2.3- Dihydrobenzofuranes

In l-chloro-2-fluoroacenaphthene [58] and in 2,3-dihalo-2,3-dihydrobenzofuran [59, 60], potassium t rt-butoxide eliminates hydrogen fluonde in preference to hydrogen chloride. trares-2-Chloro-3-fluoro-2,3-dihydrobenzofuran loses hydrogen fluoride quantitatively on treatment with sodamide in tert-butyl alcohol [60] (equation 29). 

In a recent continuation of the work on dediazoniation of 2-(2 -propenyloxy)ben-zenediazonium salts (10.55, Z = 0, n= 1, R=H) in the presence of ferrocene, Beckwith et al. (1992) found that 3-ferrocenylmethyl-2,3-dihydrobenzofuran (10.65) is formed. The results are consistent with a mechanism involving electron transfer and dediazoniation followed by homolytic attack on the ferrocenium ion. This investigation resolved a long-lasting dispute regarding the heterolytic or homolytic character of the formation of arylferrocenes from arenediazonium ions (for literature since 1955 see Beckwith et al., 1992, references 1-7). 

In order to isolate the ketoalcohol intermediate, the following experiment was carried out. A mixture of 89a (1 g, 8.2 mmol), 90a (0.77 g, 5 mmol), and K2CO3 (1.38 g, 10 mmol) was stored at room temperature for 3 h,and the crude reaction product was added to a 1 1 mixture of ether and water. From the ether solution, c/s-2-benzoyl-3-hydroxy-2,3-dihydrobenzofuran (96) was obtained (0.18 g, 15% yield). Compound 96 showed its vC=0 absorption at 1696 cm"k... 

A very impressive application of this chemistry is the total synthesis of (—)-ephedradine A 102.222 The key intermediate /rcarboxylic acid ester 101 was synthesized by intramolecular C-H insertion reaction. Upon treatment with a catalytic amount of Rh2(Y-DOSP)4, aryl diazo ester 100 possessing a chiral auxiliary underwent a C-H insertion reaction to give 101 in 63% yield and 86% de (Equation (83)). 

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-... 

Benzofuran was reduced over Raney nickel at 90° and 85 atm to 2,3-dihydrobenzofuran, at 190° and 119 atm to octahydrobenzofuran, and further hydrogenation over copper chromite at 200-300° caused hydrogeno-lysis to 2-ethylcyclohexanol [422],... 

Dihydrobenzofuran (327) reacted with lithium and a catalytic amount (5%) of DTBB in TFIF at 0°C to give mainly or exclusively the corresponding intermediate 328, which by treatment with an electrophile at the same temperature and final hydrolysis yielded functionalized phenols 329 (Scheme 96) . ... 

Bis(oxazoline) ligands have also been used in Wacker-type cycUzations. " For example, the phenolic derivative 238 was cyclized in the presence of ligand 13b complexed with palladium(ll) to yield the 2,3-dihydrobenzofuran 239 in 86% yield with an ee of 94% (Fig. 9.70). 

S)-7,4 -Dihydroxy-3 -methoxy-2-hydroxyethyl-5-hydroxypropyl-2-aryl-2,3-dihydrobenzofuran... 

Dehydrohalogenation of 2,3-dihalo-2,3-dihydrobenzofurans gives 3-halobenzo-furans [69]. Rate measurements have indicated higher difficulties in deprotonation... 

These have been used to produce indolines (80T1757) and 2,3-dihydrobenzofurans (78JA2150) (Scheme 9). 

Another simplified nomenclature adopted here relates to natural spiro-2,3-dihydrobenzofuran derivatives, such as griseofulvin. The fundamental heterocycle, named grisan, being spirobenzofuran-2(3ff)-l -cyclohexane (5), griseofulvin (7-chloro-4,6,2 -trimethoxy-6 -methyl-spirobenzofuran-2(3//)-l -[2]cyclohexene-3,4 -dione) (6) becomes 7-chloro-4,6,2 -trimethoxy-6 -methyl-2 -grisene-3,4 -dione. 

Pesticidal carbamates with 2,3-dihydrobenzofuran structures carbo-furan or NIA-9242 is methyl 2,3-dihydro-2,2-dimethyl-7-benzofuranyl-carbamate (14) NIA 10559 (15) is its 4-chloro, and NIA 10586 (16) its 4-methyl derivative. Benzofuran itself, 2,3-dibromobenzofuran and 2,3-dihydro-3-oxobenzofuran and their derivatives have very low or zero activity.26... 

Benzofuran derivatives are rare in petroleum, where sulfurated heterocycles predominate among heterocyclic compounds. Benzofurans and 2,3-dihydrobenzofurans are found, however, in the 200°-270° fraction of the distillate of California crude oil, with dibenzofurans and naphthobenzofurans.123 Alkyl-dibenzofurans have been traced in the 275°-305° fraction of petroleum with alkylnaphthalenes, 4-methyl-dibenzofuran among others.124 The distillation of humic acids with zinc powder is said to give benzofuran and hydrobenzofuran derivatives.125... 

Dihydrobenzofurans eusiderin,160 supposed to be 3-(6-allyl-2,4-di-methoxyphenoxy)-2,3-dihydro-6,7-dimethoxy-2-methylbenzofuran(52). 

Among the ewparinoid 2,3-dihydrobenzofurans, the main compounds are( - )-tremetone(17a),27,168,175,176toxol(l8),175,176hydroxytremetone... 

The final group of natural benzofurans includes the 2-phenylbenzo-furans and 2-phenyl-2,3-dihydrobenzofurans. 2-(6-Hydroxy-2-methoxy-3,4-methylenedioxyphenyl)benzofuran (64)147 has recently been isolated from yeast. Other members of the same group recently isolated from various plants are eupomatene (7-methoxy-3-methyl-2-(3,4-methylene-dioxyphenyl)-5-fi-Gms-propenylbenzofuran (65) 180 egonol (66),147,181-184... 

Among the 2-phenyl-2,3-dihydrobenzofurans, noteworthy are (+ )obtusofuran (68) with 2i ,3i configuration,187 and melanoxin (69) (2,3-dihydro-5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-6-methoxy-3-methylbenzofuran) with 2, 3iS configuration.188 Compounds with structures closely related to that of (69) have been isolated from the... 

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