Intramolecular Diels-Alder reactions of furans

Keay B. A., Hunt 1. R. Aspects of the Intramolecular Diels-Alder Reaction of Furan Dienes Leading to the Formation of Epoxydecalin Systems Adv. Cycloaddit. 1999 6 173-210... 

Although the intramolecular Diels-Alder reaction of furan 40 does not occur with classical heating (Scheme 9.10) [51], the reaction has been performed successfully in 64% yield by using microwaves and absorbing the product on to silica gel-water. 

In another approach to periplanone B by Cauwberghs and De Clercq, an intramolecular Diels-Alder reaction of furan-allene 122 afforded a mixture of two exo adducts 123 and 124 and an endo adduct (not pictured) in 90% yield and a 5 4 1 ratio (Scheme 19.23) [28], Refluxing the mixture in mesitylene (N2, 164 °C) afforded a 2 1 equilibrium mixture of 123-124 through a cydoreversion process. The Diels-Alder adduct 123 was converted to 125 via a series of synthetic manipulations, which constituted a formal total synthesis of periplanone B (126). 

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>. 

The intramolecular Diels-Alder reaction of furans, often designated as IMDAF,15 helps to overcome the sluggishness of this heteroaromatic ring system toward [4+21-cycloaddition. Not only do IMDAF reactions allow for the preparation of complex oxygenated polycyclic compounds, but they also often proceed at lower temperatures than their intermolecular counterparts.9 Even more significantly, unactivated rc-bonds are often suitable dienophiles for the internal cycloaddition. Indeed, the submitters discovered that the IMDAF reaction of a series of furanamide derivatives occurred... 

Further experiments have shown that MeAlCl2 in catalytic amounts promotes the intramolecular Diels-Alder reaction of furans because the most basic site in the system is fhe reactive site in 13 so fhat the cycloadduct does not inhibit the catalysis (Scheme 6.9). In contrast, increasing the number of equivalents of MeAlCl2 reduces fhe conversion because MeAlCh-lB interaction is the more stable of fhe complexed forms fhis might be partly because of fhe diverse aggregates preferred by MeAlCl2. 

It was first reported in 1996 that indium trichloride catalyzes the Diels-Alder reaction in water [131]. The reaction of acrolein with cyclopentadiene in the presence of 20 mol% InCl proceeds stereoselectively (endo. exo=91 9) (Scheme 8.101). Without catalyst the reaction only goes to 60% completion (endo exo=74 26). The InCh-catalyzed Diels-Alder reaction works with either cyclic or non-cyclic dienes. InCh can be recovered for reuse after the reaction is completed. Indium triflate is also an effective catalyst for intramolecular Diels-Alder reactions of furans under microwave irradiation (Scheme 8.102) [132]. 

Intramolecular Diels-Alder reactions of furan derivatives 86YGK109. Oxidative coupling of furans under the action of transition metal catalysts ... 

The efficiency of the intramolecular Diels-Alder reactions of furan has been described in several reviews, including an excellent treatise by Lipshutz. Steric factors, rather than electronic or solvent effects, appear to have the greatest influence on the outcome of the cycloaddition [1,19,20]. Electronically-disfavored cycloadditions can be brought about by creative functional group modifications. Thus, an electron-deficient furan, such as one bearing an a-keto group, can be masked and induced to undergo cycloaddition, as shown in Eq.8 [21]. 

Metz has developed a highly diastereoselective intramolecular Diels-Alder reaction of furans with vinyl sulfonates [22]. When hydroxyfuran 10 a was esterified with vinylsulfonic acid chloride, the intermediate sulfonate spontaneously underwent cycloaddition to give sultone 11a, Eq. 9. In the same manner, (-)-llb was obtained from (i )-10b which was derived from L-valine. 

Another diastereoselective intramolecular Diels-Alder reaction of furan was studied by Keay wherein the methyl group in the tether of (—)—12 directed the facial selectivity of the cycloaddition. Equilibrating conditions using a catalytic amount of Lewis acid gave the tricyclic enone (—)-13, Eq. 10 [23]. 

Keay - High pressure intramolecular Diels-Alder reaction of furan as a diene I89TL1045]... 

The tandem acylation and intramolecular Diels—Alder reaction of furan installed on the tetrahedron-P-carboline skeleton produced bridged polycyclic alkaloid-like products (13JOC9738). 

Other Applications. Indium(III) triflate catalyzes the intramolecular Diels-Alder reaction of furans in aqueous media under microwave irradiation. In a one-pot procedure, allyl bromide reacts with (2-furfuryl)anilines affording the intramolecular Diels-Alder products in good to excellent yields, in very short reaction times (eq 19). Under thermal conditions, yields of40-45% are obtained. Such products allow access to indole derivatives through cleavage of the epoxy bridge and aromatization. 

L.M. Harwood, B. Jackson, G. Jones, K. Prout, R.M. Thomas, F.J. Witt, Synthetic approaches to phorbols via the intramolecular Diels-Alder reaction of furans Influence of the dienophile upon the stereochemical control, J. Chem. Soc. Chem. Commun. (1990) 608-610. 

S.J. Burrell, A.E. Derome, M.S. Edenborough, L.M. Harwood, S.A. Leeming, N.S. Isaacs, The high pressure mediated intramolecular Diels-Alder reaction of furan dienes a synthetic approach towards daphnanes. Tetrahedron Lett. 26 (1985) 2229-2232. 

Catalysis of Diels-Alder Reactions. MeAlClz has been used as a catalyst for Diels-Alder " and retro-Diels-Alder reactions. MeAlCl2 is the catalyst of choice for intramolecular Diels-Alder reactions of furans (eq 1) due to the ease of handling and reaction workup. ... 

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