Bromofuran

Apparatus Chap. I, Fig. 1,11. The outlet is connected via a plastic tube with a trap, cooled at —78 °C. 

Introduction of a bromine atom by reaction of a lithium derivative with free bromine is probably not limited to the case of 2-lithiofuran. In other cases the use of the less aggressive complex of bromine and dioxan could be considered. 

A solution of ethyllithium in 500 ml of Et20 is prepared from 70 g (0.64 mol) of ethyl bromide and 12 g (1.7 mol) of lithium (see Chap. I, Exp. 1). The excess of lithium is separated off and the solution is transferred into the reaction flask. Freshly distilled furan (37.4 g, 0.55 mol) is added at 0 °C keeping the temperature of 

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Directive effects on lithiation have also been studied. The regiospecific /3-metallation of A-methylpyrrole derivatives and 2-substituted furans has been effected by employing the directive effect of the oxazolino group (82JCs(Pl)1343). 2-Substituted furans and thiophenes are metallated in the 5-position. The formation of 2-lithio-3-bromofuran on treatment of... 

Bromofuran [22037-28-1 ] M 147.0, b 38.5 /40min, 50 /110min, 102.5-103 /atm, d 1.661, n 1.4970. Purified by two steam distillations and dried over fresh CaO. It can be dried over Na metal (no obvious reaction) and fractionated. It is not very soluble in H2O but soluble in organic solvents. Freshly distilled, it is a clear oil, but darkens on standing and eventually resinifies. It can be stored for long periods by covering the oil with an alkaline soln of hydroquinone and redistilled when required. It forms a characteristic... 

Very many naturally occurring 3-alkyl- or 3-acylfurans are now routinely synthesized by preparing a substrate for treatment with 3-furyllithium, itself made from 3-bromofuran according to Fukuyama, Tokoroyama, and Kubota, who used it to obtain pyroangensolide and fraxinellone.212 Equally, 2-lithiofuran is used for such natural products as the acetylenic furans from Alphonsea ventricosa213 and other compounds.214 For the synthesis of the sesquiterpenoid sponge-metabolite pleraplysillin-2 78, the lithiofuran 79 and therefore the bromofuran 80 was needed to secure the orientation a suitable preparation was devised for 80.215... 

The oxidation of 2,5-disubstuted furans by singlet oxygen was exploited for the synthesis of [5,5,5] and [6,5,6] bis-spiroketals <06OL1945>. An unusual regioselective photooxidation of 3-bromofuran to 2- and 3-bromo- hydroxybutenolides, as depicted below, was reported. The mechanism for the observed base-dependent regioselective deprotonation of the endoperoxide intermediate was not determined <06OL4831>. 

Commercially available 3-bromofuran is prepared from furfural [1, 2], 3-Iodofuran can be synthesized by sequential deiodination of tetraiodofuran [3],... 

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]. 

Like most aryl halides, furyl halides and furyl triflates have been coupled with a variety of organostannanes including alkenyl, aryl, and heteroaryl stannanes in the presence of catalytic palladium. Carbamoylstannane 66 was prepared by treating lithiated piperidine with carbon monoxide and tributyltin chloride sequentially. The Stille reaction of 66 and 3-bromofuran then gave rise to amide 67 [61]. In another example, lithiation of 4,4-dimethyl-2-oxazoline followed by quenching with MesSnCl resulted in 2-(tributylstannyl)-4,4-dimethyl-2-oxazoline (68) in 70-80% yield [62], Subsequent Stille reaction of 68 with 3-bromofuran afforded 2-(3 -furyl)-4,4-dimethyl-2-oxazoline (69). 

The intermolecular Heck reaction of 3-bromofuran and tosylallyamine 88 gave adduct 89 under the classical Heck conditions [79], Subsequent Rh-catalyzed hydroformylation with ring closure occurred regioselectively to furnish the hydroxypyrrolidine, which was dehydrated using catalytic HC1 to afford dihydropyrrole 90. 

By lithiation of 4-methyloxazole with n-BuLi and subsequent quenching with trimethyltin chloride, Dondoni et al. prepared 2-trimethylstannyl-4-methyloxazole [18], which was then coupled with 3-bromofuran to provide the expected furylthiazole. 

Costanzo et al. <2002MI87> published the synthesis of the furyl-substituted pyrazolo[3,2-f][l,2,4]triazine derivative 146 by Suzuki coupling of the iodo compound 145 with 2-furylboronic acid. The yield was found to be moderate (38%). It may be important to mention that these authors also tried to transform 145 to a heteroaromatic boronic acid and to carry out cross-coupling of this compound with 3-bromofuran. Unfortunately, however, this approach failed and only homo-coupling occurred. 

The electroreductive couphng process can also been performed with heteroaryl halides as 2- or 3-bromothiophene or 3-bromofuran instead of aryl hahdes. 

Acetyl-3-bromofuran (1141) was prepared by Friedel-Crafts acylation of 3-bromofuran (1140). Wittig reaction of 1141 with methyltriphenylphosphonium bromide and butyllithium led to 3-bromo-2-propenylfuran (1142), which, on Sonogashira coupling with ethyl 2-ethynylphenylcarbamate (1143), provided N-protected (2-isopropenylfur-3-yl)ethynylaniline 1144. The TBAF-promoted... 

Bromofuran undergoes metal-halogen exchange at -78 C in THF (tetrahydrofuran) to yield 3-lithiofuran, but when this product is warmed to about -40 °C it rearranges to 2-lithiofuran (Scheme 6.26b). 

Efficient synthesis of 2-chlorofuran is best achieved by decarboxylation of 2-chlorofuran-5-carboxylic acid (63JGU1397) or via the lithium derivative of furan. When furan or 3-bromofuran were treated in turn with ethyl-lithium and hexachloroethane, 2-chlorofuran (48%) or 3-chlorofuran (54%) was formed, uncontaminated by any polychlorinated products (73SC213). Chlorodesilylation of ethyl 5-trimethylsilyl-2-furoate with sul-furyl chloride in acetonitrile gave the 5-chloro ester in —85% yield (91MI4). 

Halofuranes also couple with amines, although usually less efficiently than halothiophenes. 2-, and 3-bromofurane were converted into the... 

Treatment of 9 with 3-lithiofuran (3-bromofuran, nBuLi) affords a 1 1 mixture of diastereomeric carbinols, which are readily separated by silica gel chromatography. However, the undesired C-2 -epimer of 28 is efficiently converted to the other diastereomer by oxidation of the alcohol with Dess-Martin periodinane and subsequent stereoselective oxazaborolidine-catalyzed reduction to give the desired 2 -(/ )-carbinol exclusively. This recycling of the undesired 2 -(S)-epimer allows for the transformation of 9 to 28 in 95 % yield overall. 

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