Reduction benzo furans

Cathodic reduction 67) of 2,3-dihydrobenzofuran (5(5) was also achieved. The optimum conditions were 0.25 M (C4H9)4NBF4 in THF-4% H20 and a constant low current (4 mA cm-2). The reactant was consumed after transfer of charge equivalent to 3 F mol-1 and the product was the tetrahydrobenzofuran (57) in 59% yield. Tetra-hydrobenzofuran (57) could also be obtained directly by cathodic reduction of benzo-furan (55) when charge in excess of 2 F mol-1 was transferred. 

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>. 

At 0°C, the reduction of benzo[ ]furan 82 with lithium in the presence of a catalytic amount of -di -tert-butylbiphenyl (DTBB, 5mol%) in THF was observed to give 2-vinylphenol in high yield, as illustrated in Equation (81) <2002T4907>. 

Chloromercurio-benzo[ ]furans 107 were key intermediates for the syntheses of natural product XH14 and its analogs. The synthesis proceeded by the palladium-catalyzed carbonylation reaction as a pivotal step. The 3-chloromercurio-benzo[ ]furan 107 was also reduced to form its hydride derivative by NaBH4 reduction, as illustrated in Scheme 54 <2002JOC6772>. 

Tetrathianes. (1) Oxidative dimerization of a,a-disuhstituted alkanedithioic acid dianions (Scheme 38) or 1,1-dithiols (Equation 17) - very limited examples and a-monosuhstituted alkanedithioic acids decompose (2) reductive or pyrolytic dimerization of gi OT-disulfenyl dichlorides (Equation 18) - only malonate-derived examples (3) reaction of a-chloro sulfenyl chlorides with sodium trithiocarhonate (Equation 19) - only malonate-derived examples (4) sodium thiophenoxide-catalyzed reaction of thioketones with elemental sulfur (5) reaction of benzo-furan-3(2//)-one with S2CI2" (6) UV irradiation of a CS2 solution of a diazirine (7) reaction of a 2,2,4-trisubstituted-1,3-dithietane with Oxone (Scheme 54)". Method (4) is the most convenient and general of these. 

We decided to investigate one final substrate that contained our desired side chain for the intramolecular Diels-Alder cycloaddition as well as a small and removable cyano group. Our synthesis is outlined in Scheme 11. Phenol 53 was alkylated with chloroacetonitrile, then condensed to form 2-cyano benzo-furan 54. Subsequent quatemarization to 56 was accomplished with sodium hydride and a bromocrotcMiate (55) electrophile. Following phenol ether deprotection and reduction of the benzylic ketone with sodium borohydride, we were in a position to evaluate the dearomatization step. Unfortunately, all attempts to access the quinone epoxide 58 under classic or modified Adler-Becker reaction conditions failed. With these results, we closed the book on the second chapter in our vinigrol saga and went back to the drawing board. 

C2-alkynylation of (benzo)furans 7 and 12 was achieved selectively under gold catalysis with hypervalent ethynylbenziodoxolone reagents (TIPS-EBX (10)) (Scheme 3) (2013AGE6743, 2013BJOC1763). Under mild conditions, a broad set of substituted furans 7 and benzofiirans 12 were successfully alkynylated (11 and 13) albeit for the latter a higher reaction temperature and an additional (super)stoichiometric zinc salt was needed. Waser has shown the instantaneous formation of bis(triisopropyl-silyl)diyne via reaction of TIPS-EBX 10 with AuCl (2012CEJ5655). Therefore the mechanism likely involves oxidative addition of Au with TIPS-EBX 10 followed by electrophUic C—H auration, with elimination of 14 and reductive elimination (Scheme 4). 

Benzo[b]furan, 2-nitro-reduction, 4, 74, 647 Benzo[b]furan, 5-nitro-mass spectrometry, 4, 583 Benzo[b]furan, 2-(4-nitrophenyl)-properties, 4, 708 Benzo[b]furan, 2-phenyl-bromination, 4, 605 chloromethylation, 4, 607 nitration, 4, 604 photochemical reactions, 4, 636 properties, 4, 697 Benzo[b]furan, 3-phenyl-synthesis, 4, 697... 

Benzo[c]furan, 1-cyan 0-3-phenyl-synthesis, 4, 683 Benzo[c]furan, 1,3-diatyl-cycloaddition reactions, 4, 635 reduction, 4, 614 synthesis, 4, 701 Benzo[c]furan, 1,3-di-t-butyl-synthesis, 4, 703 Benzo[c]furan, 1,3-dihydro-NMR, 4, 572-574, structure, 4, 549 synthesis, 4, 683 Benzo[c]furan, 4,7-dihydro-synthesis, 4, 682... 

