Intermolecular furans

In contrast to intermolecular furan-carbonyl adducts, intramolecular oxetanes of this type often undergo retro-[2 + 2] cycloaddition when subjected to hydrolytic conditions10. Alternatively, oxymercuration and epoxidation give controlled functionalization of the oxetanes79. 

It is estimated that thiophene reacts with phenyl radicals approximately three times as fast as benzene. Intramolecular radical attack on furan and thiophene rings occurs when oxime derivatives of type (112) are treated with persulfate (8UCS(Pt)984). It has been found that intramolecular homolytic alkylation occurs with equal facility at the 2- and 3-positions of the thiophene nucleus whereas intermolecular homolytic substitution occurs mainly at position 2. 

The combination of two successive [4+2] cycloadditions has already been described by Diels and Alder [la] for the reaction of dimethyl acetylenedicarboxylate with an excess of furan. A beautiful, more modern, example is the synthesis of pagodane (4-5) by Prinzbach [2], in which an intermolecular Diels-Alder reaction of 4-1 and 4-2 to give 4-3 is followed by an intramolecular cycloaddition. The obtained 4-4 is then transformed into 4-5 (Scheme 4.1). 

Fully substituted furan as depicted below was prepared from a Baylis-Hillman adduct in the presence of sulfuric acid in a moderate yield. Intermolecular Friedel-Crafts reaction is one of steps to give rise to the final tetrasubstituted furan <06T8798>. 

As noted above, formation of a furan [4 + 3]-cycloadduct during irradiation of a 4-pyrone was advanced as evidence for the zwitterionic intermediate. This process can be moderately efficient (equation 4)68, and can be envisioned as an approach to substituted cyclooctanoids. Besides the formation of three new carbon-carbon bonds, an additional attractive feature is the complete diastereoselectivity, arising from a compact [4 + 3]-cycloaddition transition state with approach from the face opposite the epoxide. However, the generality of the intermolecular reaction is limited, as competing [2 + 21-photodimerization, solvent trapping and rearrangement often predominate58. 

Condensed benzo[i>]furan molecules can be prepared by inter- or intra-molecular Diels-Alder reactions from furo[3,4-b]benzofurans, and some interesting intermolecular examples are listed below. As can be seen, the furo[3,4-i>]benzofuran 60 underegoes Diels-Alder reactions with naphtho-l,4-quinone in the presence of Znl2 as a Lewis acid to form the aromatized cycloadduct. When the diene precursor reacts with benzo-l,4-quinone in the absence of Znl2, the product is obtained as an endo-exo mixture <00JCS(P1)1387>. 

An intermolecular version of a [4+2] cycloaddition-retrofragmentation of alkyne-oxazoles can be adapted to the synthesis of 2,3,4-trisubstituted furan in high regioselectivity if acetylenic aldehydes are used as starting materials. The product of this reaction is a pivotal intermediate for the synthesis of (-)-teubrevin G <00JA9324>. 

Diastereoselective syntheses of dihydrobenzo[f>]furans have been accomplished by a rhodium-catalyzed regioselective and enantiospecific intermolecular allylic etherification of o-iodophenols as a key step, providing the corresponding aryl ally ether 122, which leads to a dihydrobenzo[b]furan by treatment of the intermediate aryl iodide with tris(trimethylsilyl)silane and triethylborane at room temperature in the presence of air <00JA5012>. 

Palladium chemistry involving heterocycles has its unique characteristics stemming from the heterocycles inherently different structural and electronic properties in comparison to the corresponding carbocyclic aryl compounds. One example illustrating the striking difference in reactivity between a heteroarene and a carbocyclic arene is the heteroaryl Heck reaction (vide infra, see Section 1.4). We define a heteroaryl Heck reaction as an intermolecular or an intramolecular Heck reaction occurring onto a heteroaryl recipient. Intermolecular Heck reactions of carbocyclic arenes as the recipients are rare [12a-d], whereas heterocycles including thiophenes, furans, thiazoles, oxazoles, imidazoles, pyrroles and indoles, etc. are excellent substrates. For instance, the heteroaryl Heck reaction of 2-chloro-3,6-diethylpyrazine (1) and benzoxazole occurred at the C(2) position of benzoxazole to elaborate pyrazinylbenzoxazole 2 [12e]. 

One active field of research involving the Heck reaction is asymmetric Heck reactions (AHR). The objective is to achieve enantiomerically-enriched Heck products from racemic substrates using a catalytic amount of chiral ligands, making the process more practical and economical Although intermolecular Heck reactions that occurred onto carbocyclic arenes are rare, they readily take place onto many heterocycles including thiophenes, furans, thiazoles, oxazoles,... 

Two groups independently demonstrated that the strategy for the preparation of 55 could be used for the synthesis of 2-substituted-3-allenylbenzo[b]furans 59 (Scheme 3.31). The synthesis of 59 was achieved by intermolecular cyclization between alkynylphenols 56 and propargyl carbonates 57 [67] or by intramolecular rearrangement of (2-alkynylphenyl)propargyl ethers 58 [67, 68]. 

The key reaction in Jung et al. s proposed assembly of Plaunol B (81a) and C (81b) was an intermolecular Diels-Alder reaction between a diene and an allenic lactone that should give the exo-methylene group in the natural product (Scheme 19.16) [20], The phenyl-substituted lactone 83 was prepared as a model for the eventual furan lactone of the plaunols. Cydoaddition of 82 possessing a TBS enol ether and... 

