Addition furans, 2,3-dihydro

In contrast to the rich chemistry of alkoxy- and aryloxyallenes, synthetic applications of nitrogen-substituted allenes are much less developed. Lithiation at the C-l position followed by addition of electrophiles can also be applied to nitrogen-containing allenes [10]. Some representative examples with dimethyl sulfide and carbonyl compounds are depicted in Scheme 8.73 [147, 157]. a-Hydroxy-substituted (benzotriazo-le) allenes 272 are accessible in a one-pot procedure described by Katritzky and Verin, who generated allenyl anion 271 and trapped it with carbonyl compounds to furnish products 272 [147]. The subsequent cyclization of 272 leading to dihydro-furan derivative 273 was achieved under similar conditions to those already mentioned for oxygen-substituted allenes. 

The use of cyclic alkenes as substrates or the preparation of cyclic structures in the Heck reaction allows an asymmetric variation of the Heck reaction. An example of an intermolecular process is the addition of arenes to 1,2-dihydro furan using BINAP as the ligand, reported by Hayashi [23], Since the addition of palladium-aryl occurs in a syn fashion to a cyclic compound, the 13-hydride elimination cannot take place at the carbon that carries the phenyl group just added (carbon 1), and therefore it takes place at the carbon atom at the other side of palladium (carbon 3). The normal Heck products would not be chiral because an alkene is formed at the position where the aryl group is added. A side-reaction that occurs is the isomerisation of the alkene. Figure 13.20 illustrates this, omitting catalyst details and isomerisation products. 

In order to achieve 2-nitration, acetyl nitrate may be used as the reagent, but unlike pyrrole a semi-stable adduct, 5-acetoxy-2,5-dihydro-2-nitrofuran, is formed as an intermediate product (Scheme 6.22). This eliminates acetic acid when treated with pyridine. Furan also undergoes initial bromination or chlorination (X = Br or Cl) in ethanol at -40 °C, but then addition of two ethoxyl units occurs with the expulsion of halide ion (Scheme 6.23). 

The major products formed from hexoses that react in aqueous acidic solution are 5-(hydroxymethyl)-2-furaldehyde, levulinic acid, and polymeric materials. In addition, many minor dehydration products are found. In a study41 of D-fructose, 2-(2-hydroxyacetyl)furan (13), 2-acetyl-3-hydroxyfuran (isomaltol 16), 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one, and 3,4,5-trihydroxy-3,5-hexadien-2-one (acetylformoin) were identified. Products not formed solely by dehydration mechanisms include acetone,56 formaldehyde, acetalde-... 

The reaction worked with both internal and terminal alkynes (except silylated alkynes) and in many solvents, even in the neat alcohol added [105]. The mechanism proposed involved two catalytic cycles first, gold catalysis would lead to dihydro-furan by a fast intramolecular reaction then, the subsequent slower intermolecular reaction would be produced by the addition of alcohol to the enol ether to deliver a ketal (Scheme 8.18). 

Raney nickel reduction of 2-benzyl-5-ethylselenophene (71) yields 1-phenylheptane (72), a conversion analogous to the much used reductive desulfurization of thiophenes (73JGU871). The electrochemical reduction of selenophene-2-carboxylic acid gives a mixture of dimeric products the major product is compound (73). This is in contrast to the 2,5-dihydro derivatives obtained by electrochemical reduction of thiophene and furan carboxylic acids (82CS( 19)95). Wolff-Kishner reduction of 2-selenienyl 2 -thienyl ketone gives, in addition to the expected methylene derivative, 2-(pentenyl)thiophene (72ZOB1780). 

Cyclopentannelated tetrahydrofurans 169 [129] and substituted dihydro-furans 171 [130] can be synthesized by the treatment of functionalized al-kynyliodonium salts 168 and 170 with the appropriate nucleophile (Scheme 64). Alkynyliodonium salts 168 and 170, the key precursors in these reactions, are conveniently prepared from the appropriate alkynylstannanes and can be used without additional purification. 

As demonstrated below, a Lewis acid-mediated reaction was utilized in the synthesis of dihydro[b furan-based chromen-2-one derivatives from l-cyclopropyl-2-arylethanones and allenic esters <070L4017>. The TiCh-catalyzed anti-Markovnikov hydration of alkynes, followed by a copper-catalyzed O-arylation was applied to the synthesis of 2-substituted benzo[6]furan <07JOC6149>. In addition, benzo[6]furan-based heterocycles could be made from chloromethylcoumarins <07SL1951>, substituted cyclopropanes <07AGE1726>, as well as benzyne and styrene oxide <07SL1308>. On the other hand, DBU-mediated dehydroiodination of 2-iodomethyl-2,3-dihydrobenzo[6]furans was also useful in the synthesis of 2-methylbenzo[Z>]furans <07TL6628>. 

At 0°C, with HBr 4-bromo-4,5-dihydro-2-(2-pyrrolyl)furanium bromides 284 are seen in the NMR spectra, resulting from the addition of HBr to the protonated furan moiety (Scheme 63) <1998MI30>. Thus, it is demonstrated that under certain conditions pyrrole compounds can undergo electrophilic addition like nonaromatic unsaturated systems. 

