4.5- Dihydrobenzo furan, reactions

The review by Barrett (Ref. 127) documents synthetic application of hetero-substituted nitroalkenes (see also Chapter 4). 1-Chloro-l-nitroalkenes are readily obtained either by the Henry reaction of chloronitromethane with aldehydes or chlorination of l-nitroalkenes. Dauzonne and coworkers have used 1-chloro-l-nitroalkenes for construction of dihydrobenzo-furan or dihydrobenzopyran frameworks. (Eq. 5.83).133... 

These methods utilize molecules of type B (p. 362) (=104) a. Synthesis of Benzofurans by Thermal Ring Closure and Cyclodehydrogenation (Thermal, Catalytic or Photochemical) of o-Substituted Phenols. The Hansch Reaction. o-Alkylhydroxy-compounds on heating with a suitable catalyst give either a benzofuran or a 2,3-dihydrobenzo-furan with the same number of carbon atoms.285-292 Side products are formed by decomposition of the starting material. The initial phenol can be o-alkylated and ring-closed in one stage. 

The same intermediate occurs in the Lehmann method463 for converting the methiodides of phenolic Mannich bases into 2,3-dihydrobenzo-furans, through reaction with dimethyloxosulfonium methylide. Thus, o-benzoquinone methide (207) leads to 2,3-dihydrobenzofuran according to Scheme 4. Similarly, 2-naphtholgives l,2-dihydronaphtho[2,l-6]furan through 208 and 209, formed and rearranged in situ.i6i The reaction has been applied to the synthesis of polycyclic benzofurans.483,485... 

Pd/C in AcOH515 539 or on Pd/BaS04 in AcOH,534 the reaction proceeds through to the 2,3-dihydrobenzofuran stage. Some catalysts (Raney nickel at 60° 50 kg/cm2) lead directly from 237 to 2,3-dihydrobenzo-furan derivatives, without going through the acetoxy derivatives.516 The corresponding benzofuran derivative is obtained under normal pressure.516... 

Dinitro-6-phenyliodonium phenolate (146) is a stable iodonium zwitterion484. It reacts under photolytic conditions with various alkenes, alkynes and aromatic compounds to afford 2,3-dihydrobenzo[ ]furans, benzo[6]furans and 6-aryl-2,4-dinitrophenols. The mechanism involves hypervalent iodine compounds (iodinanes, 147) and is illustrated for the reaction with an aromatic compound (equation 127). Compounds 148 are the major products when ArH = PhH, PhOCH3 or 1,4-dimethoxybenzene. With furan and thiophene, 149 is the principal product. The reaction does not proceed with chlorobenzene and nitrobenzene. 

Substituted-2-phenylbenzo[. ]furans were able to undergo a palladium-catalyzed hydrogenation reaction to give their corresponding 2,3-dihydrobenzo[ ]furans, but the yields are quite low (Scheme 51) <2002T4261>. 

A Pd-catalyzed oxidative cyclization of phenols with oxygen as stoichiometric oxidant in the noncoordinating solvent toluene has been developed for the synthesis of dihydrobenzo[ ]furans (Equation 136). Asymmetric variants of this Wacker-type cyclization have been reported by Hayashi and co-workers employing cationic palladium/2,2 -bis(oxazolin-2-yl)-l,l -binaphthyl (boxax) complexes <1998JOC5071>. Stoltz and co-workers have reported ee s of up to 90% when (—)-sparteine is used as a chiral base instead of pyridine <2003AGE2892, 2005JA17778>. Attempts to effect such a heteroatom cyclization with primary alcohols as substrates, on the other hand, led to product mixtures contaminated with aldehydes and alkene isomers, which is in contrast to the reactions with the Pd(ii)/02 system in DMSO <1995TL7749>. 

A three-component domino reaction catalyzed by palladium that produces 4,5-disubstituted dihydrobenzo[ ]furans from readily available starting materials has been developed by Pache and Lautens. The reactions of iodobenzenes of type 61 with Bui and tert- mx acrylate, as shown, give good yields of cyclization products (Scheme 96) <2003OL4827>. A reaction mechanism which involves sequential alkylation-alkenylation has been proposed. 

It was found that molybdenum hexacarbonyl effectively catalyzes a tandem Claisen rearrangement—cyclization reaction of allyl aryl ethers 173 to produce the dihydrobenzo-furans 174 in goocl yields (equation 80) . However, the methallyl aryl ethers 175 under the same conditions (40 mol% of catalyst Mo(CO)g in refluxing toluene for 55 hours) gave good yields of the corresponding 2,2-dimethylchromans 176 (equation 81) . 

Uozumi et al. reported the palladium-catalyzed asymmetric heterocyclization. The reaction of the o-allylphenol 180 in the presence of [Pd(CH3CN)4]-(BF4)2 and (S,S)-i-Pr-boxax gave the dihydrobenzo-furan 181 in 91% yield with 97% ee (Scheme 60).132c... 

Thehydroxybenzofuranderivative,5-hydroxy-2-oxo-3-phenyl-2,3-dihydrobenzo-furan underwent 2-alkylation and ring closure with 4-(2-n-butoxyethoxy)mandelic acid in acetic acid at 110°C containing sulphuric acid during 9 hours, followed by oxidation by the addition of ammonium persulphate with further reaction at 110°Cfor 1 hour (ref.72). 

A strategy for the catalytic diarylation of alkenes involved the migratory insertion of alkenes into an Ar-Cu complex to generate a new C(sp )-Cu complex, which subsequently underwent reaction with an aryl iodide to facilitate vicinal diarylation of an alkene. The method provided access to 2,3-dihydrobenzo[ ]furan-containing products (14JA14730). 

