Synthesis of Benzo furans

An interesting application of the Fujiwara-Moritani/oxidative Heck reaction for the synthesis of benzo furans was recently reported by the Stoltz lab [31]. A variety of allyl phenyl ethers (all containing electron-rich aryl components) react with 10 mol% palladium acetate, 20 mol% ethyl nicotinate, 20 mol% sodium acetate, and one equivalent of benzoquinone at 100°C to provide benzofurans in 52-79% yield (e.g. 16—>17). The mechanism of this transformation begins with arene palladation of Pd(II) followed by olefin insertion, p-hydrogen elimination, and olefin isomerization to the thermodynamically favored benzofuran product. The resulting Pd(0) species is then oxidized to Pd(ll) thus regenerating the active catalyst. 

A solvent-free synthesis of benzo[b]furan derivatives 10-79, a class of compounds which is often found in physiologically active natural products, was described by Shanthan Rao and coworkers. These authors heated phosphorane 10-71 for 8 min in a microwave oven and obtained the benzo[b]furan 10-74 in 73% yield (Scheme 10.18) [25]. The sequence is initiated by an intramolecular Wittig reaction, providing alkyne 10-72 this underwent a subsequent Claisen rearrangement to give the intermediate 10-73. Also in this case, normal oil-bath heating gave much lower yields (5%) of the desired product the authors hypothesize that the micro-... 

A versatile and regioselective synthesis of benzo[b]furans, naphthalenes, indoles and benzothiophenes was achieved by reaction of o-alkynylarene and heteroarene carboxaldehyde derivatives in the presence of iodonium ions. The reaction mechanism was also discussed <06CEJ5790>. 

Condensation of salicylaldehyde and its derivatives with a variety of esters of chlo-roacetic acids in the presence of TBAB led to the synthesis of benzo[fo]furans by means of a solid-liquid PTC reaction under the action of microwave irradiation [33], This was a modification of one of the most popular routes to substituted benzo[fo]fu-... 

The synthesis of benzo[Z>]furan derivatives has become a very active field because these molecules have been recently identified as having a variety of biological activities. For example, they can function as inhibitors of protein tyrosine phosphatase IB with antihyperglycemic properties <00JMC1293>, as well as potent and short-acting p-blockers in the treatment of various cardiovascular diseases . An inexpensive, reusable clay has been utilized to catalyze a facile cyclodehydration under microwave without solvent to form 3-substituted benzo[2>]furans from substituted a-phenoxy acetophenones 104. One of the important features of this procedure is that all the selected cyclodehydration reactions are complete in less than 10 minutes <00SL1273>. 

Ebel s method is an adaptation of the Stoermer synthesis of benzo-[h]furans and involves the 0-alkylation of a phenolate anion (229, Scheme 58) with a 2-halocyclohexanone (230). The resultant 2-phenoxycyclo-hexanone 231 is then cyclized by poly phosphoric acid, usually at 100°C, or sometimes by concentrated sulfuric acid, to afford a 1,2,3,4-tetrahydrodi-benzofuran (232). Dehydrogenation to the dibenzofuran is often effected with palladized charcoal, but 2,3-dichloro-5,6-dicyano-l,4-benzoquinone ... 

Heating of 19 (xylene, 170°C) with 61 yielded isomers 62 (mp 294-295°C) and 63 (mp 300°C) in a total yield of 54% (ratio 1 1)5 the oxanorbor-nadiene seems to react exclusively in an exo manner. In his paper on the synthesis of benzo[c]furan, Warrener described the reaction of 15 with... 

A useful synthesis of benzo[c]furans, based on experiments described by Ried, has been published by White et It consists of the Diels-Alder reaction of an acyclic diene with dibenzoylacetylene (146) and subsequent ring closure of the resulting 1,2-diaroylcyclohexadiene with /j-toluenesulfonic acid in benzene there has, however, been one report where this... 

Benzo[c]furans are suitable starting materials for the synthesis of benzo[c]thiophenes " treatment of 138 with PjSj yields 1,3-diphen-ylbenzo[c]thiophene (for an improved procedure see Wittig et... 

Synthesis of benzo[c]furans and isoindoles (181) is also possible by the addition of benzyne to the respective monocycles (178), followed by reduction (179 — 180) and pyrolysis. In an alternative procedure, (179) is reacted with 3,6-bis(2-pyridyl)-l,2,4,5-tetrazine, which affords (181) under far less vigorous conditions via a retro Diels-Alder reaction of the intermediate (182). 4-Phenyl-1,2,4-triazoles pyrolyze to form isoindoles (Section 3.4.3.12.2). 

The synthesis of benzo[6]furans utilize many classical and well-known reactions. The cyclodehydration of aryloxyaldehydes is a noted method for high yields, several benzo[6]furans unsubstituted in the heterocyclic ring being prepared by this method the... 

A broadly applicable synthesis of benzol/-]furans by Warrener relies on DielsAlder/retro DielsAlder reactions with s-tetrazines. Using this methodology with 3,6-di(pyridin-2-yl)-i -tetrazine 162 the generation of an isolable 5,6-(bistri-methylsilyl)benzo[c]furan 163 has been achieved (Scheme 97) <2002T9413, CHEC-III(3.07.6)551>. 

In the following scheme, the benzo[Z>]furan core of ( )-frondosin B was built up by the palladium-catalyzed quinone reduction, followed by Lewis acid-mediated benzo[Z>]furan formation <07OL3837>. In the total synthesis of bisabosquals, the core structure of benzo[ ]furan was constructed by an epoxide-ring opening reaction <07T10018>. 

As illustrated in Equation (77), the regioselective nitration of 2-(trimethylstannyl)benzo[/)]furan was also applied to the synthesis of 2-nitrobenzo[ ]furan. The reaction proceeded by an initial treatment of benzo[ ]furan 82 with -BuLi/ MesSnCl, and was then followed by reaction with tetranitromethane (TNM) or dinitrogen tetroxide <2003EJ01711>. 

An efficient approach for asymmetric syntheses of benzo[ ]furan-l-alkylamines was developed by reaction of 2-lithiated benzoMfuran with aldehyde-SAMP-derived hydrazones (SAMP = (3 )-(—)-l-amino-2-methoxymethyl-pyrolidine Equation 84). In this way, an efficient synthesis of hydrazine 91 was achieved <2004TA747>. 

As can be seen in Scheme 58, a new synthesis of 7-lactams was also achieved by reaction of benzo[, ]furan-derived vinyl sulfilimines with dichloroketene, a reaction which proceeded through a [3,3] sigmatropic rearrangement <20050L839>. 

Benzo[/ ]furyl-4-chloromethyl-l,3-oxazole 127, an important intermediate for the synthesis of potent and highly selective D3 receptor ligands, was realized by a direct condensation of benzo[/ ]furan-2-carbamide and 1,3-dichloro-propan-2-one (Equation 108) <2003JME3822>. 

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