As can be seen in the scheme below, insertion reactions of aldehydes to the C-H bond of aromatic ketimines by using a rhenium catalyst provided benzo[c]furans via a mechanism involving consecutive steps of C-H bond activation, insertion of aldehyde, intramolecular nucleophilic cyclization, reductive elimination, and elimination of aniline <06JA12376>. 

These compounds are less common than indole (benzo[ ]pyrrole). In the case of benzo[i>]furan the aromaticity of the heterocycle is weaker than in indole, and this ring is easily cleaved by reduction or oxidation. Electrophilic reagents tend to react with benzo[Z ]furan at C-2 in preference to C-3 (Scheme 7.21), reflecting the reduced ability of the heteroatom to stabilize the intermediate for 3-substitution. Attack in the heterocycle is often accompanied by substitution in the benzenoid ring. Nitration with nitric acid in acetic acid gives mainly 2-nitrobenzo[Z ]furan, plus the 4-, 6- and 7-isomers. When the reagent is in benzene maintained at 10 °C, both 3- and 2-nitro[ ]furans are formed in the ratio 4 1. Under Vilsmeier reaction conditions (see Section 6.1.2), benzo[Z ]furan gives 2-formylbenzo[6]furan in ca. 40% yield. 

Only one other photooxide of a benzo[c]furan has been described. Hydrocarbon 232 on treatment with oxygen in methanol gives 233 in 96% yield further treatment with oxygen in benzene or tetrahydrofuran leads to 234 probably the corresponding benzo[c]furan is involved. Whereas reduction with triphenylphosphine in benzene or KI in acetic acid gives 235, 2 hours reflux in benzene leads to 235, 236, and 237 in 7, 48, and 3% yield, respectively. 

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). 

Benzo[6]furan is cleaved on reduction with excess sodium in liquid ammonia, followed by quenching with ammonium chloride or methanol, to produce 2-ethylphenol (69%). 2-Methyl- and 2-phenyl-benzo[6]furan similarly yield 2-propylphenol (54%) and 2-(2-phenylethyl)phenol (45%) (59JA2795). Similarly, 5-methoxybenzo[6]furan, on reduction with 2 mol of lithium and a limited amount of t- butanol, gives the cleavage product, but by operating with 2 mol each of lithium and f-butanol, 5 -methoxy-2-methylbenzo[6 jfuran supplies the 2,3-dihydro compound. With excess of the alcohol, however, 5-methoxy-2,3,4,7-tetrahydrobenzo[6]furan is secured so that the reduction is stepwise (67JOC2794). 

Benzo[c]furans undergo very rapid photooxidation. 1,3-Diphenylbenzo[c ]furan yields the oxide (368) on sensitized photooxygenation in ether at -50 °C. Reduction of the oxide with potassium iodide in acetic acid affords 1,2-dibenzoylbenzene and reaction with methanol supplies the hydroperoxide (369). 

Few simple amines are known in either the furan or the benzo[Z>]furan series. Simple nitrofurans on attempted reduction by mild chemical methods suffer what is probably a deaminative degradation. Similarly, attempted reduction of 2-nitrobenzo[6]furan affords not the amine but the product of its hydrolysis, benzofuran-2(3/f )-one. 

Treatment of diarylphthalins, obtained by reduction of diarylphthalides, with sulfuric acid results in rearrangement to yield a mixture of benzo[c]furans and anthrones (34JA1406). When diarylphthalins (441) were reacted with sulfuric acid the benzo[c]furans (442) were isolated. A dimeric benzo[c]furan (443) was obtained when the phthalin (444) was treated with acetic anhydride or phenyl isothiocyanate. 

The generation of benzo[c]furan as a transient species by retro Diels-Alder reactions has been used for synthetic purposes. l,3-Diphenylbenzo[c]furan and derivatives are obtained by reduction of the corresponding o-dibenzoylbenzenes with zinc in acetic acid. Other metals have also been used. 

Diphenylbenzo[c Jfuran (233) is obtained on treatment of o-dibenzoylbenzene (232) with zinc dust in acetic acid (28JCS2089, 39LA(541)238). A number of benzo[c]furans have been prepared by reduction of o-dibenzoylbenzenes with potassium and sodium borohy-drides (66JOC4082), triphenyl phospite (72JCS(Pl)2728) and metals (sodium, lithium, potassium) (61JCS2965, 74JOC146). Photochemical reduction of (232) to (233) can be accomplished in ethanol. 

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