As in the palladium(II)-catalysed indole annulation, a diastereomerically pure substrate was designed to help elucidate the mechanism of the benzofuran and dihydrobenzo-furan syntheses (Scheme 9.21). When aryl allyl ether 163 was treated with the palladium oxidation catalyst, dihydrobenzofuran 164 was produced as an exclusive di-astereomer in 60% yield. This observation confirmed that an oxidative Heck reaction pathway, featuring arene palladation, alkene insertion and /3-hydride elimination, was operative. 

Asymmetric synthesis of the rocaglamides was accomplished by employing [3+2] photo-cycloaddition mediated by functionalized TADDOL based chiral Brpnsted acids. The synthesis consisted of a [3+2] dipolar cycloaddition, a base-mediated a-ketol rearrangement and a hydroxyl-directed reaction <06JA7754>. Asymmetric synthesis of 1,2-dihydrobenzo /j]furans was achieved by adamantylglycine derived dirhodium tetracarboxylate catalyzed C-H insertion <06OL3437>. 

As can be seen below, another route for the preparation of spiroannulated 1,3-dihydrobenzo[c]furans (vide supra) was reported by Hotha, who made use of an AuCl, promoted intramolecular Diels-Alder reaction <06TL3307>. 

Dihydrobenzo[b]furans can be synthesized by using Pd(dba)2/PhsFcP(r-Bu)2 as an efficient catalyst at room temperature, and some interesting discussions related to this catalyst discovery are also addressed <00JA10718>. Buchwald also shows that bulky, electron-rich o-biarylphosphines are effective in PdfOAcfe-catalyzed cross-coupling reactions for the generation of 2,3-dihydrobenzo[6]furans <00JA12907>. 

Kitazume and Zulfiqar have investigated the Claisen rearrangement of several aromatic allyl ethers in ionic Hquids, catalyzed by scandium(III) trifluoromethane-sulfonate [72]. The reaction initially gave the 2-aUylphenol but this reacted further to give 2-methyl-2,3-dihydrobenzo[b]furan (Scheme 5.1-41). The yields in this reaction were highly dependant on the ionic liquid chosen, with [EDBU][OTf giving the best yields (e.g., 91 % for R = 6-CH3). Reactions in [BMIMjlBFJ and [BMIM][PF j gave low yields (9-12 %). 

Dihydrobenzo[c]furan (136) has been prepared in a thermolysis reaction from 5,6-dimethylene-7-oxabicyclo[2,2.1]heptene (135) in benzene at ISO C. The mechanism of Scheme 2 accounts for this result. 

The syntheses described in this subsection rely upon the availability of o-diaroylbenzenes. A few methods seem to be of broader applicability. As Adams and co-workers have shown, the Diels-Alder reaction of dienes and diaroylethylenes gives 4,5-diaroylcyclohexenes, which on subsequent treatment with catalytic amounts of acid (sulfuric or phosphoric) form 4,7-dihydrobenzo[c]furans. Subjecting these compounds to the action of 2 moles of bromine in acetic acid in the presence of sodium acetate resulted in diaroylbenzenes (Eq. fi). - - ... 

Dihydrobenzo[c]furans have been dehydrogenated directly to benzo[c]furans using / -chloranil in xylene.lo .ioe stereochemistry of the 4,5-diaroylcyclohexenes is generally not known. Sometimes two isomers have been isolated. As was reported by Adams and Geissman, the reaction of 2,4-hexadiene with dibenzoylethylene gave a major product in 66% yield (mp 136—137°C) in addition, an isomeric compound (mp 86-88 C, 5%) was isolated. Two isomeric adducts (mp 120°C, 178-179°C) have also been obtained from the reaction of 1,4-diphenylbutadiene with dibenzoylethylene. Both cis- and tra 5-dibenzoylethylene with 2,3-dimethylbutadiene gave the same stereoisomer. ... 

Benzo[6]furans and 2,3-dihydrobenzo[6]furans have been obtained by condensation of quinones with compounds having an active methylene group (B-74MI31201) and 2-aminobenzo[6 ]furan derivatives are obtained with malononitrile (68M2359). The reaction of p-benzoquinone with enamines also affords benzo[6]furans. 

The 2,3-dihydrobenzo[l,2-7 5,4-3 ]difuran 705 can undergo a cycloaddition reaction with tetrazine 706 followed by furan ring opening and lactonizaton to afford the pyridazino-fused coumarin 707 (Scheme 174) <2005T4805>. Similarly, benzo[l,2-3 5,4-7 ]difurans 708 react with tetrazine 706 to form the pyridazino-fused coumarins 709 and 710 (Equation 283) <2005T4805>. 

The reaction mechanism of photocyclization of aryl vinyl ethers was derived from results obtained by means of flash photolysis. The ground state intermediate rearranges by mono-or bi-molecular 1,4-hydrogen shifts to yield the products (Scheme 62) (81JOC978). The photocyclization of 2-aryloxyenones was used in the total synthesis of ( )-lycoramine (77JA8065). The formation of dihydrobenzo[6 ]furans by radical cyclization from o-allenyl-oxyarenediazonium salts with tri-n-butyltin(IV) hydride was successful (81CC136). 

Substituted-2,3-dihydrobenzo[h]furans were obtained in very good yields by SRN1 photo-stimulated reactions in liquid ammonia from appropriate halo-aromatic compounds ortho-substituted with a suitable double bond and Me3Sn, Ph2P, I3" and CH2N02 anions. 

---