That deprotonation of enol radical cations is a plausible reaction can be deduced from Yoshida s work [107,113] on the electrooxidative addition of 1,3-dicarbonyl compounds 14 in acetonitrile to substituted olefins yielding dihydro-furans 18 as [3 + 2] cycloaddition products in good to excellent yields. Al-... 

At this point, participation of the allyl side chain must 1 e recognized, because an n-butoxy derivative reacts in a different fashion. At least two routes, A and B, are open to pivotal intermediate IV (see Scheme 23.1). While the electron reorganization that leads to alkoxycarbene V (route A) and dihydro-furan (VII) via its addition to the terminal alkene would be justified by the high temperatures employed at which other carbenes have been thermally generated, the prior cyclization of zwitterion IX (route B) and its ensuing 1,2-hydrogen shift followed by C-C bond fragmentation in X—the natural precursor of products II and VII—would perhaps be more feasible. 

A similar removal of benzeneselenenic acid from l,l-dichloro-la-phenylseleninyl-la,9b-di-hydro-l//-cyclopropa[/]phenanthrene (2) at ambient temperature was used to generate 1,1-dichloro-l//-cyclopropa[/]phenanthrene as a short-lived intermediate which was trapped by addition of methanol.Elimination of the elements of HSe Mcj from 3, derived from la-methylselenacyclopropa[/]phenanthrene and la,9b-dihydro-l//-cyclopropa[/]phenanthrene after alkylation, gave a mixture of the alternative cyclopropene, which were both trapped with furan. 

Conflicting results were reported for the reaction of 1,3-diphenylisobenzofuran with benzocyclopropene. Reaction in chloroform (207 days) reportedly gave the unsymmetrical 5,10-diphenyl-10,ll-dihydro-5,10-epoxy-5//-dibenzo[a,c/lcycloheptene (7) in 71% yield,which was derived from addition of the furan to one of the lateral cyclopropane bonds. However, under similar conditions, other authors also report the formation of the isomeric exo and endo Diels-Alder adducts 6 and 8 in low yield.Under optimum conditions (tetrahydrofuran, 80 °C, 3 days), the enr/o-adduct 6 was isolated in 52% yield.The formation of the unsymmetrical adduct 7 was ascribed to a radical reaction, similar to that observed in the addition of buta-1,3-diene to benzocyclopropene. 

For the addition of furan and benzofuran to benzocyclopropene, a diradical mechanism has been proposed for the formation of 4. Similarly, AT,At-dimethyl- or A-methyl-A-phenyl-hydrazones of a,/ -unsaturated aldehydes (acrylaldehyde and 2-methylacrylaldehyde) reacted by radical addition at the C-C double bond with benzocyclopropene at 45 C to yield a dihydro-indene derivative 5. The addition of tetracyanoethene to benzocyclopropene giving dihydro-indene 6a is, however, believed to be preceded by electron transfer from benzocyclopropene to tetracyanoethene.Cyclopropa[b]naphthalene reacted similarly with tetracyanoethene to give the dihydroindene derivative 6b in 44% yield. 

Methoxy- and 2-acetoxy-furans are available from 2,5-dimethoxy- and 2,5-diacetoxy-2,5-dihydro-furans (18.1.1.4) via acid-catalysed elimination. They undergo Diels-Alder cycloadditions the adducts can be further transformed into benzenoid compounds by acid-catalysed opening. 3,4-Dihydroxyfuran is undetectable in tautomeric equilibria between mono-enol and dicarbonyl forms the dimethyl ether behaves as a normal furan, undergoing easy a-electrophilic substitution, mono- or dilithiation at the a-position(s), and Diels-Alder cycloadditions. 2,5-Bis(trimethylsilyloxy)furan is synthesised from succinic anhydride it too undergoes Diels-Alder additions readily. Both furan-2- and -3-thiols can be obtained by reaction of lithiated furans with sulfur in each case the predominant tautomer is the thiol form. ... 

Addition to the side-chain of the aldimine from 4-anisaldehyde and aniline occurred in its reaction with the furan-2,3-dione shown with toss of carbon monoxide by heating in benzene during 2 hours to give 2-(4-methoxy-phenyl)-3,6-diphenyl-2,3-dihydro-4H-1,3-oxazine-4-one in 93% yield (ref.131)... 

In all these conversions of (31) (for example, with diazapropane) a dihydro adduct (e.g. (32)) was formed first <84H(22)2479> which upon oxidation afforded a partly unsaturated fused system (e.g. (33)). Irradiation of this compound (33) resulted in splitting off a molecule of nitrogen and formation of a biradical which, in the presence of furan, could be trapped and the adduct (36) was formed. This reaction represents a unique example of a 1,4-addition of a 1,3-diradical to a diene <87AJC2037>. 

The influence of the organic moiety of the azide in cylcoadditions to enol ethers is analogous to that in additions to enamines. Comparative cycloadditions of 4-(methoxyphenyl)-, 4-(nitrophenyl)-, and 4-toluene-sulfonyl azide to 2,3-dihydro-furan show that the rate of cycloaddition increases dramatically in the sequence mentioned (Huisgen et al., 1965). Yet, the dihydrotriazoles formed (2.174) are stable only in the case of the first aryl azide mentioned. With 4-toluenesulfonyl azide the product of dediazoniation (2.175) was the only compound detected (96% yield). Analogous results were obtained with 3,4-dihydro-2//-pyran. 

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