2- Aryl-2,3-dihydrobenzofurans

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)). 

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

Flavanones undergo a variety of transformations by HTI or other hypervalent iodine reagents. In methanol, at room temperature, they were dehydrogenated to the corresponding flavones [40], A similar dehydrogenation occurred in chromanones [41]. Dramatic solvent effects occurred when methanol was replaced by other solvents. Thus, in trimethyl orthoformate ring-contraction was the main pathway and methyl 2-aryl-2,3-dihydrobenzofuran-3-carboxylates the major products, accompanied by substantial amounts of 3-methoxyflavones [42] ... 

Certain olefinic substrates undergo thermally-forbidden [2 + 2] type cycloaddition in the presence of Lewis acid catalysts through coordination to the acceptor molecules. Scheme 111 illustrates the enantiose-lective version of this reaction (277). Some thio acetylenes can also be used. Substantial asymmetric induction has been observed in cycloadditions of styrenes and 1,4-benzoquinones using a stoichiometric amount of a chiral Ti(IV) complex (272). The [2 + 2] cycloadducts are readily rearranged to 2-aryl-2,3-dihydrobenzofurans. 

I-A group this group contains at least one five-membered, oxa-cyclic ring, usually the 2-aryl-2, 3-dihydrobenzofuran ring. About 60 oligomers... 

Aryl-2,3-dihydrobenzofurans The [3+2]cycloaddition of benzoquinones with styrenes is high yielding, and it has been applied to the synthesis of ptero-carpans and neolignans. 

Kurosawa W, Kan T, Fukuyama T. An efficient synthesis of optically active trani -2-aryl-2,3-dihydrobenzofuran-3-carboxylic acid esters via C—H insertion reaction. Synlett 2003 1028-1030. 

An improved procedure for the rapid synthesis of aryl dihydrobenzofurans with a boron tribromide-mediated cyclization was discussed and is shown below <03HCA343>. In the second total synthesis of diazonamide A, the late key step accounting for the dihydrobenzofuran formation was a DIBAL-H mediated lactam reduction and cyclization <03AG(E)1753>. 

Group D other bibenzyls, including aryl-dihydrobenzofurans, phthalides, dihydroisocoumarins, etc. 

The synthesis of dihydrobenzofurans has been developed by Pena and coworkers by the formal insertion of arynes into the C-O o-bond of epoxides. The reaction was carried out in the presence of CsF in MeCN, and the dihydrobenzofurans 76 were formed as a single regioisomer (Scheme 33) [56]. The reaction can be rationalized as the initial addition of epoxide oxygen on aryne generating the zwitterionic intermediate 77 followed by cyclization of 77 to furnish 76. In this reaction, the 2-aryl dihydrobenzofuran 78 was not detected presumably due to the enhanced stability of the positive charge at the benzylic position resulting from the cleavage of zwit-terion 77. 

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]. 

Benzofurans and dihydrobenzofurans have been prepared on polymeric supports by the palladium-mediated reaction of 2-iodophenols with dienes or alkynes (Entries 1 and 2, Table 15.9). This reaction is closely related to the synthesis of indoles from 2-iodoanilines, and probably proceeds via an intermediate palladacycle (Figure 15.3). Benzofuran and isobenzofuran derivatives have also been prepared on cross-linked polystyrene by intramolecular addition of aryl radicals to C=C double bonds and by intramolecular Heck reaction. 

Allyloxy)iodoarenes react with Sml2 to yield radical anions, which undergo thermal fragmentation. The resulting aryl radicals can cyclize to dihydrobenzofurans (Entries 8-10, Table 15.9). The radical obtained after cyclization can be reduced and treated with a proton source such as water or an alcohol to yield alkanes, or with carbonyl compounds to yield alcohols (Entry 10, Table 15.9). 

Heteroannelation of 1,3-dienes with a variety of oxygen- or nitrogen-containing aryl iodides affords dihydrobenzofurans or nitrogen heterocycles.3... 

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 value of Eox for BH 4 is not known, but the borohydride radical, BH4 has been characterized by e.s.r and UV spectroscopy in oxidations of the anion by hydroxyl or azide radicals under pulse-radiolysis conditions (Symons et al., 1983 Horii and Taniguchi, 1986). Most borohydride reductions seem to be straightforward hydride transfers, but stepwise processes occur in the reductions of aryl bromides or iodides under photochemical or di-t-biftyl peroxide initiation. Radical intermediates are shown by the formation of 3-methyl-2,3-dihydrobenzofuran in the reduction of o-allyloxyiodobenzene (Abeywickrama and Beckwith, 1986). 

The synthesis of a variety of dihydrobenzofuranes can be accomplished via the Aryl SN1 mechanism. The acetone-sensitized irradiation of various o-chlorophenyl allyl ethers in polar solvents affords the aryl cation, which adds onto the tethered double bond following the 5-exo-trig mode leading to (dihydro)benzofurans. The reaction is solvent-dependent, and byproducts are also generally obtained. The best results are found when ethyl acetate is used. Depending on the substrate employed, the cation intermediate can yield products as a result of proton elimination or trapping by chloride ions (Scheme 10.54) [70],... 

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]. 

In spite of the reduced nucleophilicity of o-CH30 by resonance interaction with the aromatic nuclei, the p electrons of the oxygen assist the participation of the aryl ring in the partial C—Cl bond cleavage in the transition state, which eventually leads to formation of the corresponding cyclic product, dihydrobenzofuran. The mechanism for the two parallel processes is given in equations 84 and 85. 

Pd-catalyzed aryl etherifications to yield dihydrobenzofurans have been achieved by Hartwig and co-workers using bulky ferrocenylphosphine ligands (Equation 135) <2000JA10718> and by Buchwald and co-workers using bulky electron-rich o-biarylphosphine ligands <2000JA12907>. 

An iridium(lll)-catalyzed tandem Claisen rearrangement-intramolecular hydroaryloxylation protocol has been described that allows the transformation of allyl aryl ethers to dihydrobenzofurans under mild conditions (Scheme 95) <2005TL1237>. An in rl/ -generated PPh3AuOTf complex also proved to be an efficient catalyst for this transformation <2006SL1278>. 

When the Heck cyclization is carried out under oxidative conditions (intramolecular Fujiwara-Moritani arylation), spirocyclic dihydrobenzofurans are formed in good yields directly from aryl ethers (Equation 139) <2004AGE6144>. 

The C-H insertion reaction of aryldiazoacetates to furnish dihydrobenzofurans is best carried out with dimeric rhodium(ll) catalysts. Rh2(PTTL)4 has proven to be the catalyst of choice for the asymmetric version of this process, providing exclusively j-2-aryl-3-methoxycarbonyl-2,3-dihydrobenzofurans with an ee of up to 94% (Equation 142) <2002OL3887>. 

More recently, elegant mechanistic studies on intramolecular Meer-wein reactions by Beckwith et al. considerably extended the utility of diazonium salts. They showed that many electron donors could convert an arenediazonium cation into an aryl radical which cyclized in good yield to form dihydrobenzofurans and indolines. The final radical was functionalized as a halide, sulfide, or ferrocene. Thus, the credentials of diazonium salts as electron acceptors were well established, and the stage was set to investigate the interaction between diazonium salts and TTF. 

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