Cycloadditions of Furan

Intramolecular cycloadditions of furans are a useful method for creating an oxygenated cyclohexane ring in rigid cycloadducts. Thus, a MeAICI2-catalyzed intramolecular reaction [40] of compounds 34 leads stereoselectively to tricyclic cycloadducts (Equation 3.8). The reaction yield is strongly dependent on the quantity of the catalyst and the type of substituent at the olefmic double bond. Cycloadduct 35 (R = R2 = Me, Ri = R3 = R4 = H) was then converted [40b] into 1,4-epoxycadinane (36). 

Good yields and high diastereoselectivities were obtained by using zeolites in combination with Lewis-acid catalyst [21]. Table 4.7 illustrates some examples of Diels-Alder reactions of cyclopentadiene, cyclohexadiene and furan with methyl acrylate. Na-Y and Ce-Y zeolites gave excellent results for the cycloadditions of carbocyclic dienes, and combining these zeolites with anhydrous ZnBr2 further enhanced the endo diastereoselectivity of the reaction. An exception is the cycloaddition of furan that occurred considerably faster and with better yield, in comparison with the classic procedure [22], when performed in the presence of sole zeolites. 

The Diels-Alder cycloaddition of furan and acrylic acid, in the presence of hydroquinone as a polymerization inhibitor, provided enrfo-7-oxabicy-clo[2.2.1]hept-5-ene-2-carboxylic acid - (29) in a yield of 45%. Compound 29 was found to be the most accessible and important starting-material for the synthesis of various racemic carba-sugars, as well as their enantiomers. 

Cycloaddition of furan (5) has again been performed successfully under pressure and solvent-free conditions [12, 44], Usually, however, the cycloaddition of furan and heterocyclic compounds requires a Lewis-acid catalyst to give good yields. 

Cycloaddition of furans followed by a subsequent transformation is still adopted as a useful strategy to prepare fluorine-containing benzene derivatives and isoquinoline compounds <00SL550>. The cycloaddition adduct can also be converted to a trifluoromethyl substituted cyclohexanone compound via hydrogenation and hydrolysis. Examples of these transformations are illustrated below. 

The [3 + 2] cycloaddition of furan proceeds in the reaction of 5M in protic solvent (HFIP), where deprotonation from the initially formed intermediate 28 does not take place and intramolecular cyclization predominates in the termi-... 

An elegant application of the [3 + 4] cycloaddition methodology was showcased in model studies directed toward the synthesis of the core skeleton of CP-263114 115 (Scheme 14.12) [103]. The key step is the intramolecular [3 + 4] cycloaddition of furan with the siloxy-substituted vinyldiazoacetate in 112. The oxabicychc system 113 was obtained in 68% yield and was converted in eight steps to furnish the core structure 114 [103]. 

One of the drawbacks associated with the cycloadditions based on 27 is the low reactivity of halogenocyclopropenes towards dienes. This may be overcome if furans or isobenzofurans are used instead. The aromatization of the adducts is, however, not straightforward. For example, reaction of the exo-a.dd iCt of 27 to diphenylisobenzofuran (DPHIBF, 44) with BuLi affords no cycloproparene, but a product 46, where the bromo substituent is replaced by hydrogen. Aromatization may, however, be effected by use of low-valent titanium. This sequence provides a simple access to 48. The parent 42 is also available by this route from 45 via 47. Exposure of adducts of furans, such as 49, to low-valent titanium leads, however, to mixtures of benzocyclopropehe (1) and 1,6-dihalogenocycloheptatriene (51). Cycloaddition of furans to tetrahalogenocyclopropenes may equally be realized, but the adducts decompose in the presence of low-valent titanium and afford no cydoproparenes. 

Photochemical cycloadditions of furans have also been reported occasionally. The photochemical reaction of furan and 3-cyano-2-methoxypyridines (in benzene solution) results in the formation of 1 1 adducts 16 and 17 (accompanied by a transpositional pyridine and a pyridine dimer) <99JCS(P1)171>. 

Thermally unstable azetidines may be obtained by irradiation of furan in the presence of oxazolinones or 3-ethoxyisoindolone by [7r2s+ .2s] cycloaddition (Scheme 90) (75JA7298). Benzophenone photosensitized [ 2S+W2S] cycloaddition of furan to dimethylmaleic anhydride yields an adduct (34%). This reaction has been extended to 2,5-dimethylfuran and other maleic anhydrides and maleimides (76CA(84)120785). 

Density functional theory computational studies have been used to determine die importance of secondary orbital interactions for the stability of transition-state structures for die 4 + 2-cycloaddition of furan with cyclopropene.175 Kinetic studies of die 2 + 4-cycloaddition of 2-cyclopropylidene acetates with furan and dimethylful-vene suggest a mechanism involving diradicals or zwitterions as intermediates.176 Cyclopropene, produced by die reaction of allyl chloride with sodium bis(bimediyl-silyl)amide, reacts with 1,3-diphenylisobenzofuran to produce both endo- and exo-Diels-Alder cycloadducts isolated for the first tune.177... 

The Lewis acid-catalysed 4 + 3-cycloaddition of furan with chiral allylic dioxolans ( ) produced cycloadducts with high diastereoselectivity.177 Theoretical calculations have... 

Scheme 25 Synthesis of ROMP monomers via Diels-Alder cycloaddition of furan with different dienophiles [26]...

In accordance with this prediction, cycloaddition of furan and benzaldehyde (R1 = H) furnishes almost exclusively the (Sico-oxetane, whereas reaction with methyl benzoate (R1 = OMe) furnishes mainly the endo-oxetane C1998JOC3847, B-2004MI62-1, 2004JA2838>. 

The photo-[4+2] cycloaddition of furan with Pummerer s ketone 102 [70,71] gives evidence for the intermediacy of the highly twisted enone intermediate 103, and a biradical cycloaddition pathway (Sch. 23). The structures of the endo and exo products 104 were confirmed by X-ray crystallography [72,73]. In a related comparison of cyclohexenone and cyclopentenone photochemistry, conditions that gave [4+2] adducts for the cyclohexenone produced only [2+2] adducts from cyclopentenone [74]. 

The inter- and intramolecular Diels-Alder reactions of furans, and their applications to the synthesis of natural products as well as synthetic materials, were reviewed <1997T14179>. HfCU promoted the endo-seXccuve. inter-molecular Diels-Alder cycloadditions of furans with a,/3-unsaturated esters <2002AGE4079>. The cycloaddition between furan and methacrylate was also achieved under these conditions, providing, however the o-isomer as the major cycloadduct. A catalytic enantioselective Diels-Alder reaction between furan and acryloyl oxazolidinone to provide the < 46i-adduct in 97% ee was achieved by using the cationic bis(4-fer7-butyloxazoline)copper(ll) complex 55, as shown in Equation (41) <1997TL57>. 

A complexation-induced intramolecular Diels-Alder cycloaddition of furan is depicted in Scheme 34. Upon exposure to silica gel, the alkyne-Co2(CO)6 complex 61 was transformed to the cycloadduct that contained a seven-membered ring <20000L871>. This facile process was supposed to be arisen from the bending of the linear triple bond to a structure with a 140° angle between the two carbon substituents in the cobalt complex 61. 

In contrast to the extensively developed type-I intramolecular [4+3] cycloadditions as illustrated above, type-II intramolecular [4+3] cycloadditions with cation moieties tethered to the 3-position of furans have not been shown to be versatile transformations. As shown in Equation (51), an attempt on the cycloaddition of furan 69 only resulted in a low yield of the fused tricycle product that resembled the BC ring of ingenol <2003JOC7899>. 

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