Furan 2- vinyl-, cycloaddition

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). 

The enantiomerically pure, doubly activated a, /j-olefinic sulfoxides 46-5095 98 undergo highly diastereoselective Diels-Alder cycloadditions with cyclopentadiene, and pyridyl vinylic sulfoxide 5199 reacts diastereoselectively with furan. It is noteworthy that olefins singly-activated by only a sulfinyl group are not effective partners in Diels-Alder cycloadditions, as we have found after many attempts and as has been reported recently98. 

In the full account of this work, Padwa et al. (41) demonstrated that the 1,3-dipolar cycloaddition is an endo cycloaddition and the regiochemistry is consistent with that of a HOMO-dipole controlled process as judged from the products 91 and 92 that arise from the reaction between isomiinchnone 90 and methyl propiolate and phenyl vinyl sulfone, respectively (Scheme 10.15). Iso-miinchnone 90 is also trapped with DMAD to give the expected furan in 41% yield. 

It was shown <1998CCC681> that [l]benzothieno[3,2-3]furan 60, due to its low furan aromaticity, possesses dienophilic behavior and reacts with electron-rich dienes with the formation of a new heterocyclic system [l]ben-zothieno[3,2-3][l]benzofuran 93. Furthermore, it was reported <1999CCC389> that introduction of a vinyl moiety at C-2 of 57 created a reactive diene 94, which reacted with various dienophiles. Thus, both cycloaddition reactions led to new derivatives of heterocycle 93 substituted in the benzofuran part of the heterocyclic system (Scheme 10). 

Furanodecalins can be readily obtained in good yield using intramolecular cycloadditions of simple unsaturated esters as dienophiles. The (2 ,8Z)-nonadienoate 300, when heated to 290°C was converted into the c/s-furanodecalin 301 in quantitative yield. Thermolysis of the (2E, 8 )-nonadienoate 302, gave cw-furanodecalin 301 and the trans isomer 303 in a ratio 45 55. The same methodology is equally suited to 3-vinyl furans (88TL2107). 

Regiospecific cycloaddition of 65 a, b, and c to furan has also been observed. None of the oxazolinones give photoadducts with other olefins, including methyl vinyl ether, cyclohexene, cis-2-butene, trans-2-butene, and styrene. 

As an extension of this work, photoinduced [2+2]-cycloadditions of 1-acetylisatin (13) with cyclic enolethers (furan, benzofuran, 2-phenylfuran, 8-methoxypsoralen), and acyclic enolethers (//-butyl vinyl ether and vinyl acetate) were investigated which afforded the spiro-oxetanes in high yields (82-96%) and with high regio- and diastereoselectivity (Sch. 4) [19]. Treatment of the furan-derived oxetane 15 with acid resulted in oxetane ring opening and yielded the 3-(furan-3-yl)indole derivative 16. 

Theoretical and experimental studies revealed a mechanistic twist of the concerted [8+2] cycloaddition between dienylbenzo[c]furans and dimethyl acetylenedicarboxylate (DMAD). Thus, DFT calculation at the (U)-B3LYP/6-31+G(d) level had suggested a stepwise mechanism involving the formation of a zwitterionic intermediate for the [8+2] cycloaddition between DMAD and dienylbenzo[c]furans with electron-donating methoxy groups in the diene moiety. When no electron-donating substituents are present in the diene moiety of the dienylbenzo[c]furan, computational results indicated an alternative mechanism in which a [4+2] reaction occurs between the furan moiety and DMAD, and was followed by a [l,5]-vinyl shift <07JA10773>. 

Vinyl-substituted benzo[c]furans can be prepared by reaction of n-alkynylbenzaldehydes with chromium Fischer carbene complexes. Initially a benzo[c]furan chromiumtricarbonyl complex is believed to be formed which is converted into an alkylidenephthalan derivative or can be trapped with electron-deficient dienophiles with excellent ( 3 ti-selectivity (Equation 128) <20000L1267>. More elaborate vinylidene Fischer carbene complexes yield dienyl benzo[c]furans that undergo [8-1-2] cycloaddition with DMAD to furnish furanophane derivatives <2003JA12720>. An equilibrium between 7] -(o-ethynylbenzoyl)rhenium complexes and rhenium benzo[f]furyl carbene complexes has been observed. These species behave like other benzo[< ]furans in the reaction with DMAD <20040M4121>. 

For this comparison die [4 + 2] cycloadditions of methyl vinyl ketone to cyclopentadiene and to furan are chosen as reference reactions (Scheme 60, Table 9). Smectile clays, with the interlayer cations exchanged by CH" or Fe" ions, catalyzed the addition of cyclopentadiene in providing the endo product (258 Y = CH2) at a drastically reduced reaction temperature in high yield together with 10% of the exo product (259 Y = CH2) (entries 3,4). These results are comparable with those obtained under aqueous reaction conditions (entry 2), which supports the idea that die presence of water pockets in clays could account for their catalytic activity. The Lewis acidity as well as one-electron-transfer processes, involving the internal Fe " or Ci" cations, have also been invoked as possible explanations. 

There are just a few one-pot reactions in which two carbon-carbon bonds are simultaneously formed. One of these is the ancient but exceedingly useful Diels-Alder reaction, for which furans are particularly popular dienes. Consequently there would be nothing unusual about having compound I and methyl vinyl ketone (MVK) coupled in a Diels-Alder cycloaddition mode except for the fact that 2,5-disubstituted furans are known to be reluctant dienophiles. However, the amino group at C-2 considerably increases the reactivity of the furan nucleus as a diene by injecting electron density into the ring s x system. This phenomenon is underscored by the regiospecificity of the cycloadditon. 

Cycloaddition of vinylketenes, produced in situ from the dehydrohalogenation of appropriately substituted unsaturated acid chlorides, with alkenes provides a convenient source of 2-vinyl-cyclobutanones. Oxidation with ruthenium(III) chloride trihydrate gave the corresponding P-oxo acid, which by treatment with oxalyl chloride and diazomethane, successively, led to the desired 2-(2-diazoacetyl)cyclobutanones. These diazo ketones are thermally labile and rearrange upon brief heating in refluxing xylene to give the spiro[cyclopropane-l,5 -furan-2 (5 i/)-ones] 2 (Table 2). ... 

Koizumi observed a diastereoselective cycloaddition between furan and chiral vinyl sulfoxides 6 [15]. While the analogous p-tolylsulfinyl acrylates were completely unreactive in this reaction, the 2-pyridyl (Py) substituent signifi-... 

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