Homofuran

This strategy to prepare rran.r,as-configurated functionalized dienes like 34 has elegantly been exploited for syntheses of HETEs (hydroxyeicosatetraenoic acids) and leukotrienes 27). These metabolites of arachidonic acid have received much attention due to thek biological activity. Syntheses of HETEs, for instance, follow the principle outlined in Eq. 12 with the acid catalysed ring opening of homofuran derivatives 36 to 37 as the stereoselective key step. 

Examples of the solvent-influenced competition between concerted [4 -I- 2]Diels-Alder type cycloaddition reactions and 1,4-dipolar reaction pathways with zwitterionic intermediates can be found in references [677-679], For example, in solvents of low polarity (CHCI3, CH2CI2), homofuran reacts with tetracyanoethene to form the seven-membered [4 -I- 2]cycloadduct A in quantitative yield. In solvents of high polarity (CH3CN), however, the [2- -2]cycloadduct B predominates, formed via a 1,4-dipolar activated complex and a zwitterionic intermediate [679] cf. Eq. (5-142). 

Cyclopropanation of 1-oxy-1,3-dienes is not regioselective . However, certain homofuran derivatives can yield highly electrophilic dienes as demonstrated in equation 86 . This reaction has served as one of the basic steps in a synthesis of the arachidonic acid metabolite 5-HETE (5-hydroxyeicosatetraenoic acid) . 

Similarly, vinylcyclopropane (1) gives only [2 -I- 2] cycladdition products with TONE, leaving the three-membered ring intact (see Section 2.2.1.2.2.). Preorientation of the vinylcyclopropane in the synperiplanar or synclinal conformation (rule 1), as realized in the bicyclohexene system 2, should enhance the reactivity towards dienophiles however, this is clearly insufficient. Additional strain (rule 2) or jc-donor substitution (3, rule 3) are further options to enhance the reactivity per se they seem to be insufficient. The combination of two activating principles, however, realized in homofuran (4, rule 1 -t- 3) or benzvalene (6, rule 1 -f 2) sufficiently peps up the reactivity of the embedded vinylcyclopropane system such that homo-diene-type cycloadditions occur (see Section 2.2.1.2.1.). 

Thus, 7t-donor substituents or additional strain is needed for additional activation to perform a smooth [27t + 2ff + 27i] cycloaddition. 7t-Donor-activated systems include homofuran (2),... 

Homothiophene and homofuran (10, X = S, O) are the most reactive substrates. They are easily prepared by carbene addition (using diazomethane as carbene precursor) to thiophene and furan, respectively. Since carbene insertion into the a-carbon-hydrogen bond of diethyl ether (which is usually used as a solvent) competes with carbene addition to the aromatic system, the diazomethane solution for carbene generation is most conveniently prepared using the reactant as solvent. ... 

In nonpolar solvents homothiophene and homofuran react with TCNE at room temperature within 20 minutes to give the bridged seven-membered ring compounds 11 in quantitative yield. Homofuran forms a red, and homothiophene a deep blue, charge-transfer complex with TCNE. During the course of the reaction the color fades and the product crystallizes. ... 

TCNE (256 mg, 2.0 mmol) and homofuran (164 mg, 2.0 mmol) or homothiophene (196 mg, 2.0 mmol) were dissolved in CHjClj (10 mL). The deep red color in the case of furan, or the deep blue color in the case of thiophene, faded within about 20 min. The solvent was removed to give colorless crystals in quantitative yield. 

In more polar solvents both homofuran and homothiophene give [4-1-2] and [2 4-2] cycloaddition products (mode selectivity), the ratio of products being dependent on the polarity of the solvent. ... 

The results are consistent with a concerted [2n- -lseven-membered ring and a forbidden [2n -h 2 i] cycloaddition, proceeding via a dipolar intermediate. The dipolar intermediate 14 has been trapped with methanol. For the reaction of homofuran with TCNE in acetonitrile the enthalpy and entropy of activation of the individual steps have been measured and are given in [kcal mol ] and [cal mol K ]. Formation of the [2-1-2] adduct 13 is reversible. 

Singlet oxygen and 4-phenyl-l,2,4-triazoline-3,5-dione also react with homofuran affording the [2 + 2] cycloadducts. 

The protolytic transformation of homofuran derivative 15 into methyl ( , )-6-oxohexa-2,4-dienoate is one of the key steps in a synthesis of the arachidonic acid metabolite 5-HETE. Activated, low acidity zeolites can be used to induce the isomerization of cyclo-propanes. " ... 

In so called homo Diels-Alder reactions, in which double bonds are replaced by three-membered rings or two 7r-bonds of the reactive 1,3-diene are bridged by an sp -hybridized group, a powerful pressure-induced acceleration and hence highly negative activation volumes comparable to those of the ordinary Diels-Alder reactions have been observed. Examples of the pressure effect on homo-Diels-Alder reactions are shown in Scheme 2.7. The reaction of homofuran with fumaronitrile (Scheme 2.7, entry (8)) [52] seems to be an exception in which the activation volume is significantly less negative than those in other cases. With the use of fumaronitrile and maleonitrile ((E)- and (Z)-NC-CH= CH-CN) as dienophiles it was es-... 

Herges and Ugi reported an analogous reaction between homofuran and tetracyanoethylene which leads to a seven-membered ring product (Eq. 45). These authors, however, favor a concerted pathway for this... 

The most simple way to combine the two ideas, fixing of the geometry in cis conformation and activation by an electron donating substituent, is bridging the system with the substituent. Our first trial was homofurane and tetracyanoethylene. 

The a-homobenzenes have been the subject of extensive investigation. The results of these investigations, to 1994, are summarized in the review by Williams and Kurtz.Several other formal bond homoaromatics have been prepared and/or studied since 1994. No claim is made for aromatic stabilization of their ground states nor that these compounds should be categorized as homoaromatic. Klamer et al. extended their earlier mechanistic work on the a-homofurans 105,106, and 107 to the thermolysis of the bridged bishomofuran lOS. ... 

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