Intramolecular Diels—Alder reactions without prior 1,4-addition of oxygen (cf. previous section) have similarly been postulated for a number of [2.2]paracyclophane analogs. When [2](2,5)furano[2](l,4)naphthalen-ophane (42) is heated in excess dimethyl acetylenedicarboxylate at 100 °C, a polycyclic compound of structure 134 is formed. The mechanism of formation of 134 is most probably as follows 101> the furan moiety reacts as active diene component in an intermolecular Diels—Alder reaction to give 135. This is followed by further intramolecular 1,4-addition with the unsubstituted naphthalene ring as diene component to give the product 133, which has been isolated. 

The use of cyclic alkenes as substrates or the preparation of cyclic structures in the Heck reaction allows an asymmetric variation of the Heck reaction. An example of an intermolecular process is the addition of arenes to 1,2-dihydro furan using BINAP as the ligand, reported by Hayashi [23], Since the addition of palladium-aryl occurs in a syn fashion to a cyclic compound, the 13-hydride elimination cannot take place at the carbon that carries the phenyl group just added (carbon 1), and therefore it takes place at the carbon atom at the other side of palladium (carbon 3). The normal Heck products would not be chiral because an alkene is formed at the position where the aryl group is added. A side-reaction that occurs is the isomerisation of the alkene. Figure 13.20 illustrates this, omitting catalyst details and isomerisation products. 

The Pd-catalyzed electro-cleavage of the C—O bond of allyl aryl ether proceeds smoothly in a DMF-Bu4NBp4-(Mg)-(Stainless Steel) system, giving depro-tected products in 73 99% yield [437]. The sp-sp intermolecular coupling reaction with the Pd water-soluble catalyst prepared in situ from Pd(II) acetate and sul-fonated triphenylphosphine in an MeCN-H2O system yields diynes in 45 65% yields [438]. Similarly, the sp -sp coupling of 2-iodophenols or 2-iodoanilines and terminal alkynes followed by intramolecular cyclization gives indol and furan... 

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]. 

Intermolecular Addition Formation of Unsaturated Ethers and Furans... 

In CHEC-II(1996) <1996CHEG-II(7)229>, intermolecular Diels-Alder reactions were conducted with furan to give nonaromatic species. This example explores the reaction of the diene 259 with dihydrofuran. The reaction proceeds with 100% conversion to give a mixture of stereoisomeric products, one of which, 260, is obtained in pure form (Equation 91) <2001HCA513, 2005EJ01142>. 

An interesting one-pot, five-component domino process using an intermolecular Diels-Alder reaction of furans with AT-phenylmaleimide as its final step has been used to construct the central core of indolo[2,3- ]carbazoles (Equation 86) <2002AGE4291>. Thus, aminooxazoles produced from an Ugi three-component reaction undergo acylation/intramolecular Diels-Alder/retro-Diels-Alder cycloreversion with pentafluorophenyl arylprop-2-ynoates to give furan derivatives. Subsequent Diels-Alder cycloaddition at elevated temperatures with A -phenylmaleimide produces carbazoles in good yields (Table 5). 

The reaction worked with both internal and terminal alkynes (except silylated alkynes) and in many solvents, even in the neat alcohol added [105]. The mechanism proposed involved two catalytic cycles first, gold catalysis would lead to dihydro-furan by a fast intramolecular reaction then, the subsequent slower intermolecular reaction would be produced by the addition of alcohol to the enol ether to deliver a ketal (Scheme 8.18). 

There is a growing number of examples in which furans undergo Diels-Alder reaction in an intramolecular manner. If conditions are favourable, these reactions occur more easily, and often with higher stereoselectivity, than their intermolecular counterparts. Allusion... 

When the diazoesters (240) and (241) were thermally decomposed in the presence of copper(II) acetoacetate ester as catalyst, an intermolecular carbene reaction occurred, the resulting benzo[c]furans (242) and (243) were not isolated but were trapped as the Diels-Alder adducts with N- methylmaleimide and dimethyl acetylenedicarboxylate (76CL287). 

The pyrolytic reactions of pentafluorophenyl and heptafluoro-2-naphthyl propargyl ethers give product mixtures containing benzo- and naphtho[6]furan derivatives, resulting from initial Claisen rearrangement followed by further intra- and intermolecular reactions.31 34... 

One of us has used molecular polarization potentials (MPP) to study the interaction of aromatic molecules, including furan, thiophene, and pyridine with a positive unitary charge, these maps being powerful tools for the study of intermolecular interactions and chemical reactivity [129,130], This kind of study leads us to examine theoretically the problem of the interaction between cations and anions with aromatic rings. We were pioneers in proposing that, in parallel with cation-7i-systems (for instance, benzene), there should exists anion-perfhiorinated-7i-systems (for instance, hexafluorobenzene) [131]. These studies include tetrafluorofuran and tetrafluorothiophene (128, 129). Simultaneously, Mascal et al. [132] described the same phenomenon but with 1,3,5-triazine (130) and 2,4,6-trifluoro-l,3,5-triazine (131) as acid 7i-systems. The group of the University of Palma de Mallorca has published a large number of papers on this topic [133] that are well summarized in a two recent reviews [134,135],... 

PhsPAuOTf has been shown to catalyse the intermolecular addition of phenols and carboxylic acids to terminal alkenes, RCH2CH=CH2, at 85 °C in toluene with Markovnikov selectivity to produce RCH2CH(OR)Me.131 AUCI3 triggers the electrophilic 6(0)ir n-endo-dig cyclization of 2-(alk-l-ynyl)alk-2-en-l-ones to produce highly substituted furans in analogy with other electrophiles (see above Scheme 3).40... 

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