Dihydrofurans reactions

The oxidative reaction of furan with bromine in methanol solution or an electrochemical process using sodium bromide produces 2,5-dimethoxy-2,5-dihydrofuran (19), which is a cycHc acetal of maleic dialdehyde. The double bond in (19) can be easily hydrogenated to produce the corresponding succindialdehyde derivative. Both products find appHcation in photography and as embalming materials, as well as other uses. 

Hexafluoro-2,5-dihydrofuran [24849-02-3] is distilled into sulfur trioxide [7446-11-9] at 25°C. Addition of trimethyl borate [121-43-7] initiates a reaction which upon heating and distillation leads to a 53% yield of difluoromaleic anhydride. Dichloromaleic anhydride [1122-17-4] can be prepared with 92% selectivity by oxidation of hexachloro-1,3-butadiene with SO in the presence of iodine-containing molecules (65). Passing vaporized... 

These precursors are prepared by reaction of fuming nitric acid in excess acetic anhydride at low temperatures with 2-furancarboxaldehyde [98-01-1] (furfural) or its diacetate (16) followed by treatment of an intermediate 2-acetoxy-2,5-dihydrofuran [63848-92-0] with pyridine (17). This process has been improved by the use of concentrated nitric acid (18,19), as well as catalytic amounts of phosphoms pentoxide, trichloride, and oxychloride (20), and sulfuric acid (21). Orthophosphoric acid, -toluenesulfonic acid, arsenic acid, boric acid, and stibonic acid, among others are useful additives for the nitration of furfural with acetyl nitrate. Hydrolysis of 5-nitro-2-furancarboxyaldehyde diacetate [92-55-7] with aqueous mineral acids provides the aldehyde which is suitable for use without additional purification. 

Ph2CHC02-2-tetrahydrofuranyl, 1% TsOH, CCI4, 20°, 30 min, 90-99% yield. The authors report that formation of the THF ether by reaction with 2-chlorotetrahydrofuran avoids a laborious proce ure that is required when dihydrofuran is used. In addition, the use of dihydrofuran to protect the 2 -OH of a nucleotide gives low yields (24-42%)." The tetrahydrofuranyl ester is reported to be a readily available, stable solid. A tetrahydrofuranyl ether can be cleaved in the presence of a THP ether. ... 

When the reaction of perfluQro-3,4-dimethyl-3-hexene with methanol is performed in the presence of pyridine, a perfluorinated dihydrofuran is formed, probably by a process involving generation of an anionic oxygen atom by nucleophilic cleavage of a supposed intermediate ether [27] (equation 24)... 

Several modifications of the Feist-Benary furan synthesis have been reported and fall into two general classes 1) reactions that yield furan products 2) reactions that yield dihydrofuran products. One variant that furnishes dihydrofiirans uses substrates identical to the traditional Feist-Benary furan synthesis with a slight modification of the reaction conditions. The other transformations covered in this section involve the combination of P-dicarbonyls with reagents that are not simple a-halocarbonyls. Several reactions incorporate a-halocarbonyl derivatives while others rely on completely different compounds. 

Three other modifications of the standard conditions provide synthetically useful strategies for the preparation of dihydrofurans. One method, called the interrupted Feist-Benary reaction, utilizes milder reaction conditions to stop the final dehydration step. For example, Calter combined bromide 47 with dicarbonyl 48 to produce dihydrofuran 49 as a mixture of diastereomers. He examined the scope and diastereoselectivity of this process and applied this reaction toward the synthesis of the polycyclic core of the zaragozic acids. A method principally designed to yield practical syntheses of cyclic ketodiesters also furnished a dihydrofuran via a variation of the interrupted Feist-Benary reaction. ... 

Another procedure relies on a domino Michael-O-alkylation reaction sequence to yield a variety of dihydrofurans. Combination of cyclohexanedione (30) with vinyl bromide 50 in the presence of l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) provides dihydrofuran 51 in 83% yield. Numerous 1,3-dicarbonyls and vinyl bromides are amenable to this methodology, and thus a wide range of products like 51 are available via this strategy. 

