4- -2,3-dihydrobenzofuran

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). 

Besides the parent system oxonin (l),5,6 which is thermally unstable and undergoes a valence isomerization to 3a,7a-dihydrobenzofuran (2) above 35 C, some annulated derivatives are known. All reported systems are nonaromatic and exist in nonplanar conformations. 

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). 

Stable cA-1-phenyl-1-cyclohexene 24 photodimeiizes via Diels Alder cycloaddition to trans adduct 25 (Equation 1.33) [66] and the photoexcitation of dihydrobenzofuran-fused cyclohexenone 26 in net furan gives the trans fused Diels-Alder adduct 27 (Equation 1.34) [67]. 

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>. 

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... 

Sheldon and co-workers (Elings et al, 1995) have used H-Mordenite to rearrange allyl phenyl ether to 2-allyl phenol and subsequent cyclysation to 2-methyl dihydrobenzofuran. 

Secoquettamine (234) and dihydrosecoquettamine (235) together with their probable biogenetic precursor quettamine (236) form a small group of alkaloids. They were isolated by Shamma et at. (179) from Berberis baluchista-nica in yields of 0.00036,0.00017, and 0.0012%, respectively. These alkaloids incorporate either a benzofuran or a dihydrobenzofuran ring within the molecular framework, and the seco ones possess the /V,W-dimethylaminoethyl substituent. The structures of these bases were determined on the grounds of spectral data as well as by total synthesis. There is one chiral center at C in dihydrosecoquettamine (235) however, the base was isolated in the form of a racemic mixture (179). 

Tephrosone 33, a flavonoid belonging to the tephrorin family (vide supra), was found to possess a dihydrobenzofuran framework . Moreover, a metabolite of Penicillium brevicompactum, namely brevione A 34 was found to contain a spiro system . Neomarinone 35, another metabolite from a marine actinomycete, constitutes an intriguing sesquiterpenoid skeleton <00TL2073>. 

The intramolecular G-H insertion of aryldiazoacetates is a very powerful strategy for synthesizing heterocyclic rings such as dihydrobenzofurans and dihydrobenzopyrans. The first effective asymmetric copper-catalyzed C-H activation reaction was reported by the group of Sulikowski in the synthesis of the anti-tumor antibiotic FR-66979 93 (Scheme 7)123 219 The G-H insertion of the aryldiazoacetate 90 formed four diastereomeric products 91a, 91b, 92a,... 

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)). 

Claisen rearrangementThe allyl ether 1 when heated rearranges and cyclizes slowly and in low yield to the dihydrobenzofuran 2. However, the dianion (NaH) of 1 rearranges in refluxing DMF mainly to the isomeric dihydrobenzofuran 3, a precursor to the antibiotic ( )-atrovenetin (4). 

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 Heck reaction on polymer-bound iodoarenes is assisted by the addition of a catalytic amount of tetra-n-butylammonium bromide and has been employed in the synthesis of 4-carboxycinnamic esters and amides [33], and 4-aminosulphonyl-cinnamic esters [34], It has also been reported that the presence of an equimolar equivalent of benzyltriethylammonium chloride aids the Pd(II)-mediated reaction of A -acyl-2-iodoanilines with vinylidene carbonate, which leads to A -acyl-2-hydroxy-indolines providing a convenient route to the indoles (80-90%) [35], The catalysed reaction of 2-hydroxy- and 2-tosylaminoiodobenzene with 1,2-dienes produces 1,2-dihydrobenzofurans and 1,2-dihydroindoles, respectively [36]. 

A convenient preparation of dihydrobenzofurans has been achieved from the appropriately functionalized ort/ o-halophenol derivatives. Treatment of the aryl iodide (5)-33 with (TMS)3SiH and EtsB in the presence of air at room temperature, gave the aryl radical which cyclized in a 5-exo-trig mode and provided the bicyclic derivatives 34/35 as a 29 1 mixture of diastereoisomers in favour of 34 (Reaction 7.40) [51]. 

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],... 

Other examples of the iodonium ylide-based syntheses of furan derivatives involve cycloaddition reactions with alkenes or alkynes. Although the majority of these syntheses involve stable iodonium ylides (86JOC3453 94T11541) (e.g., Eqs. 16 and 17), in some cases the ylides are unstable and are generated in situ (92JOC2135) (e.g., Eq. 18). In the case of alkenes, dihydrofuran derivatives are obtained (Eqs. 16-18). This synthetic route is especially useful for the synthesis of dihydrobenzofuran derivatives that are related to the neolignan family of natural products (Eq. 18). 

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) . ... 

A new synthetic method of benzofuran was reported (equation 39). The [3,31-sigma-tropic rearrangement of Af-trifluoroacetyl enehydroxylamines 136 obtained in situ by acylation of oxime ethers 135 in the presence of trifluoroacetic anhydride lead to the synthesis of cyclic or acyclic dihydrobenzofurans 138. The effects of base and temperature on the reaction products were studied. A similar pathway to that of Fisher indolization was proposed. The acylimine formed by the [3,3]-sigmatropic rearrangement of the V-trifluoroacetyl enehydroxylamine 136 gave the dihydrobenzofuran 137 by an intramolecular cyclization or the benzofuran 138 after elimination. 

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