Intramolecular cycloadditions of furans

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). 

Further examples of inter- and intramolecular cycloadditions of furans have been reported. Tochtermann and coworkers succeeded in the synthesis of 2(3)-8(9)-bis-anhydrolactarufin 18, starting with furan and dimethyl acetylenedicarboxylate (DMAD) <97T13703>. 

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... 

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-... 

Bicyclopropylidene (1) does not undergo an intermolecular Diels-Alder reaction with furan and 2-methoxyfuran even under high pressure. Intramolecular cycloadditions of compounds 160 with a furan tethered to bicyclopropylidene, however, were easily brought about under high pressure (10 kbar) and gave cycloadducts 161 stereoselectively in yields ranging from 32 to 95% (Scheme 35) [58]. 

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]. 

The intramolecular cycloaddition of nitrile oxides to substituted furans was reported to occur with low stereoselectivity (274). Inserting a stereogenic unit within the chain connecting the dipole and dipolarophile did not increase the stereoselectivity (274). 

C-acylation by the action of aluminum chloride (79BCJ3314). The unusual pathway to construction of 2,3,4-trihydronaphtho[6c]oxepine 474 is based on the intramolecular cycloaddition of a furan fragment to a benzyne (86AJC635). 

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). 

A simple procedure to prepare 5-aryl- and 5-pyridyl-2-furaldehydes from inexpensive, commercially available 2-furaldehyde diethyl acetal was reported. The reaction proceeded in a four-step, one-pot procedure and the yield of coupling step was usually between 58-91% <02OL375>. A facile route to 3,4-furandicarboxylic acids was developed. DDQ-oxidation of 2,5-dihydrofuran derivatives, which were produced from dimethyl maleic anhydride, furnished the desired esters of furan-3,4-dicarboxylic acid <02S1010>. The furan-fused tetracyclic core of halenaquinol and halenaquinone possessing antibiotic, cardiotonic, and protein tyrosine kinase inhibitory activities was synthesized. Intramolecular cycloaddition of an o-quinodimethane with furan gave the adduct as a single isomer via an enrfo-transition state, which was converted to trisubstituted furan by oxidation-elimination reactions <02T6097>. 

Several additional examples of the intramolecular cycloaddition of unactivated acetylenes with isomiinchnones were reported by Maier [30]. This cycloaddition approach represents an efficient method for providing rapid access to annulated furans present in several sesqui- and diterpenes, such as the panicu-lides [51],furanonaphthoquinones [52],furodysin,andfurodysinin [53,54].The decomposition of acyclic acetylenic diazoimides 102 and 103 with Rh2(OAc)4 resulted in cycloaddition and retro-Diels-Alder extrusion of methyl isocyanate to give annulated furans 104 and 105 in good yield. The overall transformation is closely related to the intramolecular Diels-Alder reactions of acetylenic oxa-zoles extensively studied by Jacobi and coworkers [55]. 

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>. 

As depicted in Scheme 41, an intramolecular cycloaddition of the furan 2,3-double bond of a furan tethered to a cyano-substituted benzocyclobutene via an intermediate quinone dimethide was used for the synthesis of the tetracyclic core of halenaquinol and halenaquinone <2001SL1123, 2002T6097>. The reaction proceeded via an OT,7i9-transition state to produce the cycloadduct 72 exclusively. A related chemistry is shown in Equation (56), in... 

Intermolecular [3+2] 1,3-dipolar cycloaddition of a D-glyceraldehyde-derived nitrile oxide to the 4,5-double bond of 2-methylfuran gave a 60 40 diastereomeric ratio of the two furoisozaxoline isomers. This chemistry was employed in the synthesis of L-furanomycin <2005EJ03450>. As depicted in Scheme 43, an intramolecular cycloaddition of a furan with a carbonyl ylide dipole proceeded under rhodium-catalyzed microwave-promoted conditions to provide the cycloadduct in a modest yield <20040L3241>. 

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]. 

West has recently reported intramolecular [4 + 4] cycloadditions of furan and 2-pyrone under photolysis in aqueous solution [49]. The exo and endo adducts are obtained in varying ratios when 31 bearing a variety of substituents is photolyzed in an aqueous solution of LiCl, Eq. 21. 

The intramolecular cycloaddition of a furan ester was reported several years ago to yield a tricyclic adduct [Eq. (21)].53... 

Cycloadditions of diene intermediates derived from 3-sulfolenes have been utilized to synthesize a variety of compounds. Diels-Alder reaction of furan 202 with excess DMAD initially gave intermediate 3-sulfolene 203. Extrusion of sulfur dioxide gave diene 204 which further reacted with DMAD to give ester 205 . Similarly, 2-bromopyrrole 206 reacted with excess DMAD to give ester 207 . Finally, an intramolecular cycloaddition of the diene derived from 3-sulfolene 208 gave ketone 209 . 

Gold-catalyzed intramolecular [4+2] cycloaddition of furans with alkynyl substituents led to the formation of phenol derivatives, A mechanistic study showed that a transposition of the oxygen from the carbon atoms of furan to the former terminal carbon of the alkynes seemed to occur through an intramolecular mode and the epoxide depicted below was presumably an intermediate <01OL3769>. 

Intramolecular Diels—Alder cycloaddition of furans (IMDAF) for natural product synthesis 13AHC(110)1. 

D. Margetic, R.N. Warrener, Container systems 11 an experimental study of the high-pressure intramolecular cycloaddition of tethered furans and anthracenes onto norbomane cyclobutene-l,2-diesters. J. Heterocycl. Chem. 51 (2014) 1369-1379. 

For the intramolecular cycloaddition of alkynes to furane derivatives, gold catalysts have proven to be a good choice. The Hashmi group was able to realize this transformation to generate bicyclic phenol derivatives such as 35 in good yields (Scheme 13.18) [19]. 

Intramolecular cycloaddition reactions of allylic cations with participation and/ or formation of heterocycles, mainly [4+3]-cycloaddition to furan system 97T6235. 

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