The final variation of the Feist-Benary furan synthesis encompasses reactions of 1,3-dicarbonyls with 1,2-dibromoethyl acetate (52). For example, treatment of ethyl acetoacetate (9) with sodium hydride followed by addition of 52 at 50°C yields dihydrofuran 53. The product can be easily converted into the corresponding 2-methyl-3-furoate upon acid catalyzed elimination of the acetate, thus providing another strategy for the synthesis of 2,3-disubstituted furans. 

The only known reaction of a furan with a dihalocarbene is that recently reported between benzofuran and dichlorocarbene in hexane at 0°. The initial adduct (7) could not be isolated but on hydrolysis gave the ring-expanded product 8, possibly via 9, in 15% yield. Benzothiophene was recovered in 92% yield under the same conditions. 2,5-Dihydrofuran reacted with dichloro- and dibromo-carbene to give the products of allylic insertion, 2-dihalogenomethyl-2,5-dihydrofuran, as well as the normal addition products. ... 

When the translactonization reaction of 67 (R , R = Me, Et) was conducted in acetic acid (R" = Me) as a reaction solvent, at the boiling point, somewhat different results were obtained A mixture of products identified as the furanones 68 and the 4-benzoylamino-5-oxo-2,5-dihydrofuran-2-yl acetates 69 were obtained (Scheme 21) (97T1843). 

Reduction of 3,5,5-tris-aryl-2(5// )-furanones 115 (R, R, R = aryl) with dimethyl sulfide-borane led to the formation of the 2,5-dihydrofurans 116 in high yields. However, in the case of 3,4-diaryl-2(5//)-furanones 115 (R, R = aryl R = H or r = H R, R = aryl), the reduction led to a complicated mixture of products of which only the diarylfurans 117 could be characterized (Scheme 36) (88S68). It was concluded that the smooth conversion of the tris-aryl-2(5//)-furanones to the corresponding furan derivatives with the dimethylsulfide-borane complex in high yields could be due to the presence of bulky aryl substituents which prevent addition reaction across the double bond (88S68). 

Our development of the catalytic enantioselective inverse electron-demand cycloaddition reaction [49], which was followed by related papers by Evans et al. [38, 48], focused in the initial phase on the reaction of mainly / , y-unsaturated a-keto esters 53 with ethyl vinyl ether 46a and 2,3-dihydrofuran 50a (Scheme 4.34). 

In a more recent work the same research group has applied cyclic and acyclic vinyl ethers in the oxazaborolidinone-catalyzed 1,3-dipolar cycloaddition reaction with nitrones [30]. The reaction between nitrone 5 and 2,3-dihydrofuran 6 with 20 mol% of the phenyl glycine-derived catalyst 3c, gave the product 7 in 56% yield as the sole diastereomer, however, with a low ee of 38% (Scheme 6.9). 

Scheme 2.37 Intramolecular reaction of an oxygen nucleophile to give dihydrofurans.

Finally, an intramolecular reaction of an oxygen nucleophile to give 2,5-dihy-drofuran derivatives 146 is shown in Scheme 2.37. Since the vinylaziridines were generated in situ by treatment of imines 143 with ylide 144, this ylide is formally acting as an equivalent of the 2,5-dihydrofuran anion [57]. 

Strictly speaking, dihydrofuran compounds do not belong to the field covered by this review. However, their behaviour in polymerization reactions is both similar and cleaner than that of their furanic counterparts and it is felt that their brief inclusion here makes the panorama more complete and perhaps clearer in some respects. 

With 2-methylfuran, ethyl 2-furoate and 2-furaldehyde similar results were obtained and in all reactions the 2,5-dihydrofuran products were favoured. The mechanism proposed involved the following steps ... 

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