[fc]furan-based fused aromatic heterocycles from bifunctional bromoenoates or bromoalkyl indoles and iodoarenes was reported, and an example is provided in the scheme below <060L3601>. 2-Alkyl- or 2-aryl-substituted benzo[ >]furans were synthesized by a copper-TMEDA catalyzed intramolecular annulation from the corresponding ketones <06OL1467>. 

The aryl radical cyclization has been successfully used for the preparation of substituted dihydrobenzo[Z)]indoline derivatives [59], An example is shown in Reaction (7.49). The diene 42 was preliminarly subjected to ring-closure metathesis using Grubbs catalyst and then treated with (TMS)3SiH and EtsB at -20 °C, in the presence of air, to provide the compound 43 with an excellent diastereoselectivity. 

When reacted with dimethyl acetylenedicarboxylate, the amines produced ben-zotriazolylaminobutendioates 188 accompanied by A-benzotriazolyl substituted 2-pyridones only in the case of 5-amino-2-methyl-2//-benzotriazole, the triazolo-9,10-dihydrobenzo[d]azepine and an unusual cyclization product, triazolo-2-oxindole (convertible into 2-methyltriazolo[4,5-/]carbostyril-9-carboxylate) were formed. The quinolones 189 were aromatized to chloroesters 190 these in turn were hydrolyzed to chloroacids 191 and decarboxylated to 9-chlorotriazolo[4, 5-/]quinolines 192 (Scheme 58) (93H259). The chlorine atom could be replaced with 17 various secondary amines to give the corresponding 9-aminoalkyl(aryl) derivatives 193, some of which exhibit both cell selectivity and tumor growth inhibition activity at concentrations between 10 and 10 " M (95FA47). 

Diazotization of substituted o-aminobenzylamines of the type 28, R = alkyl, aryl, acyl, gives 3-substituted 3,4-dihydrobenzo-l,2,3-triazines (29). o-Aminobenzylamine does not react similarly, but gives a product to which structure 30 has been assigned. Treatment of 1,8-diaminonaphthalene (31, R H) with nitrous acid gives naphtho[l,8-... 

As demonstrated below, a Lewis acid-mediated reaction was utilized in the synthesis of dihydro[b furan-based chromen-2-one derivatives from l-cyclopropyl-2-arylethanones and allenic esters <070L4017>. The TiCh-catalyzed anti-Markovnikov hydration of alkynes, followed by a copper-catalyzed O-arylation was applied to the synthesis of 2-substituted benzo[6]furan <07JOC6149>. In addition, benzo[6]furan-based heterocycles could be made from chloromethylcoumarins <07SL1951>, substituted cyclopropanes <07AGE1726>, as well as benzyne and styrene oxide <07SL1308>. On the other hand, DBU-mediated dehydroiodination of 2-iodomethyl-2,3-dihydrobenzo[6]furans was also useful in the synthesis of 2-methylbenzo[Z>]furans <07TL6628>. 

A slightly modified synthesis of dihydrobenzo[c]furan was achieved, in which the key reaction involved the exposure of a dibromide to dry alumina and one equivalent of water in toluene instead of in hexanes <07TL3039>. Another synthesis of dihydrobenzo[c]furans was reported by Hashmi and Teles <07SL1747> and an example is depicted below. Base-promoted cycloaddition of 1-aryl- or l-aryl-7-substituted-4-oxahepta-1,6-diynes in DMSO were found to involve an anionic intramolecular Diels-Alder reaction, and also resulted in the formation of dihydrobenzo[c]furans <07JA4939>. 

An efficient asymmetric synthesis of substituted methyl 2-aryl-dihydrobenzo[h]furan-3-carlx)xylate was achieved by a rhodium-catalyzed C-H bond activation route in an excellent yield, and the generated product was an intermediate applicable to the total synthesis of (+)-lithospermic acid <0 A13496>. A similar type of framework existing in ( )-E-viniferin was m e through a biomimetic transformation by a T1(N03)3-mediated oxidative dimerization of resveratrol <05T10285>. 

Friedel-Crafts based cyclization reaction was also developed to realize the key intermediate for the synthesis of bergapten <05H(65)1985>. A structurally diverse series of 2-aryl-5-substitut -2,3-dihydrobenzo[4>]furans was made via a rapid and efficient base-mediated one-pot reaetion from o-nitrotoluene and aromatic aldehydes <05JOC3727>. 

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