Dihydrobenzofuran, substituted

Photoaddhion of electron donor olefins such as vinyl ethers and stilbene to variously methyl and halogeno-substituted 1,4-benzoquinones resulted in the formation of dihydrobenzofurans via a dienone-phenol rearrangement of the primary product spirooxetanes <96H(43)619>. High-temperature water seems to be an alternative to use of acid catalysts or organic solvents by the cyclization of allyl phenyl ethers to dihydrobenzofurans <96JOC7355>. 

Derivatives of N-(2,3-dihydrobenzofuran-6-yl)aminomethylene-malonate (806) can be regarded as /V-(3-alkoxyphenyl)aminomethy-lenemalonate derivatives, and those of JV-(2,3-dihydrobenzofuran-5-yl)aminomethylenemalonate (807, R = H) can be regarded as N-(3-alkylphenyl)aminomethylenemalonates. Since the ratio of angular (5-substituted) and linear (7-substituted) products is more sensitive to the circumstances of cyclization in the case of )V-(3-alkylphenyl)aminomethy-lenemalonate (i.e., 807, R = H) than for N-(3-alkoxyphenyl)aminomethy-... 

The formation of oxygen heterocycles through carbon-oxygen bond formation was also reported. Substituted 2-(o-halophenyl)-ethanols were converted to dihydrobenzofuranes using palladium and Buchwald s bulky biaryl-type ligands (3.43.). The reaction was also efficient in the formation of six and seven membered oxygen heterocycles.53... 

Treatment of the dibromides with sodium ethoxide gives 2-bromo-methyl-2,3-dihydrobenzofurans (170) o- (2,3-dibromopropyl)phenyl acetate (188, X = OAc, R = H) gives 2-bromomethyl-2,3-dihydro-benzofuran (170, R = R1 = H).447 The following substituted 2-bromo-methyl-2,3-dihydrobenzofurans have been prepared by this method ... 

Amino-2,3-dihydrobenzofurans such as (501) and (502) are useful as antidepressants and hypotensives (70USP3513239). Substituted 5-acyl-2,3-dihydrobenzofuran-2-carboxylic acids of the type (503) possess diuretic and antitussive activities (69GEP1927393). Derivatives of the 3-phenyl-2 (3H)-benzofuranone type (504) exhibit musculotropic and anaesthetic effects. Amethone (505) is used against bronchial asthma and also shows antihistaminic activity (47JA980). 

Intramolecular substitution for chloride or fluoride is particularly effective. Oxygen heterocycles with fused benzo rings are obtained from Cr(CO>3 complexes of fluorobenzene with an o-(hydroxyalkyl) side chain.39,60 For example, complexation of 3-(2-fluorophenyl)-l -propanol with [Cr(CO>3(pyridine)3] at 25 C in ether (promoted by BF3 Et20) followed by reaction in DMSO with excess potassium f-butoxide for 3 h at 25 C gave the chroman complex (14).60 The yield in the cyclization step was 75% and iodine decomplexation was quantitative (equation 12). Efforts to produce the dihydrobenzofuran under the same... 

On the other hand, PIFA-induced oxidation of p-methoxy-substituted phenols (15) in the presence of electron-rich styrene derivatives (16) resulted in new carbon-carbon bond formation via an intermolecular 1,3-cycloaddition to afford frazzs-dihydrobenzofurans (17) stereoselectively [35,36] [Eq. (4)]. A formal synthesis of neolignans such as kadsurenone (18) and denudatin B (19) was achieved by this methodology. 

Under palladium(n) catalysis 2-alkynylbenzyl alcohols 136 can cyclize by either a 5-exo-dig process to form (Z)-l-alkylidene-l,3-dihydrobenzofurans 138 or a 6-endo-digprocess to afford 177-isochromenes 137 (Equation 66). Lower solvent polarity and alkyl, rather than aryl substitution of the alkyne favour a 6-endo-dig cyclization (Table 3) <2003T6251>. 

The tandem 5-exo [67], and 6-exo-trig cyclization-SRNl [69] reactions afford 3-substi-tuted dihydrobenzofuranes and dihydronaphtho[2,l-k]furanes (28) for the former, and 4-substituted chromanes and benzo[f]chromanes (29) for the latter. In these reactions, at least one C—C bond is formed and the products obtained are feasible for further synthetic transformation (Scheme 10.53). Another approach to O-hetero-cycles is provided via SRN1 substitutions followed by a copper-catalyzed reaction (see Scheme 10.8). 

Ring closure reactions taking place by intramolecular addition of an aromatic radical to a double bond have been widely studied on both their regio- and stereochemical aspects [93]. Aryl halides and diazonium salts substituted at ortho- position with a 0-allyl or TV-allyl chain were used for the preparation of 2,3-dihydrobenzofuranes and 2,3-dihydro-1/7-indoles under different reaction conditions. The reaction pattern involves the generation of an aryl radical 20, which reacts with the double bond in a 5-exo trig fashion to afford the exocyclic radical 21, plausible of reduction by a hydrogen donor to obtain the reduced-cyclized product 22 (Sch. 23) [93d,94]. 

Another intramolecular substitution has been used for the synthesis of an intermediate in a proposed route to 3-substituted benzofurans. A / -methylene-dihydrobenzofuran complex was obtained upon fluoride-induced removal of the SiR3 protecting group from complex 37 (Scheme 16) in an ipso SnAr process. Desilylation resulted in spontaneous cyclization to the stable methylene complex 38 in 89 % yield. No isomerization occurred and the 3-methyl benzofuran complex was not detected [21]. 

A radical cyclization onto cross-conjugated quinone monoacetals provides a general approach to 5-hydroxydihy-drobenzoj/ jfurans upon aromatization with />-toluenesulfonic acid (Scheme 99) <2003GC526>. A biomimetic route to dihydrobenzofurans employs a dihydroquinone-mediated reductive cyclization of 2-hydroxyethyl-substituted quinone precursors <2001JOC4965>. 

The radical nucleophilic substitution is perfectly suited for tandem reactions [180]. Recent examples have been reported by the Rossi group (Scheme 66). Dihydrobenzofuranes and dihydroindoles substituted at the 3-position were prepared from ortho-functionalized haloaromatic compounds in high yields [181]. The nucleophiles involved in the initial electron transfer and subsequent coupling are varied. In particular, starting form naphthyl derivative 210, phosphinyl anions lead to tricyclic phosphine oxide 211 (after oxidation) in 98% yield. 

Dioxanes have been synthesized from l-O-allyl-l,2-diols by radical addition of per-fluoroalkyl iodides and subsequent nucleophilic cyclization.561 With sodium hydride, elimination occurs from iodides such as 1.3 other bases also give unsatisfactory results, whereas N-bromosuccinimide seems to be the reagent of choice for the cyclization to 1,4-dioxane 14. Similar results arc obtained with dibromodimethylhydantoin.561 Dihydrobenzofurans are synthesized by cyclodehydration utilizing the Vilsmeier reagent (chloromethylene)dimethylam-monium chloride is most practical.562 Nucleophilic aromatic substitution reactions with catechol derivatives also give the six-membered heterocycles.563 564 1.4-Dioxan-2-ones arc pre-... 

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