Furan ring, intramolecular cycloaddition

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). 

Diterpenoids related to lambertianic acid were prepared by intramolecular cyclization of either an alkene or an alkyne with a furan ring <2005RJ01145>. On heating amine 101 with allyl bromide, the intermediate ammonium ion 102 was formed which then underwent [4+2] cycloadditions in situ to give the spiroazonium bromides 103 and 104 (Scheme 13). These isomers arose from either endo- or co-transition states. The analogous reaction was also carried out with the same amine 101 and propargyl bromide. The products 105 and 106 contain an additional double bond and were isolated in 58% yield. The product ratios of 103 104 and 105 106 were not presented. 

In contrast, substrates 149 all furnished [4 + 3]-cycloadducts 150 and 151 in yields ranging from 10-79% (Scheme 34)68. In all cases, exclusive approach of the furan from the zwitterion face opposite the epoxide ring was seen. In most cases, the exo diastereomer 151 was the major product or was formed to the exclusion of the endo diastereomer 150. The contrasting diastereoselectivity seen in inter- and intramolecular cycloadditions may result from unfavorable nonbonding interactions in the endo transition state between the tether atoms and the alkyl groups at C-2 and C-5. 

Kanematsu and co-workers devised a simple pathway to isobenzofurans and dihydroisobenzofurans starting with substituted furans of type 62. Treatment with strong base results in an alkyne-allene isomerization. Subsequent intramolecular cycloaddition, ring opening (probably oxygen lone-pair assisted), and acidic workup give 63. 

Intramolecular cycloaddition reactions have been performed on the furan-containing indoles 143, to provide an efficient route to numerous derivatives of the tetracyclic ring system 144, a structural motif of Aspidosperma and Strychnos alkaloids <02OL4643>. 

A striking example of the special effects produced by intramolecular cycloaddition is discussed by Ghisalberti et al.Si who pointed out that, if correctly poised, the furan ring can act as the dienophile instead of the diene component (Scheme 10). Otherwise the ability of furan to act as the dienophile... 

The construction of tetracyclic substrate 25 has been achieved by the intramolecular cycloaddition of a furan tethered (n = l) to a cycloalkanone using conditions related to those developed by Fohlisch, Eq. 15 [42,43]. As the ring size of the oxyallyl cation increased, products arising from cycloaddition via the less strained exo transition state predominated. Cycloadducts with n = 6,8 have also been successfully prepared as a mixture of stereo isomers [43 b]. 

A furan ring has been reported as the diene in some intramolecular [4 + 2] cycloadditions of nitriles [Eq. (7)].12... 

Alkenylmethyl) cyclic ethers are formed by the reaction of lactols and alkenes." Diels-Alder reactions. Diethylaluminum chloride deposited on silica seems to be a superior catalyst. Methylaluminum dichloride alone is effective in promoting intramolecular cycloadditions involving a furan ring as the diene. ... 

Very recently, Padwa reported a total synthesis of strychnine based on an intramolecular Diels-Alder reaction/rearrangement cascade, which was previously developed in his group to assemble the tetracyclic core ring system of indole alkaloids (Scheme 16) (174-178). Intramolecular cycloaddition reactions often benefit from higher reactivity and greater control of stereoselectivity relative to their intermolecular counterparts. Unlike Bodwell s lEDDA reaction (Scheme 13), the reaction of an electron-rich furan moiety with an N-acyl indole moiety required only a single tether. His synthesis also involved... 

The intramolecular cycloaddition of furans with vinyl-sulfonamides provided enantiopure sultams in good to excellent yields. The thermal reaction of 90, for example, produced a 54 42 mixture of five-membered ring sultams... 

Magnus, P. and Littich, R. (2009) Intramolecular cyclopropane-furan [2+4] cycloaddition followed by a cydopropylcarbinyl rearrangement to synthesize the BCD rings of cortistatin A. Org. Lett., 11, 3938-3941. 

In an attempt to study these reaction at longer wavelengths, particularly for fluorescence experiments, substrates with naphthalene chromophores 41 were examined, (Scheme 14). Again, intramolecular electron transfer was clearly demonstrated by fluorescence, but the products formed, 42 and 43, resulted from an unusual [ 2jt-I-27i] -cycloaddition of the ester carbonyl to the aromatic 7t system of the naphthalene ring. Intermolecular cycloadditions of ester carbonyls to aromatic rings are known, but only for furan. ... 

Cycloadditions of dienes with oxyallyl offer the opportunity to prepare seven-membeted ring systems. This reaction has also proved to be of importance in Ae furan series. A few examples may illustrate the value of this methodology. A tandem Pummerer rearrangement and intramolecular [4-i3]-cycloaddition with a fiiran derivative has been reported <99TL545>. For a similar reaction see <99T13999>. 

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