Furan 3,4-double bond functionalization

Benzo[Z)]furans and indoles do not take part in Diels-Alder reactions but 2-vinyl-benzo[Z)]furan and 2- and 3-vinylindoles give adducts involving the exocyclic double bond. In contrast, the benzo[c]-fused heterocycles function as highly reactive dienes in [4 + 2] cycloaddition reactions. Thus benzo[c]furan, isoindole (benzo[c]pyrrole) and benzo[c]thiophene all yield Diels-Alder adducts (137) with maleic anhydride. Adducts of this type are used to characterize these unstable molecules and in a similar way benzo[c]selenophene, which polymerizes on attempted isolation, was characterized by formation of an adduct with tetracyanoethylene (76JA867). 

One possible solution of this problem is to differentiate a radical first as electrophilic or nucleophilic with respect to its partner, depending upon its tendency to gain or lose electron. Then the relevant atomic Fukui function (/+ or / ) or softness f.v+ or s ) should be used. Using this approach, regiochemistry of radical addition to heteratom C=X double bond (aldehydes, nitrones, imines, etc.) and heteronuclear ring compounds (such as uracil, thymine, furan, pyridine, etc.) could be explained [34], A more rigorous approach will be to define the Fukui function for radical attack in such a way that it takes care of the inherent nature of a radical and thus differentiates one radical from the other. 

Intramolecular alkoxycarbonylation of alkynols is parallel to what has been described for alkenols except that functionalization of the triplebond produces a double bond. No lactone formation is observed in the Pd(II)-catalyzed oxidative cyclization-carbonylation of alkynes. Instead [(methoxycarbonyl)methylene]tetrahydrofurans are selectively formed [134, 135]. Moreover, starting from an enynol, furan-2-acetic ester is obtained resulting from a final aromatization step [136]. 

Several 1,2,4-trioxolanes are known which contain a double bond linked in some way to the ring, with interest focusing on furan endoperoxides. The alkene moiety of 2,5-dimethylfuran endoperoxide (41) can be selectively functionalized in the presence of the 1,2,4-trioxolane ring. Reaction with diimide gives the saturated ozonide <81TL3509> and a single addition product was obtained with p-nitrophenylazide, although the stereochemistry of the reaction was not determined. 

Diketone 829 closely parallels 820 in its chemical reactivity. Introduction of a functionalized bridging carbon can be achieved with ethyl formate and base . The acetate group in 8JO 6 is remarkably easily replaced with retention by simple nucleophiles, e.g, the conversion to 8JI. The implicated peristyl-3-ene-2,6-dione (8J2) can in fact be obtained as a colorless crystalline compound. Also, 8J0a spontaneously dehydrates during ketalization to produce 8JJ. The strained double bond in 832 enters readily into Diels-Alder reaction with furan to furnish a 3 1 mixture of 834a and 834b. 

The double bond of maleimides in very reactive towards electron-rich dienes, to give a normal Diels-Alder cycloaddition. Thus BMIs were used to obtain linear polyimides by reaction with several kind of dienes [46-51]. However the dienes are often difficult to prepare [51] and functionalized dienes have been used. Furan terminated oligomers react with BMIs at 70 °C leading to an oxygen-containing cycloadduct [52-57] which can react with acetic anhydride to give an aromatic imide (Fig. 13) [58-59]. 

On the basis of this palladium-mediated Michael addition cyclization process, a novel two-step synthetic entry into functionalized furan derivatives 67 has also been devised (Scheme 28). Substitution of benzylidene (or alkyli-dene) malonates for their ethoxymethylene analog (65) as activating olefins gave rise to the formation of the corresponding 2-ethoxy-4-arylidene tetrahy-drofurans 66. An in situ addition of potassium ferf-buloxidc induced a decar-boxylative elimination reaction which was followed by an isomerization of the exocyclic double bond. The entire process successively involved a conjugate addition, a palladium-catalyzed cyclization-coupling reaction, a base-induced eliminative decarboxylation, and finally, a double bond isomerization [73]. 

Without the disadvantage of using diazo compounds in the first step, Wenkert s latest monoterpenoid syntheses would be most efficient approaches, and in any case represent novel routes to well-known materials. Nezukone (754) was the result of examining the reaction between butadiene and diazopyruvic ester catalyzed by rhodium tetraacetate. The major product of the addition was the cyclopropane 758 (Scheme 62). It was known that divinylcyclopropanes could be thermolyzed to cycloheptadienes (Vol.4, p.537, Ref.600). The Wittig product from 758 thus gives a cycloheptadiene, and subsequent steps are shown in the scheme. The last step involves Grignard addition to the ester function of the enolate, then loss of water and redistribution of the double bonds.(Further examples of the use of diazo compounds will be found under perillene in the section on furans.)... 

In an example differing from regular olefins, furans have also been functionalized with this methodology. Several Tp CuL complexes were found to promote the cyclopropanation of one of the double bonds of these substrates that were obtained along with their ring-opening products. The reaction could be driven toward the latter upon treatment with elemental iodine. Also, the synthesis of ostopanic acid was described as a practical example (Scheme 9a). 

Heterocycles such as furan and pyran derivatives can easily be constructed from Knoevenagel products either after double bond isomerization or functionalization at the y- or 8-position. Hence, acid-catalyzed ring closure of (287) affords the 4,S-dihydrofurans (289), presumably via the double bond isomer (288 Scheme 56). ° Knoevenagel condensation of acrolein and malonic acid in the presence of... 

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