2-bromofurane

Furan reacts vigorously with chlorine and bromine at room temperature to give poly-halogenated products. Low temperature (-40 °C) reaction of furan with chlorine in dichloromethane yields mainly 2-chlorofuran and reaction of furan with dioxane dibromide at 0 °C affords 2-bromofuran in good yield. 2-Iodofuran is obtained by treatment of 2-furoic acid with iodine and potassium iodide in aqueous sodium hydroxide. 

An examination of the products formed by bromination of furan disclosed only addition. These were very unstable and could not be isolated but NMR analyses showed that both 2,5-dibromo-2,5-dihydrofuran (cis and trans) and 2,3-dibromo-2,3-dihydrofuran (trans only) were formed. Eventually only 2-bromofuran is left, but whether the additions are side equilibria or genuine stages on the way to the substitution product is not yet known.148... 

Bromofurans give Grignard reagents when attacked by copper-magnesium in tetrahydrofuran but, while the products can be alkylated, etc., in the expected way, no clear advantage has emerged.225... 

Rossi and associates described a Kumada coupling of 2-bromofuran with 2-thienylmagnesium bromide to assemble thienylfuran 11 [19], The reaction proceeded readily at room temperature. 

Like simple aryl halides, furyl halides take part in Suzuki couplings as electrophiles [41, 42]. Young and Martin coupled 2-bromofuran with 5-indolylboronic acid to prepare 5-substituted indole 37 [43]. Terashima s group cross-coupled 3-bromofuran with diethyl-(4-isoquinolyl)borane 38 to make 4-substituted isoquinoline 39 [44]. Similarly, 2- and 3-substituted isoquinolines were also synthesized in the same fashion [45]. 

The Hiyama coupling offers a practical alternative when selectivity and/or availability of other reagents are problematic. Hiyama et al. coupled alkyltrifluorosilane 74 with 2-bromofuran 73 to give the corresponding cross-coupled product 75 in moderate yield in the presence of catalytic Pd(Ph3P)4 and 3 equivalents of TBAF [65]. In this case, more than one equivalent of fluoride ion was needed to form a pentacoordinated silicate. On the other hand, alkyltrifluorosilane 74 was prepared by hydrosilylation of the corresponding terminal olefin with trichlorosilane followed by fluorination with C11F2. This method provides a facile protocol for the synthesis of alkyl-substituted aromatic compounds. 

Vinylations and arylations of polystyrene-bound 2-bromofurans have been accomplished by treatment with stannanes [98] or boronic acids [99] in the presence of palladium complexes. Alternatively, 2-furylstannanes can be coupled with support-bound aryl iodides or bromides in the presence of palladium or copper complexes (Entries 5-7, Table 15.8). 

With AUCI3 there was a preference for 2-bromofuran, obtained in up to 88% yield, possibly formed via the zwitterionic intermediate indicated in Scheme 12.2, whilst EtsPAu Cl exclusively produced 1-bromofuran, depicted at the bottom right-hand side of the scheme. This concept for the synthesis of halofurans has previously failed when using Pd (II) catalysts and a bromoallenyl compound a yield of only 2% of the corresponding 2-chlorofuran was obtained. 

Furan undergoes electrophilic aromatic substitution more readily than benzene mild reagents and conditions are sufficient. For example, furan reacts with bromine to give 2-bromofuran. 

Later Terent ev et oZ.112 obtained 2-bromofuran in good yield by the action of bromine in dioxan on furan at 0°. Dioxan perbromide is now available commercially and its use for similar brominations could be advantageous. 

The treatment of 1 with bromine in DMF at 0 °C afforded a dihydrofuran product (122) as a mixture of C-15 a and (5 isomers instead of the expected 2-bromofuran product (Scheme 19) [50]. However, treatment of 1 with /V-bromosuccinimide (NBS) in acetonitrile gave the desired 2-bromofuran product (123) in 38% yield. From 123, Stille coupling with tributylvinyl tin in the presence of Pd(PPh3)4 afforded the 2-vinylfuran product (124) in 58% yield [44],... 

Simply treating furan in DMF with Br2 at 20-30°C results in 70% of 2-bromofuran and 8% of 2,5-dibromofuran. Further treatment of 2-bromofuran with another equivalent of Br, at 30-40 C produces 2,5-dibromofuran in 48% yield [6, 7], Alternatively, deprotonation of furan at the C(2) position using EtLi followed by quenching with Br2 provides 2-bromofuran [8]. Similarly, quenching 3-lithiofuran, derived from halogen-metal exchange between 3-bromofuran and EtLi, with hexachloroethane yields 3-chlorofuran [9]. 

The Kumada coupling is used sparingly for the functionalization of furans. Rossi and associates described one example in which 2-bromofuran reacts with 2-thienylmagne-sium bromide to assemble thienylfuran 22 [36]. The reaction proceeds readily at room temperature in high overall yield. 

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