Reactions of C-metallated Furans

Metallation at C-3 can be achieved via metal/halogen exchange. The greater stability of a carbanion at an a-position shows up again in a mono-exchange of 2,3-dibromofuran with selective replacement of the a-bromine.  

There are many examples of the use of 2- and 3-lithiofurans in reactions with various electrophilic species, such as aldehydes and ketones,and halides. It has been shown that treatment of 2-lithiofuran with copper(II) chloride leads to 2,2 -bifuran, and with trialkylboranes to borates, subsequent treatment of which with halogen provides an excellent method for the overall introduction of alkyl groups at the furan a-position.  

3-Lithiofuran, best obtained fj-om 3-bromofuran, reacts with bis(trimethylsilyl)-peroxide to provide the trimethylsilyl ether of 3-hydroxyfuran directly. Oxidation of a 2-boronate ester is a means for the synthesis of butenolides (section 15.13.1). Furan-2- and 3-boronic acids have been made by reaction of the lithiated species with tributylborate in the usual way.  

Palladium chemistry has been utilised to introduce aryl groups to a furan a-position by substitution of hydrogen, and via boronic acids, and in Heck-type alkenylations, again at C-2, via oxidative type palladation (cf. section 2.7.2.1). 

Regioselectivity for 2-bromo over 3-bromo is displayed in palladium(0)-catalysed processes.  

3-Lithiofuran, earlier usually prepared from 3-iodofuran but now best obtained from 3-bromofuran, can be oxygenated to provide the TMS ether of 3-hydroxyfuran directly 

3-Trimethylstannylfuran can be utilised in palladium-catalysed acylation and arylation.  

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Reactions with bases reactions of C-metallated benzo[b]thiophenes and benzo[b]furans... 

REACTIONS WITH BASES REACTIONS OF C-METALLATED BENZO[ ]THIOPHENES AND BENZO[Z ]FURANS... 

The bicyclic ketone (44), obtained from the Fe2(CO)9-promoted [3 + 4] cycloaddition reaction of a,a,a, a -tetrabromoacetone and 2-isopropylfuran followed by Zn-Cu couple reduction, has been converted to the naturally occurring troponoid, /3-thujaplicin (46) (75JOC806). Hydrogenation of (44), ether cleavage, bromination and dehydrobromination gave the tropone (45), an intermediate easily converted into the tropolone (46) by a standard procedure (Scheme 10). A related [3 + 4] cycloaddition reaction of oxyallyl metallic with furan has been used to assemble the antibiotic C-nucleosides (78JA2561). 

Pure decarbonylation typically employs noble metal catalysts. Carbon supported palladium, in particular, is highly elfective for furan and CO formation.Typically, alkali carbonates are added as promoters for the palladium catalyst.The decarbonylation reaction can be carried out at reflux conditions in pure furfural (165 °C), which achieves continuous removal of CO and furan from the reactor. However, a continuous flow system at 159-162 °C gave the highest activity of 36 kg furan per gram of palladium with potassium carbonate added as promoter. In oxidative decarbonylation, gaseous furfural and steam is passed over a catalyst at high temperatures (300 00 °C). Typical catalysts are zinc-iron chromite or zinc-manganese chromite catalyst and furfural can be obtained in yields of... 

Phenylethynylcopper and phenacyl bromide afford intractable tars upon long reflux in DMF. However, at higher temperatures ( 240°C) a-haloketones can be converted in one step to furan derivatives [Eqs. (68a), (68b)] uncyclized acetylenic ketones are not isolated. The cycliza-tion is catalyzed by copper(I) through the copper-coordinated enol 128). Reaction of a,a -dibromoketones with an excess of a diorganocuprate is a new method for the a-alkylation of a ketone 231a). Only the monoalkyl derivative is isolated. The evidence points to the formation of a cyclopropanone intermediate which reacts with more of the cuprate to give an a-alkylated metal enolate. 

Similarly to the 2-chromafuran derivative 36 ° discussed in Section XII, where Cr was also bonded to CO and NO, the same study refers to a related reaction involving the isoelectronic Mn(CO)5, for which a 2-manganesafuran was observed wherein the metal-bonded substituents were solely CO. The analysis continues with an additional adjustment on the aromaticity of furan by replacement of C by a substituted manganese. The same questions brought up in Section Xll about the aromaticity of the 2-metalafuran system are valid here too. 

Conversion of -chloro amide 8 by sodium metal in diethyl ether in the presence of chlorotrimethylsilane at 0 C smoothly afforded l-[l-(trimethylsiloxy)cyclopropyl]piperidine (5) in high yield. Reaction of this silyl derivative with tetrabutylammonium fluoride in tetrahydro-furan yielded the corresponding hydroxyamine 9. These preparations of 5 and 9 serve as short, inexpensive ways of forming cyclopropanone equivalents. 

Reactions of Oxazoles. 2-, 4-, and 5-Nitro-oxazoles can be prepared by the action of dinitrogen tetroxide on the corresponding iodo-compounds. Whereas oxazoles are metallated at C-5, the acid (371) undergoes lithiation at the methyl substituent.The reaction of 2,4-dimethyloxazole with ethyl propiolate yields a mixture of the furans (373) and (374) these are formed by extrusion of acetonitrile from intermediate Diels—Alder adducts such as (372). s3... 

Already in the thirties, copper-chromite promoted by addition of an alkaline earth oxide, was a favourite commercial catalyst for various hydrogenations. In the gas-phase hydrogenation of furfural copper catalysts have been used mainly to avoid hydrogen addition on the furan ring. However, an imdesired further reduction of the furfuryl alcohol to 2-methyl-furan can sometimes occur. Bremner et al. [9] studied in details the reaction of furfural over a number of copper catalysts. These studies showed that in the hydrogenation of furfural, high temperatures (> 300°C) or the addition of chromite to the copper catalyst favoured the formation of 2-methyl-furan, whereas low temperatures (< 200°C) or the addition of alkali-metal containing compoimds favoured the formation of furfuryl alcohol. 

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